Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

OBJECTIVES: To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. RESULTS: Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. CONCLUSIONS Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.
Humans ; Tryptophan/blood* ; Retrospective Studies ; Acute-On-Chronic Liver Failure/virology* ; Male ; Female ; Middle Aged ; Adult ; Prognosis ; Hepatitis B/complications* ; Hepatitis B virus

OBJECTIVES: To investigate the impact of hepatitis B virus (HBV) infection on oral microbiota and metabolites in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and the underlying mechanisms. METHODS: This prospective study was conducted in 47 MAFLD patients complicated with chronic hepatitis B (CHB) and 48 MAFLD patients without CHB enrolled from November, 2023 to January, 2024. Fasting tongue coating samples were collected from the patients for analyzing microbial community structures and metabolites using high-throughput 16S rDNA sequencing and non-targeted metabolomics techniques, and their associations with clinical indicators and biological pathways were explored using correlation analysis and functional annotation. RESULTS: The levels of fasting blood glucose, total cholesterol (TC), gamma-glutamyl transferase (GGT), and severity of fatty liver were all significantly lower in MAFLD+CHB group than in MAFLD group. Microbiota analysis showed that the abundances of Patescibacteria (at the phylum level), Hydrogenophaga, and Absconditabacteriales (at the genus level) were significantly increased, while the abundance of Megasphaera was decreased in MAFLD+CHB group. The differential microbiota were significantly correlated with TC, GGT and low-density lipoprotein (r=-0.68‒0.75). Metabolomics analysis revealed that 469 metabolites (including lipids and amino acids) were upregulated and 2306 (including organic oxygen-containing compounds and phenylpropanoids) were downregulated in MAFLD+CHB group, for which KEGG enrichment analysis suggested abnormal activation of the linoleic acid metabolism and glycerophospholipid metabolism pathways. Correlation analysis between microbiota and metabolites indicated that Patescibacteria and Megasphaera, which were positively correlated with lipid metabolites and negatively with fatty acid metabolites, respectively, jointly affected glycolipid metabolism and oxidative stress pathways. CONCLUSIONS Compared to patients with MAFLD alone, MAFLD patients with concurrent chronic HBV infection showed lower levels in some lipid metabolism indicators and the degree of hepatic steatosis, accompanied by alterations in oral microbiota structure and metabolic profiles. The precise mechanisms involved require further investigation to be fully elucidated.
Humans ; Lipid Metabolism ; Prospective Studies ; Microbiota ; Hepatitis B, Chronic/microbiology* ; Male ; Female ; Adult ; Fatty Liver/microbiology* ; Middle Aged ; Mouth/microbiology* ; Metabolomics

BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

Objective To analyze the correlations of autoimmune diseases(AIDs)with the risk of developing pancreatic endocrine and exocrine diseases.Methods A total of 451,497 participants from the UK Biobank were recruited,with the primary outcomes being pancreatic endocrine and exo-crine diseases.International Classification of Diseases 9/10(ICD9/10)codes were used to define each AIDs,the pancreatic endocrine and exocrine diseases.Multivariable Cox proportional hazards models were employed to assess the relationships between AIDs and pancreatic endocrine and exocrine diseases,with adjustments for age,gender,ethnicity,Townsend deprivation index,smoking,alcohol consumption,body mass index,waist circumference,hip circumference,hypertension,dyslipidemia,and gallstones.Results A total of 415,497 participants were included,among which 37,482 de-veloped pancreas-related diseases during follow-up.Among patients with AIDs,the proportions of those with pancreatic exocrine and endocrine diseases were significantly increased(P＜0.05).Rheumatoid arthritis[HR(95％CI):1.438(1.161 to 1.781)],ankylosing spondylitis[HR(95％CI):1.675(1.009 to 2.780)],ulcerative colitis[HR(95％CI):1.335(1.037 to 1.719)],and Crohn's disease[HR(95％CI):1.530(1.154 to 2.028)]were all associated with an increased risk of de-veloping pancreatic exocrine diseases(all P＜0.05);additionally,rheumatoid arthritis[HR(95％CI):1.119(1.004 to 1.248)],ulcerative colitis[HR(95％CI):1.324(1.175 to 1.491)],sys-temic sclerosis[HR(95％CI):2.08(1.355 to 3.191)],and Crohn's disease[HR(95％CI):1.394(1.197 to 1.624)]were also associated with an increased risk of developing pancreatic en-docrine diseases(all P＜0.05).Conclusion Overall AIDs and some specific AIDs are associated with an increased risk of developing pancreatic endocrine and exocrine diseases,and early preven-tion of pancreatic diseases in patients with AIDs should be emphasized in clinical practice.

Objective To evaluate the comprehensive value of methicillin-resistant Staphylococcus aureus(MRSA)treatment drugs in artificial joint infections from multiple perspectives and to solve the problem of MRSA infections in artificial joints.Methods Through literature research,relevant literature was retrieved and clinical studies meeting the requirements were selected and summarized.The Analytic Hierarchy Process(AHP)was applied to collect comprehensive clinical evaluation evidence and to conduct evaluations across different dimensions according to evaluation guidelines;the Delphi method combined with AHP was used for expert anonymous questionnaire evaluation,and the data was compared and analyzed.Results A clini-cal comprehensive evaluation index model for the treatment of artificial joint infections was successfully established,and the yaahp analysis software was used to score the comprehensive clinical evaluation evidence in various directions.Treatment drugs,vancomy-cin,daptomycin,and linezolid,at various levels were calculated through the software,and it was concluded that linezolid has the highest clinical comprehensive evaluation score.Conclusion Among the treatment drugs for MRSA infections in artificial joints,linezolid has a higher clinical comprehensive value and can provide a reference for the clinical treatment of MRSA infec-tions in artificial joints.

Objective:To investigate the current status of fertility concerns among early-stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with fertility preservation, and analyze its influencing factors.Methods:Convenience sampling was used to select early-stage EC and AEH patients with fertility preservation at Peking University People's Hospital from January to December 2021 as study subjects. The study subjects were surveyed using the General Information Questionnaire, Chinese version of the Reproductive Concerns after Cancer Scale (RCAC), and Social Support Rating Scale (SSRS). Pearson correlation was employed to examine the relationship between fertility concerns and social support in early-stage EC and AEH patients with fertility preservation. Single-factor analysis and multiple linear regression analysis were used to examine the factors influencing fertility concerns in early-stage EC and AEH patients with fertility preservation.Results:A total of 170 questionnaires were distributed, and 167 valid questionnaires were collected, with a valid response rate of 98.24% (167/170). The RCAC and SSRS scores of 167 early-stage EC and AEH patients with fertility preservation were (56.58±10.58) and (34.22±8.21), respectively. Educational level, disease type and staging, marital status, and social support were statistically significant factors influencing fertility concerns among early-stage EC and AEH patients undergoing fertility preservation ( P<0.05), explaining 32.80% of the total variance. Conclusions:Early-stage EC and AEH patients with fertility preservation exhibit high levels of fertility concerns. Clinical practice should develop individualized psychological intervention programs for patients with high education level, unmarried status, high pathological grading, and lack of social support to improve their physical and mental health.

Objective:To investigate the current status of fertility concerns among early-stage endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) patients with fertility preservation, and analyze its influencing factors.Methods:Convenience sampling was used to select early-stage EC and AEH patients with fertility preservation at Peking University People's Hospital from January to December 2021 as study subjects. The study subjects were surveyed using the General Information Questionnaire, Chinese version of the Reproductive Concerns after Cancer Scale (RCAC), and Social Support Rating Scale (SSRS). Pearson correlation was employed to examine the relationship between fertility concerns and social support in early-stage EC and AEH patients with fertility preservation. Single-factor analysis and multiple linear regression analysis were used to examine the factors influencing fertility concerns in early-stage EC and AEH patients with fertility preservation.Results:A total of 170 questionnaires were distributed, and 167 valid questionnaires were collected, with a valid response rate of 98.24% (167/170). The RCAC and SSRS scores of 167 early-stage EC and AEH patients with fertility preservation were (56.58±10.58) and (34.22±8.21), respectively. Educational level, disease type and staging, marital status, and social support were statistically significant factors influencing fertility concerns among early-stage EC and AEH patients undergoing fertility preservation ( P<0.05), explaining 32.80% of the total variance. Conclusions:Early-stage EC and AEH patients with fertility preservation exhibit high levels of fertility concerns. Clinical practice should develop individualized psychological intervention programs for patients with high education level, unmarried status, high pathological grading, and lack of social support to improve their physical and mental health.

We analyzed the epidemiological features and spatial distribution characteristics of human brucellosis in Jining city from 2014 to 2023,to provide a reference for further development of targeted prevention and control strategies and measures.Descrip-tive epidemiological methods were used to analyze the epidemiological characteristics of brucellosis cases in Jining from 2014 to 2023.The spatial regional correlation of brucellosis incidence in Jining and the clustering patterns of local areas were studied through spatial autocorrelation analysis with townships as the basic unit.A total of 3 520 cases of brucellosis were reported in Jining from 2014 to 2023,and the average annual incidence rate was 4.23/100 000,thus indicating a fluctuating trend overall.Reported cases peaked from March to August,and a sex ratio of 2.71 males to 1 female was observed.The 40-59 year age group had the most reported cases(50.39％).The incidence of brucellosis in Jining showed an imbalanced spatial distribution.Brucellosis incidence showed a spatially clustered distribution(Moran's I>0,P<0.05).Hotspots were distributed primarily in Sishui,Qufu,and Zoucheng.A total of one class Ⅰ clustering area and one class Ⅱ clustering area were detected in the spatial and temporal scans,and were located in Sishui,Qufu,and Liangshan county.After pathogenic AMOS-PCR typing analysis,64 Brucella isolates collected from Jinan City from 2022 to 2024 were all of the sheep strain,and sheep biovar 3 was predominant(70.31％).In 2014-2023,although Jining City experienced a high incidence of brucellosis,a downward trend was observed.Brucellosis showed a spatial clustering pattern concentrated in the northeastern region.Therefore,awareness and education must be strengthened among brucellosis practitioners in cluster areas,to en-hance case surveillance,improve the level of protection,and achieve early detection and treatment.

Objective To verify the performance of an non competitive immune sandwich method(candidate method)in detecting 25(OH)D,and evaluate the measurement agreement of candidate method with liquid chromatography tandem mass spectrometry(LC-MS/MS,reference method).Methods According to the comparison of documents such as China National Accreditation Service for Conformity Assessment(CNAS)-GL037,the precision,linear interval,lower limit of quantitation(LOQ)and accuracy of the method for detecting 25(OH)D were verified.1 073 residual serum samples were collected from March to July 2021 and 25(OH)D was detected by the two methods.Passing-bablok regression,concordance correlation coefficient(CCC),Bland altman plots and Kappa test were used to analyze the consistency and bias.Weighted Kappa test was conducted to evaluate the consistency of two methods for clinical assessment of vitamin D nutritional status.Results The performance of candidate method:the within-run CV was lower than 5%and the in laboratory CV were lower than 10%;test results between 2.88～52.45 ng/ml showed good linear relationship;the lower limit of quantitation was 2.26 ng/ml,the bias of candidate method measuring standard reference materials were within±6%and within 15%measuring vitamin D external quality assessment scheme(DEQAS)samples.The comparison method and the reference method showed good correlation(r=0.965,CCC=0.946)with an average deviation of-1.54 ng/ml(-7.42%).The two methods coincidence rate in judging vitamin D status was 85.96%(918/1 068),and the weighted kappa value was 0.801.Conclusions The candidate method measurement performance met the clinical requirements,and showed good correlation and consistency with the reference method.