Abstract: Objective　To analyze the epidemic characteristics of soil-transmitted helminth (STH) by the spatial epidemiological method in Jiangxi Province. Methods　Surveillance data of STH in Jiangxi Province from 2016 to 2019 were collected for descriptive epidemiological analysis. The space-time permutation distribution of STH infection areas was analyzed with spatial autocorrelation, hotspot analysis methods and retrospective space-time permutation scan statistics. Results　The infection rates of STH were 1.32% (947/71 766), 1.14% (803/70 547), 0.87% (604/69 507) and 0.90% (628/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The rates of hookworm infection were 0.65% (466/71 766), 0.64% (450/70 547), 0.48% (336/69 507) and 0.52% (362/69 620), respectively, and the differences were statistically significant (P<0.01). The infection rates of Ascaris lumbricoides were 0.55% (393/71 766), 0.41% (287/70 547), 0.32% (221/69 507) and 0.32% (225/69 620), respectively, and the differences were statistically significant in different years (P<0.01). The infection rates of Trichuris trichiura were 0.17% (125/71 766), 0.10% (74/70 547), 0.08% (57/69 507) and 0.07% (49/69 620), respectively, and the differences were statistically significant among different years (P<0.01). The results of global spatial autocorrelation analysis showed that there was a spatial autocorrelation index Moran's I value of hookworm infection rate in 2016, Trichuris trichiura infection rate in 2016, 2018 and 2019, with statistical significance (P<0.05). The results of hotspot analysis, SaTScan and FleXScan spatial and temporal scanning analysis showed that there were high-value aggregation regions for each species in each year. Conclusion　The infection rates of STH, hookworm, Ascaris lumbricoides and Trichuris trichiura showed a decreasing trend and space-time clustering from 2016 to 2019. It should be taken into account in the formulation of control strategies.

BACKGROUNDThe CRF07_BC recombinant strain has been one of the most predominantly circulated HIV-1 strains in China, it is therefore necessary and urgent to develop a relevant animal model to evaluate candidate vaccines targeting HIV-1 CRF07_BC. A highly replication-competent simian/human immunodeficiency viruses (SHIV) construct containing the Chinese CRF07_BC HIV-1 env gene with the ability to infect Chinese rhesus monkeys would serve as an important tool in the development of HIV vaccines. The aim of this study was to examine whether SHIV XJDC6431 with the env fragment from a Chinese HIV-1 isolate virus could infect the human and monkey peripheral blood mononuclear cell (PBMC), establish infection in Chinese rhesus macaque.

METHODSA SHIV strain was constructed by replacing the rev/env genes of SHIV KB9 with the corresponding fragment derived from the HIV-1 CRF07_BC strain. The infectious activity of the SHIV clones was determined in vitro in PBMCs from both non-human primate animals and humans. Finally, one Chinese rhesus macaques (Macaca mulatta) was infected with one SHIV via intravenous infusion.

RESULTSOne SHIV clone designated as SHIV XJDC6431, was generated that could infect macaque and human PBMC. The virus produced from this clone also efficiently infected the CCR5-expressing GHOST cell lines, indicating that it uses CCR5 as its coreceptor. Finally, the virus was intravenously inoculated into one Chinese rhesus macaque. Eventually, the animal became infected as shown by the occurrence of viremia within 3 of infection. The viral load reached 105 copies of viral RNA per ml of plasma during the acute phase of infection and lasted for 10 weeks post infection.

CONCLUSIONSWe conclude that SHIV XJDC6431 is an R5-tropic chimeric virus, which can establish infection not only in vitro but also in vivo in the Chinese rhesus macaque. Although the animal inoculated with SHIV XJDC6431 became infected without developing a pathologic phenotype, the virus efficiently replicated with a persistent level of viral load in the plasma. This suggested that the SHIV could be used as a tool to test candidate AIDS vaccines targeting the Chinese HIV-1 CRF_07BC recombinant strain.

Animals ; Chimera ; Genes, env ; HIV-1 ; genetics ; physiology ; Humans ; Macaca mulatta ; Proviruses ; genetics ; Receptors, CCR5 ; physiology ; Simian Immunodeficiency Virus ; genetics ; physiology

OBJECTIVETo evaluate the antitumor activity of a novel class of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones in vitro, and to screen potential anticancer compounds for further study.

METHODSSeventeen compounds of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones were synthesized with solid-phase method for biological evaluation of EGFR tyrosine kinase. MTT method was used to evaluate the cytotoxic activity in vitro against three human cancer cell lines (human lung carcinoma cell line A549, human leukemia cell lines K562 and human gastric carcinoma cell line SGC7901).

RESULTSCompound 7-13 and 7-14 showed potent antitumor activities against A549 cells, with IC(50) values of 8.10 and 8.12 mol/L, respectively. Eight compounds showed proliferative inhibition effect on K562 cells, especially 7-2, 7-13 and 7-17, with IC(50) values of 2.22,0.57 and 7.20 mol/L,respectively.And compound 7-13 and 7-3 showed potent antitumor activity against SGC7901 cells, with IC(50) values of 4.20 and 9.71 mol/L, respectively.

CONCLUSIONThe synthesized compounds 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g] quinazoline-7(6H)-ketones show inhibition effects on human cancer cell lines in vitro. Compound 7-13 has anticancer activity in all three cancer cell lines, which might be used as a potential antitumor drug for further study.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Lung Neoplasms ; pathology ; Molecular Structure ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Quinazolines ; chemical synthesis ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Stomach Neoplasms ; pathology ; Structure-Activity Relationship

BACKGROUNDThe cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear.

METHODSThe left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation (SO) group, myocardial infarction model (MI) group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin (HE) stained tissue. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 (MMP-2), and tissue matrix metalloproteinase inhibitor-2 (TIMP-2). Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation.

RESULTSThe model of heart failure was established and the results of HE staining and Masson's trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III collagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/TIMP-2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio.

CONCLUSIONSThese data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.

Animals ; Atorvastatin Calcium ; Collagen ; biosynthesis ; Disease Models, Animal ; Female ; Fibrosis ; Heart Failure ; drug therapy ; pathology ; Heptanoic Acids ; pharmacology ; therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Matrix Metalloproteinase 2 ; genetics ; Myocardial Infarction ; complications ; Myocardium ; pathology ; Pyrroles ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Tissue Inhibitor of Metalloproteinase-2 ; genetics ; Ventricular Remodeling ; drug effects

Objective To study the effect of a government-provided-free highly activeantiretroviral treatment (HAART) program,on the reduction of mortality and relevant risk factorsamong adult (AIDS) patients in Henan province.Methods Data on the survival and deaths of AIDSpatients were collected from the National HAART reporting system between 2003 and 2009.Coxproportional hazards model was applied to analyze those factors that affecting the survival time of thepatients.Results 24 669 cases were enrolled to this study in Henan province,from 2003 to 2009.The overall mortality declined from 20.1/100 person-years in 2003 to 5.1/100 person-years in 2009.There was significant difference between the survival curves of different CD4 + T counts and differentnumbers of opportunistic infection syndromes.Results from the Multivariate Cox proportional hazardsregression analysis indicated that CD4+T cell counts ( ＞200 cells/μl,50-199 cells/μ l) was a riskfactor to death,with hazard ratio as 4.4 and 2.0 respectively.Hb of the patients that lower than 90,was a risk factor to death with the HR=1.8.Number of opportunistic infection (OIs) episodes was arisk factor to the mortality (HR=1.7).In addition,other risk factors would include age ( ≥60 years,old),being male,unmarried or divorced,ALT＞100 μl,and other routes of infection,other thanFormer Plasma Donors (FPDs),with HR as 2.2,1.6,1.5,1.3 and 1.2.However,the protectivefactors would include:(1)the earlier the HAART began,the longer the survival time would last(HR =0.8 ) ; (2) when one spouse had already had the infection of HIV,it seemed helpful for the otherspouse to live longer (HR=0.8).Conclusion The National Free Treatment Program hadsignificantly reduced the AIDS mortality rate.Some effective measures should be further taken tomonitor the CD4 + T and the opportunistic infection of the AIDS patients.Patients who were in need totake the HARRT should be adopted into the ART timely,At the same time,the occurrence ofopportunistic infections should be actively prevented.

Objective To study the impact of adenoviral short hairpin RNA (shRNA) targeting phosphodiesterase 5 (PDE5 shRNA) on myo-cardial cells apoptosis at early stage post -myocardial infarction ( MI ).Methods MI was induced in mice by left coronary artery ligation.Mice were randomly assigned to test group [ n=10 , adenoviral vectors inserted with shRNA sequence for the inhibition of phosphodiesterase 5 ( PDE5 ) were injected intramyocardially to infarcted and border area ] and control group ( n =10 , injection with adenoviral vectors without therapeutic PDE5 shRNA ).One week post -MI, apoptosis was evaluated by TdT-mediated dUTP nick -end labeling ( TUNEL ) , proteins were extracted from the left ventricular of heart , level of PDE5 expression was detected using Western Bloting , the level of guanosine 3′, 5′-cyclic phosphate ( cGMP) or protein kinase G ( PKG) activity in the left ven-tricular of heart was evaluated by enzyme linked immunosorbent assay (ELISA).Results One week post -MI, compared to control group, test group had reduced number of apoptotic cells in infarct and periinfarct areas, and significantly reduced cardiomyocytes apoptosis in the periinfarct regions ( P<0.05 ).Compared to control group , the level of PDE5 was significantly decreased and the levels of cGMP and PKG were significantly increased in the test group ( P <0.05 ).Conclusion It the PDE5 shRNA has protective effect on acute myocardial infarction and significantly inhibit the apopto -sis of myocardial cell which may be closely related to the increased expression of cGMP and PKG .

Objective To investigate the mechanism of drug resistance of sulbactam mediated by TEM-1 beta-lactamases and porin CarO in clinical strains of acinetobacter baumannii. Methods Twenty-four unrepeated clinical acinetobacter baumannii strains were divided into sensitive strain group (n=6) and insensitive strain group (n=18) by susceptibility testing to sulbactam.Antibiotics susceptibility test was carried out using the Kirby-Bauer method.BlaTEM-1and carO genes were amplified by PCR.Four blaTEM-1positive strains(A3,A5,1327 and C1)were selected,and their amplified products were sequenced.The quantitative real-time RT-PCR was used to analyze mRNA transcriptional levels of blaTEM-1 and carO genes. Results Resistant rates of the sensitive strain group for meropenem, imipenem, cefoperazone, ciprofloxacin,gentamicin and ampicillin were 1/6,2/6,3/6,1/6,5/6 and 5/6,and resistant rates of the insensitive strain group were 6/18,10/18,18/18,18/18 and 18/18.BlaTEM-1genes were amplified in 16 insensitive strains,and blaTEM-1was negative in sensitive strains. The carO genes were amplified in all 24 strains.There was no significative mutation in the 4 strains of blaTEM-1genes. The promoters of the strains A3, A5 and 1327 were P4, and C1 was P3. There was a positive correlation between the mRNA expression of blaTEM-1and the MIC value of sulbactam (rs=0.551, P=0.027). There was no difference in the mRNA expression of carO between the two groups.Conclusion The clinical strains are seriously resistant to antibiotics.The main resistance mechanism of clinical strains to sulbactam is the high mRNA expression of blaTEM-1,and the promoter may be one of the reasons of high expression of TEM-1.

Objective: Renal fibrosis is the most common manifestation of chronic kidney disease(CKD).Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it,there is an urgent need to identify novel therapies.Hydrogen sulfide(H2S)is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body.This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application.Data sources: Literature was collected from PubMed until February 2019,using the search terms including "Hydrogen sulfide,""Chronic kidney disease," "Renal interstitial fibrosis," "Kidney disease," "Inflammation factor," "Oxidative stress," "Epithelial-to-mesenchymal transition," "H2S donor,""Hypertensive kidney dysfunction,""Myofibroblasts,""Vascuar remodeling,""transforming growth factor(TGF)-beta/Smads signaling,"and "Sulfate potassium channels."Study selection: Literature was mainly derived from English articles or articles that could be obtained with English abstracts.Article type was not limited.References were also identified from the bibliographies of identified articles and the authors' files.Results: The experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress,inhibiting the activation of fibrosis-related cells and their cytokine expression,ameliorating vascular remodeling and high blood pressure,stimulating tubular cell regeneration,as well as reducing apoptosis,autophagy,and hypertrophy.Therefore,H2S represents an alternative or additional therapeutic approach for renal fibrosis.Conclusions: We postulate that H2S may delay the occurrence and progress of renal fibrosis,thus protecting renal function.Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.

The objective of this study was to investigate the effect of cyclooxygenase-2 (COX-2) in the angiogenesis of bone marrow in leukemia patients. 51 patients with newly diagnosed acute leukemia were taken as study objects, 18 healthy volunteers were enrolled in the control group. Bone marrow microvessel density (MVD) in bone marrow biopsy tissue section was determined with immunohistochemistry method, the vascular endothelial growth factor level in serum was detected with ELISA method and the expression of cyclooxygenase-2 in bone marrow cells was assayed by flow cytometry. The results showed that the MVD, VEGF level, positive rate of COX-2 expression in leukemia group all obviously increased as compared with the control group (p < 0.05). The correlative coefficients of MVD, VEGF level and COX-2 expression rate were 0.614, 0.423 and 0.577 respectively (p < 0.05). In conclusion, as well as solid tumors, leukemia may be also a angiogenesis-dependent malignant tumor. Coordination of COX-2 with VEGF may promote angiogenesis in bone marrow.
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; metabolism ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Infant ; Leukemia ; metabolism ; pathology ; Male ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; Surgical Flaps ; Thumb ; surgery ; Toes