Objective To analyze the risk factors for the development of chronic critical illness(CCI)in septic shock patients in the intensive care unit(ICU).Methods A retrospective analysis was conducted on 102 sepsis shock patients admitted to the ICU of the hospital from August 2018 to May 2023.According to their clinical dates,they were divided into CCI group(n=60)and rapid recovery(RR)group(n=42).Multi-ple logistic regression analysis was perform to identify independent risk factors for developing CCI in septic shock patients,and construct their receiver operating characteristic(ROC)curves to evaluate their predictive value for CCI.Results The prolonged duration of hypernatremia(OR=1.770,95％CI:1.147-2.731,P=0.010)and low acute physiology and chronic health(APACHEⅡ)scores(OR=1.212,95％CI:1.025-1.433,P=0.025)were independent risk factors for CCI in ICU septic shock patients.The occurrence of acute gastrointestinal injury(OR=0.060,95％CI:0.011-0.341,P=0.002)and peak blood sodium levels during ICU(OR=0.812,95％CI:0.662-0.995,P=0.044)were protective factors.Conclusion For septic shock pa-tients,special attention should be paid to its related independent risk factors and protective factors to improve the prognosis of septic shock patients.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

Objective:Metabolic alkalosis has raised concerns in patients receiving continuous renal replacement therapy (CRRT) via regional citrate anticoagulation (RCA). This study searched for alkalosis-related factors and mechanisms.Methods:It's a retrospective study of alkalosis in patients who received CRRT for at least 12 hours with RCA in a tertiary hospital between April 2017 and April 2020. Demographic features, baseline laboratory results, CRRT metrics and laboratory results at 12h after CRRT was recorded. Patients was grouped based on whether alkalosis exist at 12h after CRRT, and multivariable logistic regression analysis was used to identify risk factors for alkalosis during CRRT with citrate anticoagulation.Results:The 59 patients meeting the inclusion criteria were 49% male, with a mean age of (55±18) years old, and 42% had alkalosis by 12 hours after CRRT. No significant differences in demographic features or laboratory results were observed patients with or without alkalosis. CRRT metrics, including blood flow rate, citrate rate, replacement fluid rate and total effluent rate, were significantly different among groups ( P<0.01). Multivariable Logistic regression analysis indicated that the citrate rate was a risk factor for alkalosis ( OR=1.088, 95% CI 1.020-1.161, P =0.010). In patients receiving no NaHCO 3 and without alkalosis, the linear regression analysis described the relationships of citrate with replacement fluid rate (citrate rate = 0.090 × replacement fluid rate + 56.581; R2 = 0.6918) and total effluent rate (citrate rate = 0.099 × total effluent rate + 2.449). Conclusions:This retrospective observational study demonstrated that CRRT metrics are highly associated with alkalosis after 12 hours of CRRT. Without NaHCO3 infusion, a 10-fold linear correlation was observed between citrate and total effluent rate in patients without metabolic alkalosis.

Acute pancreatitis(AP),one of the most common acute abdominal conditions in clinical practice,is typically self-limiting.However,approximately 20%of cases progress to severe acute pancreatitis,characterized by persistent systemic inflammatory response syndrome and multiple-organ dysfunction syndrome,with a high mortality rates.The pathogenesis of AP involves complex pathophysiological processes,and in recent years,the role of oxidative stress(OS)in AP has garnered increasing attention.OS refers to an imbalance between reactive oxygen species production and antioxidant capacity following endogenous or exogenous stimuli,which can lead to pancreatic cell injury,exacerbation of inflammatory responses,and organ dysfunction.Notably,antioxidants have demonstrated efficacy in reducing OS-induced pancreatic damage and multi-organ dysfunction in animal models.This article reviews current molecular mechanisms of OS in AP,its role in disease progression and recent advances in antioxidant-based therapeutic strategies for AP.

Acute pancreatitis(AP),one of the most common acute abdominal conditions in clinical practice,is typically self-limiting.However,approximately 20%of cases progress to severe acute pancreatitis,characterized by persistent systemic inflammatory response syndrome and multiple-organ dysfunction syndrome,with a high mortality rates.The pathogenesis of AP involves complex pathophysiological processes,and in recent years,the role of oxidative stress(OS)in AP has garnered increasing attention.OS refers to an imbalance between reactive oxygen species production and antioxidant capacity following endogenous or exogenous stimuli,which can lead to pancreatic cell injury,exacerbation of inflammatory responses,and organ dysfunction.Notably,antioxidants have demonstrated efficacy in reducing OS-induced pancreatic damage and multi-organ dysfunction in animal models.This article reviews current molecular mechanisms of OS in AP,its role in disease progression and recent advances in antioxidant-based therapeutic strategies for AP.

Attention deficit hyperactivity disorder is a common neurodevelopmental disorder characterized by persistent attention deficit, hyperactivity, and impulsive behaviors that are not consistent with developmental age.Academic and vocational difficulties, social exclusion, and delinquent behaviors are manifested in daily life.It is also commonly accompanied by psychiatric problems.At the same time, mental problems are common, and the overall quality of life is greatly affected, placing a heavy burden on society as well as the family.International attention deficit hyperactivity disorder experts have developed a common and comprehensive International Classification of Functioning, Disability and Health core set of classifications for assessing individual functioning in attention deficit hyperactivity disorder.

Objective This study used resting-state functional magnetic resonance imaging(rs-fMRI)to investigate the changes of local brain regional homogeneity in patients with depression and childhood maltreatment,and we calculated the relationship between altered ReHo values and the severity of childhood maltreatment.Methods 25 patients with depression and childhood maltreatment,25 patients with depression without childhood maltreatment,and 25 age,gender,and education-matched healthy controls were prospectively enrolled.All subjects underwent resting-state functional magnetic resonance imaging and ReHo analysis.One-way analysis of variance was used to compare the group differences,along with multiple comparison correction.Pearson correlation analysis was used to explore the relationship between region ReHo values with clinical scales.Results Compared with the group of depression without childhood maltreatment,the abnormal brain regions of depression with childhood maltreatment are mainly located in the dorsolateral prefrontal cortex,cerebellum,parietal gyrus,and precentral gyrus.The ReHo values of depression with childhood maltreatment in the left cerebellum and the left dorsolateral prefrontal cortex are correlated with the severity of childhood maltreatment.Conclusions Depression with childhood mal-treatment is associated with changes in local spontaneous brain activity,which are correlated with the severity of childhood maltreatment.The brain changes in the dorsolateral prefrontal cortex and cerebellum may explain the neurobiological mechanisms of depression with childhood maltreatment.

Objective:To develop a perinatal depression screening scale for Chinese urban version and test its reliability and validity.Methods:Naturally conceived women who were≥12 weeks of gestation and had regular prenatal examinations or delivered within four weeks in Xi'an and Foshan were recruited using convenience sampling. Initial entries were created through clinical interviews and expert validation of 50 of these pregnancies. Further item screening and testing for reliability and validity using correlation analysis, critical ratio method, homogeneity test, and factor analysis were performed. The final questionnaire was formed and then used to test the subjects. Fifty women who had completed the questionnaire effectively were selected for retesting 10 to 15 days after the initial evaluation. A structural equation model was constructed using the Edinburgh Postpartum Depression Scale (EPDS) as the reference criterion to conduct the scale's exploratory and confirmatory factor analysis. The receiver operating characters curve was used to determine the cut-off point of the scale.Results:(1) 1 300 questionnaires were issued, and 1 049 valid questionnaires were received with a recovery rate of 80.7%. Among them, 601 were used for exploratory and correlation analysis, and 448 were used for confirmatory factor analysis. (2) The initial entries of the scale totaled 63. After eliminating indicators that did not meet the requirements for item analysis, the final scale consisted of 22 entries in total. The final scale consisted of six dimensions, including "abnormal mood", "loss of interest and pleasure," "sleep disorder," "self-blame and guilt," "decline in conscious thought ability," and "lack of energy". (3) The correlation coefficients between the above six dimensions and EPDS were 0.609, 0.322, 0.423, 0.522, 0.545, and 0.516, respectively. The one between the total scale and EPDS was 0.715 (all P<0.01). (4) The confirmatory factor analysis of each model and the scale showed an acceptable fit and a stable factor structure with indices Chi-square/degrees of freedom =2.504, square root of approximation error=0.058, standardized root mean square residual=0.048, comparative fit index=0.925, Tueker-Lewis index=0.911. After retaining 22 items, the Cronbach's coefficients of the six dimensions ranged from 0.708 to 0.870. (5) The test-retest reliability of the total scale, six dimensions, and 22 items were 0.936, 0.786-0.846, and 0.720-0.886, respectively. (6) The receiver operating characteristic curve of the scale was drawn with EPDS≥13 as the cut-off value, and the area under the curve (AUC) of EPDS was 0.808 (95% CI: 0.744-0.872). When the original cut-off point was 21, the Youden index was the max (0.561), with sensitivity and specificity of 0.952 and 0.609, respectively. The Kappa value was 0.691, indicating that the scale was consistent with EPDS. Conclusion:This study preliminarily established a Chinese urban version of the perinatal depression screening scale with a stable factor structure and good reliability and validity.

Objective:To develop a perinatal depression screening scale for Chinese urban version and test its reliability and validity.Methods:Naturally conceived women who were≥12 weeks of gestation and had regular prenatal examinations or delivered within four weeks in Xi'an and Foshan were recruited using convenience sampling. Initial entries were created through clinical interviews and expert validation of 50 of these pregnancies. Further item screening and testing for reliability and validity using correlation analysis, critical ratio method, homogeneity test, and factor analysis were performed. The final questionnaire was formed and then used to test the subjects. Fifty women who had completed the questionnaire effectively were selected for retesting 10 to 15 days after the initial evaluation. A structural equation model was constructed using the Edinburgh Postpartum Depression Scale (EPDS) as the reference criterion to conduct the scale's exploratory and confirmatory factor analysis. The receiver operating characters curve was used to determine the cut-off point of the scale.Results:(1) 1 300 questionnaires were issued, and 1 049 valid questionnaires were received with a recovery rate of 80.7%. Among them, 601 were used for exploratory and correlation analysis, and 448 were used for confirmatory factor analysis. (2) The initial entries of the scale totaled 63. After eliminating indicators that did not meet the requirements for item analysis, the final scale consisted of 22 entries in total. The final scale consisted of six dimensions, including "abnormal mood", "loss of interest and pleasure," "sleep disorder," "self-blame and guilt," "decline in conscious thought ability," and "lack of energy". (3) The correlation coefficients between the above six dimensions and EPDS were 0.609, 0.322, 0.423, 0.522, 0.545, and 0.516, respectively. The one between the total scale and EPDS was 0.715 (all P<0.01). (4) The confirmatory factor analysis of each model and the scale showed an acceptable fit and a stable factor structure with indices Chi-square/degrees of freedom =2.504, square root of approximation error=0.058, standardized root mean square residual=0.048, comparative fit index=0.925, Tueker-Lewis index=0.911. After retaining 22 items, the Cronbach's coefficients of the six dimensions ranged from 0.708 to 0.870. (5) The test-retest reliability of the total scale, six dimensions, and 22 items were 0.936, 0.786-0.846, and 0.720-0.886, respectively. (6) The receiver operating characteristic curve of the scale was drawn with EPDS≥13 as the cut-off value, and the area under the curve (AUC) of EPDS was 0.808 (95% CI: 0.744-0.872). When the original cut-off point was 21, the Youden index was the max (0.561), with sensitivity and specificity of 0.952 and 0.609, respectively. The Kappa value was 0.691, indicating that the scale was consistent with EPDS. Conclusion:This study preliminarily established a Chinese urban version of the perinatal depression screening scale with a stable factor structure and good reliability and validity.