Background:The association between liver dysfunction in early pregnancy and the hypertensive disorders in pregnancy (HDP) remains unclear. Methods:This retrospective cohort study included all singleton pregnant women (n = 57 386) who underwent liver function tests (LFTs) at their first antenatal visit from six to 19+6 weeks of gestation. The exposure was liver dysfunction. The primary outcome was the development of hypertensive disorders of pregnancy (HDP), categorised into gestational hypertension and preeclampsia (PE). Preeclampsia was categorised into mild and severe forms, as well as early-onset and late-onset types. Multiple logistic regression analyses were conducted to estimate the risk for HDP and its subtypes across different liver function biomarker levels. Results:Among the 50 423 women included in the study, 17.1% had abnormal liver function. The overall HDP rate was 3.9%. Across the different serum Gamma-glutamyltransferase (GGT)groups, the HDP incidence rates were 2.9% (0-12 units per litre /U/L)), 5.4% (12.1-32 U/L), 10.0% (32.1-64 U/L), and 10.5% (>64 U/L) (P < 0.001 for trend). Compared with the reference range for GGT (0-12 U/L), the group with GGT levels of 12.1-32 U/L exhibited a 48.6% greater risk (adjusted odds ratio (OR) = 1.486; 95% confidence interval (CI) = 1.344-1.642), the group with GGT levels of 32.1-64 U/L had a 50.9% increased risk (aOR = 1.509; 95% CI = 1.375-1.657), and those with GGT levels >64 U/L had a 25.0% greater risk (aOR = 1.250; 95% CI = 1.078-1.449) of HDP. We further assessed the associations between varying GGT levels and HDP subtypes (gestational hypertension, mild PE, severe PE, early onset PE, and late-onset PE), and similar results were obtained for all subtypes. Restricted cubic spline (RCS) curves revealed that elevated serum GGT levels have a dose-response relationship with HDP, along with its subtypes. Conclusions:GGT levels during early pregnancy have a dose-response relationship with the development of HDP and its subtypes.

Genetic kidney disease (GKD) is a major cause of pediatric chronic kidney disease. Many patients remain genetically unresolved by exome sequencing (ES) and copy number variation (CNV) analysis. Genome sequencing (GS) enables a comprehensive detection of genetic variations. This study evaluates a GS-based sequential strategy to determine the diagnostic yield in pediatric GKD. We recruited families with GKD from a national cohort of 23 centers from 2020 to 2024 through Chinese Children Genetic Kidney Disease Database. This sequential sequencing strategy involved initial trio-ES and Trio-CNV-seq, followed by GS in undiagnosed cases, splicing essays analysis was performed for intronic variants. A total of 735 families were enrolled. Trio-ES and Trio-CNV-seq achieved a diagnostic yield of 39.4% (35.5% from ES and 4.0% from CNV-seq). Subsequent GS identified pathogenic variants in 23 of 445 previously undiagnosed cases (5.2%), including small structural variants (5 cases), intronic variants affecting splicing function (9 cases), and variants in mitochondrion DNA (9 cases). GS showed 14% and 8.8% increase in diagnostic yield in renal tubular disease and CKD of unexplained cause. Syndromic cases exhibited a higher diagnostic yield (10.9%) than isolated cases (4.6%). These findings indicate GS-based sequential strategy improves the diagnostic yield of GKD.

Ectopic pregnancy (EP) is a leading cause of maternal morbidity and mortality in early pregnancy. Current diagnostic approaches, which rely on ultrasound scanning and blood measurements, are limited by low detection sensitivity. Herein, we propose a one-step system that uses EP-associated serum metabolic fingerprints (ESF) for efficient EP diagnosis and risk prediction. The system employs nanoparticle-assisted laser desorption/ionization mass spectrometry to rapidly record ESF. A machine learning-based diagnostic model was then used to analyze ESF from 722 participants, achieving an area under the curve (AUC) of 0.913. Simultaneously, potential metabolic biomarkers from ESF were annotated, enabling accurate diagnosis of EP across various clinical profiles (AUC 0.922). Moreover, a rupture risk prediction model was constructed, yielding an AUC of 0.885, significantly surpassing conventional clinical indicators (AUC 0.702, p < 0.05). Our work offers a rapid, effective tool for early EP diagnosis and risk stratification, marking a pivotal advancement toward precision diagnostics.

Men and women generally exhibit different sleep patterns and structures. These differences also extend to how each sex responds to sleep deprivation, a condition linked to various health issues. Although estradiol is known to influence sleep patterns, its sex-specific effects on sleep characteristics and the responses to sleep deprivation are not well understood. In our study, we used a genetic estrogen deficiency mouse model with aromatase deficiency (Ar+/-) to explore estrogens' sex-specific role in reactions to acute sleep deprivation (SD). Initially, we identified a sex difference in SD-induced sleep-wake proportions and sleep patterns in wild type (WT) mice. Then, we found that estrogens deficiency caused alterations of normal sleep pattern in females, characterized by less wakefulness and more NREM time, but not in males at baseline compared to WT mice. While SD led to significant alterations in circadian rhythm, sleep patterns, and sleep rebound in both male and female Ar+/- mice, sex differences were evident in specific responses to SD. Female Ar+/- mice exhibited a quicker and longer-lasting post-SD sleep rebound, with reduced wake time, increased sleep time, and less fragmented sleep, whereas male Ar+/- mice showed a delayed sleep rebound except for REM sleep time and REM sleep spectral alterations compared to WT mice. Our findings underscore the crucial role of endogenous estrogens in sleep regulation and its sex-specific response to sleep deprivation, which could be significant for precision sleep medicine.

To the Editor: Malignant ovarian tumors during pregnancy (MOTP) rank second after cervical cancer among gynecological malignancies diagnosed during pregnancy, and most women today hope to maintain pregnancy and preserve fertility, which complicates oncologic treatment, as all potential complications and prognoses should be carefully considered for both the mother and fetus. A coordinated approach from a multidisciplinary team involving gynecological oncologists, obstetricians, and pathologists is recommended, and each patient should be managed individually based on several important factors, including gestational week (GW) at initial diagnosis, histologic type, International Federation of Gynecology and Obstetrics (FIGO) stage, and patient preference whether to terminate pregnancy or not. Surgical intervention and chemotherapy administration should be carefully performed in cases where pregnancy is maintained. The therapeutic effects on the tumor and the potential harmful events to the fetus should be appropriately balanced. Although prior studies have shown that the prognosis of such malignancies is similar to that in the non-pregnant state, the result should be interpreted cautiously, as the sample size in these studies was not large enough to control for all prognostic factors.[1] Herein, we evaluated the current management strategies for MOTP with emphasis on the balance between mother and fetal health and oncologic and obstetric outcomes. The incidence of ovarian malignancies has increased from 1:15,000–32,000 to 1:10,000 pregnancies due to delays in childbearing and the widespread of prenatal ultrasound. Generally, the histologic types of MOTP are similar to those in non-pregnant women of the same reproductive age; however, some apparent differences in the proportion of subtypes are observed between countries and races. Previously, researchers discovered that approximately 35% ovarian tumors were classified as being of an epithelial origin, and malignant germ cell tumors (MGCTs) were found to occur at the highest frequency in MOTP, of which dysgerminoma (approximately 38%) is the most common subtype, with yolk sac tumors (30.4%), and the remaining being immature teratomas (15.7%) and mixed germ cell tumors. In contrast, tumors of epithelial origin were recently reported to account for a higher proportion of more than 65% (of which up to 30% were invasive) of all tumors, while MGCTs accounted for 16.5–18.5%, and the rest were rare tumors consisting of sarcomas and metastases from other malignancies.[2] Ultrasound is the most common method for the early detection of incidental tumors and assessment of their origin throughout the prenatal period. However, the blood flow parameters change during pregnancy, which causes the flow patterns between benign and malignant tumors to overlap. Therefore, ultrasonographic examination must be used with caution when distinguishing benign from malignant tumors, and the combination with magnetic resonance imaging (MRI) can be helpful to evaluate the origin of malignant or benign tumors. Significantly, gadolinium-enhanced MRI is not recommended, owing to the possibility of teratogenicity during fetal organogenesis. Computer tomography scans should be avoided as much as possible because the risks of early pregnancy abortion, congenital deformity, fetal growth restriction, perinatal mortality, and childhood cancer cannot be ruled out.[3] The specificity and reliability of serum tumor markers should be cautiously interpreted. The concentration of cancer antigen 125 (CA125) can fluctuate between trimesters during normal pregnancy, and previous studies indicated that an elevation in the levels by 60 U/mL above the cutoff may be helpful in decision-making processes, including follow-up. Alpha-fetoprotein (AFP) and CA125 may be linked to abnormalities of the placenta or fetus, as evidenced by publications relating elevated CA125 levels to imminent miscarriage and preeclampsia, elevated lactate dehydrogenase levels to severe preeclampsia and hemolysis, and elevated levels of liver function tests, low platelet counts, and elevated AFP levels to Down syndrome and open neural tube defects. Although the diagnostic value of ovarian tumor markers during pregnancy is limited, there are still some rules to follow, and continuous monitoring during pregnancy is helpful in oncological diagnosis.[4] As yet, no well-established optimal management strategy is available for MOTP, with the most widely accepted recommendations being based on several key factors, the most important of which are the disease stages at diagnosis and risk division, especially for early-stage epithelial ovarian cancer (EOC). The diagnostic procedures for MOTP are shown in Figure 1.Figure 1: Diagnostic procedures for MOTP. *: Reference to the standards of FSS in non-pregnancy. Note: Guidelines based on the third international consensus conferenceand 22 GW is recommended but not absolute. CT: Chemotherapy; FSS: Fertility-sparing surgery; GW: Gestational week; MGCT: Malignant germ cell tumor; MOTP: Malignant ovarian tumors during pregnancy; SCST: Sex cord stromal tumor; TOP: Termination of pregnancy.As for low-risk group in early-stage EOC (FIGO stage IA, grades 1–2, and favorable histology [serous, mucinous, or endometrioid]), standard surgical staging, which includes hysterectomy, bilateral salpingo-oophorectomy, omentectomy, cytology of peritoneal washing, systematic peritoneal biopsies in all areas of the abdomen, and pelvic and para-aortic lymphadenectomy, can be performed up to 22 GW, and should not be postponed until after delivery. Fertility sparing surgery (FSS) may be considered for patients who have a strong desire for future pregnancies and meet several selection criteria, including FIGO stage IA, grades 1–2, non-clear cell histology, and adequately comprehensive surgical staging.[1] During FSS, the uterus and normal ovaries are preserved, and a thorough examination of the ovaries and uterine surface is required. Biopsies of suspicious areas are required during surgical staging. Patients with FIGO stages IC and II, as well as FIGO stages IA or IB with unfavorable histology (such as clear cell carcinoma) and/or grade 3, are considered high-risk group in early-stage EOC. Approximately 30–50% of them develop recurrence within 5 years of primary therapy. Therefore, they are ineligible for FSS and a combination of carboplatin and paclitaxel should be recommended after full surgical staging. When MOTP is identified in the first or second trimester, optimal management involves surgical staging followed by adjuvant chemotherapy, or neoadjuvant chemotherapy (NACT) followed by staging after delivery, depending on the gestational age. NACT should be initiated after 14 GW, and it is no longer a viable option after 27 GW because it should be administered at least 3 weeks after the initial surgery, and the final course should be conducted 3 weeks or 4 weeks before the expected date of delivery to avoid maternal–fetal aplasia.[5] Accordingly, definitive surgical treatment is recommended until 34 GW. For advanced-stage EOC (FIGO stages III and IV), immediate treatment is urgent and the most effective approach is primary maximal debulking surgery (PDS), followed by adjuvant chemotherapy. Complete cytoreduction and three courses of NACT followed by interval debulking surgery could be a feasible therapeutic strategy. If EOC is detected before 12 GW, termination of the pregnancy should be discussed. For patients who are willing to continue their pregnancy, NACT should be performed starting at 14 weeks, followed by radical debulking surgery after delivery. Lymphadenectomy in such advanced stages is not associated with better outcomes; however, it does result in a higher incidence of postoperative complications. In the second trimester, either pregnancy-sparing radical debulking surgery or NACT may be recommended for patients who hope to maintain pregnancy. However, NACT or PDS performed after delivery should be considered when EOC is detected during the third trimester of gestation.[4] The treatment for MGCTs generally involves unilateral salpingo-oophorectomy with preservation of the uterus and the contralateral ovary. However, in cases of dysgenetic gonads, the removal of both ovaries is encouraged. For dysgerminoma (FIGO stage IA) or immature teratoma (stage IA-B/grade 1–2), complete surgical staging, which includes pelvic and para-aortic lymphadenectomy, may be sufficient, and adjuvant chemotherapy is not recommended. For other histological subtypes, adjuvant chemotherapy with surgical treatment involving unilateral salpingo-oophorectomy is recommended. The use of adjuvant chemotherapy in immature teratomas (stage IC/grade 3) and dysgerminomas (stages IB–IC) remains controversial, and close surveillance has been indicated as important in some studies. Specifically, MGCTs are characterized by rapid growth and high recurrence rates, except for stage I dysgerminoma and stage I immature teratoma, resulting in adverse maternal outcomes in case of delay in therapeutic initiation.[6] Sertoli–Leydig and granulosa cell tumors are characterized by an early-stage as well as a slow-growing, low-grade, and indolent course, of which tumors originating from granulosa cells were the most common (22.0%), followed by thecoma (18.6%), and Sertoli–Leydig cell tumors (8.5%). Serious maternal–fetal adverse events were reported in 41.3% of cases, including hemoperitoneum resulting in shock (13.0%), severe hypertension (8.7%), and maternal death (6.5%). Pregnant women diagnosed with sex cord-stromal tumors (SCSTs) are reported to have a higher rate of torsion and rupture than those with other histological subtypes.[6] One-third of borderline ovarian tumors are detected in women younger than 40 years of age, making them one of the most common MOTPs. Aggressive histologic characteristics, including microinvasion, micropapillary features, peritoneal implants, and intraepithelial carcinoma, may commonly be present during pregnancy. However, these aggressive histologic behaviors may be related to pregnancy physiology and resolve spontaneously. In most cases, unilateral salpingo-oophorectomy is recommended.[7] Combination therapy with paclitaxel and carboplatin is the standard treatment for EOC. According to the European Society for Medical Oncology guidelines, etoposide can be safely administered during pregnancy, if initiated after 14 GW. Although paclitaxel–carboplatin or cisplatin–vinblastine bleomycin can be administered during pregnancy, paclitaxel plus carboplatin is recommended because of the potential nephrotoxicity of cisplatin. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), may theoretically cross the placenta. VEGF signaling has been linked to unfavorable outcomes, such as a preeclampsia-like syndrome of hypertension and proteinuria, as well as early pregnancy loss. Similarly, data on the safety of poly ADP ribosome polymerase (PARP) inhibitors in pregnancy are limited. Collectively, both bevacizumab and PARP inhibitors should be avoided during pregnancy.[4] In conclusion, there are no guidelines of delivery time and delivery method for MOTP, and it should be a comprehensive consideration, involving the specific stage and histological type, GW, and the willingness to terminate or maintain the pregnancy. When continued pregnancy is desired, some crucial dilemmas in the treatment should be carefully considered, such as the probability of any delayed chemotherapeutic treatment when cancer is detected during the first trimester, and the possibility of FSS. Extensive research is required to further determine the safety of diagnostic and therapeutic procedures for pregnant women that are routinely used in non-pregnant women; particularly, long-term data analysis is required for their oncologic safety. Furthermore, although overall good fetal outcomes have been described in existing studies regarding the surgical and chemotherapeutic treatment of MOTP, long-term research on children subjected to such in utero exposure is required to fully understand the downstream effects of these treatments. Funding This study was supported by a grant from the Shanghai Municipal Key Clinical Specialty (No. shslczdzk06302). Conflicts of interest None.

Objective To evaluate the long-term efficacy of fibroid devascularization with ultrasound-guided high-intensity focused ultrasound (USgHIFU). Design A retrospective study. Setting A specialized hospital and two general hospitals in China. Population 117 patients with uterine fibroids Methods Treatment cells were arranged to cover the targeted vessels and then sonicated through steering the HIFU focal spots. Fibroid devascularization was assessed with the Adler grade obtained by color Doppler flow imaging (CDFI) and power Doppler imaging. The patients were followed up at 1-month, 3-month, 6-month, 1-year, 2-year and 3-year after treatment. Main outcome measures The non-perfusion volume rate (NPVR), fibroid volume shrinkage rate (FVSR), Adler Grade, symptom severity score (SSS) and uterine fibroid symptom and quality of life (UFS-QOL) were evaluated. Adverse events were recorded. Results NPVR Significant difference was observed in Adler grade, FV, FVSR, SSS and UFS-QOL before and after treatment ( p <0.001). The SSSs were reduced by 33.42% at 1-year, 42.32% at 2-year and 52.46% at 3-year after treatment. Conclusions USgHIFU-induced devascularization is a practical non-invasive treatment option for patients with uterine fibroid. Also, it can sustain long-term symptom improvements and could be attractive for patients who plan to become pregnant.

Sleep disturbances, encompassing altered sleep physiology or disorders like insomnia and sleep apnea, profoundly impact physiological functions and elevate disease risk. Despite extensive research, the underlying mechanisms and sex-specific differences in sleep disorders remain elusive. While polysomnography serves as a cornerstone for human sleep studies, animal models provide invaluable insights into sleep mechanisms. However, the availability of animal models of sleep disorders is limited, with each model often representing a specific sleep issue or mechanism. Therefore, selecting appropriate animal models for sleep research is critical. Given the significant sex differences in sleep patterns and disorders, incorporating both male and female subjects in studies is essential for uncovering sex-specific mechanisms with clinical relevance. This review provides a comprehensive overview of various rodent models of sleep disturbance, including sleep deprivation, sleep fragmentation, and circadian rhythm dysfunction. We evaluate the advantages and disadvantages of each model and discuss sex differences in sleep and sleep disorders, along with potential mechanisms. We aim to advance our understanding of sleep disorders and facilitate sex-specific interventions.

Membrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin‐11 (Syt11), a non‐Ca 2+ ‐binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia. Here we reported the in vivo function of Syt11 in microglial immune responses using an inducible microglia‐specific Syt11‐conditional‐knockout (cKO) mouse strain. Syt11‐cKO resulted in activation of microglia and elevated mRNA levels of IL‐6, TNF‐α, IL‐1β, and iNOS in various brain regions under both resting state and LPS‐induced acute inflammation state in adult mice. In a PD mouse model generated by microinjection of preformed α‐synuclein fibrils into the striatum, a reduced number of microglia migrated toward the injection sites and an enhanced phagocytosis of α‐synuclein fibrils by microglia were found in Syt11‐cKO mice. To understand the molecular mechanism of Syt11 function, we identified its direct binding proteins vps10p‐tail‐interactor‐1a (vti1a) and vti1b. The linker domain of Syt11 interacted with both proteins and a peptide derived from it competitively inhibited the interaction of Syt11 with vti1a/vti1b in vitro and in cells. Importantly, application of this peptide induced more cytokine secretion in wild‐type microglia upon LPS treatment, phenocopying defects in Syt11 knockdown cells. Altogether, we propose that Syt11 inhibits microglial activation in vivo and regulates cytokine secretion through interactions with vti1a and vti1b.

Impact of the development of coastal aquaculture on nitrogen (N) cycle has been a central issue in wetland ecological and environmental protection project. However, the process of N removal in offshore aquaculture remains unclear. Here this study reported the rates, abundance and community structure of anaerobic ammonium oxidation (anammox) and denitrification using N-15 isotope tracing technology, quantitative polymerase chain reaction (qPCR), and high-throughput sequencing methods in different types of aquaculture ponds including the Sinonovacula constricta ponds, the Shrimp-crab polyculture ponds and the abandoned aquaculture ponds along the coast of Fujian Province. Results showed that anammox rates in the abandoned aquaculture ponds were 1.44 +/- 0.11 nmol center dot g(-1)center dot h(-1), contributing to 15.15% +/- 1.18% of the N removal, which were significantly higher than those in the S.constricta ponds and the Shrimp-crab polyculture ponds (P < 0.01). Denitrification remained the main pathway for the N removal. The abundance of AMX, nirS, and nirK genes in the Shrimpcrab polyculture ponds was higher than the other two types of aquaculture ponds, but the anammox and denitrifying microbial community structure was the simplest. In contrast, the abandoned aquaculture ponds showed the most abundant and complex microbial community structure. Aquaculture ponds abandoned significantly increased the anammox rates and community structure. The microbial diversity, species composition, and stable substrate condition such as DO, pH, NH4+, NO3-, TN, and C:N ratio were the main factors affecting the anammox process in the abandoned aquaculture ponds. The abundance of nirS and nirK gene, the human management, and aquaculture substrate environment including DO, pH, NH4+, and NO2- enhanced the denitrification process in the S.constricta ponds and the Shrimp-crab polyculture ponds. These findings indicated that aquaculture ponds abandoned improved environmentally friendly the anammox N removal process and restored biodiversity.

为恢复濒危物种中国鲎(Tachypleus tridentatus)种群数量,2021-2022 年在福建省罗源县开展中国鲎人工驯养繁殖技术研究.基于野外自然产卵场及幼体生境观测结果,构建人工模拟产卵环境,诱导野生亲本在仿生态环境中自然受精、产卵繁殖,并开展了人工孵化和苗种培育研究.研究组初步掌握了中国鲎成体对底质的栖息及繁殖偏好习性和生态需求,形成了适宜福建沿海中国鲎的人工驯养繁殖技术,对中国鲎人工驯养和自然繁殖有重要意义,可为福建沿海中国鲎人工育苗及野外种群资源恢复提供理论基础资料.

The impact of weather variability and air pollutants on tuberculosis (TB) has been a research hotspot. Previous studies have mostly been limited to a certain area or with a small sample size of cases, and multi-scale systematic studies are lacking. In this study, 14,816,329 TB cases were collected from 31 provinces in China between 2004 and 2018 to estimate the association between TB risk and meteorological factors and air pollutants using a two-stage time-series analysis. The impact and lagged time of meteorological factors and air pollutants on TB risk varied greatly in different provinces and regions. Overall cumulative exposure–response summary associations across 31 provinces suggested that high monthly mean relative humidity (RH) (66.8–82.4

Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. Renal involvement was the most typical manifestation (95.5

Background Rather low vaccination rates for Human papillomavirus (HPV) and pre-existing cervical cancer patients with limited therapeutic strategies ask for more precise prognostic model development. On the other side, the clinical significance of circadian clock signatures in cervical cancer lacks investigation. Methods Subtypes classification based upon eight circadian clock core genes were implemented in TCGA-CESC through k-means clustering methods. Afterwards, KEGG, GO and GSEA analysis were conducted upon differentially expressed genes (DEGs) between high and low-risk groups, and tumor microenvironment (TME) investigation by CIBERSORT and ESTIMATE. Furthermore, a prognostic model was developed by cox and lasso regression methods, and verified in GSE44001 by time-dependent receiver-operating characteristic curve (ROC) analysis. Lastly, FISH and IHC were used for validation of CCL20 expression in patients’ specimens and U14 subcutaneous tumor models were built for TME composition. Results We successfully classified cervical patients into high-risk and low-risk groups based upon circadian-oscillation-signatures. Afterwards, we built a prognostic risk model composed of GJB2, CCL20 and KRT24 with excellent predictive value on patients’ overall survival (OS). We then proposed metabolism unbalance, especially for glycolysis, and immune related pathways to be major enriched signatures between the high-risk and low-risk groups. Then, we proposed an ‘immune-desert’-like suppressive myeloid cells infiltration pattern in high-risk group TME and verified its resistance to immunotherapies. Finally, CCL20 was proved positively correlated with real-world patients’ stages and induced significant less CD8 + T cells and more M2 macrophages infiltration in mouse model. Conclusions We unraveled a prognostic risk model based upon circadian oscillation and verified its solidity. Specifically, we unveiled distinct TME immune signatures in high-risk groups.

Objectives: This study aimed to provide guidance for clinical treatment and increase public confidence in COVID-19 vaccines. Methods: The Cochrane Library, Embase, PubMed, Web of Science, ClinicalKey, and other COVID-19 datasets were searched from December 2019 to May 2022. Case-control studies and prospective cohort studies of COVID-19 vaccine effectiveness and safety in pregnant women were included. Results: From day 11 to day 13, after the first dose of the COVID-19 messenger RNA vaccine, the effectiveness was 54% (95% confidence interval: 0.33-0.69). On days 14 to 27, the effectiveness was 59%. There was a 14% increase in vaccine effectiveness 28 days after the first dose was given. The inactivated vaccines showed similar effectiveness. The proportions of placental abruptions, postpartum hemorrhages, miscarriages, stillbirths, premature births, and small for gestational age infants were not significantly different between vaccinated and nonvaccinated pregnant women. Fatigue and fever were also not associated with pregnancy. Conclusion: Our findings affirm that the effectiveness varies for different types of vaccines and is significantly and positively correlated with time in the pregnant population. COVID-19 vaccines have also been deemed safe for pregnant women. Thus, we developed a comprehensive understanding of the role of vaccines in pregnant women.

BACKGROUND: There is growing evidence that disturbances in cholesterol metabolism may be involved in major depressive disorder (MDD). However, it is not known if cholesterol metabolites present in the brain and periphery can be used to diagnose and predict an MDD patient's response to antidepressant treatment. METHODS: A total of 176 subjects (85 patients with MDD and 91 healthy control subjects) were included in this study. The expression of peripheral and brain-specific oxysterols and related gene polymorphisms were investigated in all subjects. The severity of depression was measured using the 17-item Hamilton Depression Rating Scale, 16-item Quick Inventory of Depressive Symptoms-Self-Report, and Patient Health Questionnaire-9 for all patients with MDD before and after 12 weeks of antidepressant treatment.RESULTS: Patients with MDD expressed higher plasma levels of 24(S)-hydroxycholesterol (24OHC) (mainly secreted from the brain) compared with healthy control subjects, and the higher levels of 24OHC were associated with 24OHC synthetase (CYP46A1) gene polymorphisms. In patients with MDD, an improved response to the 12-week antidepressant treatment was associated with a reduction of both 24OHC and 27OHC (mainly secreted from the peripheral system) levels relative to baseline levels. Nonresponders exhibited increased levels of oxysterols at the end of treatment compared with baseline. The superior reduction in oxysterol levels correlated with better outcomes from the antidepressant treatment.CONCLUSIONS: These data suggest a potential role for oxysterols as diagnostic and treatment response-related indicators for MDD.

Aim: The aim of this study is to investigate the role of human chorionic gonadotropin (hCG) daily variations and levels prior to methotrexate treatment as predictors for treatment outcome. Methods: This retrospective study included patients who had a sonographically confirmed ectopic pregnancy at the International Peace Maternity and Child Health Hospital between November 2015 and June 2020. The associations of hCG levels and daily variations with the treatment success were evaluated by multivariable logistic regression and receiver operator characteristic (ROC) curve. Establish a nomogram that predicts how methotrexate (MTX) therapy will turn out. The performance of the model was assessed utilizing concordance index, receiver operating characteristic curves, and calibration plots. Results: The median serum hCG levels before treatment and hCG daily variation in the failure group were higher than those in the success group (487.8 vs. 270.7 IU/L, -1.86% vs. 7.29%, both p < 0.01). According to the ROC curve analysis, the cutoff values of serum hCG level before treatment and daily variations were 617.35 IU/L and 1.76%/day. By multivariable logistic regression analysis, serum hCG levels before treatment (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000 similar to 1.001) and hCG daily variations were independently associated with the treatment success (OR: 1.033, 95% CI: 1.015 similar to 1.052). The nomogram was effective at predicting the outcome of MTX treatment with a receiver operating characteristic area under the curve of 0.717 (p < 0.001). The nomogram's calibration curve was almost parallel to the ideal diagonal line. Conclusion: We successfully created a nomogram based on serum hCG levels before treatment and hCG daily changes to anticipate the result of MTX therapy, which could assist medical professionals in selecting therapeutic schedule for patients with tubal pregnancies.

Background Ovarian mature cystic teratomas (MCTs) are the most common tumors in pregnant women. The premature rupture of membranes (PROM) is a typical complication of pregnancy; however, the relationship between MCT and PROM is unknown. Therefore, we aimed to determine whether MCT is associated with the occurrence of PROM during pregnancy. Methods The data of patients with adnexal masses during pregnancy between January 2017 and August 2021 were retrospectively analyzed. Ovarian cystectomy was performed during cesarean delivery or after vaginal delivery. Univariate and multivariate logistic regression models were used for statistical analysis. Results A total of 234 patients with histopathological results were included. Among these patients, 21 occurred PROM during pregnancy, of which 11 were diagnosed with MCT. Compared with other subtypes, MCT (p=0.025) showed a stronger correlation with PROM and was an independent risk factor for PROM (odds ratio [OR], 2.811; 95% confidence interval [CI], 1.096–7.215; p=0.032). Furthermore, we found that MCT with a diameter >5 cm (p=0.0037) was more likely to promote the development of PROM than those that with a diameter <5 cm. Conclusion MCT was an independent risk factor for PROM during pregnancy. Positive actions and preventative clinical treatments should be fully taken into consideration by clinicians for pregnant women with MCTs, especially those ≥5 cm in diameter, to reduce the clinical complications related to MCT-associated PROM.

BackgroundThere is great mental stress due to the coronavirus disease 2019 (COVID-19) pandemic. However, there are no detailed psychological studies of the children with chronic kidney disease (CKD) and their guardians during the COVID-19 pandemic.ObjectiveThis study explores the psychological pressure on children with CKD and their guardians.MethodsAn online survey was conducted at 20 of the largest pediatric nephropathy departments in China, including the Rutter Parent Questionnaire, Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Overall, 885 children (589 children with CKD associated with 296 children of the control group) completed the survey together with their guardians.ResultsThere was no statistical difference between CKD children and control children regarding their Rutter behavior scores and abnormal behaviors. Nevertheless, the abnormal behavior of children might aggravate the anxiety and depression of guardians in both CKD and control groups (p < 0.05). We confirmed that the anxiety and depression of guardians in the CKD group were both significantly higher than those in the control group (p < 0.05). The guardians in the CKD group with lower annual income were more likely to experience anxiety (p < 0.05). Furthermore, the guardians whose children were older than 11 years old might be more anxious than those who were 6–11 years old. Besides, the guardians in the CKD group who watched the news for 30–60 min daily were less likely to have depression than those who watched < 10 min (p < 0.05). The subgroup results showed that the gender, the time of watching the news, the annual income of guardians, and children's age might be the most critical factors influencing guardians' psychological burden.ConclusionThe guardians in the CKD group have more severe anxiety and depression during the pandemic. The children's abnormal behavior, adolescents' pressure, low household income, and the panic about the pandemic may be the main reasons for the anxiety and depression of guardians.

When a supplier experiences a disruption, it learns how to better prevent and recover from future disruptions. As suppliers learn to become more resilient, the overall supply network also learns to become more resilient. This research draws on the organizational learning literature to introduce the concept of supply network resilience learning, which we define as the improvement of supply network resilience when suppliers learn from their own disruptions. The analysis integrates agent-based modeling, experimental design, data analytics, and analytical modeling to investigate how supplier learning improves supply network learning. We examine how two types of supplier learning, namely, learning-to-prevent and learning-to-recover, affect supply network learning. The results show that suppliers' learning-to-prevent results in a disruption-free supply network when time approaches infinity. However, the results differ across a more realistic finite time horizon. In this setting, learning-to-recover improves network learning when suppliers face a lower chance of disruption. The analysis also shows that centrally located suppliers enhance network learning, except when the risk of a disruption is high and the chance of diffusing a disruption to another supplier is high. In this setting, noncentral suppliers become more critical to supply network learning. This research provides a framework that will help practitioners understand the contingencies that influence the effect of supplier learning on the overall supply network resilience learning.