The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect.

The pathological mechanism of SARS-CoV infection was investigated. The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II. Further study revealed that the activity of the NADH-cytochrome was altered and the inner mitochondrial membrane was depolarized in the transfected human embryo lung fibroblast by the nsp10 protein gene. The cytopathic effect of the Coronavirus 229E strain appeared more extensive in these cells than in the control cells.     

Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways

We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS-associated coronavirus (SARS-CoV). In the present study, we used a murine monoclonal antibody specific for SARS-CoV nucleoprotein, and probes specific for a SARS-CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS-CoV systematically in tissues from patients who died of SARS. SARS-CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS-CoV may also be targets of SARS-CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS-CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS-CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS-CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS.     

Effects of a Short-Term “Fat Adaptation with Carbohydrate Restoration” Diet on Metabolic Responses and Exercise Performance in Well-Trained Runners

Periodized carbohydrate availability can enhance exercise capacity, but the effects of short-term fat adaptation carbohydrate restoration (FACR) diets on metabolic responses and exercise performance in endurance athletes have not been conclusively determined. This study aimed to investigate the effect of a FACR diet on measures of resting metabolism, exercise metabolism, and exercise performance. Well-trained male runners (n = 8) completed a FACR dietary intervention (five days’ carbohydrate < 20% and fat > 60% energy, plus one-day carbohydrate ≥ 70% energy), and a control high-carbohydrate (HCHO) diet for six days (carbohydrate > 60% energy; fat < 20% energy) in a randomized crossover design. Pre- and post-intervention metabolic measures included resting metabolic rate (RMR), respiratory quotient (RQ), maximum fat oxidation rate during exercise (MFO), and maximum fat oxidation intensity (FATmax). Measures of exercise performance included maximal oxygen uptake (VO₂max), running economy (RE), and 5 km running time trial (5 km-TT). In FACR compared with HCHO, there were significant improvements in FATmax (p = 0.006) and RE (p = 0.048). There were no significant differences (p > 0.05) between FACR and HCHO in RMR, RQ, VO₂max, or 5 km-TT. Findings suggest that a short-term (six days) FACR diet may facilitate increased fat oxidation and submaximal exercise economy but does not improve 5 km-TT performance.     

Deregulated microRNA-22-3p in patients with sepsis-induced acute kidney injury serves as a new biomarker to predict disease occurrence and 28-day survival outcomes

Background

Acute kidney injury (AKI) is a common and serious complication of sepsis. MicroRNA-22-3p (miR-22-3p) has been found to be involved in septic AKI progression. The purpose of this study was to analyze both the serum and urinary expression of miR-22-3p in septic AKI patients, and evaluated the clinical value of miR-22-3p in the diagnosis and prognosis of sepsis-induced AKI.

Methods

Serum and urinary expression of miR-22-3p was examined using qRT-PCR. The risk factors related with septic AKI onset were assessed using logistic analysis. A receiver-operating characteristic (ROC) curve was constructed to evaluate the diagnostic performance of miR-22-3p, and the Kaplan–Meier survival curves and Cox regression analysis were used to evaluate the predictive value of miR-22-3p for the 28-day survival of septic AKI patients.

Results

Both serum and urinary miR-22-3p expression was decreased and negatively correlated with kidney injury biomarkers in septic AKI patients. MiR-22-3p expression was a risk factor for AKI onset and had diagnostic accuracy in septic AKI patients. The expression of both serum and urinary miR-22-3p was lower in patients who died, and served as a prognostic biomarker to predict 28-day survival in septic AKI patients.

Conclusion

Serum and urinary miR-22-3p was reduced in sepsis-induced AKI patients, and served as a biomarker to predict AKI occurrence and 28-day survival in sepsis patients.

     

Application of network pharmacology and molecular docking to elucidate the potential mechanism of Astragalus–Scorpion against prostate cancer

The present study aimed to investigate the molecular mechanism of the Astragalus–Scorpion drug pair in the treatment of prostate cancer (PCa). We employed network pharmacology and molecular docking technology to retrieving the active ingredients and corresponding targets of Astragalus–Scorpion by using TCMSP, BATMAN-TCM, TCMID and Swiss Target Prediction Databases. The targets related to PCa were retrieved through GeneCards. Cytoscape software was used to construct the ‘active ingredient–target disease’ network, and GO and KEGG enrichment analyses were performed on the common targets. Autodock software was used for molecular docking verification. In total, 26 active ingredients, 340 potential targets related to active ingredients and 122 common targets were screened from Astragalus–Scorpion drug pair. The core targets of the protein–protein interaction (PPI) network were JUN, AKT1, IL6, MAPK1 and RELA, whereas the core active ingredients were quercetin, kaempferol, formononetin, 7-o-methylisomucronulatol and calycosin. Nearly 762 GO entries and 154 pathways were obtained by using the pathway enrichment analysis. Molecular docking results revealed that quercetin and kaempferol bind to AKT1 and formononetin binds to RELA, all of which were found to be stable bounds.     

Outcomes and complications of naftopidil versus tamsulosin for elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia: A systematic review and meta-analysis

We conducted a systematic review and meta-analysis to assess the outcomes and complications of naftopidil in treating elderly men with lower urinary tract symptoms secondary to benign prostatic hyperplasia and compared them with those administered with tamsulosin. A literature review was performed to identify the available randomised controlled trials concerning the comparison between naftopidil and tamsulosin for men with LUTS/BPH. We searched the following databases: the Cochrane Library Database, PubMed, Embase and Web of Science. Eleven publications involving 1,114 men (557 in the naf group and 557 in the tam group) were pooled in our analysis. We found no significant differences in the total IPSS, IPSS storage score, IPSS voiding score, quality of life index, peak urinary flow rate, average flow rate and post-void residual volumes. We assessed cardiovascular and sexual adverse events, acute urinary retention, surgical intervention, withdrawals due to any reason and withdrawals due to adverse events. The incidence of adverse events was similar among patients in naf and tam groups. In conclusion, naftopidil shared comparable efficacy and similar incidence of adverse events with tamsulosin and appears to be a promising agent for and alternative to tam. However, more prospective trials with high quality and long-term treatment duration are needed to verify this observation.     

受体－A蛋白融合蛋白制备抗P物质受体血清及其特性

受体－Ａ蛋白融合蛋白制备抗Ｐ物质受体血清及其特性ＷａｌｔｅｒＫ．Ｋ．Ｈｏ（何国强）；ＡｌｅｘｉｓＰ．Ｋ．Ｃｈｅ，郑德枢（香港中文大学；香港生物化学系，香港沙田；广州医学院神经科学研究所，广州５１０１８２）本文报告了用直肠杆菌表达Ｐ物质受体－Ａ蛋白融合...     

VEGF,bFGF及PCNA在宫颈癌中的表达及其与肿瘤增殖和血管生成的关系

目的 :探讨有关细胞因子在调控宫颈癌增殖及其血管生成中的作用。方法 :应用免疫组织化学及其组织形态学定量分析方法 ,对血管内皮细胞生长因子 (VEGF) ,碱性成纤维细胞生长因子(b FGF)和增殖细胞核抗原 (PCNA)在宫颈癌中的表达进行研究。结果 :1肿瘤细胞增殖与 VEGF的表达呈正向关系 ,而与 b FGF的表达无关 ;2 VEGF,b FGF的表达分别与微血管密度有正相关性 ,而当 VEGF和 b FGF共同表达时 ,微血管密度显著增加 ;3VEGF,b FGF在不同个体的表达具有异质性。结论 :VEGF有促进肿瘤细胞增殖及血管生成的作用。VEGF,b FGF在肿瘤血管生成过程中可能起协同作用     

58例双瓣替换术体外循环管理体会

目的：回顾５８例双瓣替换术体外循环管理状况,总结双瓣替换术中灌注技术。方法：对５８例风湿性心脏瓣膜病人施行二尖瓣、主动脉瓣替换术中体外循环手术的临床资料、心肺转汉方法和心肌保护中的难点及处理进行回顾总结分析。结果：５８例中早期死亡２例,死亡率３．４５％Ｒ。结论：只有良好的体外循环灌注技术和心肌保护,才能保证双瓣替换术病人顺利渡过围术期,降低手术死亡率。