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 To develop the Evidence-Based Health Care Related Competence Assessment Scale for Health Professionals(hereinafter referred to as the Scale),and to test its validity and reliability.Methods Based on the JBI evidence-based health care model as the theoretical framework,the initial items of the Scale were formed by reviewing the literature.Through the discussion of the research group,two rounds of Delphi expert consultation and pre-inspection,the items of the Scale were optimized.The convenience sam-pling method was adopted to extract 928 health professionals as the research subjects.The Scale conducted the validity and reliability testing.Results The Scale included the four dimensions of evidence generation,evi-dence synthesis,evidence transfer and evidence implementation,including 47 entries in total.The cumulative variance contribution rate was 59.08%.The confirmatory factor analysis results indicated that the model had good fitness.The convergent validity of all dimensions reached the standard,and the distinguishing validity was good.Finally,the Cronbach's α coefficient of the Scale was 0.971,and the split-half reliability was 0.928.Conclusion The developed Scale possesses good reliability and validity,which can be used to evaluate the competence of health professionals carrying the evidence-based healthcare related link works.

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.

Objective To investigate the prevalence of postpartum depression(PPD),parenting self-efficacy,and empathy ability in elderly parturients during the puerperium,and analyze their cor-relations.Methods A total of 506 elderly parturients who gave birth in the obstetrics department from January 2021 to December 2023 were selected as study subjects.Basic demographic informa-tion,including age,education level,marital status,employment status,and family income per month,was collected through a questionnaire survey.The Edinburgh Postnatal Depression Scale(EPDS)was used to assess the occurrence of PPD.Based on the presence or absence of PPD,elderly parturients were divided into PPD group and non-PPD(NPPD)group.The Parenting Self-Efficacy Scale(PMPS-E)was employed to evaluate parenting self-efficacy,and the Empathy Quotient Scale(EQ)was used to assess empathy ability.Multivariate logistic regression analysis was conducted to explore independent risk factors for PPD in elderly parturients.Spearman correlation analysis was used to ex-amine the relationships between PPD,parenting self-efficacy,and empathy ability.Pearson correlation analysis was employed to investigate the relationship between parenting self-efficacy and empathy ability in elderly parturients.Results A total of 495 valid surveys were collected,with a response rate of 97.82％.The survey results showed that parturients aged 35 to 40 accounted for the highest proportion(45.25％).The majority had an undergraduate or junior college education level,ac-counting for 44.65％.Married parturients accounted for 85.45％.Among occupational distribu-tions,those without fixed employment were more common,accounting for 40.00％.Most families had a monthly income of 5,000 to 10,000 Chinese yuan,accounting for 41.41％.Cesarean sec-tion was the predominant mode of delivery,accounting for 43.43％.The PMPS-E and EQ scores of elderly parturients in the PPD group were lower than those in the NPPD group(P＜0.05).Statisti-cally significant differences were observed between the PPD and NPPD groups in terms of education level,employment status,marital status,and family monthly income(P＜0.05).Multivariate logistic regression analysis revealed that low education level,unstable marital status,lack of fixed employment,and low family income per month were independent risk factors for PPD(P＜0.05).Spearman correlation analysis indicated negative correlations of PPD with parenting self-efficacy and empathy ability(r=-0.475,-0.382;P＜0.05).Pearson correlation analysis demonstrated a positive correlation between parenting self-efficacy and empathy ability(r=0.426;P＜0.05).Conclusion PPD in elderly parturients is closely related to their parenting self-efficacy and empa-thy ability.Education level,marital status,lack of fixed employment,and family income are factors influencing the occurrence of PPD.

OBJECTIVE To establish a comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance to realize the management of pediatric hierarchical diagnosis and treatment, and improve the quality of pharmaceutical care. METHODS A unified diagnosis and treatment information standard and a knowledge base of children's rational drug use rules were established among the medical institutions of Jiangxi provincial pediatric alliance. On this basis, the medical records and drug use information of patients in various medical institutions in the region were uploaded to the chain in a structured manner in real time, and a comprehensive platform for regional pharmaceutical care was built. RESULTS The comprehensive platform for regional pharmaceutical care built based on blockchain technology could share medical resources and information among medical institutions, realize rational drug use management, remote prescription review, individualized drug use guidance, popular science education, government supervision, etc., and improve the quality of pharmaceutical care. CONCLUSION The comprehensive platform for regional pharmaceutical care among Jiangxi provincial pediatric alliance can help allocate high-quality medical resources (drug safety knowledge base and pediatric pharmacists) for primary medical institutions. Further more, it lays the foundation for government supervision at the same time ensuring children’s medication safety, which has great practical significance.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.

Gastric cancer is one of the most common malignant tumors in the world. Patients with gastric cancer are often treated by surgery, radiotherapy, chemotherapy or immunotherapy, but the clinical efficacy and prognosis are poor. As an important member of ADAMs family, a disintegrin and metalloprotease 17 (ADAM17) is significantly more highly expressed in gastric cancer than in adjacent tissues. It participates in the occurrence and development of gastric cancer by mediating EGFR, TNF-α, TGF-β/Smad, Notch and Wnt, FoxM1-ADAM17 and EGFR/ERK/SP1. The high expression of ADAM17 is also closely related to the poor prognosis of gastric cancer, suggesting that ADAM17 can be used as a biological index to predict the development and prognosis of gastric cancer and has great potential to become a new therapeutic target for gastric cancer. In this paper, the mechanism, treatment and prognosis of ADAM17 in the development of gastric cancer are reviewed, in order to provide new ideas for clinical diagnosis and treatment of gastric cancer.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane protein of the immunoglobulin superfamily, is involved in mediating cell adhesion, tissue metastasis, control of immune response, and metabolic homeostasis. Studies have shown that CEACAM1 protects the liver by promoting insulin clearance and preventing fat deposition. The down-regulation of the CEACAM1 expression level leads to a vicious cycle of insulin resistance and aggravates metabolic disorders. As CEACAM1 is critical in controlling metabolic dysfunction-associated steatotic liver disease (MASLD), stimulating its pathway or regulating its expression level might be a potential new therapeutic approach for MASLD. In this paper, therefore, we summarize the research progress of CEACAM1 in MASLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by abnormal lipid deposition in the liver and its mechanism is closely related to insulin resistance, lipid metabolism disorders, oxidative stress, and abnormalities of the gut-liver axis. Currently, there is no effective treatment for this disease. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD⁺)-dependent deacetylase which performs various pathophysiological functions by interacting with different substrates. For example, it is involved in improving metabolic homeostasis, alleviating liver inflammation, promoting liver regeneration, and delaying the progression of MASLD. In this paper, we present a review of the mechanism of action of SIRT2 in MASLD to analyze the potential value of SIRT2 as a therapeutic target in MASLD.