ObjectiveTo investigate the association of serum exosomal microRNAs （miRNAs） with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B （CHB）. MethodsPeripheral serum samples were collected from six healthy adults and six patients with CHB， and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis， and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine， a rat model of liver fibrosis induced by carbon tetrachloride， and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； an analysis of variance was used for comparison between multiple groups， and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. ResultsAbnormal expression of serum exosomal miR-122-5p was observed in patients with CHB， and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis， compared with the control group， the model group had a significant reduction in the expression level of miR-122-5p in the liver （P=0.048 and 0.014）， and compared with the patients with mild liver injury， the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue （P<0.05）. Among the 84 CHB patients， the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury （P<0.001 and P=0.003）. The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis （odds ratio ［OR］=0.001， 95% confidence interval ［CI］： 0.000‍ ‍—‍ ‍0.037， P=0.005） and liver fibrosis degree （OR=0.568， 95%CI： 0.331‍ ‍—‍ ‍0.856， P=0.019）. In addition， compared with the patients with low expression of miR-122-5p， the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy （64.3% vs 38.1%， P=0.029）. ConclusionSerum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis， and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis， promote the progression of fibrosis， and affect the histological outcome of CHB patients after antiviral therapy.

Background A diverse cohort of patients and susceptible individuals congregate in healthcare facilities, where exposure to pathogenic microorganisms associated with respiratory infectious diseases constitutes a significant risk factor for cross-infection. Central air-conditioning ventilation systems improve some indoor environment indicators while exacerbating the risk of transmission of respiratory infectious diseases. Objective To investigate the distribution characteristics of microbial communities in the central air-conditioning ventilation systems of hospitals, providing a scientific basis for the selection of microbial indicators in hygiene standards for hospital central air-conditioning ventilation systems and for hospital risk early warning systems. Methods In October 2023, two central air-conditioning ventilation systems were selected from a Grade 3A hospital in Shanghai: one was an all-air air-conditioning system serving the waiting area on the ground floor, and the other was a fan coil plus fresh air system serving the outpatient area on the third floor. Samples from four different components of the ventilation systems—air outlets, filters, surface coolers, and condensate trays—were collected for high-throughput sequencing of the 16S rRNA gene to analyze bacterial communities. Alpha-diversity and beta-diversity analyses were performed to investigate the microbial community composition and diversity characteristics of the hospital central air-conditioning ventilation systems. Functional analysis was conducted to determine the relative abundance of bacterial functions in these systems.Results A total of 528 operational taxonomic units (OTUs) were identified, encompassing 20 bacterial phyla, 37 classes, 79 orders, 123 families, and 240 genera. The analysis revealed that the bacterial community was predominantly composed of Proteobacteria, Gemmatimonadates, Bacteroidetes, and Actinobacteria. The diversity analysis indicated that bacterial community richness and diversity were highest in the condensate trays, while no statistically significant differences (P > 0.05) were observed in the bacterial community composition among the air outlets, filters, and surface coolers. The functional analysis showed that the bacterial communities in the central air-conditioning ventilation systems primarily exhibited chemoheterotrophic, oxidative energy-dependent heterotrophic, and ureolytic functional characteristics. Conclusion The dominance of Proteobacteria suggests that this phylum exhibits strong adaptability in the central air-conditioning ventilation systems, possibly related to its ability to survive and reproduce under varying environmental conditions. The diversity analysis indicates that the condensate tray is a critical area for bacterial proliferation in the central air-conditioning ventilation systems. The similarity in environmental conditions among the air outlets, filters, and surface coolers result in similar bacterial community structures. The functional analysis reveals that the bacterial communities possess robust energy conversion and metabolic capabilities, potentially contributing to processes such as organic matter decomposition and nitrogen cycling within the central air-conditioning ventilation systems.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

OBJECTIVE To systematically evaluate the efficacy and safety of novel oral anticoagulants （NOAC） in the treatment of cancer-related venous thromboembolism （VTE） patients. METHODS Retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， and Wanfang database from the establishment of each database to August， 2023， randomized controlled trials （RCTs） about the efficacy of low-molecular-weight heparin （LMWH， control group） versus NOAC （trial group） in the treatment of cancer-related VTE patients were collected. After extracting the data from included clinical studies， meta-analysis was performed by using RevMan 5.0 statistical software. RESULTS A total of 7 RCTs were included， with a total of 3 790 patients. Compared with the control group， the recurrence rate of VTE in the trial group was significantly reduced （RR＝0.65， 95%CI 0.51-0.82， P＝0.000 4）， while the incidence of major bleeding was slightly higher than in the control group， but the difference was not statistically significant （RR＝1.13， 95%CI 0.83-1.53， P＝0.45）. The incidence of clinically relevant non-major bleeding （RR＝1.69， 95%CI 1.34-2.13， P＜0.000 01） and gastrointestinal bleeding （RR＝1.96， 95%CI 1.15-3.34， P＝0.01） in the trial group was significantly higher than in the control group. There was no statistically significant difference in the incidence of intracranial hemorrhage， all-cause mortality， and fatal pulmonary embolism between 2 groups （P＞0.05）. CONCLUSIONS For cancer-related VTE patients， NOAC is superior to LMWH in preventing venous thrombosis recurrence， and is not inferior to LMWH in terms of major bleeding， intracranial hemorrhage， all-cause mortality， and fatal pulmonary embolism.

Objective Endothelial injury plays a crucial role in forming deep vein thrombosis.This study aims to compare the effectiveness of various methods for creating rabbit femoral vein thrombotic models after the endothelial injuryso as to provide a solid experimental foundation for further research on the endothelial injury and deep vein thrombosis.Methods Forty-five rabbits were randomly divided into three groups(A,B,C),with 15 cases in each group and subjected to the endothelial injury using the methods of simple clamping,combined complete ligation,and combined incomplete ligation,respectively.The intravascular ultrasonic manifestations and local endothelial pathological changes were compared at 1,3,and 7 days after modeling.Results Significant differences in vascular diameter and Young's modulus values were observed after 7 days of modeling(P<0.05).In pairwise comparisons between the groups,the Young's modulus values in group C were significantly higher than those in groups A and B after 7 days of modeling(P<0.05).Pathological examination confirmed the presence of fibr-inoid thrombus in the blood vessels of group C on the seventh day of modeling.Conclusion Combining simple clam-ping and incomplete ligation can produce a relatively stable endothelial injury and thrombus formation.This method provides a robust experimental model for further investigation into deep vein thrombosis after the endothelial injury.

Cardiac myosin binding protein-C(cMyBP-C),as an important component of myocardium coarse filaments,can regulate cross-bridge circulation through phosphorylation or dephosphorylation and participates in myocardial systolic and diastolic functions.cMyBP-C plays an important role in the occurrence and development of cardiovascular diseases(CVDs)such as acute myocardial infarction,cardiomyopathy,heart failure,aortic stenosis,hypertensive myocardial hypertrophy,and myocarditis,but the specific mechanism has not been fully clarified.This article reviews the research progress on the role of cMyBP-C in CVDs,in order to provide references for the diagnosis,treatment and prognosis evaluation of CVDs.

Objective To explore the diagnostic value of the combined detection of serum allograft inflammatory factor-1 (AIF-1), growth differentiation factor-15 (GDF15), and doublecortin-like kinase 1 (DCLK1) in breast cancer. Methods A total of 114 female breast cancer patients (breast cancer group) and 114 female volunteers (control group) who underwent physical examination were selected. Enzyme-Linked immunosorbent assay was applied to detect serum levels of AIF-1, GDF15, and DCLK1. Multivariate Logistic regression was used to analyze the risk factors affecting breast cancer. ROC curve was used to analyze the diagnostic value of serum AIF-1, GDF15, DCLK1 levels in breast cancer. Results The serum levels of AIF-1, GDF15, and DCLK1 in the breast cancer group were obviously higher than those of the control group (P<0.05). The expression levels of serum AIF-1, GDF15, and DCLK1 were significantly elevated in breast cancer patients with stage Ⅲ-Ⅳ, moderate and poor differentiation, lymph-node metastasis, and Ki-67 positive (P<0.05). Serum AIF-1, GDF15, and DCLK1 were risk factors for breast cancer, and the areas under the curve (AUC) for single and combined diagnosis of breast cancer for all three were 0.834, 0.753, 0.861, and 0.930, respectively. Additionally, the combined diagnosis AUC values were significantly higher than those assessed alone (Z_{combination-AIF-1}=3.479, Z_{combination-GDF15}=5.147, and Z_{combination-DCLK1}=3.121; all P<0.05). Conclusion In breast cancer patients, the serum AIF-1, GDF15, and DCLK1 levels increase. They are risk factors for breast cancer, and the combined diagnosis of the three is more effective.

Objective:To explore the protective effect of astaxanthin on acute liver injury induced by α-amanitin in mice.Methods:In June 2023, 42 healthy SPF male Kunming mice were selected. The mice were divided into blank control group, model (0.45 mg/kg α-amanitin) group, olive oil (10 ml/kg olive oil) group, low dose (20 mg/kg) astaxanthin group, medium dose (40 mg/kg) astaxanthin group, high dose (80 mg/kg) astaxanthin group and silybin (20 mg/kg) group by random number table method. Each group had 6 animals. Mice in the blank control group were intraperitoneally injected with 10 ml/kg normal saline, and mice in the other group were injected with α-amanitin. After that, the blank control group and model group were infused with 10 ml/kg normal saline, olive oil group and astaxanthin groups were given olive oil and astaxanthin according to dose by gavage, and silybin group was injected with silybin by dose. The drug was administered once every 12 h for a total of 4 doses. After 60 h, the mice were killed, the liver weight was weighed, and the liver index was calculated. The contents of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of mice were detected, and the contents of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA) in liver tissues were also detected. One-way analysis of variance (ANOVA) was used to compare the difference of indexes among each group, and pairwise comparison was performed by Dunnett- t test. Results:The mice in the blank control group had smooth hair color, good spirit and normal behavior, while the mice in the other groups showed varying degrees of retardation and decreased diet, and no death occurred in each group. Body mass[ (26.67±1.51) g] and liver mass[ (1.23±0.14) g] in model group were significantly lower than those in blank control group [ (33.50±2.43) g and (1.87±0.16) g], and the differences were statistically significant ( P<0.05). The liver index [ (5.39±0.32) %, (5.83±0.30) %, (5.75±0.24) % and (5.78±0.16) %] in low, medium and high dose astaxanthin groups and silybin group were significantly higher than those in model group [ (4.61±0.12) %], and the differences were statistically significant ( P<0.05). Serum ALT and AST contents in model group [ (153.04±13.96) U/L and (59.08±4.03) U/L] were significantly higher than those in blank control group [ (13.77±1.29) U/L and (10.21±0.35) U/L], and the differences were statistically significant ( P<0.05). The contents of CAT, GSH and SOD in liver tissues of model group [ (9.40±2.23) U/mgprot, (3.09±0.26) μmol/gprot and (48.94±3.13) U/mgprot] were significantly lower than those of blank control group [ (26.36±2.92) U/mgprot, (6.76±0.71) μmol/gprot and (89.89±4.17) U/mgprot], the differences were statistically significant ( P<0.05). MDA content[ (6.33±0.24) nmol/mgprot] in liver tissue of model group was significantly higher than that of blank control group [ (0.91±0.21) nmol/mgprot], and the difference was statistically significant ( P<0.05). The CAT contents[ (18.64±1.76) U/mgprot, (18.20±1.76) U/mgprot, and (15.54±1.36) U/mgprot] in liver tissues of low, medium and high dose astaxanthin groups were significantly higher than those of model group, with statistical significances ( P<0.05). Compared with model group, SOD contents[ (72.16±7.44) U/mgprot, (93.18±5.28) U/mgprot, (103.78±7.07) U/mgprot, and (96.60±7.02) U/mgprot] in liver tissues of mice in low, medium and high dose astaxanthin groups and silybin group were significantly increased ( P<0.05), MDA contents [ (4.30±0.84) U/mgprot, (3.66±0.28) U/mgprot, (2.96±0.29) U/mgprot, and (2.88±0.39) U/mgprot] were significantly decreased ( P<0.05). Compared with model group, GSH content [ (7.90±1.25) μmol/gprot] in high dose astaxanthin group was significantly increased ( P<0.05) . Conclusion:Astaxanthin may alleviate acute liver injury induced by α-amanitin by alleviating oxidative stress in mice liver.

Objective To investigate the effect and mechanism of Yiguan Decoction(YGJD)on the efficacy of M1 bone marrow-derived macrophages(M1-BMDMs)in the treatment of rats with liver cirrhosis induced by 2-AAF/CCl4.Methods BMDMs were isolated and induced into M1-BMDMs by lipopolysaccharide.A total of 50 male Wistar rats were randomly divided into normal group with 5 rats and model group with 45 rats.The rats for modeling were given subcutaneous injection of 50%CCl4 twice a week.Since week 7,the rats for modeling were randomly divided into model group(M group),YGJD group,M1-BMDM group,M1-BMDM+YGJD group,and sorafenib(SORA)group,and they were given subcutaneous injection of 30%CCl4 to maintain the progression of liver cirrhosis and intragastric administration of 2-AAF.CCR2 inhibitors were added to the drinking water,and each group was given the corresponding intervention.Related samples were collected at week 9.The rats were observed in terms of serum liver function parameters,liver pathology,hydroxyproline(Hyp)content in liver tissue,hepatic stellate cell activation,hepatic fibrosis and inflammation factors,and the expression levels of molecules associated with the Wnt signaling pathway.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results Compared with the M group,the M1-BMDM+YGJD group had significant reductions in the serum levels of alanine aminotransferase,aspartate aminotransferase,and total bilirubin(TBil)(all P<0.05)and a significant increase in the content of albumin(Alb)(P<0.05),and compared with the M1-BMDM group,the M1-BMDM+YGJD group had a significant reduction in the serum level of TBil(P<0.05)and a significant increase in the serum level of Alb(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in the expression levels of CD68 and TNF-α(P<0.05).Compared with the M1-BMDM group,the M1-BMDM+YGJD group had significant reductions in Hyp content and Sirius red positive area(P<0.05).As for the non-canonical Wnt signaling pathway molecules,compared with the M1-BMDM group,the M1-BMDM+YGJD group had significantly lower mRNA and protein expression levels of Wnt5a(P<0.05)and mRNA expression level of Fzd2(P<0.05),as well as significant reductions in the mRNA expression levels of Wnt4,Wnt5b,and Fzd3(P<0.05),while there were no significant changes in the mRNA expression levels of the canonical Wnt signaling pathway molecules β-catenin,LRP5,LRP6,Fzd5,and TCF.Conclusion YGJD can enhance the therapeutic effect of M1-BMDMs on rats with liver cirrhosis induced by 2-AAF/CCl4,possibly by inhibiting the non-canonical Wnt5a/Fzd2 signaling pathway,which provides new ideas for the synergistic effect of traditional Chinese medicine on M1-BMDMs in the treatment of liver cirrhosis.

Objective:To investigate the correlation between red cell volume distribution width (RDW) variation coefficient and mortality in patients with liver cirrhosis complicated with sepsis.Methods:From 2008 to 2019, the real clinical data of patients admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center, Massachusetts Institute of Technology were selected from the American Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database. Structured Query Language was used to extract the demographic information, physiological indicators, laboratory test indicators, complications, in-hospital mortality, and sequential organ failure assessment (SOFA) score from the MIMIC-Ⅳ database. Analysis of variance and Kruskal-Wallis test were used to analyze the characteristics of patients in different quartiles of RDW variation coefficient and the correlation between RDW variation coefficient and different outcomes. The clinical and prognostic variables were included in the logistic regression model and its adjustment models for analysis. Model 1 was adjusted according to age and gender, and model 2 was adjusted according to age, gender, SOFA score, bilirubin, albumin, body weight, white blood cell count, serum creatinine, serum sodium, dialysis treatment, and with congestive heart failure or not. A cubic spline regression model was used to analyze the dose-response relationship between RDW variation coefficient and in-hospital mortality, ICU mortality, mild to moderate disorders of consciousness in patients with liver cirrhosis complicated with sepsis. Trend tests were performed to analyze the interaction between the RDW variation coefficient and the variables used for stratification.Results:A total of 1 443 patients with liver cirrhosis complicated with sepsis were included, with a median age of 59.0 (52.0, 67.0) years old. Among them, 954 (66.1%) were male and 489 (33.9%) were female. The RDW variation coefficient was 3.49±2.50. Totally 382 patients died during hospitalization, 246 patients died in ICU, and 259 patients with mild to moderate disorders of consciousness. When RDW variation coefficient was analyzed as a continuous variable, the OR values (95% confidence interval (95% CI)) of unadjusted model, model 1, and model 2 in in-hospital mortality, ICU mortality and mild to moderate disorders of consciousness were 1.12 (1.09 to 1.16), 1.14 (1.10 to 1.17), 1.08 (1.03 to 1.13); 1.11 (1.07 to 1.15), 1.12 (1.08 to 1.16), 1.07 (1.02 to 1.12); and 1.16 (1.12 to 1.20), 1.16 (1.12 to 1.20), 1.12 (1.07 to 1.17); respectively. The fourth quartile of RDW variation coefficient (>4.74, 29.08) was taken as the control group, the OR values (95% CI) of the unadjusted model, model 1, and model 2 were 3.00 (2.13 to 4.25), 3.32 (2.34 to 4.74), 1.76 (1.10 to 2.84); 3.42 (2.27 to 5.26), 3.81 (2.50 to 5.90), 1.77 (1.03 to 3.11); and 8.52 (5.23 to 14.63), 8.35 (5.10 to 14.38), 5.56 (2.87 to 11.69); respectively. There was a linear correlation between RDW variation coefficient and in-hospital mortality, ICU mortality, mild and moderate disorders of consciousness (all P<0.05). Among patients with higher SOFA scores, along with the increase of RDW variation coefficient, the increase of in-hospital mortality, ICU mortality and the incidence of mild and moderate disorders of consciousness, were more significant than those of patients with lower SOFA scores ( P=0.022, 0.024, and 0.001). Conclusion:Variation coefficient of RDW is associated with increased risk of disorders of consciousness and in-hospital mortality in patients with liver cirrhosis complicated with sepsis.