Objective To investigate the therapeutic effects and mechanisms of Hibiseu Manihot L.fructus on type 2 diabetes mellitus(T2DM)mice.Methods T2DM mice were randomly divided into normal group,model group,positive drug group,Hibiseu Manihot L.fructus total extract group,water-solube part group,and Hibiseu Manihot L.fructus ethyl acetate fraction group,with 10 mice in each group.After 4 weeks of treatment,anti-diabetic effects were evaluated by monitoring body mass,fasting blood glucose(FBG),oral glucose tolerance test(OGTT),fasting insulin(FINS),homeostasis model assessment of insulin resistance(HOMA-IR),and area under the blood glucose curve(AUC).Liver tissue status was assessed through liver index and hematoxylin-eosin(HE)staining.Results Compared with the model group,the water-solube part and total extract group showed significant improvements in mental status,food intake,body mass,excretion,and the FBG elevation was effectively suppressed,OGTT,FINS,AUC,HOMA-IR and liver index were significantly decreased(P＜0.05 or P＜0.01),the histopathological analysis revealed improved liver tissue morphology.Regarding channel protein expression,compared with the model group,the water-solube part group exhibited significantly upregulated phosphorylation levels of protein kinase B(AKT)and phosphatidylinositol 3-kinase(PI3K)in mouse liver tissue(P＜0.05),furthermore,the positive drug group,total extract group,and water-solube part group all demonstrated markedly increased phosphorylation of adenosine monophosphate-activated protein kinase(AMPK)in hepatic tissues(P＜0.05).Conclusion The water-solube part of fructus of Hibiseu Manihot L fructus.effectively alleviates T2DM symptoms(polyphagia,polydipsia,polyuria,weight loss)and glucose metabolism disorders,with hepatoprotective effects potentially mediated through PI3K/AKT pathway activation and enhanced p-AMPK expression.

Abstract OBJECTIVE To analyze the inflammation-related molecular targets of Pien Tze Huang in the treatment of hepatocellular carcinoma and to preliminary explore its mechanism. METHODS Obtain the ingredients and targets of Pien Tze Huang through TCMSP and BATMAN databases. Obtain the disease targets of hepatocellular carcinoma through Genecards, OMIM and TCGA databases. Take the intersection of compound targets and disease targets to get Pien Tze Huang’s target for the treatment of hepatocellular carcinoma. Obtain the related genes of inflammation pathway from the GSEA database, and then analyze the correlation between Pien Tze Huang’s therapeutic targets for hepatocellular carcinoma and inflammation-related genes to screen out inflammation-related targets, and explore the mechanism through GO and KEGG enrichment analysis. Then, single-factor cox analysis and LASSO regression were performed to construct related prognostic models. The 10 core targets were screened out through the protein-protein interaction(PPI) network. The model gene and the core target were intersected. The core compounds were screened out through the drug-compound-target network. Perform molecular docking verification between the core compound and the target. Construct a nomogram to assess the prognosis of patients. RESULTS Obtained 162 Pien Tze Huang targets, 522 hepatocellular carcinoma targets, 20 Pien Tze Huang therapeutic targets for hepatocellular carcinoma, and 16 inflammation-related targets. The enrichment analysis of GO and KEGG showed that their effects were mainly through biological functions such as monooxygenase activity, oxidoreductase activity, and chemical carcinogenesis-receptor activation. The ROC curve of the prognosis model calculated AUC as 0.780 in 1 year, 0.688 in 3 years, and 0.642 in 5 years, indicating that the model was reliable. The prognostic model intersects with the core target of PPI to get 5 targets: PON1, IGF2, NQO1, CCNB1 and IGFBP3. The nomogram was constructed using CCNB1, NQO1, and T staging, and its c-index was 0.726, indicating the reliability of the model. The drug-compound-target network suggested that quercetin was the core compound and targets the above two genes. CONCLUSION Pien Tze Huang’s treatment of hepatocellular carcinoma mainly uses quercetin to target CCNB1 and NQO1 to exert anti-inflammatory effects, and its prognostic model can be used to predict the survival of patients.

Lnc-HUR1 is an HBV-related long non-coding RNA, which can promote the proliferation of hepatoma cells and the occurrence and development of liver cancer. In this study we explored the effect of lnc-HUR1 on the apoptosis of hepatocellular carcinoma cells by taking the approach of immunoblotting, quantitative real time PCR, luciferase reporter assay, chromatin immunoprecipitation (ChIP) and flow cytometry. We found that overexpression of lnc-HUR1 significantly reduced the activity of caspase3/7 and the cleavage of PARP-1, while knocking down of lnc-HUR1 significantly increased the activity of caspase3/7 and promoted the cleavage of PARP-1 in HepG2 cells treated with TGF-β, pentafluorouracil or staurosporine. Consistently, the data from Annexin-V/PI staining showed that overexpression of lnc-HUR1 inhibited apoptosis, while knockdown of lnc-HUR1 promoted apoptosis. Moreover, overexpression of lnc-HUR1 up-regulated the apoptosis inhibitor Bcl-2 and down-regulated the pro-apoptotic factor BAX at both RNA and protein levels. In the CCL4-induced acute liver injury mice model, the expression of Bcl-2 in the liver tissue of lnc-HUR1 transgenic mice was higher than that of the control mice. The data from ChIP assay indicated that lnc-HUR1 reduced the enrichment of p53 on Bcl-2 and BAX promoters. All these results indicated that lnc-HUR1 inhibited the apoptosis by promoting the expression of apoptosis inhibitor Bcl-2 and inhibiting the expression of apoptosis promoting factor BAX. Further studies showed that lnc-HUR1 regulated the transcription of Bcl-2 and BAX in HCT116 cells, but had no effect on the expression of Bcl-2 and BAX in HCT116 p53^-/- cells, indicating that lnc-HUR1 regulates the transcription of Bcl-2 and BAX dependent upon the activity of p53. In conclusion, HBV upregulated lnc-HUR1 can inhibit the apoptosis of hepatoma cells. Lnc-HUR1 inhibits apoptosis by inhibiting the transcriptional activity of p53. These results suggest that lnc-HUR1 plays an important role in the occurrence and development of HBV-related hepatocellular carcinoma.
Animals ; Annexins/pharmacology* ; Apoptosis ; Carcinoma, Hepatocellular/genetics* ; Cell Proliferation ; Hep G2 Cells ; Hepatitis B virus/metabolism* ; Humans ; Liver Neoplasms/genetics* ; Mice ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology* ; Proto-Oncogene Proteins c-bcl-2/pharmacology* ; RNA, Long Noncoding/metabolism* ; Staurosporine/pharmacology* ; Transforming Growth Factor beta/pharmacology* ; Tumor Suppressor Protein p53/pharmacology* ; bcl-2-Associated X Protein/pharmacology*

Objective Mutations in polymerase gamma gene (POLG) are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy. The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid (VPA) exposure at Shanghai Children's Hospital were collected from 2015 to 2019. The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy (ILAE). Blood sampling were performed before VPA treatment. The POLG gene DNA was sequenced by either the first or the next generation sequencing (NGS). The POLG variant burden was illustrated. Liver functions were tested to describe whether they experienced VPA toxicity. Results Totally 216 Han Chinese patients were included, aged from 1 month to 15 years old, 102 were male and 114 were female. The onset age was 1 month old to 13 years old, and the epilepsy course ranged from 2 weeks to about 3 years. VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage. No patient experienced hepatic toxicity following VPA exposure. DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG. Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients, and single heterozygous mutation of c.156_158dupGCA was found in 1 patient. None of these variants showed clinical significance. Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study. POLG mutation frequency might be rare in Han Chinese, and standard VPA therapeutic dosage might be safe for Han Chinese patients.

富含半胱氨酸的酸性分泌蛋白（SPARC）；巨噬细胞；肿瘤；微环境 肿瘤微环境对肿瘤的发生、发展具有重要的调节作用。富含半胱氨酸的酸性分泌蛋白（cysteine-rich acidic secreted protein ，SPARC）和巨噬细胞作为肿瘤微环境重要基质成分，不仅对肿瘤细胞有直接的调节作用，两者的相互作用也可以影响肿 瘤的各种生物学行为变化。SPARC通过维持细胞外基质紧密结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润，或通过减少巨 噬细胞向M2功能表型方向转换，抑制肿瘤进展；另一方面， M2型巨噬细胞可以通过吞噬SPARC，从而消除SPARC对肿瘤的抑制 作用。此外，巨噬细胞还可通过自身分泌的SPARC抑制肿瘤增殖和迁移等生物学行为。本文将就SPARC维持细胞外基质紧密 结构，减少巨噬细胞等免疫细胞向肿瘤区域的浸润；抑制巨噬细胞向M2功能表型方向转换，从而发挥抑瘤作用； M2可以通过吞 噬SPARC，消除SPARC对肿瘤的抑制作用;巨噬细胞来源SPARC决定细胞外基质沉积，抑制肿瘤迁移和增殖；SPARC与巨噬细 胞相互作用在肿瘤免疫治疗的应用5个方面进行综述，为巨噬细胞来源SPARC对肿瘤不同生物学行为的调节的作用深入研究提 供借鉴。

Objective To explore the application of internet medicine technology in medical facilities.Methods The present situation of internet medicine was analyzed in foreign countries and China,and the nature and characteristics of internet medicine were researched.The three modes for internet medicine were analyzed in china.The considerations were proposed for internet medicine.Results Some suggestions were put forward from the aspects of support from the director,compliance with national regulations,information resources support,internet medical service typing,intra-hospital informatization,institutions for running and management and etc.Conclusion The government has to provide support in policy,data resource and etc.

Objective: To prepare dexketoprofen trometamol hydrogel patches, optimize the formula and evaluate in vitro transdermal properties.Methods: Dexketoprofen trometamol hydrogel patches were prepared with NP-800 as the hydrogel patch carrier, aluminum hydrochloride as the crosslinking agent, EDTA as the crosslinking modifier and glycerol as the moisturizing agent.The formula was screened by orthogonal design with the initial viscosity, holding force, peel strength and 12 h cumulative transdermal quantity as the evaluation indices to screen out the best formula.The transdermal absorption test was carried out with an improved Franz diffusion cells to compare the enhancement of Aznoe, oleic acid and menthanol on dexketoprofen trometamol hydrogel patches.Results: The best formula was as follows: the mass percentage of NP-800, glycerol, glycerol and EDTA was 5%, 0.3% , 25% and 0.15% , respectively.The transdermal enhancers had transdermal enhancement on dexketoprofen trometamol, and among them, 3% Azone had the most significant enhancement with the enhancing rate of 3.26.Conclusion: The preparation and formula of dextroxyprofen trometamol hydrogel patches are stable, reasonable and feasible.

Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; Crystallography, X-Ray ; Humans ; Nuclear Proteins ; chemistry ; genetics ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Structure-Activity Relationship ; X-linked Nuclear Protein ; chemistry ; genetics

Objective To prepare monoclonal antibody (McAb) against γ-glutamyhransferase(GGT) firmly bound to datura stramonim (DSA) leetin from primary hepatic carcinoma (PHC) tissue and establish an avidin-biotin enzyme-linked immunosorbent assay (ELISA) for evaluating the diagnostic value of serum DSA-GGT for PHC. Methods Anti-DSA-GGT monoclonal antibodies were obtained by McAb technology and purified by protein G-sepharose affinity chromatography. The McAb was labeled with biotin and avidin-biotin ELISA for measurement of serum DSA-GGT was established. Using the avidin-biotin ELISA, serum DSA-GGT levels was detected in 39 patients with PHC, and 122 patients with non-PHC diseases. The distribution of serum DSA-GGT values of 119 healthy subjects were determined by P-P plots. Optimal cut-off value for the diagnosis of PHC was determined by receiver operating characterstic (ROC) curve. Results The protein levels of McAb in the ascites derived from 5 McAb hybridoma cell strains ranged from 2. 12 to 6. 70 mg, The biotin-labeled rate varied from 48. 6% to 72. 2% respectively. The minimum detection limit of serum DSA-GGT in avidin-biotin ELISA was 2 μg/L. Intra-assay and inter-assay coefficients of variation were 8.9% and 11.5% respectively. The distribution of DSA-GGT values of 119 healthy subjects showed Gaussian distribution and its Mean ± SD was ( 1.50±0. 51 ) μg/L. Optimal cut-off value (3.25 μg/L) in the diagnosis of PHC was determined by ROC curve. DSA-GGT was positive in 26 out of 39 patients with PHC and 10 out of 122 patients with non-PHC diseases were positive. The sensitivity and specificity of this assay for the diagnosis of PHC were 66. 7% and 91.8% respectively. Conclusions The convenient avidin-biotin ELISA method was successfully established in our laboratory and it showed a good reproducibility and reliability. It may be a potential tool in the diagnosis of PHC to achieve higher sensitivity and specificity.