Cervical cancer is one of the most common gynecological malignant tumors,the five-year survival rate decreased significantly in the case of lymph node metastasis and distant metasta-sis,so the development of new anti-cervical cancer drugs is of great significance for the treatment of cervical cancer.Molecular docking technology is one of the most commonly used research methods in computer aided drug design,which is widely used in screening the effective components of drugs,finding the targets of drugs acting on tumors and exploring the mechanism of antineoplastic drugs.This paper reviews the molecular docking technology in the screening of anti-cervical cancer drugs,the determination of anti-tumor targets and the mechanism of anti-cervical cancer,in order to provide more sufficient theoretical basis for the screening of anti-cervical cancer drugs and new drug research and development.

Objective To investigate the effect of embryonic inflammatory exposure on the response of mouse offspring to interphotoreceptor retinoid-binding protein(IRBP)-induced experimental autoimmune uveitis(EAU).Methods RNA transcriptome sequencing data from eyeballs of C57BL/6J mouse offspring born to mothers with active EAU were used to screen immune-associated differentially expressed genes in the eyes of the exposed offspring.Gene fragments overlapping in the two datasets were screened using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses to identify biological pathways associated with the gene fragments.Hub genes were identified from these intersecting genes by protein-protein interaction network analysis.EAU models of maternal uveitis were established by immunization with IRBP651-670,and expression levels of the pivotal genes in the offspring exposed to inflammation by maternal uveitis were examined by fluorescence quantitative polymerase chain reaction.EAU severity,T lymphocyte proliferation,and serum cytokines were detected to investigate the immune effect in offspring from mothers with an active inflammation response to IRBP induction.Results Microarray analysis identified 72 immune-related differentially expressed genes in exposed samples compared with the findings in control samples.These genes were mainly enriched in Toll-like receptor signaling,mitogen-activated protein kinase signaling,and B cell receptor signaling pathways.Protein-protein interaction network interaction analysis screened out four hub genes,Psmc5,Psmc3,Psmd4,and Psmd8,and mRNA levels of these four genes were increased in the adult offspring from mothers with active uveitis compared with the findings in healthy offspring.In addition,the group induced with 150 μg IRBP showed an increase in the severity of clinical and pathological outcomes in offspring with EAU affected by active inflammation,compared with the healthy offspring group(P=0.0087,P=0.0410).Meanwhile,T cell proliferation in the offspring was enhanced during the inflammatory activity stage and secretion of the inflammatory cytokines interleukin(IL)-17 and IL-6 was increased(P=0.0450,P=0.0300).Conclusions Psmc5,Psmc3,Psmd4,and Psmd8 may be important genes exacerbating uveitis in offspring of mothers with active uveitis,associated with increased T cell proliferation and production of IL-17 and IL-6.

OBJECTIVES: The magnesium depletion score (MDS) is considered more reliable than traditional approaches for predicting magnesium deficiency in humans. We explored the associations of MDS and dietary magnesium intake with diabetes. METHODS: We obtained data from 18,853 participants in the National Health and Nutrition Examination Survey 2011-2018. Using multivariate regression and stratified analysis, we investigated the relationships of both MDS and magnesium intake with diabetes. To compute prevalence ratios (PRs), we employed modified Poisson or log-binomial regression. We characterized the non-linear association between magnesium intake and diabetes using restricted cubic spline analysis. RESULTS: Participants with MDS ≥2 exhibited a PR of 1.26 (95% confidence interval [CI], 1.19 to 1.34) for diabetes. Per-standard deviation (SD) increase in dietary magnesium intake was associated with a lower prevalence of diabetes (PR, 0.91; 95% CI, 0.87 to 0.96). Subgroup analyses revealed a positive association between MDS ≥2 and diabetes across all levels of dietary magnesium intake, including the lowest (PR, 1.35; 95% CI, 1.18 to 1.55), middle (PR, 1.23; 95% CI, 1.12 to 1.35), and highest tertiles (PR, 1.25; 95% CI, 1.13 to 1.37; pinteraction<0.001). Per-SD increase in magnesium intake was associated with lower diabetes prevalence in participants with MDS <2 (PR, 0.92; 95% CI, 0.87 to 0.98) and those with MDS ≥2 (PR, 0.91; 95% CI, 0.84 to 0.98; pinteraction=0.030). CONCLUSIONS MDS is associated with diabetes, particularly among individuals with low magnesium intake. Adequate dietary magnesium intake may reduce diabetes risk, especially in those with high MDS.

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

OBJECTIVES: Long-term hepatitis B virus (HBV) infection can cause recurrent inflammation in the liver, and then develop into liver fibrosis, cirrhosis, and liver cancer. The hepatic pathological change is one of the important criteria for guiding antiviral therapy in patients with chronic hepatitis B (CHB). Due to the limitations of liver biopsy, it is necessary to find valuable non-invasive indicators to evaluate the hepatic pathological changes in CHB patients and guide the antiviral therapy. This study aims to analyze the clinical characteristics of different pathological changes in CHB patients, and to explore the factors influnencing the degree of liver inflammation and fibrosis in CHB patients with normal alanine aminotransferase (ALT). METHODS: This retrospective study was conducted on 310 CHB patients. Liver biopsy was performed in all these patients. The clinical data of the patients were collected. The liver biopsy pathological results were used as the gold standard to analyze the relationship between clinical indicators and liver pathological changes. Then CHB patients with normal ALT were screened, and the independent factors influencing the degree of liver inflammation and fibrosis were explored. RESULTS: Among the 310 patients with CHB, there were 249 (80.3%) patients with significant liver inflammation [liver inflammation grade (G) ≥2] and 119 (38.4%) patients with significant liver fibrosis [liver fibrosis stage (S) ≥2]. The results of univariate analysis of total samples showed that the ALT, γ-glutamyl transferase, alkaline phosphatase, and HBV DNA were related to the significant liver pathological changes. Among the 132 CHB patients with normal ALT, the patients with liver pathology G/S≥2, G≥2, and S≥2 were 80.3% (106/132), 68.2% (90/132), and 43.2% (57/132), respectively. The results showed that the independent influencing factor of significant liver inflammation was HBV DNA>2 000 U/mL (OR=3.592, 95% CI 1.534 to 8.409), and the independent influencing factors of significant liver fibrosis were elevated alkaline phosphatase level (OR=1.022, 95% CI 1.002 to 1.043), decreased platelet count (OR=0.990, 95% CI 0.982 to 0.998), and positive in hepatitis B e antigen (HBeAg) (OR=14.845, 95% CI 4.898 to 44.995). According to the multivariate analysis, a diagnostic model for significant liver fibrosis in CHB patients with normal ALT was established, and the area under the receiver operating characteristic curve was 0.844 (95% CI 0.779 to 0.910). CONCLUSIONS The liver pathological changes should be evaluated in combination with different clinical indicators. A considerable number of CHB patients with normal ALT still have significant liver pathological changes, which need to be identified and treated with antiviral therapy in time. Among them, HBV DNA>2 000 U/mL suggests the significant liver inflammation, and the diagnostic model for significant liver fibrosis based on alkaline phosphatase, platelet count, and HBeAg can help to evaluate the degree of liver fibrosis.
Humans ; Hepatitis B, Chronic/complications* ; Hepatitis B e Antigens/therapeutic use* ; Alkaline Phosphatase ; DNA, Viral ; Retrospective Studies ; Fibrosis ; Hepatitis B virus/genetics* ; Liver Cirrhosis/etiology* ; Inflammation/drug therapy* ; Antiviral Agents/therapeutic use* ; Alanine Transaminase

Objective:To investigate the correlation between peripheral blood microRNA (miR)-27b expression and left ventricular hypertrophy (LVH) in patients with hypertensive.Methods:The clinical data of 120 patients with hypertension from February 2019 to February 2021 in Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University were retrospectively analyzed. Among them, LVH occurred in 70 cases (LVH group), none in 50 cases (NLVH group). The ventricular septal thickness (VST), left ventricular posterior diastolic wall thickness (LVPWTd) and left ventricular end diastolic diameter (LVEDD) were measured by echocardiography, the left ventricular mass (LVM) and left ventricular mass index (LVMI) were calculated. The peripheral blood expression level of miR-27b was detected by real-time quantitative polymerase chain reaction. Correlation was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of peripheral blood miR-27b in diagnosing LVH in patients with hypertensive.Results:The peripheral blood expression level of miR-27b in LVH group was significantly higher than that in NLVH group (6.37 ± 0.23 vs. 3.42 ± 0.18), and there was statistical difference ( t = 9.58, P<0.01). Pearson correlation analysis result showed that the peripheral blood expression of miR-27b was positively correlated with LVMI, VST, LVEDD and LVPWTd in hypertensive LVH patients ( r = 0.71, 0.63, 0.75 and 0.68; P<0.01). After eliminating risk factors (duration of hypertension, systolic blood pressure, diastolic blood pressure, different medications, uric acid), multiple linear regression analysis result showed that the peripheral blood expression of miR-27b was positively correlated with LVMI, VST, LVEDD and LVPWTd in hypertensive LVH patients ( β = 0.07, 0.63, 0.42 and 0.48; P<0.01). ROC curve analysis result showed that the area under the curve of peripheral blood expression of miR-27b in predicted LVH in patients with hypertension was 0.905 (95% CI 0.854 to 0.957), the optimal cut-off value was 4.45, the sensitivity was 84.0%, and the specificity was 82.9%. Conclusions:The high peripheral blood expression of miR-27b in hypertension LVH patients is positively correlated with LVMI and other echocardiographic parameters, which has a good predictive value of LVH in patients with hypertension.

Immunosuppressants, which are commonly used for liver transplantation, mainly included calcineurin inhibitors, such as ciclosporin (CsA) and tacrolimus (FK506); glucocorticoid drugs, such as prednisone and prednisolone; cytotoxic drugs, such as azathioprine, mycophenolate mofetil and cyclophosphamide; mammalian target of rapamycin (mTOR) inhibitors, such as sirolimus and everolimus; antibody drugs, such as polyclonal or monoclonal antibodies and interleukin (IL)-2 receptor antibodies, etc. Although many categories of immunosuppressants are available, FK506 is the most commonly adopted in liver transplant recipients. However, FK506 can provoke significant adverse effects in the late stage of liver transplantation, especially severe infection and nephrotoxicity. Consequently, it is an urgent task and research hot spot to develop new immunosuppressants with strong immune tolerance and mild adverse effects in clinical practice. In this article, the research progress on immunosuppressants and the research and development status of new immunosuppressants for liver transplantation were reviewed.

Objective: To explore the clinical effect and safety of minor liver resection for hilar cholangiocarcinoma (HC) of Bismuth-Corlette type Ⅲ and Ⅳ. Methods: From May 2007 to May 2017, the clinical data of 108 patients with Bismuth-Corlette type Ⅲ and Ⅳ HC underwent hepatectomy were collected and analyzed retrospectively.There were 56 males and 52 females, aged (57.2±5.3) years (ranged 48-76 years) .Among the 108 cases, there were 51 cases of type Ⅲa, 40 cases of type Ⅲb and 17 cases of type Ⅳ. Small-scale hepatectomy (≤3 hepatectomy) was performed in 70 cases, including 8 cases of 4b segment resection, 28 cases of 4b segment+5 segment resection, and 34 cases of partial 4 segment+partial 7 segment+partial 1 segment resection. Large-scale hepatectomy was performed in 38 cases (>3 segments) , of which 30 cases were treated with 2 segments+3 segments+4 segments+1 segment, and 8 cases were treated with 5 segments+7 segments+8 segments+1 segment. t′ test was used to analyze the data which did not conform to the normal distribution, and χ² test was used to calculate the incidence of postoperative complications and the 1, 3, and 5-year cumulative overall survival rate. Results: (1) The operation time of minor liver resection group ((180±25)minutes) was shorter than that of major liver resection group ((210±35)minutes) (t′=4.676, P<0.05) , the amount of blooding operation time of minor liver resection group ((310±80)ml) was less than that of major liver resection group ((500±110)ml)in the operation (t′=9.385, P<0.05) , and the difference was statistically significant. (2) The incidence of complications was lower in minor liver resection group and major liver resection group, and the difference was statistically significant (χ²=5.230, P<0.05) . (3) The actual 1-, 3- and 5-year survival rates were 87.1%, 58.4%, 30.0% and 84.2%, 57.9%,31.6%, respectively. There were no significant differences in survival rates in two groups in 1-, 3- and 5-year survival rates (χ²=0.177, P=0.674; χ²=0.005, P=0.946; χ²=0.029, P=0.865) . Conclusions Compared to patients with major liver resection, Minor liver resection for selected patients with HC of Bismuth-Corlette Ⅲ and Ⅳaccording to our criteria achieved better long-term outcomes. Chen′s biliojejunostomy is a simple, effective and safe method, which can be widely used when there are multiple biliary intestinal anastomosese.

Objective To investigate the effect of neuromuscular electrical stimulation(NMES) on muscle atrophy and muscle fiber type conversion in quadriceps muscles of rats with chronic obstructive pulmonary disease(COPD).Methods Forty-eight male SPF Wistar rats were randomly divided into three groups:the healthy control group,COPD model group and NMES treatment group,with sixteen rats in each group.Rats in the NMES treatment group were given alternating electrical stimulation at 100 Hz and 2 Hz,with each stimulation time of 30 min,7 days per week,for 4 weeks.The control group and the COPD model group were only treated with electrode sheets.After the intervention,the endurance running distance measurement,the pathological changes of rat quadriceps muscle detected by HE staining,the mRNA and protein content of MSTN,MyHC(Myosin Heavy Chain)-Ⅰ,MyHC-Ⅱ a and MyHC-Ⅱ x in quadriceps muscles determined by Realtime PCR and Western Blot were performed.Results Compared with the healthy control group,the cross-sectional area,endurance running distance and MyHC-Ⅰ mRNA and protein expressions in the quadriceps muscles were decreased[(654.7±53.7) μm2 vs.(1079.8±117.2) μm2,(396.7±42.4) m vs.(607.4 ±56.3) m,0.407 ± 0.054 vs.0.997 ± 0.069,0.884 ± 0.102 vs.1.723 ± 0.156,t =4.642,3.785,24.723 and 18.640,P =0.008,0.033,0.000 and 0.000,respectively],while MSTN,MyHC-Ⅱ a and MyHC-Ⅱx mRNA and protein expressions were increased in the COPD model group (all P ＜ 0.01)Compared with COPD model,the cross-sectional area (997.5 ± 92.4 μm2),endurance running distance(597.2±65.8 m)and the expression levels of MyHC-Ⅰ mRNA(0.884±0.097)and protein (1.534±0.182)in the quadriceps muscles were increased(t =3.734,3.602,19.988 and 13.666,P =0.035,0.043,0.000,0.000),and the mRNA and protein expression levels of MSTN,MyHC-Ⅱ a and MyHC-Ⅱ x were decreased in the NMES treatment group(all P ＜0.01).Further correlation analysis found that the protein expression of MSTN in the quadriceps muscles was negatively correlated with muscle cross-sectional area,MyHC-Ⅰ protein levels and endurance running distance(r =-0.724,0.426 and-0.536,P =0.002,0.036 and 0.007,respectively),and positively correlated with the protein expressions of MyHC-Ⅱ a and MyHC-Ⅱ x(r=0.408 and 0.392,P =0.042 and 0.048).Conclusions The expression of MSTN is increased in quadriceps muscle of COPD rats,and NMES can inhibit the expression of MSTN in quadriceps muscles.MSTN is associated with muscle atrophy and muscle fiber conversion in COPD.Inhibition of MSTN expression can improve muscle atrophy and reverse muscle fiber transformation.

Objective: To explore the efficacy of an individualized cardiac rehabilitation education model on the knowledge level of cardiac rehabilitation and cardiac rehabilitation exercise for patients after percutaneous coronary intervention (PCI). Methods: This study adopted the method of quasi-experimental research, 96 patients after PCI were randomly divided into the intervention group (49 cases), and the control group (47 cases) according to the discharge order. The intervention group received the individualized education model of cardiac rehabilitation for 12 weeks led by the cardiac rehabilitation outpatient nurse, and the control group received the routine follow-up guidance. Before and after the intervention of the two groups, the changes of cardiac rehabilitation knowledge were evaluated according to The Coronary Artery Disease Education Questionnaire-II(CADE-Q II), the compliance of cardiac rehabilitation exercise were evaluated according to heart rate band mobile APP or mobile WeChat exercise APP, the effects of cardiac rehabilitation exercise were adjusted according to a 6-minute walking test. Results: The increase scores of CADE-Q II in the intervention group after the intervention were higher than that in the control group:(10.04±2.75) points vs (5.57 ± 2.65) points, and the difference was significant (t=2.079, P < 0.05).The exercise compliance of daily aerobic exercise target rate indicated on the App of mobile phones in the intervention group were higher than that in the control group:88%(15/17) vs 53% (7/17), and the difference was significant (t=5.100, P <0. 05). The exercise compliance of daily exercises indicating on the Wechat application in the intervention group were higher than that in the control group: 82% (23/28) vs 48% (13/27), and the difference was significant (t=7.025, P <0.01).6MWD in the intervention group was higher than that in the control group: (48.77±26.67) mvs (16.77±43.65) m, and the difference was significant (t=3.534, P <0.01). Conclusion This cardiac rehabilitation education model can improve the knowledge level and compliance of cardiac rehabilitation exercise, and promote the cardiac rehabilitation of patients after PCI.