Objective We aimed to explore whether maternal exercise has epigenetic effects on improving the adverse placental environment associated with maternal overweight/obesity. Methods Based on samples collected from an RCT cohort, differentially methylated genes and expressed protein-coding RNA were identified in the placentas of 16 women with overweight and obesity who did or did not participate in an exercise intervention using the Infinium HumanMethylation850 BeadChip array and RNA Sequencing-Based lncRNA Profiling. Potential target genes were further identified by integrating this information. Then, the target genes’ methylation and expression levels were verified, and correlation analysis was performed with placental oxidative stress markers and participants’ clinical metabolic parameters. Results A total of 3608 significant differentially methylated probes were detected. The CBR1 gene, which was previously identified as a possible antioxidant, was significantly hypomethylated at CPG site promoter regions in placentas from the exercise group, and CBR1 gene expression levels were significantly higher. CBR1 gene expression levels were negatively associated with DNA methylation levels. Furthermore, CBR1 gene expression levels were negatively correlated with MDA levels in both placenta and cord blood samples and insulin resistance levels in late pregnancy. Additionally, CBR1 methylation levels were positively correlated with fasting plasma glucose and insulin resistance levels in late pregnancy. Conclusion DNA methylation is involved in the ameliorating effect of exercise on the adverse placental environment associated with maternal overweight/obesity.

To identify risk factors for COVID-19 infection and investigate the impact of COVID-19 infection on chronic kidney disease (CKD) progression and vasculitis flare in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This cohort study retrospectively analyzed the prevalence and severity of COVID-19 infection in 276 patients with AAV who were followed up. Logistic regression was employed to estimate the risk of COVID-19 infection as well as CKD progression and vasculitis flare upon COVID-19 infection. During the 6-month observation period, 213 (77.2

With the widespread transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the medical community has organized efforts to determine a series of clinical questions about the virus. Critical questions have also arisen in the area of maternal-fetal medicine and received increasing attention, as physiological and immunologic changes in pregnancy might potentially increase the susceptibility to SARS-CoV-2 infection and complications of the virus.1 Many early reports indicated that pregnant women with SARS-CoV-2 infection were not prone to experiencing severe disease.2–4 However, later studies supported pregnancy as a risk factor for severe disease associated with SARS-CoV-2 infection, like ICU admissions, invasive ventilation, extracorporeal membrane oxygen (ECMO) utilization and death.5,6 Additionally, pregnant women with severe or critical SARS-CoV-2 infection are at risk for various perinatal complications, such as cesarean section, hypertensive disorders of pregnancy, and preterm birth.2,7 Risk factors for severe or critical SARS-CoV-2 infection include advanced maternal age, increased body mass index, and underlying medical comorbidities such as asthma, chronic hypertension, and pregestational diabetes.2,7 However, the risk of fetal infection due to vertical transmission of SARS-CoV-2 is still a major concern and debated issue.8 Vertical transmission is defined as the transmission of the infectious pathogen from the mother to fetus via the placenta or ascending infection in utero (intrauterine), body fluid contact during delivery (intrapartum), or through breastfeeding after birth (postpartum). At present, the extent to which vertical transmission of SARS-CoV-2 occurs and when it occurs is unclear. This article reviews the current evidence and perspectives. Incidence Yan et al.3 conducted a cohort study with 116 pregnant patients with SARS-CoV-2 infection who delivered 100 babies. Of these neonates, 86 tested negative for SARS-CoV-2 via nasopharyngeal swab testing. An analysis by 3 major Harvard-affiliated hospitals showed that among 149 of 159 newborns (94%) that underwent testing for SARS-CoV-2 within 24 hours of delivery, none showed a positive result for SARS-CoV-2 (0/149).9 The largest cohort study was from the United Kingdom, which included 427 pregnant women with SARS-CoV-2 infection. In that study, 12 of 244 neonates who were tested by nasopharyngeal swabbing after birth were positive for SARS-CoV-2 (12/244); 6 of them were tested within 12 hours of birth.10 A systematic review and meta-analysis that included 38 cohort or case series studies showed that a pooled proportion of 3.2% for vertical transmission through testing 936 neonatal nasopharyngeal SARS-CoV-2 RNA, either immediately after birth or within 48 h of birth.11 A recent meta-analysis that included 206 cohort studies and 266 case series and case reports showed that in cohort studies, 1.8% of the 14,271 babies born to mothers with SARS-CoV-2 infection had positive results for SARS-CoV-2 based on reverse-transcriptase polymerase chain reaction (RT-PCR) analysis after birth. When the analysis was limited to babies tested in the first 24 hours after birth, the positivity rate was 0.9%. When combined the cohort studies with case series and case reports to further assess the timing of mother-to-child transmission based on the in utero exposure testing and viral persistence testing according to the categorization of World Health Organization (WHO) classification system.12 The results showed that of the 536 SARS-CoV-2–positive babies with sufficient data to apply the WHO classification system for timing of exposure and likelihood of infection, 14 were categorized as having confirmed mother-to-child transmission: seven with in utero transmission (448 assessed), two with intrapartum transmission (18 assessed), and five with early postnatal exposure (70 assessed).13 Evidence of SARS-CoV-2 intrauterine vertical transmission Since the onset of the pandemic, worldwide efforts were made to explore the possibility of vertical transmission of SARS-CoV-2. The first study from China reported a retrospective cohort of 9 pregnant women with SARS-CoV-2 infection, by RT-PCR analyses of the virus, on babies born to mothers with SARS-CoV-2 infection and their paired amniotic fluid and cord blood. The study indicated no evidence for intrauterine vertical transmission in late pregnancy.14 Subsequently, more studies have reported similar results and failed to demonstrate the intrauterine vertical transmission of SARS-CoV-2, including negative testing in newborn's nasopharyngeal swab, placental tissues, umbilical cord blood, amniotic fluid, and vaginal swabs.3,4,15,16 However, with the increasing number of published studies on SARS-CoV-2 infection during pregnancy, few cases have suggested probable intrauterine vertical transmission of SARS-CoV-2. However, most reports have been based on single positive results of neonatal nasopharyngeal SARS-CoV-2 detected by RT-PCR tests with significant differences in sample collection times.8,17–19 Thus, although strict isolation measures were undertaken for neonates, the lag time to neonatal nasopharyngeal swab raises the possibility of postnatal transmission. However, several published literatures have described the detection of SARS-CoV-2 in intrauterine tissue samples such as amniotic fluid, placenta, and umbilical cord plasma,20–29 which further supports the hypothesis that, even uncommon, there may be intrauterine vertical transmission of SARS-CoV-2. First trimester Shende et al. reported a pregnant woman tested positive for SARS-CoV-2 at 8 weeks of gestation, despite being symptomless. At 13 weeks of gestation, the ultrasound indicated fetal demise and the patient underwent dilation and curettage. SARS-CoV-2 RNA was detected in the placenta cells. In addition, viral RNA was found in the amniotic fluid and the Spike proteins of SARS-CoV-2 were immunolocalized in cytotrophoblast and syncytiotrophoblast cells of the placental villi. However, in this case, no fetal tissue was available for testing of viral particles.20 Valdespino et al.21 reported a case of spontaneous twin abortion in early pregnancy from a SARS-CoV-2 infected symptomatic mother. RT-PCR of the placenta, kidneys, and lungs for SARS-CoV-2 of 1 fetus was positive, confirmed by immunofluorescence and electron microscopy. Second trimester In one case, a SARS-CoV-2–positive pregnant mother miscarried at 19 gestational weeks. Fetal axillae, mouth, meconium, and blood samples obtained within minutes after the birth all tested negative for SARS-CoV-2 by RT-PCR. However, placental swabs from the fetal side taken within minutes of birth were positive for SARS-CoV-2 RNA.22 The second case reported a patient with SARS-CoV-2 infection who delivered at 22 weeks of gestation because of severe preeclampsia and placental abruption. SARS-CoV-2 RNA detected by RT-PCR tests in the placenta and umbilical cord samples were positive; furthermore, viral capsids were found in the trophoblast cells by electron microscopy, confirming infection of the fetal side of the placenta. However, fetal tissues (lung, myocardium, liver, kidney) showed normal histology without inflammation.23 The third case was of a premature neonate delivered at 26 weeks of gestation. SARS-CoV-2 RNA was positive in the placenta and umbilical cord blood samples. In addition, SARS-CoV-2 nucleocapsid and SARS-CoV-2 spike protein in the cytotrophoblast and syncytotrophoblast were shown to be positive by immunohistochemical analysis. No fetal tissues were tested for SARS-CoV-2.24 Another study was of a second-trimester twin stillbirth in a woman with SARS-CoV-2 infection. Placental histology and immunohistochemistry of both fetuses demonstrated SARS-CoV-2 infection, and SARS-CoV-2 RNA was detected by using RT-PCR in all tissue samples (fetal lung, kidney, heart, and liver and maternal placenta, cords, and membranes), except for the kidney of the second fetus.25 Third trimester Zamaniyan et al.26 described the detection of SARS-CoV-2 in the amniotic fluid obtained during cesarean section from a pregnant woman with severe SARS-CoV-2 infection who delivered at 32 gestational weeks. Neonatal nasopharyngeal SARS-CoV-2 just after birth was negative, but positive on the second test within 24 hours of birth. Kirtsman et al.27 reported a woman with SARS-CoV-2 infection who delivered at 35 gestational weeks by cesarean section, and SARS-CoV-2 PCR testing of the placental tissue had a positive result, as did the RT-PCR test of the neonatal nasopharyngeal swabs, plasma, and stool samples, highly suggestive of utero vertical transmission. Vivanti et al28 reported a probable case of transplacental transmission of SARS-CoV-2 during late pregnancy. The amniotic fluid and placental sample tested positive for SARS-CoV-2 by RT-PCR. In addition, the placenta showed signs of intervillous inflammation that was consistent with the severe maternal systemic inflammatory status triggered by SARS-CoV-2. RT-PCR on neonatal nasopharyngeal and rectal swabs collected 1 hours after birth and blood and nonbronchoscopic bronchoalveolar lavage fluid collected in the first 6 hours after birth were all positive for SARS-CoV-2 genes. This is probably the best evidence to date for intrauterine vertical transmission of SARS-CoV-2.28 A recent multicenter prospective study including 31 pregnant women with confirmed SARS-CoV-2 infection showed that 2 of 31 newborns tested positive for SARS-CoV-2. In addition, the SARS-CoV-2 genome was detected in one umbilical cord blood sample and in 2 at-term placentas.29 A systematic review by Kotlyar et al.11 indicated that vertical transmission of SARS-CoV-2 infection in the third trimester is possible but rare. Their results showed that of 936 neonates from mothers with SARS-CoV-2 infection, 27 tested positive for SARS-CoV-2 RNA by RT-PCR with a nasopharyngeal swab. Furthermore, SARS-CoV-2 RNA was positive for 1 neonatal cord blood sample (1/34, 2.9%), 2 placenta samples (2/26, 7.7%), and 3 fecal or rectal swab samples (3/31, 9.7%), but 51 amniotic fluid samples and 17 urine samples tested negative. In addition, neonatal serology analysis based on the presence of immunoglobulin M was positive for 3 of 82 samples (3.7%).11 Serologic assessments were also performed in neonatal serum samples to explore the possibility of intrauterine vertical transmission of SARS-CoV-2.30–34 However, thus far, no conclusive and concrete evidence was found for in utero vertical transmission of SARS-CoV-2.35 Pathological basis of SARS-CoV-2 intrauterine vertical transmission The low reported rate of SARS-CoV-2 intrauterine vertical transmission is likely because in most studies, pregnant women had mild-to-moderate symptoms that manifested during the third trimester of pregnancy, and in some cases, cesarean sections were carried out immediately given the uncertainty about the risk of mother-to-fetus transmission of the virus, especially in the early pandemic. Therefore, the nonserious condition and short time interval from clinical manifestation of SARS-CoV-2 to delivery might have weakened the fetus' chances of intrauterine infection of the virus.14,35 Notably, from a pathophysiologic viewpoint, the intrauterine SARS-CoV-2 infection for fetuses has a biological plausibility. First, it has been found that angiotensin-converting enzyme 2 receptor and transmembrane protease serine 2 required for SARS-CoV-2 entering the cells is expressed in the placenta.36–38 Although the data regarding their expression is inconsistent, and whether they have different expressions due to different gestational weeks are not clear, the angiotensin-converting enzyme 2/transmembrane protease serine 2 pathway is considered the main mechanism of transplacental invasion of SARS-CoV-2. SARS-CoV-2 can directly damage the placenta by inducing apoptosis and vascular damage. As a result, the virus can infect the fetus without the need for placental cell infection.36 In addition, the rare viraemia associated with severe SARS-CoV-2 infection may let the virus spread via the bloodstream to the uterus and then infect the fetus. Therefore, the possibility of intrauterine vertical transmission of SARS-CoV-2 requires further careful study. Knowledge gaps in SARS-CoV-2 intrauterine vertical transmission The available research until now regarding the possibility of intrauterine vertical transmission of SARS-CoV-2 has mainly involved the third trimester and shows large differences in study quality and in what data were reported. Furthermore, the finding of SARS-CoV-2 in amniotic fluid or placental tissues does not necessarily correlate with a positive RT-PCR result in the fetus or neonate.22,26,39 Thus, it is a challenge to aggregate and compare the data across studies. To date, there is a shortage of standardized international consensus definitions for the evaluation of vertical transmission of SARS-CoV-2. However, several classification systems have been initially developed to help categorize the likelihood of intrauterine transmission of SARS-CoV-2, and they all have a few requirements: (1) evidence of maternal SARS-CoV-2 infection, (2) in utero fetal SARS-CoV-2 exposure, and (3) SARS-CoV-2 persistence or immune response in the neonate.12,40,41 The studies outlining these systems emphasize that collection of appropriate specimens at appropriate times is essential to understanding of SARS-CoV-2 vertical transmission. Taking the World Health Organization12 classification system as an example to make a definite diagnosis of in utero vertical transmission, it requires 2 components. (1) Evidence of in utero exposure (RT-PCR from amniotic fluid, placental tissue, neonatal blood, upper and lower respiratory tract samples, stool, or cerebrospinal fluid; or immunoglobulin M positive); and (2) evidence of viral persistence, that is, a positive result upon repeat testing in 24 to 48 hours in sterile samples (amniotic fluid, neonatal blood, lower respiratory tract sample, or cerebrospinal fluid). In the case of fetal demise in early pregnancy, it requires fetal tissues (lung, liver, brain) for a confirmed positive result. However, in clinical practice, it is difficult to repeat the testing in 24 to 48 hours in amniotic fluid, neonatal blood, or lower respiratory tract or cerebrospinal fluid samples, making the definite diagnosis difficult. With increasing knowledge of SARS-CoV-2 vertical transmission and its clinical consequences for the fetus and neonate, the classification system might be further updated and refined. Additionally, many questions remain to be answered concerning intrauterine vertical transmission of this virus. For example, whether susceptibility to the virus is different by gestational age and whether there is a period during pregnancy when the fetus is more likely to be infected. Furthermore, does the severity of maternal illness determine the likelihood of viral transmission? Are new variants—like the Delta variant which is more aggressive and highly transmissible—able to cause more severe disease?42,43 Moreover, whether the effects of SARS-CoV-2 on the uterine vasculature and placenta can cause adverse outcomes, such as fetal growth restriction or stillbirth. To address these questions, further high-quality studies with a large sample size are needed. Longitudinal follow-up of infants born to mothers with SARS-CoV-2 infection are also needed. Furthermore, the use of animal models might accelerate our knowledge. Evidence of intrapartum and postpartum vertical transmission of SARS-CoV-2 SARS-CoV-2 is rarely detected in the vaginal swabs in infected pregnant women.3,11,44 Regarding studies about evaluation for SARS-CoV-2 in breast milk, although the virus was occasionally positive tested,45 to the potential for contamination is questionable. Furthermore, the detected SARS-CoV-2 RNA in the human milk was particle of the virus but not live virus46 Moreover, an observational cohort study reported that if correct hygiene precautions are undertaken, like consistent use of surgical masks, hand hygiene, and breast cleansing, breastfeeding can be safely carried out without the fear of SARS-CoV-2 transmission.47 Conclusions Vertical transmission of SARS-CoV-2 is possible, but rare. The relevant knowledge regarding the possible risks is still limited and controversial. Further studies investigating this issue and the subsequent fetal and neonatal consequences are needed. Further conclusive evidence regarding SARS-CoV-2 vertical transmission will help guide patient counseling and provide better obstetrical care for women with SARS-CoV-2 infection.

Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019, the virus has overwhelmed the world's health. Pregnant women as a vulnerable group, the broad implications of SARS-CoV-2 for obstetrical care and perinatal outcomes have raised concern and promoted the rapid development of research. Chinese clinicians and scientists working in obstetrics rapidly reported globally the clinical characteristics, pregnancy outcomes, and vertical transmission potential of SARS-CoV-2 infection in pregnancy on February 12, 2020[1] and published clinical management consensus specific for SARS-CoV-2 infection in pregnancy at the earliest time,[2] which were valuable for preventive and clinical practice in China and elsewhere in the early stages of the pandemic. With the passing of time and updating of information, developments have been achieved in our understanding of obstetric outcomes, vertical transmission, and therapeutics for the treatment and prevention of SARS-CoV-2 infection; furthermore, the progress shed light on the gaps in current knowledge for future work. Maternal and Fetal Outcomes. Although initial reports suggested that pregnant women with SARS-CoV-2 infection were not prone to experience severe disease,[1,3,4] as the pandemic progresses, more recent data indicated that pregnant patients with SARS-CoV-2 infection are at an increased risk for severe illness compared with non-pregnant patients. Data from the US Centers for Disease Control and Prevention, which compared 386,028 non-pregnant women of reproductive age and 23,434 pregnant women all with symptomatic SARS-CoV-2 infection, showed that pregnant patients with SARS-CoV-2 infection were at a three-fold increased risk for both intensive care unit (ICU) admission and invasive ventilation. Additionally, pregnant individuals were at a 2.4-fold increased risk of needing extracorporeal membrane oxygenation (ECMO) and a 70% increased risk of death.[5] A living meta-analysis reported similar results that pregnancy was a risk factor for severe diseases associated with SARS-CoV-2 infection, like ICU admissions, invasive ventilation, and maternal death.[6] Advanced maternal age, high body mass index, and chronic medical conditions (hypertension, pre-existing diabetes, and cardiovascular disease) are the risk factors for increased SARS-CoV-2 infection severity.[6,7] Furthermore, accumulating evidence showed that SARS-CoV-2 infection, especially severe or critical SARS-CoV-2 infection during pregnancy, might be associated with increased risks of adverse pregnancy outcomes. A meta-analysis including 42 studies involving 438,548 pregnant women with comparison data on evaluating disease severity and perinatal outcomes indicated that compared with no SARS-CoV-2 infection in pregnancy, SARS-CoV-2 infection in pregnancy was associated with 33%, 82%, and 2-fold increased risk of preeclampsia (PE), preterm birth (PTB), and stillbirth, respectively. Moreover, compared with mild SARS-CoV-2 infection, severe SARS-CoV-2 infection was strongly associated with PE, PTB, gestational diabetes, and low birth weight; and the odds ratio reached as high as 4.16, 4.29, 1.99, and 1.89, respectively.[8] Subsequently, two studies found similar findings. One of 1219 pregnant patients with SARS-CoV-2 infection showed that compared with asymptomatic patients, severe-critical SARS-CoV-2 infection was associated with 57%, 61%, and 3.5-fold increased risks of cesarean birth, hypertensive disorders of pregnancy, and PTB.[9] One showed that there was a dose-response relationship between the severity of SARS-CoV-2 infection and the risk of PE and PTB. Pregnant patients with severe SARS-CoV-2 infection had a five-fold greater risk of PTB and PE than asymptomatic patients.[10] The increased risk of PTB associated with SARS-CoV-2 infection might be driven largely by medically indicated PTB.[11] The leading indications reported included PE, small for gestational age, and fetal distress.[11] Additionally, obstetricians might opt to deliver the infant to try to save the critically SARS-CoV-2 infected mother.[12] The increased risk of PE was more likely to be associated with placental vascular and inflammatory changes, and systemic inflammation and hypercoagulability were associated with SARS-CoV-2 infection. For example, a recent view indicated that SARS-CoV-2 can cause endothelitis through infecting angiotensin-converting enzyme 2 (ACE2) which is the cellular receptor of SARS-CoV-2 that normally expressed in endothelial cells, leading to activation of thrombin, intravascular inflammation, and damage of endothelial function in multisystemic organs, which could be one mechanism by which that SARS-CoV-2 infection can be causally linked to PE.[13] Additionally, the causes of stillbirth were likely to be associated with SARS-CoV-2 placentitis, which could lead to severe placental damage.[14] Certainly, new data are highly demanded to further demonstrate the pathological mechanism between SARS-CoV-2 infection and the increased risk of adverse obstetric outcomes, thus potentially preventing and decreasing maternal and fetal mortality and morbidity by possibly identifying novel therapeutic interventions. At this time, data are insufficient to suggest an increased risk of congenital malformation associated with SARS-CoV-2 infection in pregnancy. An observational cohort study with 92 pregnancies exposed to SARS-CoV-2 infection and 292 unexposed pregnancies indicated that maternal SARS-CoV-2 infection during the first months of pregnancy was not associated with fetal major congenital malformations.[15] However, a case report study suggested that maternal SARS-CoV-2 infection in weeks 5 and 6 of embryonic development was associated with neonatal severe eye malformation.[16] Evidence indicated that in utero transmission of SARS-CoV-2 is possible based on the detection of SARS-CoV-2 in intrauterine tissue samples, such as amniotic fluid, placenta, and umbilical cord plasma.[17] Besides, placental expression of ACE2 and transmembrane protease serine 2 (TMPRSS2) required for SARS-CoV-2 entering the cells makes the transplacental transmission of SARS-CoV-2 theoretically feasible.[17] However, the rates of intrauterine vertical transmission of SARS-CoV-2 seem to be uncommon.[17] Additionally, the data on the safety of breastfeeding among mothers infected with SARS-CoV-2 are reassuring.[17] To date, the long-term health consequences of maternal SARS-CoV-2 infection for both the mother and offspring remain largely unclear. A 1-year follow-up of 7772 live births of whom 222 births with SARS-CoV-2 exposure in utero suggested that prenatal SARS-CoV-2 infection was associated with an 86% increased risk for offspring neurodevelopmental disorder, even after adjustment for confounders including PTB.[18] So we did a small case-control study from China, which also indicated that infection with SARS-CoV-2 during pregnancy may have an impact on infant neurobehavioral development between 8 months and 10 months.[19] These highlight the importance of conducting well-controlled follow-up studies to clarify the long-term effects of prenatal SARS-CoV-2 exposure on mother and child. Vaccination:Vaccination is considered the best method to reduce maternal and fetal complications of SARS-CoV-2 infection. Recent studies found that most cases of SARS-CoV-2 infection during pregnancy were among unvaccinated individuals and those who were vaccinated experienced less severe illness.[20] Thus, women planning a pregnancy are advised to get vaccinated against SARS-CoV-2. Available data on SARS-CoV-2 vaccines during pregnancy and lactation suggest that they are safe and effective.[21] However, the data are mostly focused on mRNA vaccines, those about the adenoviral vaccine or inactivated influenza virus vaccines are limited. Additionally, several questions associated with the SARS-CoV-2 vaccines are still needed to be illustrated, including optimal gestational timing of SARS-CoV-2 vaccination, extent of neonatal/infant protection with maternal vaccination, and long-term outcomes. At present, the coverage rate of SARS-CoV-2 vaccines among pregnant persons is still at a low level, the main reasons were concerns about limited information about the vaccine safety, and fear of harm to the fetus or infant. But along with more data and knowledge on vaccination in pregnant and lactating women, we believe more effective strategies to reduce vaccine hesitancy in pregnancy could be developed and the total rates of vaccination in women of childbearing age may be improved. Public Health Issues: The emergence of SARS-CoV-2 pandemic arguably represents the greatest threat to global public health in this century and has lasted longer than many of us would have expected. The pandemic not only has a direct impact of viral illness on health outcomes but also has social impacts, such as disruption of healthcare services, which may also have affected the well-being of humans. Pregnancy cannot pause and be terminated during the pandemic that created endless challenges. Studies have shown that the SARS-CoV-2 pandemic and its effects on healthcare systems have had adverse effects on pregnancy outcomes even among pregnant women without SARS-CoV-2 infection.[22] Thus, planning for robust maternity services and high-quality remote care in any emergency response is of great importance. Healthcare providers, scientific researchers, and policy-makers should learn from this pandemic and prioritize safe and accessible maternity care during the pandemic. The effect of SARS-CoV-2 pandemic has also shown a psychological impact on the mental health of pregnant and postpartum women.[23] Pregnant and breastfeeding women are vulnerable populations to mental health disorders. In the context of the pandemic, maternal psychological problems might be further exacerbated by limited social support, social isolation, change in routine associated with SARS-CoV-2 infection, and especially concerns and fears regarding the risk of morbidity and mortality associated with SARS-CoV-2 infection for themselves, their fetus, or their newborn infants. Therefore, attention should be paid to perinatal mental health during pandemic and timely intervention should be carried out to relieve psychological problems and support the health of both mothers and children. Perspective: Though the rapid advance in the field of SARS-CoV-2 infection and pregnancy is admirable, the impact of SARS-CoV-2 on the maternal/fetal unit from a population health level to a basic science level still has a lot of uncharted territories to explore. Furthermore, the continuously emerging variants of the virus with different transmissibility and varying symptoms make diagnosis, treatment, and the development of a vaccine against the virus challenging. Thus, efforts to understand the virus should continue. Funding This work was supported by a grant from the National Key Research and Development Program of China (No. 2021YFC2700700). Conflicts of interest None.

The activities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the coastal wetlands play important roles in global nitrogen cycle. However, the driving factors of activities of AOA and AOB are still unclear. We collected 62 soil/sediment samples from coastal wetlands of the Bohai area of China to assess the potential activity of AOA (PAOA) and AOB (PAOB) using specific inhibitors. At last, we introduced the structural equation modeling (SEM) to infer direct and indirect effects of variables on potential activities. The results indicated that the change in AOA-amoA gene abundance may be more independent, while AOB-amoA was closely associated with the change in abundance of amx and denitrifier. PAOA was mainly defined by AOA-amoA abundance and partially influenced by the norA gene, suggesting coupling of archaeal ammonia oxidation with nitrite oxidation. PAOB was significantly defined by the abundance of amx and denitrifier, indirectly mediated by AOB-amoA. The activity of AOA seemed to be more independent of other microbial activities, while the activity of AOB varied closely with fluctuations of other microbial species. PAOA was mediated directly by the C/N ratio and indirectly by nitrite concentration and TOC value, while PAOB was mediated directly by ammonium concentration and TOC value and indirectly by C/N ratio. The activity of AOB may be determined by several other functional gene groups and had little correlation with AOB abundance while the activity of AOA was mostly controlled by itself.

Antibiotics are pollutants that are constantly discharged into ocean and coastal wetlands and affect the growth and activity of microorganisms. Ammonia‐oxidizing archaea (AOA) and bacteria (AOB), which are very important in the global nitrogen cycle, are affected by antibiotics in the environment as well. Antibiotics have different influences on AOA and AOB microbial communities due to their different biochemical compositions and metabolic mechanisms, which change the ammonia‐oxidizing process in different environments. In this study, 62 samples from four typical coastal wetland types along the Bohai Rim were collected and treated with streptomycin sulfate and penicillin in the laboratory. The total ammonia oxidation rate decreased by 61.2–84.0% with streptomycin sulfate and decreased by 50.0–74.5% with penicillin. The significant change in abundance and community structure indicated that AOB were more inhibited than AOA by streptomycin sulfate and penicillin. Nevertheless, ecological network analysis verified that the internal association in the AOA community was more fragile than that in the AOB community. Moreover, the relationship between AOA and other nitrogen‐transforming functional archaea weakened in the presence of antibiotics, while AOB established relationships with more nitrogen‐transforming functional bacteria in the presence of antibiotics. Streptomycin sulfate had a stronger effect than penicillin due to the different inhibiting mechanisms of these antibiotics and the promotion of interspecific cooperation induced by penicillin in AOA.

To investigate the association between fibroblast growth factor 21 (FGF21) levels and glycemic response to exenatide in patients with type 2 diabetes. The exploratory analysis of a multi-center trial included 190 patients with type 2 diabetes inadequately controlled by monotherapy or combination therapy of metformin and insulin secretagogues. All participants received exenatide twice daily as an add-on therapy for 16 weeks. Serum FGF21 and other information at the baseline and end of follow-ups were obtained. Linear regression analysis was used to determine the correlations between baseline FGF21 levels and HbA1c reduction from baseline after the treatment. After 16 weeks of treatment with exenatide, a decline in the HbA1c levels from baseline was associated with higher baseline FGF21 levels among all participants (r = 0.193, P = 0.008) and in subgroup of the participants receiving background metformin monotherapy (r = 0.231, P = 0.034). Compared with patients in the lowest FGF21 quartile, patients in the highest FGF21 quartile showed a significantly weakened decline in HbA1c levels from baseline among all participants (β = − 0.16 [95% Cl − 0.31 to − 0.01], P < 0.05) and in subgroup of the participants receiving background metformin monotherapy (β = − 0.23 [95% Cl − 0.43 to − 0.03], P < 0.05), after adjusting for the confounding factors, including age, sex, and baseline HbA1c levels. The high baseline FGF21 levels are associated with poor glycemic responses to exenatide in patients with type 2 diabetes. Therefore, FGF21 could be used as a biomarker for predicting the efficacy of exenatide treatment. ChiCTR-IPR-15006558, date registered May 27, 2015.

This study aimed to evaluate which environmental factors and genetic groups were important in explaining measured activity of Ammonia-oxidizing archaea (AOA) and bacteria (AOB), which play important roles in global nitrogen cycle, providing a new insight into the mechanism of archaeal and bacterial ammonia oxidation. We sampled 62 soil/sediment samples from coastal wetlands of the Bohai area of China and assessed the abundance of functional genes involved in the nitrogen cycle, soil/sediment characteristics and the potential activity of AOA (PAOA) and AOB (PAOB) using specific inhibitors. At last, we introduced the structure equation model (SEM) to infer direct and indirect effects of variables on potential activities. The results indicated that the change in AOA- amo A gene abundance may be more independent, while AOB- amo A was closely associated with the change in abundance of amx and denitrifier. PAOA was mainly defined by AOA- amo A abundance and partially influenced by the norA gene, suggesting coupling of archaeal ammonia oxidation with nitrite oxidation. PAOB was significantly defined by the abundance of amx and denitrifier, indirectly mediated by AOB- amo A. The activity of AOA seemed to be more independent of other microbial activities, while the activity of AOB varied closely with fluctuations of other microbial species. PAOA was mediated directly by the C/N ratio and indirectly by nitrite concentration and TOC value, while PAOB was mediated directly by ammonium concentration and TOC value and indirectly by C/N ratio. The activity of AOB may be determined by several other functional gene groups and had little correlation with AOB abundance while the activity of AOA was mostly controlled by itself.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide and is now a global pandemic. One of the major concerns is whether SARS-CoV-2 can be vertically transmitted from mothers to their fetuses, thus causing congenital infection. The most conclusive evidence of intrauterine transmission of COVID-19 would be to confirm the replication of SARS-CoV-2 in fetal pulmonary tissues, but this is almost infeasible technically. Practically, the approach to investigate whether there has been intrauterine viral infection is to test for the presence of the virus in placental, amniotic-fluid, cord-blood and neonatal pharyngeal swab samples. It is important to emphasize that all of these samples need to be collected immediately after delivery using aseptic technique, in order to guarantee that the samples are not contaminated and that they represent intrauterine conditions. In the first study investigating the possibility of intrauterine vertical transmission of COVID-19 in nine pregnant women with mild to moderate manifestation of laboratory-confirmed COVID-19 in the third trimester, matched amniotic-fluid, cord-blood and neonatal pharyngeal swab samples from six neonates were tested for SARS-CoV-2, using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). All samples tested negative, suggesting that intrauterine fetal infection did not occur during the third trimester of pregnancy1. Utilizing similar methodology, Lei et al. demonstrated no evidence of vertical transmission in four pregnant women with COVID-19 in the third trimester, and vaginal secretion samples also tested negative for SARS-CoV-2 RNA2. In the study by Chen et al.3, paired placental tissues from three pregnant women with confirmed COVID-19 in the third trimester and neonatal pharyngeal swab samples were used to evaluate the potential risk of intrauterine vertical transmission, and all samples tested negative for SARS-CoV-2 RNA. Notably, a neonate born to a pregnant woman with COVID-19 tested positive for SARS-CoV-2 RNA in the pharyngeal swab sample obtained 36 h after birth, but it was subsequently confirmed that qRT-PCR testing of the placental and cord-blood samples was negative for SARS-CoV-2, suggesting that intrauterine vertical transmission might not have occurred4, 5. Thus, based on existing data, there is currently no evidence of intrauterine infection caused by vertical transmission in women with COVID-19 in the late third trimester. However, some questions remain unanswered. In the studies described above, most pregnant women had mild to moderate COVID-19 symptoms, and in all cases, symptoms manifested during the third trimester of pregnancy, therefore, the time interval from clinical manifestation of SARS-CoV-2 to delivery was short. Since the placental barrier may temporarily delay the transfer of the virus from the mother to the fetus, as observed in cytomegalovirus infection, it is uncertain whether there could be a risk of vertical transmission when SARS-CoV-2 infection occurs in the first or second trimester, or when there is a long interval between clinical manifestation and delivery. Additionally, there appear to be some mechanisms by which SARS-CoV-2 could potentially cause intrauterine infection by transplacental vertical transmission. Zhao et al. demonstrated that angiotensin-converting enzyme 2 (ACE2), which was recently identified as the putative surface receptor of sensitive cells for SARS-CoV-26, is expressed in the human placenta7. This opens up the possibility of SARS-CoV-2 spreading transplacentally through ACE2. In addition, damage to the placental barrier caused by severe maternal hypoxemia in women with COVID-19 could potentially lead to vertical transmission of SARS-CoV-2 causing intrauterine infection. Most recently, two studies explored the possibility of vertical transmission of SARS-CoV-2 in a combined total of seven affected pregnancies, by testing for SARS-CoV-2-specific antibodies (immunoglobulin G (IgG) and immunoglobulin M (IgM)) in neonatal serum samples using recently developed automated chemiluminescence immunoassays8, 9. Based on the detection of anti-SARS-CoV-2 IgM antibodies in blood samples obtained following birth from three neonates, the two studies concluded that SARS-CoV-2 could be transmitted in utero. However, in all three neonates, pharyngeal swab samples were negative for SARS-CoV-2 RNA and testing of cord-blood and placental samples was not performed thus there was no direct evidence of infection. Of note, the sensitivity and specificity of the immunoassays used in the two studies have not been evaluated extensively10. Furthermore, it is well known that IgM assays are prone to false-positive results10. When using specific IgG and IgM antibodies as a method to detect a viral infection, it is important to observe the kinetic changes of the antibodies. Zeng et al. did not evaluate the dynamic changes of anti-SARS-CoV-2 IgM and IgG antibodies in the neonates8. In the study of Dong et al., the observed decline of anti-SARS-CoV-2 IgG and IgM levels from 140.32 AU/mL (normal range is 0–10 AU/mL) and 45.83 AU/mL (normal range is 0–10 AU/mL), respectively, at 2 h after birth, to 69.94 AU/mL and 11.75 AU/mL, respectively, at 14 days of age, is not consistent with the typical profile of the body's antibody response to acute viral infection9. As the half-life of IgG antibodies is around 21–23 days and the time lag between the development of anti-SARS-CoV-2 IgM antibodies and the production of IgG antibodies is about 1 week11, 12, the rapid decline ((140.32 − 69.94)/140.32 = 50%) of anti-SARS-CoV-2 IgG antibody level in the infant within 14 days, in addition to the decline in anti-SARS-CoV-2 IgM antibody level, strongly indicates that the neonatal anti-SARS-CoV-2 IgG antibodies were derived transplacentally from the mother and their production was not actively induced by the presumed neonatal infection. In our opinion, these two studies do not provide concrete evidence to prove that SARS-CoV-2 infection can be acquired in utero. In a cohort study by Zeng et al.13, three of 33 (9%) infants were diagnosed with neonatal early-onset infection with SARS-CoV-2 based on positive qRT-PCR result in two consecutive nasopharyngeal and anal swab samples obtained on day 2 and day 4 of age. Though strict infection control and prevention measures were implemented during the delivery, the possibility of postpartum neonatal infection cannot be completely excluded because of the delay in testing. All three infants tested negative for SARS-CoV-2 RNA on day 6 (n = 2) or 7 (n = 1) of age13. Whether neonatal SARS-CoV-2 infection has the same virological profile as that of adult infection requires further investigation. High-quality research is needed to elucidate whether SARS-CoV-2 can be transmitted in utero from the mother to the fetus. First, we propose that cohort studies evaluating the risk of fetal adverse outcome, including structural malformation, miscarriage and fetal growth restriction, in pregnant women with COVID-19 contracted during the first or second trimester are essential in investigating whether vertical transmission of SARS-CoV-2 can occur. Second, collection of appropriately matched biological samples immediately after delivery, using aseptic technique, from pregnant women with COVID-19 is important to help determine whether SARS-CoV-2 can be transmitted vertically. Biological samples should include cord blood, placental tissue, amniotic fluid and amnion–chorion interface swab. Though we do not assume that the fetus can acquire the virus through the respiratory route, we believe that neonatal pharyngeal swab is also a suitable biological sample for the detection of SARS-CoV-2 RNA, as the virus is detectable in the upper airway because it is propagated proximally by epithelial cilia of the respiratory tract. In the event that a pregnant woman with COVID-19 experiences a miscarriage, testing of the miscarried fetus and placenta for SARS-CoV-2 should be undertaken, if possible. Third, in addition to testing for SARS-CoV-2 RNA by qRT-PCR, serological tests could be an important supplement to help clarify the question of vertical transmission of SARS-CoV-2. However, longitudinal follow-up of infants born to women with COVID-19 during pregnancy is required. For example, if biological samples collected immediately after birth are negative for SARS-CoV-2 RNA, but the newborn tests positive for IgM and IgG antibodies against SARS-CoV-2, longitudinal follow-up of the IgG antibody concentrations in the infant is required. If the IgG antibodies in the infant become negative within 6 months, the possibility of intrauterine infection can be ruled out, and if the IgG antibodies in the infant persist till the age of 18 months or beyond, the diagnosis of congenital infection can be confirmed after excluding the possibility of infection during infancy. In conclusion, there is currently no concrete evidence of intrauterine vertical transmission of SARS-CoV-2, but further high-quality research is needed. Virological and serological evidence is valuable to clarify this issue, however, the study design should be scientifically sound and reliable assays should be used, and longitudinal follow-up of infants for 6–18 months after birth is essential to draw reliable conclusions when serological results are used.

Aerobic ammonia oxidation, an important part of the global nitrogen cycle, is thought to be jointly driven by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in coastal wetlands. However, the activities and contributions of AOA and AOB in coastal wetlands have remained largely unknown. Here, we investigated the oxidation capability of AOA and AOB in four types of typical coastal wetlands (paddy, estuary, shallow and reed wetland) in the Bohai region in China using DNA-based stable-isotope probing (DNA-SIP), quantitative PCR and high -throughput sequencing techniques. We found that the community structure of AOB varied substantially, and the AOA structure was more stable across different coastal wetlands. The rate of AOA was 0.12, 0.84, 0.45 and 0.93 mu g N g(-1) soil d(-1) in paddy, estuary, shallow and reed wetlands, and the rate of AOB was 5.61,10.72, 0.74 and 1.16 mu g N g(-1) soil d(-1), respectively. We found that the contribution of AOA gradually increased from paddy to estuary to shallow wetland and finally to reed wetland, with values of 2.03%, 7.25%, 37.53% and 44.51%, respectively. Our results provide new insight into the mechanisms of the differences in activities and the contributions of AOA and AOB in different coastal wetlands, and our findings may contribute to further understanding of the global nitrogen cycle. (C) 2020 Elsevier Ltd. All rights reserved.

To evaluate effects of PDCA cycle in improving residency diagnosis and treatment ability of endocrine and metabolic diseases, this paper selected the problems of insufficient diagnosis and treatment ability in the results of the 2016 endocrinology examination paper as the research breakthrough point, and investigated 62 residents receiving standardized residency training to analyze main reasons of the problems such as "busy clinical work", "special clinical thinking" and "difficult to remember knowledge of endocrinology". The online teaching, daily self-education, following the law of memory to remember and re-recognize knowledge, strengthening the construction of teachers, improving teaching methods were used and evaluated. It’s found that the application of PDCA cycle can improve the residents' ability of clinical diagnosis and treatment in endocrine and metabolic diseases.

Background: Previous studies on the caronavirus (2019-nCoV)-infected pneumonia (NCIP) were based on the information from general population, and limited data are available in NCIP with pregnancy. This study aimed to evaluate clinical characteristics, pregnancy outcomes, and vertical transmission potential of pregnancy with 2019-nCoV infection. Methods: We retrospectively reviewed the data of nine pregnant patients with laboratory-confirmed NCIP hospitalized in the Zhongnan Hospital of Wuhan University from Jan 20 to Jan 31, 2020. Detailed epidemiological, demographic, laboratory, and clinical data were collected for each patient. Evidence of vertical transmission was assessed by qRT-PCR for 2019-nCoV in amniotic fluid, cord blood, breast milk and neonatal throat swab samples from 6 of 9 cases. Results: All of the 9 cases had an epidemiological exposure, which defined as having either a travel/residence history in the epidemic area or direct contacts with NCIP patients. They were all in the third trimester of pregnancy. Seven patients presented fever without chill on admission. Other atypical symptoms, including cough(4/9), myalgia(3/9), sore throat(2/9) and malaise(2/9), were also observed. Complications, including gestational hypertension(1/9), severe preeclampsia(1/9), Premature rupture of membrane(PROM) (2/9), and fetal distress(2/9), were monitored. Most of the cases(5/9) had lymphopenia (<1.0x109/L). Particularly, 3 cases showed abnormal liver function. One patient complicated with sever preeclampsia and influenza was characterized by elevated aminotransferase and no sign of fever before delivery. None of the cases developed severe NCIP or died as of Feb 3, 2020. A total of 9 live births were recorded. All tests on specimens from 6 of 9 patients, including amniotic fluid, cord blood, breast milk and neonatal throat swab samples showed negative results. Interpretation: The clinical characteristics of NCIP in pregnancy were atypical. In our limited cases, no evidence of vertical transmission was found in NCIP patients with third trimester pregnancy. Funding: Hubei Science and Technology Plan, Wuhan University Medical Development Plan. Declaration of Interest: The authors declare that there are no conflicts of interest in this manuscript. Ethical Approval: This study was reviewed and approved by Medical Ethical Committee of Zhongnan Hospital of Wuhan University (Approval Number: 2020004). Written informed consents were obtained from all enrolled patients.

目的 探讨护士主导型个案管理对胃癌术后患者胃肠功能和自护能力的影响.方法 将94例胃癌手术患者随机分为对照组和试验组,对照组按照胃癌外科护理常规进行护理,试验组在常规护理的基础上,实施护士主导型个案管理.结果 试验组患者的首次下床时间、首次排气时间、首次进食时间和术后平均住院日均短于对照组,差异具有统计学意义(p<0.05);患者的自护能力总分及自护责任感、健康知识和自护技能三个维度得分均高于对照组,差异具有统计学意义(p<0.05).结论 护士主导型个案管理能够促进胃癌术后患者的胃肠功能恢复,缩短患者术后平均住院日,提高患者自护能力.

The novel coronavirus infection (COVID-19) is a global public health emergency. Since the first case of COVID-19 pneumonia was reported in Wuhan, Hubei Province, China, in December 2019, the infection has spread rapidly to the rest of China and beyond. As of 1st March 2020, a total of 85 406 confirmed cases of COVID-19 infection have been reported, together with 39 597 recovered and discharged patients and 2933 deaths1. Huang et al.2 first reported a cohort of 41 patients with laboratory-confirmed COVID-19 pneumonia. They described the epidemiological, clinical, laboratory and radiological characteristics, as well as treatment and clinical outcome of the patients. Subsequent studies with larger sample sizes have shown similar findings3, 4. The diagnosis of COVID-19 pneumonia is based on epidemiological exposure, clinical manifestation, laboratory results, findings on computed tomography (CT) of the chest and a positive COVID-19 test result based on quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of specimens acquired from the respiratory tract. However, the fifth edition of the 'New coronavirus pneumonia prevention and control program' guideline5 has stated that, in the worst-hit areas in China (Hubei Province), suspected cases with typical chest CT findings may be diagnosed clinically with COVID-19 pneumonia, as the qRT-PCR test has a false-negative rate of at least 30%. Thus, in our opinion, in the worst-hit areas, in addition to using nucleic acid tests as the gold standard for diagnosis of COVID-19 pneumonia, a combination of laboratory results, chest CT findings and a comprehensive evaluation of the patient's medical history, epidemiological exposure and symptoms is of great importance. Pregnancy is a physiological state that predisposes women to viral infection. Over and above the impact of COVID-19 infection on a pregnant woman, there are concerns relating to the potential effect on fetal and neonatal outcome; therefore, pregnant women constitute a group that requires special attention in relation to prevention, diagnosis and management. In this Opinion, we review the clinical manifestation, neonatal outcome and risk of vertical transmission of COVID-19 infection during pregnancy. Due to the physiological changes in their immune and cardiopulmonary systems, pregnant women are more likely to develop severe illness after infection with respiratory viruses. In 2009, pregnant women accounted for 1% of patients infected with influenza A subtype H1N1 virus, but they accounted for 5% of all H1N1-related deaths6. In addition, severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), two notable strains of the coronavirus family, are both known to be responsible for severe complications during pregnancy, including the need for endotracheal intubation, admission to an intensive care unit (ICU), renal failure and death7, 8. Interestingly, the impact of COVID-19 infection on pregnant women appears to be less severe. Chen et al.9 reported the clinical characteristics of nine pregnant women with laboratory-confirmed COVID-19 in the third trimester, which comprised mainly fever and cough. Other symptoms included myalgia, malaise, sore throat, diarrhea and shortness of breath. Data from laboratory tests showed that the majority of patients had lymphopenia and increased C-reactive protein, and chest CT scans showed multiple patchy ground-glass shadows in the lungs. Pregnancy complications that appeared after the onset of COVID-19 infection included fetal distress in two of nine patients and premature rupture of the membranes in two of nine patients. None of the patients developed severe COVID-19 pneumonia or died. Another series10 of nine pregnant women with COVID-19 pneumonia presenting from mid-trimester onwards, or during the postpartum period, reported similar findings except for one woman requiring ICU care and ventilation for acute respiratory distress syndrome after the infection was diagnosed 2 days postpartum. In general, both studies reported that the clinical characteristics of the pregnant women with COVID-19 pneumonia were similar to those of non-pregnant adult patients who developed COVID-19 pneumonia2-4. These observations are also in line with what has been learned about COVID-19 pneumonia in pregnancy in several other hospitals in Wuhan, China. Pregnant healthcare professionals should follow risk-assessment and infection-control guidelines following exposure to patients with suspected or confirmed COVID-19. Adherence to recommended infection prevention and control practices is an important part of protecting all healthcare professionals in clinical settings11. Of major concern is whether the virus can be transmitted from mother to baby. In the study by Chen et al.9, of nine pregnant women with COVID-19 in the third trimester, no fetal death, neonatal death or neonatal asphyxia was observed9. Although four neonates were born prematurely, none of these deliveries was related directly to COVID-19 infection. All newborns had an Apgar score ≥ 9 at 5 min. Amniotic fluid, cord blood and neonatal throat-swab samples collected from six patients tested negative for COVID-19, suggesting there was no evidence of intrauterine infection caused by vertical transmission in women who developed COVID-19 pneumonia in late pregnancy. Furthermore, it appears that there is no risk of vertical transmission via breastfeeding. The same study confirmed that the virus was not detected in the colostrum of COVID-19-infected patients. However, as the virus is transmitted via close contact, currently in China, all newborns are separated from their infected mothers for at least 14 days, which makes direct breastfeeding unfeasible. The mothers are, however, advised to express their breastmilk in order to maintain milk production. Once they test negative for COVID-19, they are then able to breastfeed their infant. All nine of these pregnant women underwent Cesarean delivery as they were symptomatic with COVID-19 pneumonia in the third trimester of pregnancy. The time interval from the clinical manifestation of COVID-19 infection to Cesarean delivery was short (range, 1–7 days). It is therefore uncertain whether there is a risk of vertical transmission if the clinical manifestation-to-delivery interval is more than 7 days. Although previous studies have reported no evidence of congenital infection with SARS-CoV12, currently there are no data on fetal and perinatal complications, such as miscarriage, congenital anomalies, fetal growth restriction and spontaneous preterm birth, when COVID-19 infection is acquired during the first or early second trimester of pregnancy. A recent study by Zheng et al.13 demonstrated that the receptor, angiotensin-converting enzyme 2 (ACE2), of COVID-19 has very low expression in almost all cell types of the early maternal–fetal interface, suggesting that there may be no cells that are potentially susceptible to COVID-19 in the maternal–fetal interface. It is, therefore, probable that COVID-19 infection during pregnancy cannot lead to transplacental vertical transmission. We acknowledge that available clinical data on COVID-19 infection in pregnancy are limited at present, and most cases on which data are available presented in the third trimester of pregnancy. There is, therefore, a need to continue collecting data on clinical cases of COVID-19 infection in pregnancy, and to improve our understanding of the course of the disease throughout pregnancy. COVID-19 infection is highly contagious and this must be taken into consideration when planning intrapartum care. It is unclear whether, for the safety of both baby and healthcare professionals, a pregnant woman with COVID-19 infection should be allowed to deliver vaginally, which can be a rather long process. There have not yet been any studies examining whether COVID-19 infection can be transmitted during delivery. Future research could explore whether vaginal delivery increases the risk of transmission from mother to child during delivery by testing vaginal secretions. Since COVID-19 itself is transmitted mainly through respiratory droplets and by close contact, if a newborn is in close contact with an infected mother, contact infection is likely to occur. It has been reported that the youngest patient with COVID-19 infection was diagnosed 36 h after birth9. Particular attention, therefore, should be paid to the protection of neonates born to women with COVID-19 infection. In our opinion, in the event that an infected woman has spontaneous onset of labor with optimal progress, provided that appropriate preventative measures are in place, she could be allowed to deliver vaginally, but with a shortened second stage, as active pushing while wearing a surgical mask would be unfeasible. Regarding a pregnant woman without a diagnosis of COVID-19 infection, but who might be a silent carrier of the virus, we urge caution regarding the practice of active pushing while wearing a surgical mask, as it is unclear whether there might be an increased risk of exposure to any healthcare professional attending the delivery without full personal protective equipment, because forceful exhalation may significantly reduce the effectiveness of a mask in preventing the spread of the virus by respiratory droplets. It is therefore crucial to acquire a detailed history from the mother regarding travel, occupation, contact and cluster (TOCC). For a woman with TOCC risk factors but without a diagnosis of COVID-19 infection, appropriate precautions should be taken. In summary, based on the available clinical and research data, the clinical characteristics of patients with COVID-19 infection presenting from mid-trimester onwards are similar to those of non-pregnant adults. Currently, there is no evidence that pregnant women are more susceptible to COVID-19 infection and that those with COVID-19 infection are more prone to developing severe pneumonia. There is also no evidence of vertical mother-to-baby transmission of COVID-19 infection when the maternal infection manifests in the third trimester. Our opinions are in line with the recommendations of the Centers for Disease Control and Prevention11. COVID-19 infection should not be the sole indication for delivery; rather, the patient should be duly assessed, and management, timing and mode of delivery should be individualized, dependent mainly on the clinical status of the patient, gestational age and fetal condition14. Ongoing collection of clinical data and research is underway with the aim of answering questions in relation to the risk of congenital infection and the optimal intrapartum management, and timing and mode of delivery. Lastly, we would like to pay tribute to all frontline medical professionals who are working tirelessly to bring the COVID-19 epidemic under control.

BACKGROUND:The coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2, is a global public health emergency. Data on the effect of coronavirus disease 2019 in pregnancy are limited to small case series.OBJECTIVE:To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of severe acute respiratory syndrome coronavirus 2 infection.STUDY DESIGN:Clinical records were retrospectively reviewed for 116 pregnant women with coronavirus disease 2019 pneumonia from 25 hospitals in China between January 20, 2020, and March 24, 2020. Evidence of vertical transmission was assessed by testing for severe acute respiratory syndrome coronavirus 2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples.RESULTS:The median gestational age on admission was 38+0 (interquartile range, 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. Of the 116 cases, there were 8 cases (6.9%) of severe pneumonia but no maternal deaths. One of 8 patients who presented in the first trimester and early second trimester had a missed spontaneous abortion. Of 99 patients, 21 (21.2%) who delivered had preterm birth, including 6 with preterm premature rupture of membranes. The rate of spontaneous preterm birth before 37 weeks' gestation was 6.1% (6/99). One case of severe neonatal asphyxia resulted in neonatal death. Furthermore, 86 of the 100 neonates tested for severe acute respiratory syndrome coronavirus 2 had negative results; of these, paired amniotic fluid and cord blood samples from 10 neonates used to test for severe acute respiratory syndrome coronavirus 2 had negative results.CONCLUSION:Severe acute respiratory syndrome coronavirus 2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of severe acute respiratory syndrome coronavirus 2 infection when the infection manifests during the third trimester of pregnancy.

Excessive nitrogen (N) loadings from human activities have led to increased eutrophication and associated water quality impacts in China's coastal wetlands. Denitrification accounts for significant reduction of inorganic N to nitrous oxide (N2O) or dinitrogen gas (N-2), and thereby curtails harmful effects of N pollution in coastal and marine ecosystems. However, the molecular drivers and limiting steps of denitrification in coastal wetlands are not well understood. Here, we quantified the abundances of functional genes involved in N cycling and determined denitrification rates using N-15 paring technique in the coastal wetland sediments of Bohai Economic Rim in eastern China. Denitrification accounting for 80.7 +/- 12.6% of N removal was the dominant pathway for N removal in the coastal wetlands. In comparison, anaerobic ammonium oxidation (ANAMMOX) removed up to 36.9 +/- 7.3% of inorganic N. Structural equation modeling analysis indicated that the effects of ammonium on denitrification potential were mainly mediated by the relative abundances of nosZ/nirS, nirS/(narG + napA) and amoA/nirK. Denitrification was limited by the relative strength of two steps, namely N2O reduction to N-2 and nitrite (NO2-) reduction to nitric oxide (NO). Our results suggest that the relative abundances of functional genes which are more stable than sediment chemical compounds in the context of environmental changes are indictive of denitrification potential in coastal wetlands. (C) 2018 Elsevier Ltd. All rights reserved.

Objective To explore the status and influencing factors of spiritual needs of patients with gastrointestinal cancer, so as to help the medical staffs to provide spiritual care for patients with gastrointestinal cancer. Methods The general information questionnaire, disease information questionnaire and the Spiritual Needs Assessment for Patients(SNAP) were used to investigate the spiritual needs of 116 patients with gastrointestinal cancer, analyze the influencing factors of the spiritual needs. Results The spiritual needs score of the patients with gastrointestinal cancer were 32-92(69.7 ± 16.9) points. Regression analysis showed that the influencing factors were religious belief, age of illness and number of children (R2=0.480, F=12.353, P<0.01). Conclusions The level of spiritual needs of the gastrointestinal cancer patients is at middle level.With different religious beliefs, age of illness and children number, the level of spiritual needs is different.

Objective To summarize the experience of diagnosis and treatment of diabetic muscle infarction.Methods To summarize the experience of diagnosis and treatment of 1 patient with diabetic muscle infarction in our hospital.ResultsIn This was a 40 year old woman presented with bilateral lower limb mass with pain for 1 month.After differential diagnosis work up,she was finally diagnosed with diabetic muscle infarction.After tight control of her blood glucose level and antiplatelet therapy,her condition improved.Conclusion Diabetic muscle infarction is a rare complication of diabetes mellitus.Early identification and correct diagnosis of this complication is of great significance to improve the prognosis.

Objective To explore the effect of behavior and psychological intervention on the emotion and quality of life of patients with advanced gastric cancer undergoing laparoscopic D2 radical operation. Methods From January 2014 to December 2015, 186 patients of advanced gastric cancer undergoing laparoscopic D2 radical resection who were treated in the Center of Gastrointestinal Tumor were enrolled. The patients were divided into control group and intervention group (93 cases in each group) by simple random sampling method according to the order of admission. The control group was given routine nursing, and the intervention group was given psychological intervention and behav-ior in addition to routine care. The two groups were compared on the emotion and quality of life. Results Anxiety and depression scores of the intervention group were (42.19 ± 7.75), (43.61 ± 8.28), lower than (50.62 ± 7.61), (54.41 ± 8.3) of the control group, and the differences were statistically significant (P<0.05). Physiological function (55.96±6.47), physi-ological role (50.19 ± 7.72), body pain (47.31 ± 7.95), general health (49.38 ± 7.28), energy (56.99 ± 7.31), social function (51.53 ± 7.34), emotional function (46.97 ± 7.48), mental health (52.60 ± 7.39) were higher than those in the control group of (47.78±7.72), (45.08 ±7.56), (40.47±5.95), (45.42±7.36), (51.40±6.49), (45.55±7.08), (42.36±6.38), (45.33±7.61), and the differences were statistically significant (P<0.05). Conclusion Behavioral and psychological intervention can signifi-cantly improve the negative emotions of patients with gastric cancer, improve the quality of life of patients after operation.