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.

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 analyze the relationship between MyD88L265P and CD79B mutations in tumor tissue and the prognosis of primary central nervous system lymphoma(PCNSL).Methods 18 PCNSL patients with normal immune function(no history of HIV infection and immunosuppressants administration)who were diagnosed by craniotomy or stereotaxic biopsy in the Second Hospital of Lanzhou University from August 2018 to November 2020 were retrospectively analyzed.Real-time quantitative PCR and first-generation sequencing techniques were respectively used to detect MyD88L265P and CD79B mutations in tumor tissues of 18 PCNSL patients.Univariate analysis and Cox regression multivariate analysis were performed for indicators that may be associated with first progression-free survival(PFS)and overall survival in PCNSL.Results The mutation rate of MyD88L265P was 38.9%,the mutation rate of CD79B was 33.3%,and the co-mutation rate of MyD88L265P/CD79B was 27.8%in PCNSL tissue of 18 patients.Univariate analysis showed that the PCNSL patients with multiple lesions,deep involvement of lesions,and tissue CD79B mutation had a statistically significant shorter time of PFS(P<0.05).Multivariate analysis showed that deep lesion involvement(HR=0.135,95%CI 0.023-0.799,P<0.05)and CD79B mutation(HR=0.149,95%CI 0.028-0.800,P<0.05)in PCNSL tissue were independent prognostic factors for PCNSL patients.Conclusion The frequency of MyD88L265P and CD79B mutations was high in tumor tissues of 18 PCNSL patients,and these two gene mutations may be associated with poor prognosis of PCNSL,especially CD79B mutation.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Objective:To investigate gene mutation characteristics of primary central nervous system lymphoma(PCNSL)through whole exome sequencing(WES)to 18 patients with PCNSL.Methods:Tumor tissues from 18 patients with diffuse large B-cell lymphoma who were diagnosed with PCNSL in Department of Hematology,Lanzhou University Second Hospital from September 2018 to December 2020 and had normal immune function,no history of HIV or immunosuppressant therapy were collected.High-throughput-based WES was performed on the tumor tissues,with an average sequencing depth of＞100 x.After data processing and bioinformatics analysis of sequencing results,the mutation maps and mutation characteristics of 18 PCNSL patients were obtained.Results:Obvious somatic mutations were detected in all 18 patients.The median number of somatic mutations was 321.Missense mutations were most prominent(accounting for about 90％),and the mutation type was dominated by C＞T(50.2％),reflecting the age-related mutation pattern.Among the top 15 frequently mutated genes,PSD3,DUSP5,MAGEB16,TELO2,FMO2,TRMT13,AOC1,PIGZ,SVEP1,IP6K3,and TIAM1 were the driver genes.The enrichment results of driver gene pathways showed that RTK-RAS,Wnt,NOTCH,Hippo and Cell-Cycle pathways were significantly enriched.The tumor mutation burden was between 3.558 48/Mb and 8.780 89/Mb,and the average was 4.953 32/Mb,which was significantly higher than other cancer research cohorts in the TCGA database.Conclusions:PCNSL occurs somatic missense mutations frequently,mainly point mutations,and the mutation type is mainly C＞T.The driver genes are mainly involved in RTK-RAS,Wnt,NOTCH and Hippo pathways,indicating that the above pathways may be related to the pathogenesis of PCNSL.PCNSL has a significantly high tumor mutation burden,which may explain the efficacy of PD-1 inhibitors in PCNSL.

Objective:To investigate the effects of ATG5 and ATG7 genes on the sensitivity of multiple myeloma(MM)cell line RPMI-8226 cells to ferroptosis.Methods:CRISPR/Cas9 technology was used to knock out the autophagy key genes ATG5 and ATG7 in RPMI-8226 cells.Western blot was used to identify gene knockout cells,and detect the expression changes of autophagy-related proteins P62 and LC3B.Flow cytometry was used to detect the change of sensitivity of gene knockout cells to RSL3.The content of intracellular ferrous ions and reactive oxygen species(ROS)level in gene knockout cells were detected.Results:Western blot result confirmed that ATG5 and ATG7 genes were knocked out successfully in RPMI-8226 cells.The result of flow cytometry showed that the cell viability of RPMI-8226 cells was dose-dependent on different concentrations of RSL3(r=-0.969).RSL3(10 μmol/L)was used to induce ferroptosis in cells of control group and gene knockout groups,then the cell viability in gene knockout groups were both higher than control group after 48 hours(both P＜0.001).After knocking out the ATG5 and ATG7 genes,the content of intracellular Fe2+decreased significantly compared with control group(both P＜0.01),and the ROS level also decreased(both P＜0.001).Conclusion:Knockout of ATG5 and ATG7 genes can inhibit the ferroptosis of MM cells,and LAP pathway may be involved in the regulation.

Objective To investigate the effect of parent-child alienation on depression in surface ship officers and soldiers based on the theory of"diathesis-stress",and the mediating role of resilience between parent-child alienation and depression in them.Methods A cross-sectional study was conducted on 599 officers and soldiers from a surface ship unit.The participants were surveyed with inventory of alienation toward parents,connor-davidson resilience scale and patient health questionnaire-9 to obtain and analyze their demographic-military characteristics of their depression scores.The participants with depression scores ≥5 were recruited as the subjects,and Spearman correlation analysis was used to explore the correlation among parent-child alienation,resilience and depression.On the basis of hierarchical regression analysis,AMOS software was used to establish a structural equation modelling of intermediary effects.Results The depression score was 1(0,4)in the participants,and the depression scores of those with service length ≥11 years were comparatively higher than those with shorter length.Our results indicated that parent-child alienation was positive correlated with depression(r=0.451,P＜0.001),while resilience was negatively correlated with depression and parent-child alienation(r=-0.412,-0.407,P＜0.001).Regression analysis revealed that parent-child alienation had a direct positive predictive value for depression(β=0.574,P＜0.001),and resilience showed a negative predictive value for depression(β=-0.211,P＜0.01).Model analysis displayed that resilience had a significant mediating role in the effect of parent-child alienation on depression among these surface ship officers and soldiers,with an effect value of 0.088,and accounting for 15.86％of the total effect.Conclusion Parent-child alienation has a significant influence on depression among surface ship officers and soldiers,with resilience playing a partial mediating role.

Molecular imprinting is a biomimetic technique that simulates the specific recognition of biological macromolecules such as antibody. Based on molecular imprinting and high-specificity affinity analysis,the biomimetic imprinting affinity analysis (BIA) possesses many advantages such as high sensitivity,strong tolerance,good specificity and low cost,and thus,it has shown excellent prospects in food safety detection,pharmaceutical analysis and environmental pollution monitoring. In this review,the construction methods of recognition interfaces for BIA were summarized,including bulk polymerization,electro-polymerization and surface molecular imprinting. The application of molecularly imprinted polymers in different analysis methods,such as radiolabeled affinity analysis,enzyme-labeled affinity analysis,fluorescence-labeled affinity analysis,chemiluminescence affinity analysis and electrochemical immunosensor was mainly discussed. Furthermore,the challenges and future development trends of BIA in practical application were elucidated. This review might provide new reference ideas and technical supports for the further development of BIA technique.