ObjectiveTo investigate the therapeutic mechanism of Xuefu Zhuyutang （XFZYT） for metabolic-associated fatty liver disease （MAFLD） through integrated network pharmacology and animal experiments. MethodsNetwork pharmacology was utilized to predict the core components， key therapeutic targets， and signaling pathways of XFZYT in the treatment of MAFLD. For animal experiments， a rat model of MAFLD was established by feeding a high-cholesterol diet for 4 weeks. Intervention was then administered with low-dose （2 g·kg^-1） and high-dose （4 g·kg^-1） XFZYT for 2 weeks. Biochemical assays were performed to measure the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL）. In addition， the activities of superoxide dismutase （SOD） and catalase （CAT） and levels of malondialdehyde （MDA） and glutathione （GSH） in the serum were measured. The same way was adopted to measure the levels of TC and TG in the liver tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to quantify the serum levels of interleukin （IL）-6， IL-1β， and tumor necrosis factor-alpha （TNF-α）. Histopathological evaluations included hematoxylin and eosin （HE） staining for liver tissue morphology， Oil Red O staining for lipid deposition， and dihydroethidium （DHE） probe staining for reactive oxygen species （ROS） levels. Western blot analysis was conducted to assess the protein levels of AMP-activated protein kinase （AMPK）， phosphorylated （p）-AMPK， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， nuclear factor-kappa B （NF-κB）， and p-NF-κB in the liver tissue. Untargeted metabolomics analysis of the serum was performed by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. ResultsNetwork pharmacology analysis predicted 155 potential targets of XFZYT for MAFLD treatment， with core targets including signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， TNF， and IL-6. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment primarily implicated the AMPK signaling pathway. Animal experiments demonstrated that compared with the normal group， the model group exhibited dyslipidemia， hepatic function impairment， pronounced hepatic lipid deposition， and inflammatory manifestations， with elevated serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， reduced HDL and GSH levels plus decreased SOD and CAT activities （P<0.05）， downregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and upregulated protein level of p-NF-κB （P<0.05） in the liver tissue. Compared with the model group， XFZYT intervention groups showed significant amelioration of dyslipidemia and hepatic function impairment， markedly reduced hepatic lipid deposition and inflammatory cell infiltration， decreased serum levels of AST， ALT， TC， TG， LDL， and MDA （P<0.05）， increased HDL and GSH levels plus enhanced SOD and CAT activities （P<0.05）， upregulated protein levels of Nrf2， HO-1， and p-AMPK （P<0.05）， and downregulated protein level of p-NF-κB （P<0.05）. Serum metabolomics revealed 511 differentially expressed metabolites （231 upregulated and 280 downregulated） between normal and model groups， while XFZYT groups versus model group showed 94 differential metabolites （51 upregulated and 43 downregulated）. Among them， 11 metabolites displayed the most significant alterations， with enriched pathways including glycerolipid metabolism， cholesterol metabolism， and insulin resistance， multiple of which demonstrated AMPK association. ConclusionXFZYT alleviates MAFLD by regulating the AMPK signaling pathway and associated metabolic networks.

Objective:To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) .Methods:This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate.Results:(1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference ( χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences ( P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions:Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

Objective To investigate the effect of focused solution-oriented short-term intervention combined with social skills training based on WeChat on the recovery of discharged schizophrenia patients.Methods A total of 200 schizophrenia patients discharged from Shaoxing Seventh People's Hospital from January 2022 to December 2023 were selected as study subjects,and divided into study group and control group by random number table,with 100 patients in each group.During the course of the study,11 and 29 cases were lost in study group and control group,respectively,and finally 89 cases were in study group and 71 cases in control group.The control group received routine post-discharge follow-up,while the study group received a 6-month intervention focused solution-oriented short-term intervention combined with social skills training based on WeChat.Before and after the intervention,the positive and negative syndrome scale(PANSS),stigma scale for mental illness(SSMI-C),morning side rehabilitation stats scale(MRSS),and adherence to medication were assessed.Results After the intervention,the total scores of PANSS,SSMI-C,and MRSS in study group were significantly lower than those in control group,and the adherence to medication was higher than that in control group,with statistically significant differences(P＜0.05).Conclusion Focused solution-oriented short-term intervention combined with social skills training based on WeChat can reduce the stigma of mental illness in discharged schizophrenia patients,improve their adherence to medication,stabilize their condition,and play a positive role in promoting their recovery.

Hepatocellular carcinoma is one of the most common malignant tumors in the world, which is a serious threat to human health. HBV infection is one of the most common causes of hepatocellular carcinoma.The diagnosis of most hepatocellular carcinoma has progressed to the middle and late stage, and the prognosis is poor. Early detection, diagnosis and treatment are important supports to improve the clinical outcome of hepatocellular carcinoma. In recent years, scholars at home and abroad have established various hepatocellular carcinoma risk prediction models, which are conducive to improving the early diagnosis rate of hepatocellular carcinoma and reducing the mortality rate. This article reviews the risk factors and risk prediction models of chronic hepatitis B associated hepatocellular carcinoma, in order to provide reference for HBV-associated liver cancer risk monitoring and management decision.

AIM:To investigate the effect of paeoniflorin(PF)on TLR4/MyD88 signaling pathway in liver of rats with metabolic dysfunction-associated fatty liver disease.METHODS:SPF grade male SD rats were randomly divid-ed into four groups:normal control(NC)group,model control(MC)group,low-dose paeoniflorin(PL)group,and high-dose paeoniflorin(PH)group.The normal group was given standard diet,and the other three groups were given high-fat diet for 8 weeks.From the fifth week,rats in paeoniflorin groups were given low dose(25 mg·kg-1·d-1)or high dose(50 mg·kg-1·d-1)paeoniflorin for 4 weeks.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC)and triglyceride(TG)were measured by biochemical method.The levels of tumor necrosis factor(TNF)-α was detected by ELISA.Pathological change of the liver was detected with hematoxylin-eosin(HE)staining and oil red O staining,and evaluated semi-quantitatively with the nonalcoholic fatty liver disease activity score(NAS).The expres-sion levels of TLR4,MyD88 and phosphorylated nuclear factor(p-NF)-κB p65 in liver tissues were detected by immuno-histochemistry and Western blot.RESULTS:Compared with the NC group,rats in the MC group showed increased TC,TG,ALT,AST and TNF-α in serum(P<0.05),and more lipid droplets in hepatocytes and inflammatory cell infiltration in the portal area,with higher NAS,TLR4,MyD88 and p-NF-κB p65 proteins in liver tissue(P<0.05).However,pae-oniflorin could reduce TC,TG,ALT,AST and TNF-α in serum(P<0.05),improve histopathological changes of liver,decrease the NAS scoring(P<0.05),and inhibit hepatic TLR4/MyD88/p-NF-κB p65 expressions(P<0.05).CONCLU-SION:Paeoniflorin could improve the lipid metabolism disorder and reduce liver inflammation during MAFLD,and the latter effect might be in part related to the inhibition of TLR4/MyD88 signaling pathway.

Objective To investigate the expressions of Krüppel like factor 5 (KLF5) and tumor necrosis factor receptor superfamily member 11a (TNFRSF11a) in cervical cancer tissues and their effect on proliferation,migration,and invasion of HeLa cells. Methods Microarray technology was used to detect the mRNA expression of gene in cytocine stimulusin cervical tissues,and the result was verified by real-time fluorescence quantitative polymerase chain reaction. The expressions of KLF5 and TNFRSF11a in cervical tissues were detected by double immunofluorescence staining. HeLa cells were transfected with specific small interfering RNA to knock down the endogenous TNFRSF11a and KLF5 and were infected with adenovirus containing KLF5 to over-express KLF5,respectively. Protein level was detected by Western blot. The regulatory effect of KLF5 on candidate target gene (TNFRSF11a) was determined by dual-luciferase reporter assay. The activity of the cell proliferation,migration,and invasion was detected by using cell counting kit-8 assay and Transwell assay. Results The results of microarray technology showed that the expressions of KLF5 and TNFRSF11a were significantly higher in cervical squamous cell carcinoma tissues compared with normal cervical tissues (P=0.002,P=0.045),and real-time fluorescence quantitative polymerase chain reaction showed that the mRNA expressions of KLF5 and TNFRSF11a were significantly higher in cervical intraepithelial neoplasia (CIN) Ⅰ,CINⅡ-Ⅲ and cervical squamous cell carcinoma tissues compared with normal cervical tissues (KLF5:F=32.79,P=0.018,P=0.014,and P=0.011;TNFRSF11a:F=36.72,P=0.013,P=0.010,and P=0.009) and double immunofluorescence staining showed that the protein expressions of KLF5 and TNFRSF11a were significantly higher in CIN Ⅰ,CIN Ⅱ-Ⅲ and cervical squamous cell carcinoma tissues compared with normal cervical tissues (KLF5:F=42.38,P=0.014,P=0.008,and P=0.002;TNFRSF11a:F=35.42,P=0.021,P=0.012,and P=0.004) and increased with the carcinogenesis. The experiment in vitro confirmed that KLF5 promotes proliferation,migration,and invasion of HeLa by up-regulating TNFRSF11a expression. Clinical analysis showed that the expression of TNFRSF11a mRNA was positively correlated with tumor pathological grading,clinical stage,depth of invasion,and lymph node metastasis (all P<0.05). Conclusion KLF5 and TNFRSF11a are related to cervical cancer. KLF5 promote the proliferation,migration,and invasion of cervical cancer cells partly by upregulating the transcription of TNFRSF11a.

Objective To reduce the incidence of psychotic inpatients fall events , improve the quality of care and ensure patient safety using healthcare failure modes and effects analysis (HFMEA).Methods According to HFMEA method, we set up anti-fall group, drew anti-fall flow chart, performed causes analysis of failure mode and potential risks, calculated risk priority number (RPN), identified critical failure modes and related causes, developed improvement programs and implemented.Results After the implementation of the HFMEA, RPN value of five key patterns were significantly lower than before ( P<0. 05). 0. 64% fall rate before the implementation in hospitalized patients decreased to 0. 28%. Conclusions It can reduce the incidence of falls and improve the quality of nursing care using the HFMEA management to perform root cause analysis and process improvement of potential failure modes of falls.