Objective To study the inhibitory effect of oxymatrine on hepatitis B virus(HBV) in vitro. Methods Microparticle enzyme immunoassay, bDNA signal amplification assay was used for determining secrected HBsAg/HBeAg in the culture medium, HBV DNA from core particles in the cytoplasm and MTT colorimetric assay was used to assay the oxymatrine cytotoxity. Results The inhibitory rates of HBsAg and HBeAg were 40.57% and 48.27% by oxymatrine at the concentration of 2 000 ?g/ml. At 100～2 000 ?g/ml, it can remarkably decrease the level of viral core associated HBV DNA in the cytoplasm. No significant toxicity was shown in such concentrations. Conclusion Oxymatrine has a potential anti HBV activity in vitro.

Objective To investigate the effect of folic acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells(PBMC). Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid (n=5)or placebo(n = 5) , one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras,tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group (t= -4. 739,P<0. 05) , however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8%(t= -4. 079,P<0. 05), while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras、E-cadherin、p16INK4Aand hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin,p16INK4Aand hMLH1.

Objective To study the effects of extracellular-signal regulated kinase mitogenactivated protein kinase (ERK-MAPK) signaling pathway inhibition on histone phosphorylation and the related gene expression in human colorectal cancer cells.Methods Two human colorectal cancer cell lines (SW1116 and HCT116) were cultured and treated with gradient(0,20,40/μmol/L) doses of ERK-MAPK signaling pathway inhibitor U0126.Cell viability was determined by cell counting kit 8 (CCK-8) assay.Cell cycle distribution was assessed by flow cytometry.The expression levels of histone H3 kinases including ribosomal S6 serine-threonine kinase (RSK-2) and mitogen-and stressactivated protein kinase 1 and 2 (MSK1 and MSK2),and the levels of histone H3 (Ser10) phosphorylation and c-Fos protein were detected using Western blotting.Results Treatment of these two human colorectal cancer cell lines with ERK-MAPK inhibitor resulted in a time and dose-dependent inhibition of cell proliferation significantly. Proliferation rate of HCT116 was reduced to 47% at 72 hours after 40/μmol/L U0126 treatment. Cell cycle analysis showed that the percentage of phase G0/G1 cells significantly increased (P<0. 01) and the percentage of phase S cells decreased (P<0.01) after treatment with ERK-MAPK inhibitor. The expression of MSK1 and RSK2 reduced obviously in both of human colorectal cancer cell lines treated with U0126, which resulted in a 28% and 40% reduction of levels of MSK1 and RSK2 as compared with control HCT116 cells respectively,while no detectable change in the expression of MSK2 was found. Consistent with this, the expression level of histone H3 (ser10) phosphorylation was markedly down-regulated by ERK-MAPK inhibitor, and the related protein c-Fos expression decreased accordantly. Conclusions Decreased ERK-MAPK signaling pathway may reduce histone H3 (Ser10) phosphorylation via suppression of the activity of histone H3 kinase including MSK1 and RSK2, but not MSK2, consequently decrease the expression of c-Fos protein, which results in the inhibition of colorectal cancer cells proliferation.

Objective to determine the basal levels of several pancreas-related endocrine hormones in patients with chronic pancreatitis.Methods according to inclusion and exclusion criteria,consecutive patients from February 2016 to August 2016 in Department of Gastroenterology,Changhai Hospital,Second Military Medical University and ten healthy control (matched for age and gender) were included.Basal levels of glucagon-like peptide 1,pancreatic polypeptide,Secretin,glucagon,somatostatin between groups of CP vs healthy control,CP with abnormal glycometabolism vs CP with normal glycometabolism and alcoholic CP vs non-alcoholic CP were compared.Results a total of 53 patients with chronic pancreatitis and 8 healthy subjects were included in this study.(1) CP vs healthy controls:the level of secretin in healthy control patients is significant lower than that in CP patients;(2) CP with abnormal glycometabolism vs CP with normal glycometabolism:the level of triglyceride and somatostatin is significant lower than that in CP patients;the prevalence of patients with chronic alcohol consumption and the level of glucagon-like peptide 1 in CP with abnormal glycometabolism is significant higher than that in CP with normal glycometabolism;(3) the prevalence of abnormal glycometabolism in alcoholic CP group is significant higher than that in non-alcoholic CP.The results above are all of statistical significance.Conclusions in addition to dysfunction of islets/3-cells,CP also easily affects the level of other pancreas-related hormones such as secretin,somatostatin and glucagon-like peptide 1.Otherwise,chronic alcohol consumption is also strongly related with abnormal glycometabolism,the mechanism deserves further researches.

Objective To analyze the effect of eukaryotic expression vector containing sense and antisense DNA methyltransferase (DNMT1) gene on the transcript level of tumor associated genes in human colon cancer cell line. Methods Recombinant plasmid, including sense DNMT1 (HMT) and antisense DNMT1 (THM) gene, were constructed and transfected into SW1116 cell by using the lipofectamine. Then G418 filtration was performed. The expression of DNMT1 protein was examined by Western blotting. The transcription level of hMLH1, hMSH2, c myc and p16 INK4A genes were detected by RT PCR. Results The sense and antisense eukaryotic expression vectors were successfully constructed and then the constructed recombinant plasmids were transfected into SW1116 cell. The protein levels of DNMT1 have been up regulated and down regulated in SW1116 cells transfected with HMT and THM plasmids, respectively. The mRNA level of hMLH1, hMSH2, c myc gene were down regulated in the sense DNMT1 transfected cell. The mRNA level of hMSH2 was up regulated in the antisense DNMT1 transfected cell. However, the transcription level of p16 INK4A gene could not be associated with DNMT1 in SW1116 cell.Conclusion DNMT1 can regulate the expression of the tumor associated genes in human colon cancer cell line SW1116.

Educational reform of pathophysiology oriented to clinical application is to pass the physician qualifica -tion examination .One of essential approach is to implement pathophysiology teaching with the translational medical philosophy and promote the harmonious development of physician -patient relationship with the utilization of the de-velopment and changes of disease in the teaching process .In that way, the pathophysiology in basic and clinical medicine is worthy of the name of “bridge”, and ultimately achieves the goal of “the transformation and develop-ment of the cultivation of clinical application talents”.

Immune checkpoint inhibitors(ICIs)treatment significantly prolonged the survival period of patients with lung cancer, liver cancer, and malignant melanoma and other solid malignant tumors and improved the quality of life.But at the same time a variety of immune-related adverse reactions(irAEs)appeared.The incidence of immune-mediated liver injury(IMH)caused by ICIs is increasing but the severity is different.To diagnose IMH earlier and perform individualized diagnosis and treatment, it is necessary to have a reasonable application of drug treatment.

Objective To summarize the research status and hotspots of Wumei Pills;To provide ideas and methods for the follow-up research of Wumei Pills.Methods Related literature about Wumei Pills was retrieved from CNKI,VIP,Wanfang Data and CBM from the establishment of the databases to January 12,2023.The publication time,author,author unit and keywords were collected and extracted through NoteExpress 3.0 software to manage bibliographic data.VOSviewer 1.6.18 software was used to conduct co-occurrence and clustering analysis,and construct keyword time superposition network.Results After screening,a total of 2 105 articles were included,involving 3 554 authors,such as Yan Shuguang,Fan Heng,and Hui Yi.They were from 1 135 units,such as Dongzhimen Hospital of Beijing University of Chinese Medicine,Shandong University of Traditional Chinese Medicine and Beijing University of Chinese Medicine.The included articles contained 2 565 keywords,which appeared 7 061 times,and the research involved 4 main directions:digestive system diseases(ulcerative colitis),study on TCM classics(Shang Han Za Bing Lun),medical cases and experience,and biliary ascariasis.The hotspots of Wumei Pills were scattered in recent years.Six meridian disease to appear,opening and closing pivots,intestinal microbiota,serum inflammatory factors and insomnia were research hotspots in recent 3 years.Conclusion The research of Wumei Pills mainly focus on the research of digestive system diseases,TCM classics,medical cases and experience,and biliary ascariasis.Theoretical research of TCM and mechanism research possibly become new hotspots of this field.

The quality of life of elderly patients with lung cancer can be affected by various symptoms such as frailty, coexistence of multiple diseases, malnutrition, and decreased function.Identifying these potential problems through reasonable and effective assessment, and providing early intervention and symptom management, can help improve the quality of life of patients.Although several methods have been developed, applied, and clinically verified to evaluate the quality of life in elderly patients with lung cancer, they all have their limitations.Therefore, choosing the appropriate evaluation method has become a practical challenge in clinical settings.This article aims to review the different methods used to assess the quality of life of elderly patients with lung cancer, providing theoretical guidance for clinicians and researchers.

Objective To analyse the clinical effect and safety of Alimta (Pemetrexed) combined with cisplatin treatment (PP) on elderly patients with non small cell lung cancer (NSCLC).Methods We retrospectively analyzed the clinical data of 40 cases of NSCLC patients treated with Pemetrexed combined with cisplatin for first-line chemotherapy,and 24 cases of them continually received single Pemetrexed for maintenance treatment (PP + C).Then we compared the results with 35 patients in the non-Pemetrexed regimen (control group) and 26 patients with best supportive care (BSC) in the same period.The adverse reactions and short-term efficacy [response rate (RR),disease control rate (DCR)] were evaluated.Time to progression (TTP),median survival time (MST),one-year and three-year survival rates and follow-up overall survival (OS) were calculated.Results Among 40 patients with Pemetrexed regimen,2 patients had complete remission (CR),and the RR was 47.8％,which was better than 42.8％ (P =0.026) in the control group.The main adverse reactions of pemetrexed regimen were myelosuppression,fatigue,nausea and vomiting,but all were tolerated and no treatment-related death occurred.24 patients received single Pemetrexed maintenance therapy.The MST of the PP + C group was superior to the other groups (P =0.03,P ≤0.05);the median OS of the PP + C group,the control group,and the BSC group reached 13.2,10.4 months and 8.6 months,respectively (P ≤ 0.001).Conclusions For elderly patients with advanced NSCLC,especially adenocarcinoma,the combination of Pemetrexed and cisplatin is a better treatment option.It is convenient to administer and has less toxicity and adverse reactions related to chemotherapy.Patients with better PS score after first-line treatment can obtain longer survival period after maintenance treatment.