Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.

Objective:To explore the funding status and research hotspots of the National Natural Science Foundation of China (NSFC) for projects in the field of TCM for the prevention and treatment of heart failure.Methods:The research projects of TCM in the prevention and treatment of heart failure funded were retrieved from NSFC Big Data Knowledge Management Service Platform from January 1, 2010 to December 31, 2023. Excel 2022 software was used to analyze the data of the number of funded projects, the amount of funding, the supporting units and the regions. VOSviewer 1.6.20 software was used to analyze the co-occurrence of keywords with frequency≥3.Results:A total of 202 research projects were funded with a total funding amount of 89.8 million RMB, and the number and amount of projects showed a fluctuating upward trend. The funding categories were mainly general programs and youth science foundation projects. There were 42 supporting units involved, and TCM universities and colleges were the main recipients of funding. Regional distribution was uneven, mainly in Beijing, Shanghai, Guangdong and other regions. There were 17 secondary discipline codes involved, and the discipline categories were concentrated in Internal Medicine of TCM (H3108), Clinical Basis of Integrative Medicine (H3302) and Cardiovascular Pharmacology of Chinese Medicine (H3209). Therapeutic modalities covered compounding, monomers, proprietary Chinese medicines, and drug pairs, and research hotspots included aspects of myocardial energy metabolism remodeling, mitochondrial autophagy, macrophage polarization, endoplasmic reticulum stress, calcium homeostasis, ferroptosis, exosomes, micro-RNAs, and so on.Conclusion:NSFC has provided strong support to the research in the field of TCM for heart failure. In the future, the supporting units should pay attention to the interdisciplinary integration and development to promote the vigorous development of TCM.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Liver fibrosis is a chronic liver injury resulting from factors like viral hepatitis, autoimmune hepatitis, non-alcoholic steatohepatitis, fatty liver disease, and cholestatic liver disease. Liver transplantation is currently the gold standard for treating severe liver diseases. However, it is limited by a shortage of donor organs and the necessity for lifelong immunosuppressive therapy. Mesenchymal stem cells (MSCs) can differentiate into various liver cells and enhance liver function when transplanted into patients due to their differentiation and proliferation capabilities. Therefore, it can be used as an alternative therapy for treating liver diseases, especially for liver cirrhosis, liver failure, and liver transplant complications. However, due to the potential tumorigenic effects of MSCs, researchers are exploring a new approach to treating liver fibrosis using extracellular vesicles (exosomes) secreted by stem cells. Many studies show that exosomes released by stem cells can promote liver injury repair through various pathways, contributing to the treatment of liver fibrosis. In this review, we focus on the molecular mechanisms by which stem cell exosomes affect liver fibrosis through different pathways and their potential therapeutic targets. Additionally, we discuss the advantages of exosome therapy over stem cell therapy and the possible future directions of exosome research, including the prospects for clinical applications and the challenges to be overcome.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective To explore the value of the albumin-to-alkaline phosphatase ratio(AAPR)with modified Glasgow prognostic score(mGPS)in assessing the response to and prognosis of intravesical Bacillus Calmette-Guérin(BCG)therapy in patients with non-muscle invasive bladder cancer(NMIBC).Methods A total of 153 high-risk NMIBC patients treated with intravesical BCG in our hospital during Jan.2018 and Oct.2021 were enrolled.Patients were divided into response and non-response groups based on the treatment efficacy,and into good and poor prognosis groups based on the clinical outcomes.AAPR and mGPS were calculated.The relationship between AAPR,mGPS and BCG treatment non-response was analyzed with multivariate logistic regression.Clinical data and scores were compared between prognosis groups.The associations between AAPR,mGPS,and poor prognosis after BCG treatment were assessed with a Cox proportional hazards model.Patients were stratified into high-and low-A APR groups,and into mGPS 0,1,and 2 groups.Kaplan-Meier survival curves were plotted for progression-free survival(PFS)across different AAPR and mGPS strata.The diagnostic performance of AAPR combined with mGPS in predicting treatment non-response and poor prognosis was evaluated using receiver operating characteristic(ROC)curves.Results Among the 153 patients,the response rate to BCG treatment was 71.90％(110/153),the 3-year poor prognosis rate was 45.75％(70/153),and the 3-year PFS rate was 54.25％(83/153).Increased AAPR was identified as an independent protective factor for both treatment response and good prognosis,while higher mGPS was an independent risk factor(P＜0.05).The 3-year PFS rate was significantly higher in the high-AAPR group than in the low-A APR group(P＜0.001).Among the mGPS groups,the 3-year PFS rate was lowest in the mGPS 2 group,followed by mGPS 1 and mGPS 0 groups(P＜0.001).The area under the ROC curve(AUC)for AAPR with mGPS in predicting BCG treatment non-response and poor prognosis was 0.864 and 0.901,respectively,significantly higher than using AAPR(0.774,0.781)or mGPS alone(0.798,0.809)(P＜0.05).Conclusion Lower AAPR and higher mGPS are associated with non-response and poor prognosis in NMIBC patients undergoing intravesical BCG therapy.The combination of AAPR and mGPS has high predictive value.

Objective:To analyze the expression level of protein arginine methyltransferase 5 (PRMT5) in pancreatic cancer tissues and its correlation with prognosis using bioinformatics methods, and to explore its potential mechanisms.Methods:Expression analysis of the PRMTs family members was performed based on the gene expression profiles of 178 pancreatic cancer tissues from the Gene Expression Profiling Interactive Analysis (GEPIA) database and 171 normal pancreatic tissues from the TCGA and GTEx databases. Using the median expression level of PRMTs family members in pancreatic cancer tissues as the cutoff, patients were divided into high-expression and low-expression groups, and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) were plotted. The correlation between PRMT5 expression and the expression of oncogenes such as KRAS, TP53, BRCA1, BRCA2, and SLC39A4 was analyzed. Functional enrichment analysis was conducted on genes similar to PRMT5, and a protein-protein interaction (PPI) network was constructed to analyze the interaction relationships among these similar genes. Pancreatic cancer PANC1 and AsPC-1 cells cultured in standard medium served as the control group, while PANC1 and AsPC-1 cells cultured in medium supplemented with the PRMT5 inhibitor EPZ015666 served as the intervention group. Cell viability was assessed using the CCK-8 assay, and cell cycle progression was analyzed by flow cytometry.Results:The expression level of PRMT5 in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues and showed a significant negative correlation with both OS and DFS. Patients with high PRMT5 expression had a shorter median survival time compared to those with low expression (17.2 months vs 19.5 months). PRMT5 expression was significantly positively correlated with the expression of oncogenes KRAS, TP53, BRCA1, BRCA2, SLC39A4, and KLF5. Genes similar to PRMT5 were primarily enriched in cell cycle-related signaling pathways, and NOP58 identified as a hub gene in the PPI network. Compared to the control group, the proliferation activity of PANC1 and AsPC-1 cells in the intervention group was significantly reduced [(67.3±1.9)% vs (100±4.4)% for PANC1; (60.5±2.7)% vs (100.0±1.7)% for AsPC-1], and the proportion of cells in the G1 phase was significantly increased [(51.6±0.7)% vs (35.3±2.7)% for PANC1; (51.2±0.9)% vs (29.7±2.2)% for AsPC-1]. All these differences were statistically significant (all P values <0.05). Conclusions:High expression of PRMT5 was closely associated with poor prognosis in pancreatic cancer patients, and it may contribute to pancreatic cancer progression by regulating the cell cycle.

Objective:To explore the efficacy and safety of one-hole split endoscope (OSE) minimally invasive surgery for the treatment of single-segment thoracic ossification of the ligamentum flavum (TOLF).Methods:This retrospective non-randomized controlled study included 41 patients with single-segment TOLF who underwent surgery at Qilu Hospital of Shandong University between July 2019 and July 2023. Patients were divided into two groups: the OSE group (19 cases) treated with one-hole split endoscope minimally invasive surgery and the open group (22 cases) treated with traditional laminectomy and pedicle screw fixation. There were no significant differences between the two groups on gender, age, disease duration, affected segment, presence or absence of dural ossification, and residual cross-sectional vertebral canal area on CT ( P>0.05). Additionally, perioperative surgical time, estimated blood loss (EBL), incision length, hospital stay duration, hospitalization costs and follow-up duration were compared. The Japanese Orthopaedic Association (JOA) score and Oswestry Disability Index (ODI) were compared preoperatively and at the last follow-up. Complications were also recorded. Results:All patients successfully completed the surgery with no significant differences at the last follow-up ( P>0.05). Compared with the open group, the OSE group had a significantly shorter operative time (133.1±16.8 vs. 160.5±22.6 min), lower EBL (91.2±15.0 vs. 192.5±43.8 ml), shorter incision length (2.6±0.5 vs. 7.9±1.9 cm), reduced hospital stay (3.9±0.8 vs. 5.6±0.8 days), and lower hospitalization costs (34,874.9±4,568.6 vs. 53,162.3±9,815.6 yuan) (all P<0.05). AAt the final follow-up, JOA scores (8.5±0.8 vs. 8.6±1.2) and ODI values (16.7%±2.1% vs. 17.7%±4.4%) showed no significant differences between the OSE and open groups ( P>0.05). During the perioperative period and follow-up, complications occurred in 2 patients in the OSE group (1 cerebrospinal fluid leak, 1 poor wound healing) and in 8 patients in the open group (5 cerebrospinal fluid leaks, 1 neurological deterioration, 2 poor wound healing). Conclusion:OSE minimally invasive surgery is an effective treatment for single-segment thoracic ossification of the ligamentum flavum. Compared with open surgery, it provides advantages such as minimal invasiveness and fewer complications.