Objective To investigate the improvement effect of Necrostatin-1 (Nec-1) on mouse models with immune checkpoint inhibitor (ICI) -associated myocarditis (ICIAM) and potential mechanism. Methods Ten male BALB/c mice aged 6-8 weeks were selected to construct the ICIAM models. The echocardiography and serum myocardial injury markers were used to assess cardiac function of mice. The levels of inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Hematoxylin-eosin (HE) staining was used to evaluate myocardial inflammation, and Masson staining was used to evaluate myocardial fibrosis. The expressions of myocardial necroptosis proteins including receptor-interacting protein kinase 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and their phosphorylated forms were detected by Western blotting. The spleen lymphocytes were extracted and co-cultured with HL-1 cell line. Cell viability was measured by cell counting kit-8 (CCK-8). The release of reactive oxygen species (ROS) and changes of mitochondrial membrane potential were observed. RIP1, RIP3, MLKL and their phosphorylated forms were determined. The levels of markers of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were measured. Results Nec-1 significantly improved the cardiac function injury of mice induced by ICI, and inhibited the release of TNF-α and IL-1β in plasma of ICIAM mice (P＜0.001); inhibited expressions of phosphorylated RIP1, RIP3 and MLKL (P＜0.05); decreased MDA activity, and increased SOD and GSH-Px activity (P＜0.001). In HL-1 cells, Nec-1 intervention inhibited the RIP1-RIP3-MLKL pathway (P＜0.05), improved decrease of the cell viability induced by lymphocytes (P＜0.001), decreased ROS release, increased mitochondrial membrane potential, inhibited MDA activity, and increased SOD and GSH-Px activities (P＜0.001). Conclusions Necroptosis plays an important role in the occurrence and development of ICIAM，but Nec-1 could alleviate the progression of ICIAM by inhibiting necroptosis induced by oxidative stress in cardiomyocytes; RIP1 maybe a new target in treatment of ICIAM.

ObjectiveTo observe the clinical effectiveness and safety of Dingchan Granule （定颤颗粒） for paroxysmal atrial fibrillation with syndrome of qi stagnation and blood stasis. MethodsUsing a randomised， double-blind， placebo controlled study method， 90 patients with paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome were divided into 45 cases each in the treatment group and the control group. Both groups were given conventional western medicine treatment， and the treatment group was additionally treated with Dingchan Granule， while the control group was treated with Dingchan Granule placebo， both of which were taken orally for 8 g each time twice a day. Both groups were treated for 8 weeks. We compared the clinical effectiveness， the improvement of traditional Chinese medicine （TCM） symptoms and the recovery rate of atrial fibrillation between the two groups. We compared the number and duration of atrial fibrillation episodes， TCM symptoms score， atrial fibrillation symptom classification， 24-hour average ventricular rate， Pittsburgh Sleep Quality Index （PSQI）， anxiety index， depression index before and after treatment， and evaluated the safety of the two groups. ResultsThe total clinical effectiveness rate in the treatment group was 82.22% （37/45）， which was better than 60.00% （27/45） in the control group （P＜0.05）. The total effective rate of TCM syndrome effectiveness in the treatment group was 88.89% （40/45）， which was better than 66.67% （30/45） in the control group （P＜0.05）； and the rate of atrial fibrillation regression in the treatment group was 26.67% （12/45）， better than 6.67% （3/45） in the control group （P＜0.05）. The number and duration of atrial fibrillation episodes in both groups were significantly decreased （P＜0.01）， and the number and duration of atrial fibrillation episodes in the treatment group were lower than those in the control group （P＜0.01）. The TCM syndrome scores of both groups after treatment were significantly lower than before treatment （P＜0.01）， and the scores of the treatment group was lower than those of the control group （P＜0.05）. The severity of atrial fibrillation symptoms and the grading of atrial fibrillation symptoms in both groups after treatment were improved （P＜0.01）， and the degree of symptom improvement in the treatment group was better than that in the control group （P＜0.01）. The 24-hour average ventricular rate of both groups after treatment was significantly lower （P＜0.01）. The PSQI， anxiety index and depression index of the treatment group were all lower than before treatment （P＜0.01）， while the PSQI and anxiety index of the control group were both lower than before treatment （P＜0.01 or P＜0.05）， the PSQI， anxiety index and depression index of the treatment group being lower than those of the control group （P＜0.05 or P＜0.01）. No adverse events occurred in both groups， and no abnormalities were observed in blood， urine， stool routine， liver and kidney function， and coagulation function indexes. ConclusionDingchan Granule for paroxysmal atrial fibrillation with qi stagnation and blood stasis syndrome can alleviate clinical symptom， improve TCM symptom scores， increase atrial fibrillation recovery rate， stabilise the average ventricular rate， and significantly improve the quality of sleep， alleviate the anxiety and depression， with a good safety profile.

Objective:To systematically evaluate the clinical efficacy of Ruiyun procedure for hemorrhoids(RPH)combined with milligan-morgan hemorrhoidectomy(MMH)in the treatment of mixed hemorrhoids compared with MMH alone.Methods:Relevant literature was retrieved from China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their establishment to Jan 2023 using computers.Clinical randomized controlled trials(RCTs)of RPH combined with MMH and MMH alone in the treatment of mixed hemorrhoids were selected and analyzed,and meta-analysis was conducted using RevMan5.3 software.Results:A total of 30 RCTs were included,involving 4 609 patients.Results of Meta-analysis showed that there were statistically significant differences in surgical efficacy(RR=1.05,95% CI:1.02-1.08,P= 0.003),postoperative margin edema(RR=0.36,95% CI:0.27-0.49,P＜0.01),postoperative anal pain(RR=0.35,95% CI:0.23-0.53,P＜0.01),postoperative rectal bleeding(RR=0.35,95% CI:0.17-0.72,P=0.004),postoperative anal stenosis(RR=0.26,95% CI:0.11-0.59,P=0.001)and postoperative urinary retention(RR=0.77,95% CI:0.63-0.93,P=0.007)between RPH combined with MMH group and MMH group.Conclusion:Compared with MMH alone,RPH combined with MMH in the treatment of mixed hemorrhoids can reduce the incidence of postoperative side effects,such as postoperative margin edema,anal pain,rectal bleeding,anal stenosis,and urinary retention,with a relatively higher efficiency.

Objective:To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus(SLE)in a real-world setting,and to analyze the related factors of low disease activity and clinical remission.Methods:One thousand patients with SLE were enrolled from 11 teaching hospitals.Demographic,clinical and laboratory data,as well as treatment regimes were collec-ted by self-completed questionnaire.The rates of low disease activity and remission were calculated based on the lupus low disease activity state(LLDAS)and definitions of remission in SLE(DORIS).Charac-teristics of patients with LLDAS and DORIS were analyzed.Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission.Results:20.7％of patients met the criteria of LLDAS,while 10.4％of patients achieved remission defined by DORIS.Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration,compared with non-remission group.Moreover,the rates of anemia,creatinine eleva-tion,increased erythrocyte sedimentation rate(ESR)and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group.Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission.The results of Logistic regression analysis showed that increased ESR,positive anti-dsDNA antibodies,low level of complement(C3 and C4),proteinuria,low household in-come were negatively related with LLDAS and DORIS remission.However,hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission.Conclusion:LLDAS and DORIS remission of SLE patients remain to be improved.Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Objective To observe the pathological changes of heart failure caused by transverse aortic constriction in rats.Methods Partial thoracotomy was performed to the second rib and the transverse aortic constriction was performed between the innominate and left carotid arteries to establish a model of heart failure in 24 rats.The same operation was performed on another 8 rats, except for the ligation of the transverse aorta.Echocardiographic assessment, hemodynamic measurement, myocardial histopathological examination and NT-proBNP measurement were performed to the sham group at 12 weeks and model group at 4 weeks, 8 weeks, 12 weeks after the operation.Result At 4 weeks after the operation, NT-proBNP, EF, FS and -dp/dtmax of the model group was significantly increased and LVESV, +dp/dtmax of the model group were significantly decreased (P<0.05).At 8 weeks after the operation, EF and-dp/dtmax of the model group were increased and +dp/dtmax of the model group was significantly decreased (P<0.05).At 12 weeks after the operation, NT-proBNP, EF and +dp/dtmax of the model group were decreased, and LVESV, LVEDV and -dp/dtmax of the model group were increased (P<0.05).The cardiomyocytes became hypertrophic and lined up in disorder at 4 weeks after the operation.Pathologic examination of the myocardial tissue showed connective tissue proliferation and inflammatory cell infiltration at 8 weeks after the operation, and cardiomyocyte apoptosis and collagen fiber deposition at 12 weeks after the operation.Conclusions Transverse aortic constriction induces heart failure in rats.The pathological processes are compensatory hypertrophy at 4 weeks after the operation, initial reaction of decompensation at 8 weeks after the operation, and heart failure at 12 weeks after the operation.

Objective To understand the prevalence of mild cognitive impairment(MCI) and to compare the geographical distribution for the early prevention and treatment of disease,and to provide the reference basis for the establishment of related policies.Method Systematical search method and inclusion criterion were made and relative English and Chinese database such as China biology medicine disc (CBMdisc),China national knowledge infrastructure (CNKI),VIP database (VIP),WanFang,Pubmed,excerpta medica database (EMBASE),the cochrane library were searched.Tailored quality evaluation standard of epidemiological research was used to evaluate study quality for each included study.I2 was used to measure the heterogeneity between studies,and relevant model of meta-analysis and subgroup analysis were carried out to merger and analyze data.Subgroup analysis was used to explore heterogeneity.Results Overall,in the present 40 relevant articles were included.The quality assessment was good (median score was 15).Meta-analyses were conducted for 40 cross-sectional studies investigating the prevalence of MCI,the pooled prevalence of MCI was 14.5％ (95％CI 12.8％-16.2％).Subgroup results showed that in recent years,the prevalence rate has been gradually increased over time.There was a higher prevalence in those who were older.The prevalence rate of female were higher than that of male(16.0％(95％CI 14.2％-17.9％) vs.12.6％(95％CI 10.8％-14.4％)),rural were higher than that of urban (18.2％(95％CI 14.2％-22.1％) vs.13.6％ (95％ CI 11.9％-15.3％)).Prevalence was decreased while cultural level rising,and that of single (including single,divorce or live alone) elderly was higher than married people.Conclusion MCI in China have a high prevalence.Over the past decade,the prevalence and incidence of MCI were significantly affected by age,gender,education level,marital status,place of residence and other factors.

Objective To understand the prevalence of mild cognitive impairment(MCI) and to compare the geographical distribution for the early prevention and treatment of disease,and to provide the reference basis for the establishment of related policies.Method Systematical search method and inclusion criterion were made and relative English and Chinese database such as China biology medicine disc (CBMdisc),China national knowledge infrastructure (CNKI),VIP database (VIP),WanFang,Pubmed,excerpta medica database (EMBASE),the cochrane library were searched.Tailored quality evaluation standard of epidemiological research was used to evaluate study quality for each included study.I2 was used to measure the heterogeneity between studies,and relevant model of meta-analysis and subgroup analysis were carried out to merger and analyze data.Subgroup analysis was used to explore heterogeneity.Results Overall,in the present 40 relevant articles were included.The quality assessment was good (median score was 15).Meta-analyses were conducted for 40 cross-sectional studies investigating the prevalence of MCI,the pooled prevalence of MCI was 14.5％ (95％CI 12.8％-16.2％).Subgroup results showed that in recent years,the prevalence rate has been gradually increased over time.There was a higher prevalence in those who were older.The prevalence rate of female were higher than that of male(16.0％(95％CI 14.2％-17.9％) vs.12.6％(95％CI 10.8％-14.4％)),rural were higher than that of urban (18.2％(95％CI 14.2％-22.1％) vs.13.6％ (95％ CI 11.9％-15.3％)).Prevalence was decreased while cultural level rising,and that of single (including single,divorce or live alone) elderly was higher than married people.Conclusion MCI in China have a high prevalence.Over the past decade,the prevalence and incidence of MCI were significantly affected by age,gender,education level,marital status,place of residence and other factors.

Objective To investigate the clinical efficacy of autologous dendritic cells and cytokine-induced killer cells (DC/CIK) combined with transcatheter arterial chemoembolization (TACE) in the treatment of moderate and advanced hepatocellular carcinoma (HCC). Methods Sixty patients with moderste and advanced HCC were randomly divided into two groups: the experimental group (n = 32), in which the treatment of DC/CIK combined with TACE was used, and the control group (n=28), in which TACE treatment was used only. The parameters of tumor size , serum alpha-fetoprotein , survival rate , the median survival time and quality of life , were detected in patients of the two groups before and after corresponding therapy . Results ( 1 ) After receiving corresponding treatments, the efficient rates of DC/CIK combined with TACE and TACE only were 87.50% and 64.29%, respectively, with significant difference;(2) The level of serum AFP decreased in the two groups after corresponding treatment, with no significant difference; (3) The 6-month survival rate was 96.88%and 92.85%, and the 1-year survival rate was 84.38%and 64.29%, the 2-year survival rate was 65.63%and 42.86%in the experimental group and in the control group, respectively. And the median survival time was 21 months and 17 months in the experimental group and the control group, respectively, with no significant difference; (4) The quality of life was improved significantly in the DC/CIK combined with TACE group after treatment. Conclusions Administration of DC and CIK combined with TACE can prolong the survival time, increase the survival rate and especially improve the life quality of HCC patients. It is a promising approach for the treatment of patients with moderate and advanced HCC.

Objective To study the relationship between expression of matrix metalloproteinases-7 (MMP-7) and clinicopathological characteristics in patients with primary non-smaU cell lung cancer(NSCLC). Methods MMP-7 in 20 normal people and 60 advanced NSCLC patiens were detected with reverse-transcription-polymerase-chain-reaction. Gelatum image analysator analyzed the result. Results The amount of MMP-7 was less in normal people (30.000) than in NSCLC patients(41.231) significantly(P<0.05); the level of MMP-7 was no correlated with gender, age, pathology pattern, tumor size, was inverse correlation with differentiation, and was positive correlation with clinical stages(P <0.05). Conclusion The level of MMP-7 is closely correlated with tissue differentiation and clinical stages of NSCLC, which may serve as a parameter for determining tumor invasion and metastatic.

Objective To study the variety and significance of immune function in lung cancer patients.Methods 68 pretherapy lung cancer patients and 20 healthy volunteers with peripheral blood samples by flow cytometry.Results The proportion of CD+3T cells,CD+4T cells and the ratio of CD4/CD8 decreased in lung cancer patients,while the proportion of CD+8T cells and natural killer cells increased.Serum levels of TNF-α,IL-4,IL-6,IL-10 were significantly increased in patients compared with healthy controls,while the ratio of Th1/Th2 was decreased.(2)The natural killer cells level was negatively correlated with the CD3,CD4,CD8 levels respectively.The CD4 level was negatively correlated with the levels of IL-6,IL-10 respectively.(3)No statistically significant relationship was found between the peripheral blood lymphocyte,Th1-Th2 cytokines and pathological type,lymph node metastasis,distant metastasis.Conclusion Immune suppression was very common in lung cancer patients,particularly cell mediated immunity suppressed markedly.The proportion and function of CD+4T cells decreased significantly.which may resulted from the Th1,Th2 imbalance.Natural killer cells and CD+8T cells increased significantly,but could not prevent tumor development,which may resulted from these factors that suppress immune response in tumor microenvironment.