Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.

Wound healing is a complex and highly regulated process to maintaining the skin barrier function. Wounds of diabetic patients are hard or even not healing. Non-healing diabetic foot ulcers can lead to lower-extremity amputations. Diabetic wound healing problem is the main complication that leads to high disability rate of diabetes and can threaten the lives in severe cases. The healing of skin wounds requires the synergy of multiple factors to restore the injured skin to its barrier function. The mechanisms that cause it difficult to heal diabetic wounds are complex, including oxidative stress, chronic inflammation, decreased neovascularization, peripheral neuropathy, and imbalance of extracellular matrix accumulation and remodeling. This review classifies mechanisms of diabetic wound healing and provides a reference for its further research.

A double targets of high throughput screening model for xanthine oxidase inhibitors and superoxide anion scavengers was established. In the reaction system of xanthine oxidase, WST-1 works as the probe for the ultra oxygen anion generation, and product uric acid works as xanthine oxidase activity indicator. By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector, the changes of these indicators' concentration were observed and the influence factors of this reaction system to establish the high throughput screening model were studied. And the model is confirmed by positive drugs. In the reaction system, the final volume of reaction system is 50 μL and the concentrations of xanthine oxidase is 4 mU x mL(-1), xanthine 250 μmol x L(-1) and WST-1 100 μmol x L(-1), separately. The Z'-factor of model for xanthine oxidase inhibitors is 0.537 4, S/N is 47.519 9; the Z'-factor of model for superoxide anion scavengers is 0.507 4, S/N is 5.388 9. This model for xanthine oxidase inhibitors and superoxide anion scavengers has more common characteristics of the good stability, the fewer reagent types and quantity, the good repeatability, and so on. And it can be widely applied in high-throughput screening research.
Enzyme Inhibitors ; pharmacology ; Free Radical Scavengers ; pharmacology ; High-Throughput Screening Assays ; Superoxides ; Uric Acid ; Xanthine ; Xanthine Oxidase ; antagonists & inhibitors

OBJECTIVETo discuss the effect of the association of Shiquandabutang with Hetaokun on the protection to liver and immunity of tumor mouse S180.

METHODThrough the comparison between tumor transplanted and tumor cultured completely out of cell body, the effect was investigated, with Hetaokun singly used and Shiquandabutang associated with Hetaokun, on the level of SGPT, licking up function of monocyte macrophage, thymus index, spleen index and transform percentage of lymphocyte of the mouse S180. The scanning electron micrographs indicated the protective function of the association of Shiquandabutang with Hetaokun for liver.

RESULT12.5 mg x kg(-1) Hetaokun could obviously restrain the tumor when it was singly used at 73.1%, but it increased SGPT at the same time. The association of Shiquandabutang with Hetaokun could protect liver of the mouse S180. SGPT (P > 0.05) was compared with the common ones and the result showed that the association of shiquandabutang with Hetaokun could make K value increase (P > 0.01). Through the scanning electron micrographs, association of two medicines was found to change liver cells little and expansion of rough Neizhiwang was not found. Compared with the control group, the immunity of the two tumor mouse groups taking the medicine mentioned above was promoted obviously.

CONCLUSIONThe association of Shiquandabutang with Hetaokun can enhance the efficiency and decrease poison of them to body. With the promotion of immunity of the body, the efficiency is enhanced on the whole.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; Benzoquinones ; isolation & purification ; pharmacology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Fruit ; chemistry ; Juglans ; chemistry ; Liver ; pathology ; Lymphocyte Activation ; drug effects ; Macrophages ; immunology ; Male ; Mice ; Mitochondria, Liver ; drug effects ; Mitochondrial Swelling ; drug effects ; Phagocytosis ; drug effects ; Plants, Medicinal ; chemistry ; Sarcoma 180 ; immunology ; pathology

Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.
Administration, Intravenous ; Animals ; Caffeic Acids ; pharmacokinetics ; Chromatography, Liquid ; Drugs, Chinese Herbal ; pharmacokinetics ; Lactates ; pharmacokinetics ; Macaca mulatta ; Mass Spectrometry ; Plant Roots ; chemistry ; Salvia miltiorrhiza ; chemistry

OBJECTIVETo observe the effect of Cangfu Congxian Decoction (CCD) on oxidative stress in granulosa cells of polycystic ovary syndrome (PCOS) patients.

METHODSForty PCOS patients underwent in vitro fertilization-embryo transfer (IVF-ET) were assigned to the treatment group and the control group 1 according to random digit table, 20 in each group. Patients in the treatment group took CCD (200 mL, once in the morning and once in the afternoon) 2 months before IVF-ET, while those in the control group 1 took no Chinese medical decoction. Recruited were another 20 patients undergoing IVF-ET for tubal factors (as the control group 2). The clinical effect of IVF-ET were observed, including oocyte retrieval number, 2 pronuclear (2PN) fertilization rate, good quality embryo rate, clinical pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) induced transplantation cancel rate. The expression of relative oxygen species (ROS) in granulosa cells was detected using cell immunofluorescence combined with confocal microscopy and FCM.

RESULTSCompared with the control group 1, occyte retrieval number, 2PN fertilization rate, and good quality embryo rate increased in the control group 2 and the treatment group (P <0. 05). OHSS induced transplantation cancel rate decreased in the control group 2 (P < 0.05). Fluorescence intensity of ROS decreased in the treatment group and the control group 2, as compared with the control group 1 (P < 0.01).

CONCLUSIONCCD increased good quality embryo rate by down-regulating the expression of ROS protein in ovarian granulosa cells, and correcting in vivo oxidative stress.

Drugs, Chinese Herbal ; therapeutic use ; Embryo Transfer ; Female ; Fertilization in Vitro ; Granulosa Cells ; drug effects ; metabolism ; Humans ; Oocyte Retrieval ; Ovarian Hyperstimulation Syndrome ; prevention & control ; Oxidative Stress ; drug effects ; Polycystic Ovary Syndrome ; drug therapy ; Pregnancy ; Pregnancy Rate ; Reactive Oxygen Species ; metabolism

Background Eicosapentaenoic acid(EPA)function as the critical lipid mediators involved in several biological events in human body and play important role in suppressing the genesis of vascular endothelial growth factor (VEGF),migration and proliferation of vascular endothelial cells.Many ocular diseases were proved to be associated with neovascularization.Objecfive The purpose of this study was to investigate the inhibitory effect of EPA on the proliferation of human umbilical vein endothelial cells (HUVEC) indueed by VEGF. Methods HUVEC strain was cultured and passaged,and difierent concentrations of EPA were added to the medium with and without VEGF.The cultured cells were identified by antiofactor Ⅷ polyclonal antibody.The suppressing role of different concentrations of EPA on the proliferation of VEGF-induced or-uninduced HUVEC was assessed by MTT method.The influence of difierent concentrations of EPA on the cellular cycle of VEGF-induced HUVEC was assayed using flow eytometry.The expression of Flk-1,a receptor of VEGF,in the HUVEC Was detected by immunohistochemistry. Results Cultured HUVEC showed the ftlsiform in shape and presented with the cobblestone-like arrangement with the positive response for Ⅷ factor-related antigen.Various concentrations of EPA showed obviously inhibitory effect on VEGF-induced or-unindueed HUVEC at a dose-dependent manner (F=23.072.P=0.000).The inhibitory ability of EPA on VEGF-induced HUVEC was stronger than VEGF-uninduced HUVEC(F=41.417,P=0.000).In 24,48 and 72 hours,the action of EPA on the proliferation of HUVEC was gradually enhanced with the prolong of time(F=1.495,P=0.236).Cell cycle analysis indicated that EPA arrested VEGF-induced HUVEC in G0/G1 phase.The ratio of HUVEC in G0/G1 phase in EPA group was(75.83±1.56)%,and that in control groups was(68.62±1.44)%,showing a significant difference between them(t=-5.88,P=0.00),and no apoptosis of HUVEC was found in both groups.Flk-1 was strongly expressed in the cellular nucleus and cytoplasm in control group.However,the positive expressing intensity of Flk-1 in the HUVEC weakened,and the positive cell number was evidently less in EPA group. Conclusion EPA can inhibit the proliferation of VEGF induced HUVEC through arresting the synthesis of DNA of HUVEC and downregulate the expression of Flk-1 in HUVEC.These results suggest that EPA might exert an antiangiogenic effect.

Clinical data of a child with acquired immunodeficiency syndrome characterized by ischemic stroke who was admitted to the Pediatric Intensive Care Unit of Children′s Hospital Affiliated to Soochow University in January 2019 were retrospectively analyzed.The child is a 6 years and 4 months old boy with a history of thrombocytopenic purpura and recurrent respiratory infections.The main complaint was " the right limb weakness for more than 10 days" . The head magnetic resonance imaging (MRI) revealed extensive abnormal signals in the bilateral frontal and parietal lobes and the formation of softening foci in the left thalamus and outer capsule.Blood routine showed white blood cell 4.88×10 9/L, lymphocyte ratio 0.291, lymphocyte count 1.42×10 9/L, hemoglobin 99 g/L, and platelet 23×10 9/L.Lymphocyte subsets included CD3 + 84.1%, CD3 + CD4 + 0.2%, CD3 + CD8 + 61.4%, CD4 + /CD8 + 0, CD3 -CD 19+ 9.2%, CD3 -CD 16+ 56+ 6.1%, and CD 19+ CD 23+ 5.8%.Pretransfusion tests suggested human immunodeficiency virus (HIV) (+ ), and that other results were negative.Both parents of the child were infected with HIV.This paper demonstrates that neurological involvement is not rare in HIV infection, and stroke is the most common cause of clinical focal neurological deficits in HIV-infected children.Screening with MRI is recommended for high-risk children with neurologic symptoms or neurocognitive dysfunction.

Objective To explore the effect of chemokine CXCL12 and its receptor CXCR4 on proliferation,migration and invasion of epithelial ovarian cancer cells.Methods CXCR4 and CXCL12 mRNA and protein expression of human ovarian cancer cell line CAOV3 was detected by RT-PCR and immunocytochemistry.Integrin ?1 and vascular endothelial growth factor-C(VEGF-C)mRNA expression were detected in CAOV3 cells stimulated by CXCL12.The CAOV3 cells were divided into 6 groups:control group(un-stimulated),experimental group 1(stimulated by 100 ng/ml CXCL12),experimental group 2 (stimulated by 10 ng/ml CXCL12),experimental group 3(100 ng/ml CXCL12 and 10 ?g/ml neutralizing CXCR4 antibody),experimental group 4(100 ng/ml CXCL12 and 1 ?g/ml CXCR4 antagonist AMD3100),experimental group 5(10 ?g/ml neutralizing CXCR4 antibody or ascites).Methyl thiazolyl tetrazolium(MTT)was used to analyze the effects of different concentrations of CXCL12 on CAOV3 cell proliferation.Transwell invasion chamber and reconstructed basement membrane(Matrigel)were used to evaluate effect of various concentrations of CXCL12 and ascites on CAOV3 cell migration and invasion. Results CAOV3 cells expressed CXCR4 mRNA(0.70?0.10)and protein,but did not express CXCL12 mRNA or protein.Immunostaining of CXCR4 was mainly located in cytoplasm.CXCR4 mRNA was up- regulated after 100 ng/ml CXCL12 stimulation(1.24?0.14;t=-7.1088,P=0.0021).Integrin ?1 mRNA was greatly increased at 3 hours by stimulation of 100 ng/ml CXCL12(before and after stimulation 0.53?0.10,1.53?0.16;P0.05).Experimental group 1 stimulated the migration and invasion of CAOV3 cells in chemotaxis assay compared with control group and experimental group 2(number of cell migration respectively 523.3?25.2,108.0?7.2,211.7 ?24.7,number of cell invasion respectively 39.3?4.0,4.0?1.0,15.7?3.1;P

Objective To study the mechanisms of extrarenal arterial blood supply of renal malignancy for its interventional therapy.Methods Routine abdominal aortography and selective questionable feeding arteriography were performed in 141 patients with renal malignancy.The characteristics and formation mechanisms of extrarenal arterial blood supply for renal malignancy were analyzed.Results Of the 141 patients,extrarenal arterial blood supply of renal malignancy were found in 51 patients and there were 87 branchs.The breakthrough of renal capsule with malignancy were found in those 51 patients.No extrarena]arterial blood supply of renal malignancy was found in 90 patients,including 50 patients with and 40 patients without the renal capsule breakthrough with malignancy.The emerge of extrarenal arterial blood supply of renal malignancy were significantly different(x~2 = 31.64,P