Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Objective To understand the distribution and antimicrobial resistance changes of bacteria isolated from pleural and peritoneal effusion in Hunan Province,and provide reference for correct clinical diagnosis and rational antimicrobial use.Methods Data reported by member units of Hunan Provincial Antimicrobial Resistance Survei-llance System from 2012 to 2021 were collected.Bacteria antimicrobial resistance surveillance method was imple-mented according to technical scheme of China Antimicrobial Resistance Surveillance System(CARSS),and WHO-NET 5.6 software was used to analyze the data of bacteria isolated from pleural and peritoneal effusion as well as antimicrobial susceptibility testing results.Results From 2012 to 2021,a total of 28 934 bacterial strains were iso-lated from specimens of pleural and peritoneal effusions from member units of Hunan Provincial Antimicrobial Re-sistance Surveillance System,with 5 752 strains from pleural effusion and 23 182 from peritoneal effusion.The top five bacteria isolated from pleural effusion were Escherichia coli(n=907,15.8％),Staphylococcus aureus(n=535,9.3％),Klebsiella pneumoniae(n=369,6.4％),Staphylococcus epidermidis(n=452,7.9％),and Staphy-lococcus haemolyticus(n=285,5.0％).The detection rate of methicillin-resistant Staphylococcus aureus(MR-SA)from pleural effusion was 24.3％-39.2％,and that of methicillin-resistant coagulase negative Staphylococcus(MRCNS)was 58.8％-77.1％.The top five bacteria isolated from peritoneal effusion were Escherichia coli(n=8 264,35.6％),Klebsiella pneumoniae(n=2 074,9.0％),Enterococcus faecium(n=1 458,6.3％),Staphylo-coccus epidermidis(n=1 383,6.0％),and Pseudomonas aeruginosa(n=1 152,5.0％).The detection rate of MRSA from peritoneal effusion was 22.1％-52.4％,which presented a decreasing trend(P=0.004).The detec-tion rate of MRCNS was 60.4％-79.4％.The resistance rates of Enterobacterales from peritoneal effusion to ce-fazolin,cefuroxime,ceftriaxone and cefepime all showed decreasing trends(all P＜0.05).Vancomycin-,linezo-lid-,and teicoplanin-resistant Staphylococcus strains were not found in pleural and peritoneal effusions.The resis-tance rates of Enterococcus faecium to most tested antimicrobial agents were higher than those of Enterococcus fae-calis.The resistance rates of Enterobacterales to imipenem and meropenem were ≤8.5％.The resistance rates of non-fermentative Gram-negative bacilli to imipenem and meropenem were ≤43.3％.Conclusion The data structure of Hunan Antimicrobial Resistance Surveillance System for pleural and peritoneal effusions from 2012 to 2021 is relatively complete.The constituent and antimicrobial susceptibility of isolated pathogenic bacteria vary in different years.

Objective:To observe the changes in semen parameters after COVID-19 infection and clarify its impact on male fertility.Methods:We collected semen samples from 82 male patients infected with COVID-19 in the past 2 months(the infection group)and 14 normal healthy men(the control group),obtained their semen parameters and compared them between the two groups before and after COVID-19 infection.Results:There were no statistically significant differences in the baseline semen parameters between the infection and control groups(P＞0.05),nor in the semen volume within the infection group before and after infection(P＞0.05).Compared with the normal controls,the patients showed significantly decreased sperm concentration,total sperm count,percentage of progressively motile sperm,sperm motility and percentage of morphologically normal sperm after COVID-19 infection(P＜0.05),which were reduced even more significantly in those with than in those without fever during infection(P＜0.05).No sta-tistically significant difference was observed in the semen quality of the patients with normal body temperature before and after COVID-19 infection(P＞0.05).Spearman correlation analysis showed no significant correlation between semen parameters and the severity of fever during infection(P＞0.05).Conclusion:COVID-19 infection decreases the semen quality of the patient,and fever dur-ing infection is a significant influencing factor.The severity of fever,however,is not related to the reduction of semen quality.

Objective:To preliminarily estimate and study the effect of nucleic acid testing in blood screening on the residual risk (RR) of transfusion transmitted HBV infection (TTI HBV).Methods:Using the NAT yield/WP ratio model and adopting the relevant data of information management system of practice comparison working party in the Mainland of China, this paper analyzed the trend of the RR of TTI HBV among 18 blood centers from 2015 to 2019 in China, and compared the impact of two kinds of blood screening strategies which were ELISA+ ID-NAT/MP-NAT (individual-donation nucleic acid testing or mini-pool nucleic acid testing) and ELISA + MP-NAT on RR in 2019.Results:The overall trends of the 5-year RR of HBV among 18 blood centers showed by trend chi square test were NAT single positive rate trend χ2= 39.42( P<0.01) and residual risk trend χ2= 279.792( P<0.01); The influence on RR from the differences of ELISA+ ID-NAT/MP-NAT and ELISA+ MP-NAT was statistically significant, and chi square test showed that χ2= 7.4( P<0.01). Conclusions:Since the implementation of nucleic acid testing in the blood screening in China from 2015, the residual risk of transfusion transmitted HBV infection has decreased year by year. The observed two blood screening strategies which dominated in China may lead to discrepancy in the residual risk of TTI.

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Objective:To explore the diagnostic value of anti-HCV and HCV RNA so as to provide an accurate and efficient detection strategy for the diagnosis of HCV in intravenous drug users.Methods:527 plasma samples from intravenous drug users were collected, and preliminary anti-HCV ELISA screening test was performed. A recombinant immunoblot assay (RIBA) was used as confirmatory assay for reactive antibody samples. All samples were tested for HCV RNA, followed by analysis of anti-HCV screening test, RIBA and HCV nucleic acid test results.Results:Anti-HCV ELISA results were reactive in 386 out of 527 intravenous drug users and non-reactive in 141. Among the 386 reactive antibody samples detected by RIBA, 370 cases were anti-HCV positive, 6 cases were anti-HCV indeterminate and 10 cases were anti-HCV negative. Anti-HCV ELISA and RIBA positive coincidence detection rate was 95.85% (370/386), and 70.21% (370/527) among intravenous drug users. HCV RNA was negative in all 10 anti-HCV RIBA non-reactive samples. 376 anti-HCV RIBA-positive and indeterminate samples were tested for HCV RNA, of which 56.93% (300/527) were current HCV infection, and 14.42% (76/527) were past HCV infection. Among 141 anti-HCV ELISA negative samples, the residual risk by anti-HCV ELISA screening for HCV RNA was 1.52% (8/527). HCV viral load distribution among intravenous drug users showed that the high viral load value (>10 7 IU/ml) and low viral load values (< 10 2 IU/ml) accounted for 1.95% and 2.27%, respectively, while the samples with viral load value of 1×10 2 ~ 1×10 7 IU/ mL accounted for 95.78% (295/308), and were mainly distributed in 1×10 5 ~ 1×10 6 IU/ml (37.99%). ELISA + RIBA + NAT assay detection strategies had differentiated 300 cases of current HCV infection, 76 cases of past HCV infection and 10 cases of false positive anti-HCV results, while ELISA+NAT assay detection strategies had only detected 300 cases of current HCV infection. However, of the 386 positive subjects screened for antibodies, 10 (2.59%) were undifferentiated false positives. Conclusion:Intravenous drug users are the high-risk population of HCV infection with high prevalence and high viral load. Anti-HCV screening for intravenous drug users will have a certain degree of residual risk. Therefore, anti-HCV ELISA screening and nucleic acid detection strategy can accurately diagnose the current infected patients; however, it cannot distinguish the false positive results of antibody screening.

HCV infection is of global concern with the characteristic of insidious onset. Laboratory testing stands indispensably for clinical diagnosis with antibody assay and nucleic acid testing the main methods being adopted. For early detection and diagnosis of HCV infection, it is important to choose the best detection method and diagnostic strategy. This paper reviews the HCV nucleic acid testing methods, as well as performance evaluation of reagents and current strategies.

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.
Adrenomedullin ; metabolism ; Animals ; Blood Pressure ; drug effects ; physiology ; Hypertension ; etiology ; Lipopolysaccharides ; pharmacology ; Male ; Neuropeptides ; metabolism ; Obesity ; complications ; Rats, Sprague-Dawley ; Receptors, Adrenomedullin ; drug effects ; metabolism ; Sympathetic Nervous System ; drug effects ; metabolism ; Toll-Like Receptor 4 ; metabolism

BACKGROUNDDecoy receptor 3 (DcR3) is a protein with anti-apoptotic effect that belongs to the tumor necrosis factor receptor superfamily. DcR3 is highly expressed in a variety of malignant tumors including cholangiocarcinoma and its expression was found to be related to the clinical stage, the invasion, and the metastasis of the tumor. This in vitro study aimed to investigate the effect of downregulated expression of DcR3 on cell viability, cell apoptosis, and cell cycle in cholangiocarcinoma cell line TFK-1.

METHODSThree different cell lines were cultured: human cholangiocarcinoma TFK-1, human biliary epithelial carcinoma HuCCT-1, and human cholangiocarcinoma RBE. The cholangiocarcinoma cell line with the highest expression of DcR3 was selected for further investigation. The expression of DcR3 was silenced/knocked down by transfection with DcR3-siRNA in the selected cell line. Various biological phenotype parameters such as cell viability, apoptosis, and cell cycle were observed.

RESULTSThe mRNA and protein levels of DcR3 were measured in the three cell lines, and TFK-1 was selected. After the treatment with DcR3-siRNA for 48 h, DcR3 mRNA and protein expression in the treatment group were 38.45% (P < 0.01) and 48.03% (P < 0.05) of that of the control, respectively. It was found that the cell viability decreased to 61.87% of the control group (P < 0.01) after the downregulation of DcR3 in cholangiocarcinoma cell line TFK-1 by transfection with DcR3-siRNA, while the percentage of apoptotic cells was 2.98 times as compared with the control group (P < 0.05). Compared with the control group the ratio of G0/G1increased, and the ratio of G2/M decreased in the treatment group. However, the differences were not statistically significant.

CONCLUSIONSThe effect of DcR3 on the growth and apoptosis of cholangiocarcinoma has been demonstrated. DcR3 is not only a predictive marker for malignant tumor but it is also likely to be a potential target for cancer gene therapy. Further studies should focus on exploring the binding ligand of DcR3, the signaling pathway involved, and the molecular mechanism for the regulation of DcR3 expression in cholangiocarcinoma.

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