Objective To investigate the levels of activated Stat3 (p‐Stat3) and the expression levels of SOCS3 as well as their clinical significance and its impact on the pathogenesis ,progression ,and prognosis in patients with gastric cancer .Methods The levels of p‐Stat3 and SOCS3 were tested in 53 cases of gastric cancer tissues (test group) and 27 cases of adjacent non cancerous tis‐sues (control group) by immunohistochemistry (IHC) .The clinical pathological and follow up data were analyzed .Results The levels of activated p Stat3 were significantly higher in gastric cancer tissues than in non cancerous tissues .The levels of SOCS3 were lower in cancer tissues than in non cancerous control tissues (P<0 .05) .p‐Stat3 showed significantly different levels among TNM stages and tumor differentiation ,and the expression levels of SOCS3 were negatively associated with cancer invasion ,lymph node metastasis and TNM stages in cancer patients (P<0 .05) .Furthermore ,a negative correlation was observed between the levels of activated p‐Stat3 and SOCS3 in gastric cancer tissues (r= -0 .492 ,P<0 .05) .Kaplan Meier survival analyses indicated that the p‐tat3 levels were negatively correlated with total survival of gastric cancer patients ,the higher the levels of p‐Stat3 was ,the lower the total survival rate would be (χ2 = -5 .05 ,P<0 .05) .On the contrary ,the levels of SOCS3 showed a positive correlation with total survival (χ2 =10 .852 ,P<0 .05) .Conclusion Increased a p‐Stat3 and decreased expression of negative Stat3 regulator SOCS3 may play important roles in the development and progression of gastric cancer ,both of which would potentially serve as prognostic mark‐ers for gastric cancer .

Studies have found that metformin is not only the preferred drug for lowering blood sugar, but also shows lipid-lowering and weight-loss effects. The purpose of this study was to use a hyperlipidemia hamster model to investigate the lipid-lowering effect of metformin and its effect on important metabolic pathways in lipid metabolism disorders. Fifty golden hamsters were divided into a control group, a model group, metformin high- and low-dose groups, and a simvastatin group. A high-fat diet was fed for 1 week to create the model, and then drug was administered for 11 weeks with the high-fat diet. Serum was taken for measurement of blood lipid and blood glucose at 2, 6, and 9 weeks after administration, and at weeks 3, 5, and 9 feces and urine were collected for ¹H NMR metabolomics tests. After 11 weeks of intravenous injection of [U-¹³C₆] glucose, serum was collected for a ¹³C NMR metabolic flux test. The results showed that the administration of metformin can significantly reduce blood lipids and glucose levels and can significantly affect metabolic pathways such as sugar metabolism, lipid metabolism, ketone metabolism, amino acid metabolism, and intestinal flora metabolism. The results of the metabolic flux analysis showed that the high-fat diet reduced the metabolism of tricarboxylic acids by 37.48%. After administration of low and high doses of metformin the metabolism of tricarboxylic acid increased by 98.14% and 143.10%, respectively. After administration of simvastatin tricarboxylic acid metabolism increased by 33.18%. The results indicate that metformin has a significant effect on promoting energy metabolism. This study used a combination of metabolomics and metabolic flow to explore the effect of metformin on lipid metabolism disorders and quantifies changes in the key pathway of energy metabolism-the tricarboxylic acid cycle. This study provides useful information for the study of the efficacy and mechanism of metformin, as well as a practical technical method for the screening of lipid-lowering drugs based on a hamster model.

Objective: To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). Methods: Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed. Results: The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. Conclusions The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.

BACKGROUNDIt has been found that cardiac protection afforded by ischemic preconditioning (IPC) is significantly reduced in the senescent myocardium. ADAMTS-1 (a disintesrin and metalloprotease with thrombospondin type 1 motifs) has been shown to inhibit angiogenesis in a variety of in vitro and in vivo assays. The aim of this study was to investigate the age-associated differences in ADAMTS-1 protein expression in rat myocardium after ischemic preconditioning.

METHODSSixty-four young (4 months) and old (24 months) male Sprague-Dawley rats were randomly assigned to an IPC group (40 rats) or a sham group (rats). A model of delayed IPC was induced and rats were sacrificed and myocardial samples were harvested from the ischemic-reperfused region for immunohistochemical detection of ADAMTS-1 at serial time points after IPC. A model of myocardial infarction was produced by ligation of the left anterior descending coronary artery in additional sets of young and old rats after sham or IPC procedures, then age-associated myocardial infarction survival after IPC was calculated.

RESULTSADAMTS-1 expression increased significantly in old rats compared to young rats (P < 0.05). The mean densities of ADAMTS-1 protein at 0, 6, 12, and 24 hours in young-IPC group after IPC were 0.05 ± 0.01, 0.13 ± 0.03, 0.16 ± 0.04, and 0.12 ± 0.03 vs. 0.07 ± 0.03, 0.20 ± 0.03, 0.24 ± 0.05, and 0.21 ± 0.04 in old-IPC group. IPC resulted in diminished survival rates (5/35 vs. 6/14, old-IPC group vs. old-sham group, P < 0.05), reduced left ventricular fractional shortening ((13.9 ± 2.8)% vs. (18.3 ± 2.3)%, P < 0.05) and increased the myocardial infarction size ((37.9 ± 3.2)% vs. (32.8 ± 5.1)%, P < 0.05) in the older rats.

CONCLUSIONSCardioprotection with IPC is attenuated in the older heart. ADAMTS-1 expression induced by IPC is greater in old rats. Over-expression of anti-angiogenic factors might be a potential mechanism behind reduced protection after IPC associated with aging.

ADAM Proteins ; metabolism ; ADAMTS1 Protein ; Aging ; metabolism ; physiology ; Animals ; Immunohistochemistry ; Ischemic Preconditioning, Myocardial ; Male ; Myocardial Infarction ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVEto observe the effect of ischemia preconditioning (IPC) on the expression of pro-angiogenic VEGF, PDGF and anti-angiogenic ADAMTS-1, and arteriogenesis.

METHODSrat heart IPC model was made by 4 circles of occluding the LAD for 6 min followed by 6 min of reperfusion. The expression of VEGF, PDGF-B and ADAMTS-1 in the ischemic area was examined with immunohistochemistry at 6, 12 and 24 h after IPC. IPC plus myocardial infarction model was induced by LAD ligation 24 h after IPC, 14 days later, the anti-SM-α-actin antibody was used to detect the mature neovascularization in the border of the infracted area.

RESULTSVEGF, PDGF-B and ADAMTS-1 were significantly upregulated in the ischemic area in IPC group compared with the control group (P < 0.05). Density of mature arteries was also significantly increased in IPC plus MI group than that in MI group (P < 0.05).

CONCLUSIONIPC promoted the formation of mature new arteries which may be modulated by upregulating VEGF, PDGF-B, and ADAMTS-1 expressions.

ADAM Proteins ; metabolism ; ADAMTS1 Protein ; Animals ; Arteries ; metabolism ; pathology ; Ischemic Preconditioning ; Male ; Neovascularization, Physiologic ; Proto-Oncogene Proteins c-sis ; metabolism ; Rats ; Rats, Sprague-Dawley ; Up-Regulation ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVESTo examine the gene expression profile of bone morphogenetic protein 2 (BMP-2) and vascular endothelial growth factor (VEGF) during entochondrostosis of mice and explore the expression rules and effects between BMP-2 and VEGF, and to detect the expression of VEGF in BMP-2 induced entochondrostosis in vivo.

METHODScDNA microarray technique with 34,000 genes was used to analyze the gene expression profiles during entochondrostosis in the limbs of mice embryo from E10 to E14. Pathway analysis of BMP-2 and VEGF was performed with GCOS1.2 software. An experimental model of femoral muscular pouch in 20 mice was adopted. The expression of VEGF was examined by in situ hybridization method and immunohistochemical method in BMP-2 induced entochondrostosis in vivo.

RESULTSThe expression signals of VEGF mRNA and VEGF appeared in cytoplasm during condensation of mesenchymal cell. As the mesenchymal cells differentiated into precartilage, the expression signals decreased in mesenchymal cells, but increased in chondrocytes and kept getting denser in the process of cartilage maturity. The peak expression of VEGF mRNA and VEGF in the experimental group appeared on the 14th day, accompanied by numerous hypertrophic chondrocytes. When mature cartilage calcified and new bone trabecula formed, the expression of VEGF mRNA and VEGF decreased in chondrocytes, but still expressed moderately in the osteoblasts and osteocytes.

CONCLUSIONSThe finding reveals a complex pattern of gene coexpression of BMP-2 and VEGF during the critical period of entochondrostosis. It's feasible for the clinical application of BMP-2 in orthopedics.

Animals ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Cell Differentiation ; genetics ; Chondrocytes ; cytology ; metabolism ; Gene Expression ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Male ; Mice ; Oligonucleotide Array Sequence Analysis ; Osteoblasts ; cytology ; metabolism ; Osteogenesis ; genetics ; RNA, Messenger ; genetics ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

OBJECTIVETo investigate the effect of lamivudine, interferon alpha and oxymatrine treatment for surviving hepatic failure patients with hepatitis B.

METHODS200 hepatitis B patients, including 100 subacute or acute-on-chronic hepatic failure survivals (group A), and 100 chronic (group B, n=100) hepatic failure survivals, were enrolled in this study. Patients in group A received interferon alpha (n=35), lamivudine (n=33) , or combinational lamivudine and oxymatrine (n=32) therapy for six months; Patients in group B received lamivudine (n=49), or combinational lamivudine and oxymatrine (n=51) therapy for six months, respectively. After the treatment, all patients were followed-up for six months.

RESULTSAt the end of follow-up, all patients in group A survived, while in group B three patients (6.1%) receiving lamivudine, and four (7.8%, P>0.05) receiving combinational therapy died; more than 90% of all survivals had their HBV DNA loss. The HBeAg/anti-HBe seroconversion rate in patients of group A treated with interferon alpha (9/17, 52.9%) was higher than that in patients treated with combinational lamivudine and matrine (5/16, 31.3%, P<0.05), which was higher than that in the patients treated with lamivudine alone (1/17, 5.9%, P<0.01), and the Knodell histological activity index score in patients treated with lamivudine (7.2+/-0.8, P<0.05) was lower than that in patients treated with interferon alpha (8.2+/-1.3, P<0.05), and the best efficacy was found in receiving combinational therapy (6.9+/-0.7, P<0.01); Lamivudine or lamivudine in combination with matrine significantly inhibited the intrahepatic inflammatory activities, but had no effect on the existing fibrosis in group B patients.

CONCLUSIONLong term nucleotide analogues treatment may delay the progress of fibrosis in hepatitis B-induced hepatic failure survivals, and the administration of matrine in time may further enhance the anti-fibrotic effect of nucleotide analogues.

Adolescent ; Adult ; Alkaloids ; administration & dosage ; therapeutic use ; Antiviral Agents ; administration & dosage ; therapeutic use ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hepatitis B ; complications ; drug therapy ; pathology ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; drug effects ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Lamivudine ; administration & dosage ; therapeutic use ; Liver Failure ; blood ; drug therapy ; pathology ; Liver Function Tests ; Male ; Middle Aged ; Quinolizines ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult

Aim Human TMPRSS2 is a transmembrane serine protease.In this paper, the structure and func¬tion of the protein were systematically analyzed by bioinformatics, the codon was optimized and the pro- karvotie expression vector was constructed to explore the molecular mechanism of SARS-CoV-2 infecting host cells.Methods The recombinant expression vector pET-22b-TMPRSS2 was generated by molecular clo¬ning technology.The homology, functional sites, sub¬cellular localization, three-dimensional structure and evolutionary characteristics of TMPRSS2 protein were systematically analyzed by using analytical tools such as Protparam, NetPhos3.1, Blast, Clustal X2 and MEGA7.0.Results The prokarvotic expression plas- mid was constructed correctly; TMPRSS2 belongs to medium molecular weight protein, which is composed of 492 amino acid residues.The theoretical isoelectric point is 8.12, the molecular extinction coefficient is 118 145 L • mol~1 • cm"1 , and the half-life is 30 h; TMPRSS2 has 15 potential glycosylation sites and 49 possible phosphorylation sites.It is a transmembrane hydrophilie protein without signal sequenee.In addi¬tion, the protein has 13 potential B-cell epitopes and 7 T-eell epitopes.Seeondarv structure analysis showed that random coil accounted for the highest proportion of TMPRSS2 protein ( 0.453 3) , followed by extended strand (0.252 0).Sequence comparison and evolu¬tionary analysis showed that the highest sequence con¬sistency and closest genetic relationship with human TMPRSS2 was Pan troglodytes, followed by gorilla.Conclusions Human-derived TMPRSS2 protein is ev- olutionarilv conserved and functionally important.Hie results of this study can help to reveal the structure and mechanism of action of TMPRSS2 protein, provide ide¬as for the diagnosis and treatment of COYID-19, and accelerate the research and development process of new drugs targeting TMPRSS2 protein.

OBJECTIVESTo evaluate the effectiveness and safety of Guipi Decoction (, GPD) as an adjunctive in the treatment of depression.

METHODSA review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1.

RESULTSNine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug signifificantly improved the symptoms of depression [weighted mean difference (WMD):-3.09; 95% confifidence interval (CI):-4.11 to-2.07] and increased the rates of effectiveness (OR: 4.75; 95% CI: 2.66-8.51) as well as recovery (OR: 1.73; 95% CI: 1.17-2.56). The adverse effects of GPD were not found to be signifificant in these studies.

CONCLUSIONSThe fifindings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any serious adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.

OBJECTIVETo evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.

METHODSSeventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.

RESULTSAfter 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.

CONCLUSIONrhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.

Animals ; Bone Marrow ; pathology ; Bone Marrow Cells ; pathology ; Gamma Rays ; Granulocyte Colony-Stimulating Factor ; pharmacology ; Hematopoiesis ; drug effects ; Hematopoietic Stem Cells ; cytology ; Humans ; Interleukin-2 ; pharmacology ; Macaca mulatta ; Radiation Injuries ; drug therapy ; Random Allocation ; Recombinant Proteins ; therapeutic use ; Thrombopoietin ; pharmacology ; Whole-Body Irradiation