ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer (BC) by using two-sample Mendelian randomization (MR). Methods This study employed a two-sample MR analysis, with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−) from the BCAC Consortium as the outcome variables. For causal inference, inverse variance weighting (IVW) was employed as the primary analytical method, alongside multiple consistency validation approaches, including MR-Egger, weighted median, weighted mode, simple mode, and Bayesian weighted Mendelian randomization. Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality. Results Significant causal associations were identified for specific immune cell phenotypes across subtypes. In HR+ BC, the HER2+ subtype was associated with seven immunophenotypes (five protective and two risk increasing), whereas the HER2− subtype was associated with eight immunophenotypes (four protective and four risk increasing). In HR− BC, the HER2+ subtype was associated with five immunophenotypes (one protective and four risk increasing), and the HER2− subtype (triple-negative BC) was associated with seven immunophenotypes (six protective and one risk-increasing). CD28+CD45RA−CD8+ T cells and naive CD8+ T cells have a bidirectional causal relationship with HR+/HER2+ breast cancer, Whereas the expression of CD8 on CD39+CD8+ cells also has a bidirectional relationship with HR+/HER2− breast cancer. Furthermore, CD4−CD8− NKT cells exhibited opposing effect directions in HER2+ versus HER2− subtypes. Conclusion From a genetic perspective, this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC, revealing heterogeneity in immune regulation.

Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

OBJECTIVE To investigate the distribution,drug resistance and molecular characteristics of the Staph-ylococcus aureus strains isolated from intensive care unit(ICU)environment in some hospitals of Shanghai Pudong New Area so as to provide bases for prevention and control of infections.METHODS The specimens were collected from ICU environment of 8 medical institutions in Pudong District in 2019 and 2023,the S.aureus strains were i-solated and identified.The drug susceptibility testing was performed by microbroth dilution method.The drug re-sistance genes and virulence genes were predicted based on virulence factors of bacterial pathogens,the compre-hensive antibiotic resistance database(mcmaster.ca)and PubMLST,multilocus sequence typing(MLST)and phylogenetic analysis were performed.RESULTS Totally 3408 samples were collected,and the isolated S.aureus strains accounted for 1.29％(44/3408);the isolated strains form both the shared articles and the articles that health care workers directly contact accounted for 20.45％.The drug resistance rate to penicillin was highest(72.73％,32/44);the strains were completely susceptible to vancomycin,rifampicin,sulfamethoxazole-trime-thoprim,daptomycin and nitrofurantoin.The methicillin-resistant Staphylococcus aureus(MRSA)strains accoun-ted for 25.00％.The multi-drug resistance rate was 40.91％.The strains carried 26 types of drug resistance genes in total,covering 9 categories;the carrying rate of fluroquinolones resistance gene nor A was 100.00％.The strains carried 12 types of enterotoxin genes,the carrying rate of sea gene was highest(50.00％,22/44),some of the strains carried lukS-PV,lukF-PV and tsst gene.There were 14 types of sequence type(ST),dominated by ST7(13/44,29.55％),and novel ST type ST9342 was discovered.The phylogenetic analysis showed that all of the strains were divided into 2 major branches,and the strains with the same ST type were phylogenetically close on the evolutionary tree.CONCLUSIONS The S.aureus strains are prevalent in ICU environment and are highly re-sistant to antibiotics.The strains exhibit various ST types,which,to a certain degree,is associated with the path-ogenicity.

Metabolic reprogramming is a crucial feature of cancer.Among various metabolic processes,oxidative phosphorylation(OXPHOS)metabolism serves as the primary biochemical pathway for energy production and significantly influences tumorigenesis and tumor development.Therefore,this study aims to explore the impact of the metabolic characteristics of lung squamous cell carcinoma(LUSC)on its ma-lignant properties.By analyzing the single-cell transcriptome sequencing data of LUSC,lung adenocarci-noma,and normal lung tissues from the gene expression profile database,it was found that the OXPHOS signaling pathway and molecules related to ATP synthesis were remarkably enriched in LUSC tissues.Based on the OXPHOS signal intensity score,LUSC cells were classified into OXPHOShigh and OXPH-OSlow groups.Bioinformatics analysis revealed that 126 transcription factors were highly expressed in both LUSC tumor tissues and the OXPHOShigh group.Notably,the expression levels of cancer stem cell-related signals(such as SOX2,SOX9,POU2F1,CDX1,ARID3A,EZH2,and KLF5)were significantly en-hanced in the OXPHOShigh cell subset(P＜0.05).Treatment of LUSC cells with an OXPHOS antagonist significantly inhibited the sphere formation rate of H520 and SKMES-1 cells,which is a key characteristic of cancer stemness(P＜0.05).Analysis of cell-cell communication data from the LUSC single-cell tran-scriptome indicated that the signal emission and reception in OXPHOShigh cells were stronger than those in OXPHOSlow cells.Moreover,fibroblasts showed significant interaction with OXPHOShigh-LUSC cells.Co-culture of LUSC cell lines H520 and SKMES-1 with human lung fibroblast-like cell lines significantly in-creased the sphere formation rate of tumor cells(P＜0.05).Additionally,the levels of ATP,NADH-ac-tive enzymes,and reactive oxygen species(ROS)in co-cultured H520 and SKMES-1 cells were signifi-cantly elevated(P＜0.05).The results of this study confirm that the OXPHOS pathway is a key signal involved in LUSC metabolism,which is closely associated with the characteristics of cancer stem cells and the regulatory signals of fibroblast interactions.This finding holds promises for providing novel strategies for tumor treatment.

OBJECTIVE To investigate the distribution,drug resistance and molecular characteristics of the Staph-ylococcus aureus strains isolated from intensive care unit(ICU)environment in some hospitals of Shanghai Pudong New Area so as to provide bases for prevention and control of infections.METHODS The specimens were collected from ICU environment of 8 medical institutions in Pudong District in 2019 and 2023,the S.aureus strains were i-solated and identified.The drug susceptibility testing was performed by microbroth dilution method.The drug re-sistance genes and virulence genes were predicted based on virulence factors of bacterial pathogens,the compre-hensive antibiotic resistance database(mcmaster.ca)and PubMLST,multilocus sequence typing(MLST)and phylogenetic analysis were performed.RESULTS Totally 3408 samples were collected,and the isolated S.aureus strains accounted for 1.29％(44/3408);the isolated strains form both the shared articles and the articles that health care workers directly contact accounted for 20.45％.The drug resistance rate to penicillin was highest(72.73％,32/44);the strains were completely susceptible to vancomycin,rifampicin,sulfamethoxazole-trime-thoprim,daptomycin and nitrofurantoin.The methicillin-resistant Staphylococcus aureus(MRSA)strains accoun-ted for 25.00％.The multi-drug resistance rate was 40.91％.The strains carried 26 types of drug resistance genes in total,covering 9 categories;the carrying rate of fluroquinolones resistance gene nor A was 100.00％.The strains carried 12 types of enterotoxin genes,the carrying rate of sea gene was highest(50.00％,22/44),some of the strains carried lukS-PV,lukF-PV and tsst gene.There were 14 types of sequence type(ST),dominated by ST7(13/44,29.55％),and novel ST type ST9342 was discovered.The phylogenetic analysis showed that all of the strains were divided into 2 major branches,and the strains with the same ST type were phylogenetically close on the evolutionary tree.CONCLUSIONS The S.aureus strains are prevalent in ICU environment and are highly re-sistant to antibiotics.The strains exhibit various ST types,which,to a certain degree,is associated with the path-ogenicity.

The incidence of apoplexy remains persistently high among the older population.Based on the traditional Chinese medicine principle of"treating the elderly by focusing on the fu",this paper explores the holistic connotation of"fu".It proposes that the onset of apoplexy in the elderly is characterized by obstruction,stagnation,depression,and sluggishness,which should be treated from six fu viscera,xuanfu,and collaterals.The interconnected hierarchical network of these three systems,serving as macro-and micro-channels for qi and fluid metabolism,plays a central role in both disease development and treatment.The failure of the six fu viscera to descend and the upward invasion of turbid yin are identified as prerequisites for apoplexy onset,whereas yang qi stagnation and xuanfu blockage act as key pathogenic drivers,and the core mechanisms involve phlegm-stasis-toxin accumulation,and dysfunction of the collaterals and fu.In the treatment,acute phase requires unblocking fu viscera and restoring xuanfu patency;chronic phase focuses on dredging collaterals and opening xuanfu;and recovery phase emphasizes tonifying combined with regulating xuanfu.The understanding of"treating the elderly by focusing on the fu"emphasizes that the pathogenesis of the disease should be changed to individual conditions;"six fu viscera-xuanfu-collaterals"exhibits a pathological mechanism characterized by the transmission and reception of pathogenic factors,as well as progressive mutual involvement;in clinical practice,treatment should meticulously assess the severity and nuances of the condition,prioritizing method that emphasizes unobstructed flow;additionally,therapy should be essential to protect stomach qi and integrate therapeutic attacks within a framework of supplementation.These principles offer valuable reference for the differentiation and treatment of apoplexy.