Background: Coronavirus disease-2019 (COVID-19) epidemic is spreading globally. Sex differences in the severity and mortality of COVID-19 emerged. This study aims to describe the impact of sex on outcomes in COVOD-19 with a special focus on the effect of estrogen. Methods: We performed a retrospective cohort study which included 413 patients (230 males and 183 females) with COVID-19 from three designated hospitals in China with a follow up time from January 31, 2020, to April 17, 2020. Women over 55 were considered as postmenopausal patients according to the previous epidemiological data from China. The interaction between age and sex on in-hospital mortality was determined through Cox regression analysis. In addition, multivariate Cox regression models were performed to explore risk factors associated with in-hospital mortality of COVID-19. Results: Age and sex had significant interaction for the in-hospital mortality ( P < 0.001). Multivariate Cox regression showed that age (HR 1.041, 95% CI 1.009–1.073, P = 0.012), male sex (HR 2.033, 95% CI 1.007–2.098, P = 0.010), the interaction between age and sex (HR 1.118, 95% CI 1.003–1.232, P = 0.018), and comorbidities (HR 9.845, 95% CI 2.280–42.520, P = 0.002) were independently associated with in-hospital mortality of COVID-19 patients. In this multicentre study, female experienced a lower fatality for COVID-19 than male (4.4 vs. 10.0%, P = 0.031). Interestingly, stratification by age group revealed no difference in-hospital mortality was noted in women under 55 compared with women over 55 (3.8 vs. 5.2%, P = 0.144), as well as in women under 55 compared with the same age men (3.8 vs. 4.0%, P = 0.918). However, there was significantly difference in women over 55 with men of the same age group (5.2 vs. 21.0%, P = 0.007). Compared with male patients, female patients had higher lymphocyte ( P < 0.001) and high-density lipoprotein ( P < 0.001), lower high sensitive c reaction protein level ( P < 0.001), and lower incidence rate of acute cardiac injury (6.6 vs. 13.5%, P = 0.022). Conclusion: Male sex is an independent risk factor for COVID-19 in-hospital mortality. Although female mortality in COVID-19 is lower than male, it might not be directly related to the effect of estrogen. Further study is warranted to identify the sex difference in COVID-19 and mechanisms involved.

INTRODUCTION Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection spread worldwide. OBJECTIVES The aim of the study was to identify the clinical characteristics and risk factors associated with severe incidence of SARS-CoV-2 infection. PATIENTS AND METHODS All adult patients (median [IQR] age, 52 [37-58] years) consecutively admitted to the Dabieshan Medical Center from January 30, 2020 to February 11, 2020 were collected and reviewed. Only patients diagnosed with COVID-19 according to the World Health Organization interim guidance were included in this retrospective cohort study. RESULTS A total of 108 patients with COVID-19 were retrospectively analyzed. Twenty-five patients (23.1%) developed severe disease, and of those 12 patients (48%) died. Advanced age, comorbidities (most commonly hypertension), higher blood leukocyte count, neutrophil count, higher C-reactive protein level, D-dimer level, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score were associated with greater risk of COVID-19, and so were lower lymphocyte count and albumin level. Multivariable regression showed increasing odds of severe COVID-19 associated with higher SOFA score (odds ratio [OR], 2.45; 95% CI, 1.302-4.608; P = 0.005), and lymphocyte count less than 0.8 x 10(9)/l (OR, 9.017; 95% CI, 2.808-28.857; P <0.001) on admission. Higher SOFA score (OR, 2.402; 95% CI, 1.313- 4.395; P = 0.004) on admission was identified as risk factor for in-hospital death. CONCLUSIONS Lymphocytopenia and a higher SOFA score on admission could help clinicians to identify patients at high risk for developing severe COVID-19. More related studies are needed in the future.

Background Information regarding characteristics and risk factors of COVID-19 amongst middle-aged (40–59 years) patients without comorbidities is scarce. Methods We therefore conducted this multicentre retrospective study and collected data of middle-aged COVID-19 patients without comorbidities at admission from three designated hospitals in China. Results Among 119 middle-aged patients without comorbidities, 18 (15.1%) developed into severe illness and 5 (3.9%) died in hospital. ARDS (26, 21.8%) and elevated D-dimer (36, 31.3%) were the most common complications, while other organ complications were relatively rare. Multivariable regression showed increasing odds of severe illness associated with neutrophil to lymphocyte ratio (NLR, OR, 11.238; 95% CI 1.110–1.382; p < 0.001) and D-dimer greater than 1 µg/ml (OR, 16.079; 95% CI 3.162–81.775; p = 0.001) on admission. The AUCs for the NLR, D-dimer greater than 1 µg/ml and combined NLR and D-dimer index were 0.862 (95% CI, 0.751–0.973), 0.800 (95% CI 0.684–0.915) and 0.916 (95% CI, 0.855–0.977), respectively. SOFA yielded an AUC of 0.750 (95% CI 0.602–0.987). There was significant difference in the AUC between SOFA and combined index ( z = 2.574, p = 0.010). Conclusions More attention should be paid to the monitoring and early treatment of respiratory and coagulation abnormalities in middle-aged COVID-19 patients without comorbidities. In addition, the combined NLR and D-dimer higher than 1 μg/ml index might be a potential and reliable predictor for the incidence of severe illness in this specific patient with COVID-19, which could guide clinicians on early classification and management of patients, thereby relieving the shortage of medical resource. However, it is warranted to validate the reliability of the predictor in larger sample COVID-19 patients.

Background: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population. Methods: This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: " worsening" if moderate or severe acute respiratory distress syndrome criteria were met, " persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and " improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2. Results: Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening. Conclusions: Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.

BACKGROUND:We explored the effects of high-volume hemofiltration(HVHF) by different ultrasound directing on the plasma N-terminal pro-B-type natriuretic peptide(NT-Pro-BNP), extra vascular lung water index (EVLWI), liquid net balance quantity and prognosis in patients with septic shock.METHODS:Overall, 107 intensive patients with septic shock were enrolled by retrospective analysis from Department of Intensive Care Unit (ICU) of the Shandong Provincial Hospital affiliated to Shandong University from 2014-2017. According to HVHF by different ultrasound directing, all the patients were divided into two groups ((ultrasonic cardiac output monitor (USCOM), group A, n=51cases)) and ((critical bedside ultrasound (CBU), group B, n=56cases)).RESULTS:The value of CI in group A had a significant positive correlation with the value of PCCI by the PiCCO2 monitoring (P<0.05). The lung ultrasound water B lines in group B also had a significant positive correlation with the value of EVLWI by the PiCCO2 monitoring. The cumulative liquid net balance quantity in group B had a more significant elevation than group A after treatment 7th d. The level of EVLWI after treatment 48 h and 72 h, the level of plasma NT-Pro-BNP, the levels of P(A-a)DO2,OI and blood lactic after treatment 72 h, and the APACHE II scores and SOFA scores after treatment 7thd were reduced more significantly in group B than group A (P<0.001). The mortality at 28th day had a more significant decrease in group B than group A.CONCLUSION:It could decrease the level of NT-Pro-BNP, EVLWI, P(A-a)DO2, which then improves pulmonary oxygenation. Consequently, it decreased the APACHE II and SOFA scores and improved the 28th survival rate of patients.

The members of the LUNG SAFE Investigators and the ESICM Trials Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error.

Objective To investigate the impact of weekly data feedback and full-time supervision on nosocomial infection control.Methods A retrospective study was conducted to analyze the incidence of nosocomial infection in our ICU and the rate of missing report from January,2014 to December,2016.A weekly nosocomial infection data feedback included:publicity of nosocomial infection data of each beds from each doctor in charge,i.e.incidence of nosocomial infection,nosocomial pathogens,multidrug-resistant bacteria,reporting of infection,isolation and notification of nosocomial infection.Daily full-time supervision included:hand hygiene of all medical staff,aseptic medical procedures,coordination and supervision of auxiliary person (guards,caregivers,cleaners),daily disinfection of equipments,environment in the unit.Results The nosocomial infection rate before and after the implementation of weekly data feedback were 9.90％ (199/2019) and 5.50％ (124/2239) respectively,with a statistically significant difference (x2=28.239,P ＜ 0.001).The nosocomial infection rate before and after the implementation of full-time supervision were 8.40％ (83/993) and 3.30％ (41/1246) respectively,with a statistically significant difference (x2=27.131,P ＜ 0.001).The rate of missing report for nosocomial infection decreased to 0 after the implementation of weekly data feedback and full-time supervision (Z=-4.538,P=0.00).Conclusion Weekly data feedback may reduce nosocomial infection rate.Full-time supervision may further reduce the nosocomial infection rate.Weekly data feedback weekly and full-time supervision may improve the compliance of nosocomial infection control and quality of management.

Objective:To investigate the influence of combined use of atorvastatin (ATO) and low molecular weight heparin (LMWH) on the inflammatory reaction and pulmonary protection functions in rats with sepsis.Methods:A total of 122 healthy male Sprague-Dawley (SD) rats were divided into five groups using a random number table: sham-operated group (sham group, n =10),sepsis group (n =10),ATO group (n =34),LMWH group (n =34),and ATO combined with LMWH group (ATO+LMWH group, n =34).The rat model of sepsis was reproduced by cecal ligation and puncture (CLP),while in sham group, rats were only subjected to laparotomy without cecum ligation and puncture. The rats of each pretreatment group received relevant therapies for 5 days, either gastric perfusion with ATO 20 mg/kg or subcutaneous injection with LMWH 100 U/kg or both before operation. The sepsis severities of the model animals were scored according to the modified sepsis severity assessment standards of experimental animals. Ten rats in each group were calculated the 7-day cumulative mortality rate. Blood samples from 6 rats in each group were collected to determine the levels of tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1 β) and high mobility group protein box-1 (HMGB1) contents in plasma using enzyme linked immunosorbent assay (ELISA)before operation (0 hour) and 4,8,12,and 24 hours post operation. The lung tissue was harvested 24 hours after operation, and the pulmonary pathology was assayed by hematoxylin and eosin (HE) staining using optical microscope.Results:① The sepsis severity grades of sepsis group were significantly higher than those of sham group at 4 hours after operation (score:12.2 ± 2.0 vs.7.2 ± 0.5,P ＜ 0.05).Furthermore, they displayed a gradually increasing tendency, with the 7-day cumulative mortality rate being 90％ (9/10).The sepsis severity grades in ATO group, LMWH group, and ATO+LMWH group showed a significant decrease compared with sepsis group at 8 hours after operation (12.2± 2.0,11.2±2.2,10.0± 1.7 vs.16.6±2.5,all P ＜ 0.05).The 7-day cumulative mortality rates in ATO group, LMWH group, and ATO+LMWH group were 60％ (6/10),60％ (6/10),and 40％ (4/10),respectively, all of which was significantly lower than that of sepsis group (all P ＜ 0.05).② The levels of TNF-α,IL-1 β and HMGB1 have not shown much variations in the sham group after operation; the levels of pro-inflammatory cytokines in other 4 groups were significantly increased after operation compared with those before operation; the levels of TNF-α,IL-1β,and HMGB 1 reached peak at 4,8,and 24 hours, respectively. The levels of pro-inflammatory cytokines in sepsis group were significantly higher than those in the sham group. However, the levels of pro-inflammatory cytokines in ATO group, LMWH group, and ATO+LMWH group were significantly lower than those in sepsis group [4-hour TNF-α (ng/L):668.3 ± 124.6,536.5 ± 118.5,496.5 ± 108.5 vs.783.8 ± 134.7;8-hour IL-1 β (ng/L):2 476.7 ± 137.8,2 460.4± 171.2,2 090.0 ± 151.2 vs.2 873.9 ± 295.6;24-hour HMGB1 (μg/L):654.4± 154.4,659.0± 134.6,609.4±90.5 vs.859.3 ± 167.5,P ＜ 0.05 or P ＜ 0.01].③ It was showed by optical microscopy that the pulmonary tissue morphology was normal in sham group and that the damage of pulmonary pathology was relatively severe in sepsis group. Compared with sepsis group, the damage of pulmonary pathology in ATO group, LMWH group, and ATO + LMWH group was alleviated obviously, and the most obvious improvements were found in ATO + LMWH group.Conclusions:Either ATO or LMWH could decrease sepsis severity, suppress the release of plasma pro-inflammatory cytokines at the early and late stages, alleviate the damage of pulmonary pathology, and reduce the 7-day cumulative mortality rate. Therefore, the combined treatment of sepsis using both ATO and LMWH resulted in better outcomes than implemented individually.

The aim of the present study was to investigate the effect of atorvastatin combined with low-molecular-weight heparin (LMWH) on plasma early inflammatory cytokine levels as well as pulmonary pathophysiology of rats with sepsis. A total of 122 rats were randomly divided into five groups including the sham operation group (n=10), CLP group (n=10), atorvastatin group (n=34, 20 mg/kg/day), LMWH group (n=34, 100 IU/kg/day), and atorvastatin combined with LMWH group (n=34). Blood samples from 6 rats in each group were collected to detect TNF-α, IL-1β and HMGB1 concentration in plasma by linked immunosorbent assay at baseline and postoperatively at 4, 8, 12 and 24 h. Pulmonary pathophysiology was observed postoperatively at 24 h. The remaining 10 rats in each group were used to calculate the 7-day cumulative mortality rate. Compared to the sham operation group, the scores in CLP were greater than those of the sham operation group (P<0.05). Compared to the CLP group, the sepsis severity scores of the atorvastatin, LMWH, and atorvastatin combined with LMWH groups decreased gradually. Significant difference was detected in the four groups (P<0.05 0.01). Compared to the sham operation group, at 4, 8, 12 and 24 h, the TNF-α, IL-1β and HMGB1 levels in plasma in CLP increased significantly (P<0.01). Compared to the CLP group, the TNF-α, IL-1β and HMGB1 levels of plasma in other groups decreased gradually, and there was a significant difference in the four groups (P<0.01). At 24 h post operation, compared to the sham operation group, the damage of pulmonary pathophysiology in CLP was more severe. Compared to the CLP group, the damage of pulmonary pathophysiology in other groups was slight. Compared to the CLP group, the 7-day cumulative mortality rate in other groups decreased significantly (P<0.05). In conclusion, atorvastatin, combined with LMWH can decrease sepsis severity, plasma inflammatory cytokine levels, pulmonary pathophysiology, and the 7-day cumulative mortality rate. Atorvastatin, and LMWH may therefore be useful for the treatment of sepsis due to its ability to inhibit the release of TNF-α, IL-1β and HMGB1 in septic rats.

OBJECTIVE:To investigate the effect of tolerogenic dendritic cells (Tol-DC) generated by Rapamycin (Rapa) on the differentiation of Treg/Th17 cells and explore the possible mechanism of tolerance induction.METHODS:DC progenitors from mouse bone marrow were propagated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin (IL)-4 stimulation for 6 days in the presence or absence of Rapa (20 ng/ml). During DC culture, morphology of cell was observed under electron microscope. Cell surface expression of CD11c, CD40 and CD80 was analyzed by flow cytometry. The antigen-presenting function of DC was determined by one-way mixed leukocyte reactions. In vivo, the recipient BALB/c mice receiving transplantation of skin allograft from C57BL/6 mice were divided into control, Rapa, immature DC (imDC) and Tol-DC group. The survival time of the skin allograft was observed and Treg/Th17 cells were analyzed by flow cytometry in each group.RESULTS:The immunephenotypic analysis showed that in comparison with those in the control group and the LPS group the expression of the co-stimulatory molecules CD40 and CD80 were significantly lower in the Rapa-group and Rapa+LPS group. The ability to stimulate proliferation of T cells of the same genotype in the Rapa-group was significantly inhibited (P<0.01). In the in vivo experiment, the mice's survival time remarkably prolonged, the percentage of Treg cells was enhanced and Th17 cells was reduced in the mice's spleen in Tol-DC group.CONCLUSIONS:Tol-DC generated by Rapamycin can significantly induce immune tolerance through up-regulate Tregs and down-regulate Th17 cells. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro-generated Tol-DCs, which can be loaded with donor antigen, and potentially used to promote organ transplant tolerance.

纵隔血肿临床上相对少见，其治疗较困难，通常根据出血量多少以及是否危及生命所选的治疗方案存在较大差异。出血量少者多采取保守治疗，待其自行吸收；对出血量多或危及生命的血肿多采取创伤性较大的手术以清除血块；而对于尚不危及生命，等待自行吸收可能造成可预见性的临近组织器官损害的纵隔血肿，临床选择何种治疗方案较为困难。现报告前纵隔血肿所致气管狭窄在B超引导下经皮穿刺治疗成功治愈1例。

BACKGROUND:Previous studies on immunosuppression and anti-rejection after organ transplantation mainly focused on effects of T lymphocytes-mediated immune response and immunosuppressive agents on T lymphocytes. Effects of dendritic cel s were unclear. The manifestation and mechanism of immunosuppressive agent effects on dendritic cel s are not identical. OBJECTIVE:To compare the effects of different immunosuppressive agents on expression and function of costimulatory molecules of dendritic cel s, and to explore the mechanism of action of immunosuppressive agents. METHODS:20μg/L rapamycin, 0.04 mg/L mycophenolate, 10μg/L tacrolimus and 1 mg/L cyclosporine A were separately added during bone marrow cel s of C57BL/6 mice were differentiated into dendritic cel s. RESULTS AND CONCLUSION:Flow cytometry results revealed that CD40 expression in each group:rapamycin<tacrolimus<cyclosporine A<mycophenolate mofetil (P<0.01);CD86 expression:rapamycin<tacrolimus<cyclosporine A=mycophenolate mofetil (P<0.01). There was no significant difference in CD80, CD11c and major histocompatibility complex II expression among groups (P>0.05). One-way mixed lymphocyte reaction&nbsp;results displayed dendritic cel costimulatory T cel proliferation in each group:rapamycin<mycophenolate mofetil<tacrolimus=cyclosporine A (P<0.05). The results confirmed that rapamycin, tacrolimus, cyclosporine A, and mycophenolate mofetil exerted immunosuppression by suppressing CD40 and CD86, especial y rapamycin. Above medicines do not noticeably inhibit major histocompatibility complex II expression, but suppress T cel proliferation, and the inhibitory effect of rapamycin on cel proliferation is strongest.

目前,我国现阶段医疗资源总体分布不均衡,基层及偏远地区的医院普遍存在着医疗水平偏低的情况.由于受到技术、设备及人才等限制,二级医院的重症监护病房(ICU)医疗水平良莠不齐,救治水平不高.而寻求上级医院专家会诊或转运至上级医院,又受到时间、距离及费用等因素的制约.

目前,我国现阶段医疗资源总体分布不均衡,基层及偏远地区的医院普遍存在着医疗水平偏低的情况.由于受到技术、设备及人才等限制,二级医院的重症监护病房(ICU)医疗水平良莠不齐,救治水平不高.而寻求上级医院专家会诊或转运至上级医院,又受到时间、距离及费用等因素的制约。

Objective To investigate peoples' awareness degree and attitudes about organ donation in current China.Methods A questionnaire regarding organ donation was designed,including 20 little questions distributed in 10 groups,most of which were choice questions.The major question was people's attitudes on organ donation,and the development of organ donation.The survey was held in the outpatient hall,bustling commercial district and four professional colleges.The interviewees were randomly selected,and their gender,age,education background,profession or major filed were asked to be indicated on the paper.Results 2930 valid questionnaires were acquired in all.The proportion of men to women was nearly 1 ∶ 1.2,with mean age of 38.12 years old; more than 90％ of the interviewees knew organ transplantation,and could choose.some of the transplantable organs;more than 95％ knew organ donation,but the time varied; nearly 90％ of the interviewees approved cadaveric organ donation,and 73％ of them would like to donate their organs post mortem.People who know more about organ failure and organ transplantation can give more supports to organ donation.The young students have much enthusiasm to organ donation,but much professional knowledge is also needed to firm their attitudes.The approval percentage of living organ donation was 65.3％,obviously lower than cadaveric organ donation ( P ＜ 0.05 ).85.7％ of the interviewees approved to compensate the donators family appropriately.62.9％ suggested using media and various kinds of education to increase people's knowledge about organ donation,and only 20％ chose appropriate legislation.Conclusion At present,the public are aware of some general knowledge about organ transplantation and organ donation.Most of the public approve organ donation and would like to donate their organs post mortem.The popularization of organ transplantation can give facilitation to organ donation.Most of the interviewees believe appropriate compensation is necessary for the donator's family.Media and education can promote the development of organ donation.

BACKGROUND:Sensitized recipients have a high risk of immunological graft loss due to hyperacute rejection and/or accelerated acute rejection. The presence of major histocompatibility complex class I-related chain A (MICA) antibodies has also been described associated with an increased rate of kidney-allograft rejection. The aim of this study was to describe the expression of MICA antibodies in sensitized recipients of renal transplantation and evaluate its influence on the kidney transplantation recipients.METHODS:A total of 29 sensitized recipients were included in this study. All patients received the MICA antibodies detection before and after protein A immunoadsorption. Panel reactive antibody (PRA), HLA-matches, acute rejection and postoperative one to four-week serum creatinine level were also collected and analyzed, respectively. No prisoners were used in this study.RESULTS:Eight patients (27.6%) in all 29 sensitized recipients expressed the MICA antibodies but did not show higher acute rejection rate than the non-expressed patients (3/8, 37.5% vs. 8/21, 38.1%; P = 1.000). Recipients with PRA > 40% showed higher expression levels of MICA antibodies than the recipients with PRA < 40% (7/16, 43.8% vs. 1/13, 8.3%; P = 0.044). HLA mismatch did not have any effect on the expression of MICA antibodies (P = 1.000). MICA antibodies positive group had higher serum creatinine level than the control in postoperative one week ((135.4 ± 21.4) µmol/L vs. (108.6 ± 31.6) µmol/L, P = 0.036), but no significant difference in postoperative four weeks ((89.0 ± 17.1) µmol/L vs. (77.1 ± 15.9) µmol/L, P = 0.089). MICA antibodies decreased significantly after protein A immunoadsorption.CONCLUSIONS:MICA antibodies increase in the sensitized recipients, which have significant effects on the function of allograft in early postoperative period. Protein A immunoadsorption can decrease MICA antibodies effectively in sensitized recipients.