ABSTRACT
@#Abstract:Objective To improve the replication level of varicella⁃zoster virus(VZV)in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon(IFN)related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1(IFNAR1)silenced MRC⁃5 cell line(MRC⁃5IFNAR1⁃)was constructed by CRISPR/Cas9 gene editing technology,which was determined for the relative expression of IFNAR1 mRNA,and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit(PFU)assay, to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells,and the relative expression of IFNAR1 mRNA decreased by 73%;The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection;In addition,168 h after VZV infection,the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells,and provided a reference for expanding production of VZV vaccine.
ABSTRACT
Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.
Subject(s)
Humans , Carcinoma, Renal Cell/drug therapy , Immunotherapy/adverse effects , Kidney Neoplasms/drug therapy , Retrospective StudiesABSTRACT
Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.
Subject(s)
Humans , Carcinoma, Renal Cell/drug therapy , Immunotherapy/adverse effects , Kidney Neoplasms/drug therapy , Retrospective StudiesABSTRACT
Purpose: Chronic inflammation in the liver is a key trigger for liver injury and fibrosis in various liver diseases. Given the anti-inflammatory and antioxidant effects of Saffron, this study aimed to investigate the pharmacological effects of Saffron on hepatic inflammation and fibrosis. Methods: The mice model of hepatic fibrosis was constructed using CCl4, and Saffron was administered at low (10 mg/kg) and high (20 mg/kg) doses by gavage. Then, the changes in liver function, liver inflammation and fibrosis markers were evaluated. The effects and mechanisms of Saffron on hepatic stellate cells were further investigated in in-vitro experiments. Results: Saffron improved liver function, reduced liver inflammation and attenuated liver fibrosis in a dose-dependent manner in hepatic fibrosis mice. Furthermore, Western blotting showed that Saffron significantly inhibited JAK/STAT3 phosphorylation in fibrotic livers. Conclusions: Saffron can attenuate liver fibrosis by inhibiting the JAK/STAT3 pathway and the activation of hepatic stellate cell, providing a theoretical basis for the development of new anti-fibrotic drugs.
Subject(s)
Animals , Rats , Crocus , Liver Cirrhosis , Liver DiseasesABSTRACT
ABSTRACT Introduction: Volleyball has become popular worldwide, and its athletic standard has risen. The skills of jumping into a net test athletes' lower limb strength and speed. Objective: Study the effects of deep jumping exercises on the explosive strength in the lower limbs of volleyball athletes. Methods: Through the experimental method, logical analysis method, and mathematical statistics method, the kinematics and the results of the practical tests on the 8 muscles of the athletes' lower limbs were studied. The training took place for 8 weeks of training intervention, and the characteristic biomechanical structure of the athletes' lower limb muscles during the deep jump was established. Results: The landing time of the athletes in the deep jump group was improved, with a change of 0.03s. The deep jump group increased in time by 0.02s, indicating that the jumping ability was significantly improved. Conclusion: The deep jump training method reduces the time spent landing, with a strong level of evidence. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: O voleibol tornou-se popular em todo o mundo, e seu padrão atlético elevou-se. As habilidades de salto em rede, testam a força dos membros inferiores e a velocidade dos atletas. Objetivo: Estudar os efeitos dos exercícios de salto profundo sobre a força explosiva nos membros inferiores dos atletas de voleibol. Métodos: Através do método experimental, método de análise lógica e método de estatística matemática, foram estudas a cinemática e os resultados dos testes práticos nos 8 músculos dos membros inferiores dos atletas. O treinamento deu-se por 8 semanas de intervenção de treinamento, e a estrutura característica biomecânica dos músculos dos membros inferiores dos atletas durante o salto profundo foi estabelecida. Resultados: O tempo de pouso dos atletas no grupo de salto profundo foi aprimorado, com uma mudança de 0,03s, o grupo de salto em profundidade teve um aumento de tempo em 0,02s, indicando que a capacidade de salto foi significativamente aprimorada. Conclusão: O método de treinamento de salto profundo reduz o tempo gasto no pouso, com forte nível de evidência. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: El voleibol se ha hecho popular en todo el mundo y su nivel deportivo ha aumentado. Las habilidades de salto en red, ponen a prueba la fuerza de los miembros inferiores y la velocidad de los atletas. Objetivo: Estudiar los efectos de los ejercicios de salto profundo sobre la fuerza explosiva en los miembros inferiores de los deportistas de voleibol. Métodos: Mediante el método experimental, el método de análisis lógico y el método de estadística matemática, se estudiaron la cinemática y los resultados de las pruebas prácticas de los 8 músculos de los miembros inferiores de los atletas. El entrenamiento se llevó a cabo durante 8 semanas de intervención, y se estableció la estructura biomecánica característica de los músculos de las extremidades inferiores de los atletas durante el salto en profundidad. Resultados: El tiempo de aterrizaje de los atletas del grupo de salto profundo mejoró, con un cambio de 0,03s, el grupo de salto en profundidad tuvo un aumento de tiempo de 0,02s, lo que indica que la capacidad de salto mejoró significativamente. Conclusión: El método de entrenamiento de salto profundo reduce el tiempo empleado en el aterrizaje, con un fuerte nivel de evidencia. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
ABSTRACT
Objective:To study the effects of cisapride on digestive symptoms and gastrointestinal hormones in elderly peritoneal dialysis patients.Methods:Forty-two elderly patients with renal failure undergoing peritoneal dialysis in our hospital from July 2017 to December 2017 were randomly selected as the study group.Meanwhile, 20 healthy elderly people in the corresponding time period were selected as the control group.Control group received continuous ambulatory peritoneal dialysis(CAPD)and other conventional basic therapy, and study group received cisapride as add-on therapy to treatment for control group.Serum levels of somatostatin(SS), motilin(MOT)and vasoactive intestinal peptide(VIP)were compared between the two groups.Gastrointestinal symptoms, serum levels of gastrointestinal hormones and biochemical indexes were compared before and after treatment in the study group.Results:The score of acid reflux, nausea, abdominal distension, belching and constipation were lower in the study group after treatment than before treatment( t=4.42, 4.32, 6.80, 6.29 and 6.76, all P=0.00). Before treatment, levels of MOT, SS and VIP were higher in the study group than in the control group[(636.65±32.02)pmol/L vs.(228.47±28.74)pmol/L, (64.02±16.32)mg/L vs.(42.38±6.42)mg/L, (118.64±17.68)ng/L vs.(58.62±11.63)ng/L, t=48.44, 7.47 and 15.93, all P=0.00]. The level of MOT was lower after than before treatment[(385.36±19.64)pmol/L vs.(636.65±32.02)pmol/L, t=43.36, P=0.00], and the levels of SS and VIP had no significant difference before versus after treatment( t=-0.11 and -0.42, P=0.91 and 0.68). After treatment, the level of MOT was still higher in the study group than in the control group[(385.36 ±19.64)pmol/L vs.(228.47 ±28.74)pmol/L, t=22.08, P=0.00]. There was no significant difference in blood urea nitrogen(BUN), creatinine, haemoglobin and kt/v levels between before and after treatment( P>0.05). The level of albumin(ALB)was higher after than before treatment[(38.60±1.89)g/L vs.(37.71±1.96)g/L, t=2.12, P=0.04]. Conclusions:Gastrointestinal symptoms are common in elderly patients with peritoneal dialysis, and the accumulation of gastrointestinal hormones is obvious, which leads to gastrointestinal dysfunction.The conventional treatment in combination with cisapride can improve gastrointestinal symptoms and reduce serum MOT level in these patients.
ABSTRACT
Objective: To clone CDS sequence of Dioscorea opposita SUS gene and analyze the protein structure,in order to provide a theoretical basis for the regulation mechanism of SUS gene and the synthesis mechanism of D.opposita polysaccharides.Method: Total RNA in D.opposita was extracted and reverse-transcribed into first strand of cDNA.Specific primers were designed according to an annotated SUS gene sequence obtained from the laboratory D.opposita genome database,and the coding region of the SUS gene was obtained by gene cloning technique and the protein sequence characteristics were analyzed by protein prediction analysis software.Result: A 2 448 bp gene sequence was cloned with a complete open reading frame (ORF).The gene was named DoSUS1.The formula of protein encoded by DoSUS1 gene in D.opposita was C4209H6534N1115O1205S23,and the molecular weight was 9 788.32,the total number of amino acids was 815,the theory isoelectric point (PI) was 6.10,the extinction coefficient was 110 505,the aliphatic index (AI) was 94.15,the instability index was 32.18,and the grand average of hydropathicity (GRAVY) was-0.225.It was a stable and soluble acidic protein.There were phosphorylation sites in the DoSUS1 amino acid sequence,with no transmembrane region and signal peptide.The secondary structure and the tertiary structure showed that DoSUS1 was an α class protein.Functional domain predictions showed that DoSUS1 had sucrose synthesis domain and glycosyl transfer domain.The homology alignment showed that the amino acid sequence of DoSUS1 was more than 80% similar to the amino acid sequence of the aligned monocots.The phylogenetic tree showed that DoSUS1 was closely related to SUS of monocotyledon evolution.Conclusion: The coding sequence of SUS gene was cloned from D.opposita for the first time,and its protein structure was analyzed to lay a foundation for further studying the roles of SUS in the growth and polysaccharide synthesis of D.opposita.
ABSTRACT
The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely owing to its robust self-renewal and multilineage differentiation abilities. The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination. Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states are characterized by distinct molecular features and functional outputs. Recent advances in high-resolution epigenome profiling, single-cell transcriptomics, and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination. Here, we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity, and the application of cell cycle manipulation for cell fate conversion. These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field, and may facilitate its potential application in translational medicine.
Subject(s)
Animals , Humans , Cell Cycle , Cell Physiological Phenomena , Epigenomics , G1 Phase , G2 Phase , Translational Research, BiomedicalABSTRACT
The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely owing to its robust self-renewal and multilineage differentiation abilities. The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination. Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states are characterized by distinct molecular features and functional outputs. Recent advances in high-resolution epigenome profiling, single-cell transcriptomics, and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination. Here, we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity, and the application of cell cycle manipulation for cell fate conversion. These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field, and may facilitate its potential application in translational medicine.
ABSTRACT
OBJECTIVES@#To investigate the effects of Astragaloside IV (AST) on diastolic function of rat thoracic aorta rings which was injured by microvesicles derived from hypoxia/reoxygenation (H/R)-treated human umbilical vein endothelial cells (HUVECs), and the mechanism of AST.@*METHODS@#H/R-induced endothelial microvesicles (H/R-EMVs) were generated from cultured HUVECs under the condition of hypoxia for 12 hour/Reoxygenation for 4 hour, H/R-EMVs were stored in D-Hank's solution. Male Wistar rats were underwent thoracotomy, the thoracic aorta with intact endothelium were carefully removed and cut into 3~4 mm rings. The experiment was divided into six groups. H/R-EMVs group:thoracic aortic rings of rats were incubated in culture medium and treated with H/R-EMVs in a final concentration of 10g/ml; different doses of AST groups:thoracic aortic rings of rats were treated with 10, 20, 40, 60 mg/L AST co-incubated with 10g/ml H/R-EMVs respectively; control group were treated with the same volume of D-Hank's solution. Duration of incubation was 4 h, each group was tested in five replicate aortic rings. Effects of AST on endothelium-dependent relaxation were detected. The production of nitric oxide (NO) and the level of endothelial NO synthase (eNOS), phosphorylated eNOS (p-eNOS, Ser-1177), serine/threonine kinase (Akt), phosphorylated Akt (p-Akt, Ser-473), extracellular regulated protein kinases (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2, Thr202/Tyr204) of rat thoracic aortic rings were detected.@*RESULTS@#Teng/ml H/R-EMVs could impaire the relaxation of rat thoracic aortic rings significantly (<0.01). Compared with H/R-EMVs group, relaxation of rat thoracic aortic rings was increased by 20, 40 and 60 mg/L AST in a concentration-dependent manner (<0.01), the level of NO production was also enhanced (<0.05, <0.01). The level of t-eNOS, t-Akt and ERK1/2 was not changed, but the level of p-eNOS, p-Akt and p-ERK1/2 increased by the treatment with AST (<0.01).@*CONCLUSIONS@#AST could effectively ameliorate endotheliumdependent relaxation of rat thoracic aortic rings impaired by H/R-EMVs in a concentration-dependent manner, the mechanism might involve the increase in production of NO, and the protein level of p-eNOS, p-Akt and p-ERK1/2.
Subject(s)
Animals , Humans , Male , Rats , Aorta, Thoracic , Cell-Derived Microparticles , Pathology , Human Umbilical Vein Endothelial Cells , In Vitro Techniques , MAP Kinase Signaling System , Nitric Oxide , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Rats, Wistar , Saponins , Pharmacology , Triterpenes , Pharmacology , VasodilationABSTRACT
Objective To report the clinical characteristics of alien hand syndrome(AHS). Methods Eight AHS inpatients from July,2015 to July,2017 were reviewed from the etiology,clinical manifestations, imaging characteristics and outcome. Results The etiology of the patients was cerebrovascular disease. The clinical features included alien hand (8 cases), movement disorder(8 cases),cognitive disorder(5 cases),speech disorder(4 cases)and affective disorder(3 cas-es).Imaging indicated the lesions involved callosum(8 cases),frontal lobe(2 cases),parietal lobe(3 cases),tem-poral lobe(2 cases)and basal ganglial region(1 case).There were four cases healing,two improving,two of re-mission after medicine and rehabilitation. Conclusion ASH is mainly resulted from cerebrovascular disease, in which callosum and frontal lobe are mostly in-volved,features in different forms,and prognoses well.
ABSTRACT
Objective To study the effects of cisapride on symptoms of digestive and gastrointestinal hormones in chronic renal failure patients.Methods There were 46 cases of chronic renal failure patients in this paper,all patients were given routine treatment of the underlying disease and were randomly divided into two groups.23 patients were additionally treated with cisapride as research group,and the others as control group.The gastrointestinal symptoms,serum somatostatin (SS),motilin (MOT) and vasoactive intestinal peptide (VIP) and other gastrointestinal hormones and renal function in two groups of patients were compared before and after treatment.Results The score of acid reflux,nausea,vomiting,abdominal distension,belching and other symptoms of hard feces and other gastrointestinal after treatment were significantly lower than that before treatment in research group and after treatment in control group (all P < 0.05).There was no significant change between before and after treatment in SS and VIP of two group (all P > 0.05),and MOT in control group (P >0.05),but the MOT in research group was decreased significantly(P < 0.05).There was no significant difference in Scr,Ccr and BUN between the control and research group after treatment (all P > 0.05).Conclusion Conventional treatment combined with cisapride can improve the effect of gastrointestinal symptoms in patients with chronic renal failure,while reducing serum motilin level.
ABSTRACT
Objective: To evaluate the anti-inflammatory property of both glycyrrhizic acid (GA) and glabridin in reducing inflammation to accelerate wound regeneration on 3T3-L1 and NIH-3T3 fibroblast cell lines. Methods: Cell proliferation and viability assay (MTT assay), scratch wound healing assays, and quantitative real-time PCR were conducted to investigate the effects on cell proliferation, cell migration, and expression of CXC chemokine ligand 5 inflammation gene respectively. Results: Results showed that at a low concentration of 1 × 10
ABSTRACT
<p><b>OBJECTIVE</b>To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles (MVs) from myocardial ischemic preconditioning (IPC) treated rats (IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion (I/R) injury in rats.</p><p><b>METHODS</b>Myocardial IPC was elicited by three.cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending (LAD) coronary artery. Platelet-free plasma (PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFR PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 µm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure (MAP), heart rate (HR) and ST-segment of electro-cardiogram (ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin (HE) staining. The activity of plasma lactate dehydrogenase (LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining.</p><p><b>RESULTS</b>Total IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs (LMVs) and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (<1 Vm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats (P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR (P<0.01), decreased ST-segment and LDH activity (P < 0.05, P < 0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment (P < 0.01).</p><p><b>CONCLUSION</b>The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.</p>
Subject(s)
Animals , Rats , Cell-Derived Microparticles , Metabolism , Coronary Vessels , Pathology , Flow Cytometry , Heart Rate , Ischemic Preconditioning, Myocardial , Myocardial Infarction , Myocardial Reperfusion Injury , Myocardium , Pathology , PhenotypeABSTRACT
PURPOSE: To analyze the correlation of polymorphisms of toll-like receptor 7 (TLR7) (rs179009) and toll-like receptor 9 (TLR9) (rs187084) in hepatitis C virus (HCV) infections in the Han population. MATERIALS AND METHODS: The genotypes of TLR7IVS2-151 in HCV infection were detected by Sanger sequencing using polymerase chain reaction-restriction fragment length polymorphism to determine the TLR9 T-1486C single nucleotide polymorphisms (SNP) for all enrolled patients. RESULTS: We found no significant difference between males with spontaneous clearance of HCV versus those chronically infected [chi2=2.71, p=0.10, odd ratios (OR)=0.58, 95% confidence interval (CI) 0.31-1.11]. However, significant differences were found for the distribution of TLR7 (rs179009) in females (chi2=9.46, p=0.01). In females, a significant difference was also found between chronic hepatitis C and those with spontaneous clearance of HCV in terms of TLR7 IVS2-151G/A allele frequencies (chi2=9.50, p=0.00, OR=0.46, 95% CI 0.28-0.75). In HCV-infected patients, no significant association was found between the frequency of TLR9 genotypes and alleles. CONCLUSION: The site of TLR7 IVS2-151 (rs179009) G/A may be a factor for susceptibility of chronic HCV in the female Han population. TLR9T-1486C (rs18084) SNP may not play a major role in HCV infection. However, individual risk profiles for HCV infection did vary by sex and this relationship should be further investigated.
Subject(s)
Female , Humans , Male , Alleles , China , Confidence Intervals , Gene Frequency , Genotype , Hepacivirus , Hepatitis C , Hepatitis C, Chronic , Hepatitis , Methods , Polymorphism, Single Nucleotide , Toll-Like Receptor 7 , Toll-Like Receptor 9 , Toll-Like ReceptorsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of microvesicles (MVs) derived from hypoxia/reoxygenation (H/R)-treated human umbilical vein endothelial cells (HUVECs) on endothelium-dependent relaxation of rat thoracic aortic rings.</p><p><b>METHODS</b>H/R injury model was established to induce HUVECs to release H/R-EMVs. H/R-EMVs from HUVECs were isolated by ultracentrifugation from the conditioned culture medium. H/R-EMVs were characterized using 1 μm latex beads and anti-PE-CD144 by flow cytometry. Thoracic aortic rings of rats were incubated with 2.5, 5, 10, 20 μg/ml H/R-EMVs derived from H/R-treated HUVECs for 4 hours, and their endothelium-dependent relaxation in response to acetylcholine (ACh) or endothelium-independent relaxation in response to sodium nitroprusside (SNP) was recorded in vitro. The nitric oxide (NO) production of ACh-treated thoracic aortic rings of rats was measured using Griess reagent. The expression of endothelial NO synthase (eNOS) and phosphorylated eNOS (p-eNOS, Ser-1177) in the thoracic aortic rings of rats was detected by Western blotting. Furthermore, the levels of SOD and MDA in H/R-EMVs-treated thoracic aortic rings of rats were measured using SOD and MDA kit.</p><p><b>RESULTS</b>H/R-EMVs were induced by H/R-treated HUVECs and isolated by ultracentrifugation. The membrane vesicles (< 1 μm) induced by H/R were CD144 positive. ACh-induced relaxation and NO production of rat thoracic aortic rings were impaired by H/R-EMVs treatment in a concentration-dependent manner (P < 0.05, P < 0.01). The expression of total eNOS (t-eNOS) was not affected by H/R-EMVs. However, the expression of p-eNOS decreased after treated with H/R-EMVs. The activity of SOD decreased and the level of MDA increased in H/R-EMVs treated rat thoracic aortic rings (P < 0.01).</p><p><b>CONCLUSION</b>ACh induced endothelium-dependent relaxation of thoracic aortic rings of rats was impaired by H/R-EMVs in a concentration-dependent manner. The mechanisms included a decrease in NO production, p-eNOS expression and an increase in oxidative stress.</p>
Subject(s)
Animals , Humans , Rats , Acetylcholine , Pharmacology , Aorta, Thoracic , Physiology , Cell Hypoxia , Endothelium, Vascular , Physiology , Human Umbilical Vein Endothelial Cells , Cell Biology , In Vitro Techniques , Nitric Oxide , Metabolism , Nitric Oxide Synthase Type III , Metabolism , Nitroprusside , Pharmacology , Oxidative StressABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect on pre-exposure prophylaxis (PrEP) to prevent HIV infection in high risk populations.</p><p><b>METHODS</b>A computerized literature searching had been carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wanfang, Tsinghua Tongfang database and related websites to collect relevant papers (from establishment to June 2012) with the key words of pre-exposure prophylaxis, HIV, AIDS, high risk populations, relative risk, reduction. All randomized controlled trials (RCT) papers about using single or compound antiretroviral drugs (ARVs) orally or topically before HIV exposure or during HIV exposure in high risk populations were enrolled. Meta-analysis was conducted using Stata 10.0 to calculate the pooled RR value (95%CI). Consistency test was performed and publication bias was evaluated.</p><p><b>RESULTS</b>Finally 5 RCT papers were enrolled, including 10 271 persons who were at high risk of HIV infection. The number of the experimental group was 5929, among which 116(1.96%) became infected. The number of the control group was 4342, among which 201(4.63%) became infected. Meta-analysis showed that the pooled relative risk (RR) and 95%CI was 0.49 (0.39 - 0.61), P < 0.05, indicating that the persons in experimental group had a 0.49 times lower risk of HIV infected, as compared with the control group. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 825.</p><p><b>CONCLUSION</b>PrEP was an effective and safe protection measure to reduce HIV infection in high risk populations.</p>
Subject(s)
Humans , Anti-HIV Agents , Therapeutic Uses , HIV Infections , Randomized Controlled Trials as Topic , RiskABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of adenosine A2A receptor knockout (A(2A)RKO) on relationship between continuous activation of phospho-c-Jun N-terminal kinase (P-JNK) and expression of nerve cell apoptosis in hippocampus CA1 domain of newborn mice after hypoxia/ischemia brain damage(HIBD) and its potential mechanism.</p><p><b>METHODS</b>A(2A)RKO mice and adenosine A2A receptor wildtype (A(2A)RWT) littermates (n = 80) were divided into Sham operation group (S) and model group (M), 1, 3 and 7 day after HIBD, totally 8 groups. HIBD was developed with 7 day-old neonatal mice according classical Rice-Vannucci method. It was tested the effect of A(2A)RKO on short-term neurofunctional outcomes consisted of three developmental reflexes (righting, geotaxis and cliff aversion), the changes of brain pathology with hematoxylin-eosin (HE) staining and Nissl staining, the expressions of nerve cell apoptosis with terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling(TUNEL) staining and P-JNK were observed by immunohistochemistry.</p><p><b>RESULTS</b>The neurological behavior injuries and brain histopathological damages and nerve apoptosis cells were aggravated in A(2A)RKO newborn mice after HIBD. The positive expressions of P-JNK were significantly higher in the ischemic hippocampus CA1 domain after HIBD than ones in group S respectively (P < 0.01), reaching to peak at 1 day and then began gradually decreasing. P-JNK expression in model knockout(MKO) at 1, 3 and 7 day increased greatly compared to those in the previous time point of corresponding model wildtype (MWT) (P < 0.01, P < 0.05, P > 0.05); there was a positive correlation between the expressions of P-JNK and nerve cell apoptosis after HIBD in newborn mice(r = 0.837, P < 0.01).</p><p><b>CONCLUSION</b>Early continuous activation of P-JNK might be involved in the aggravated nerve apoptosis cells and brain damage induced by A(2A) RKO newborn mice after HIBD.</p>
Subject(s)
Animals , Mice , Animals, Newborn , Apoptosis , Hypoxia-Ischemia, Brain , Metabolism , Pathology , JNK Mitogen-Activated Protein Kinases , Metabolism , Mice, Knockout , Neurons , Metabolism , Pathology , Receptor, Adenosine A2A , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of promoting male circumcision among the general population in the high HIV prevalence areas of Guangxi Province.</p><p><b>METHODS</b>We interviewed 590 male residents from Hezhou and Qinzhou areas of Guangxi Province and conducted intervention using male circumcision promotion materials and various methods. If the subjects were willing and had no contraindication, they were referred to the appointed hospitals to receive circumcision. We conducted follow-up visits at 6 and 9 months after intervention for the changes in the subjects' knowledge, attitude and practice related to male circumcision.</p><p><b>RESULTS</b>The male circumcision knowledge, willingness and operation rate were significantly improved after intervention (P < 0.05), but with no significant difference between the two follow-up visits (P > 0.05). The number of those who knew that phimosis and redundant prepuce were the reasons for circumcision increased from 66.1% at baseline to 81.9% and 79.8% at the two follow-up visits; those who knew that circumcision could prevent AIDS and sexually transmitted diseases increased from 28.0% to 77.4% and 78.6%; those who knew that surgical complications could be pain, bleeding and infection increased from 29.5%, 19.3% and 39.3% to 72.5%, 58.2% and 59.4% at the first follow-up and 75.0%, 57.0% and 63.0% at the second; those who were willing to receive circumcision increased from 35.3% at baseline to 59.6% and 61.3% at the two follow-up visits; and the rate of surgery increased from zero to 12.7% and 16.1%.</p><p><b>CONCLUSION</b>The promotion of male circumcision among the general population in the high HIV prevalence areas of Guangxi Province significantly improved their knowledge, attitude and practice related to AIDS prevention. And the promotion activities should focus on the publicity of AIDS knowledge, risks of phimosis and redundant prepuce, and safety of circumcision.</p>