模拟失重大鼠胸主动脉收缩功能的变化可能与Rho激酶改变有关

目的:观察模拟失重大鼠胸主动脉收缩功能的变化及Rho相关的蛋白激酶（Rho-associated protein kinase,ROCK）表达的改变,并探讨二者之间的关系。方法: 以尾部悬吊4周建立模拟失重大鼠模型并观察模拟失重对胸主动脉的主要生理的影响。采用离体血管环功能实验检测大鼠胸主动脉的收缩反应性变化;通过蛋白印迹技术检测大鼠胸主动脉ROCK II蛋白的表达。结果: 与对照组相比,悬吊组氯化钾、苯肾上腺素诱导的大鼠胸主动脉收缩功能均明显增强（P<0.05）。用ROCK特异性抑制剂Y-27632孵育1 h后,两组胸主动脉的收缩反应均显著降低至同一水平,两组间无统计学差异。蛋白印迹结果显示,悬吊组ROCK II的表达增加。结论: ROCK表达的改变可能在模拟失重大鼠胸主动脉收缩功能增强中发挥重要作用,去除ROCK的作用可消除模拟失重大鼠与正常大鼠胸主动脉收缩功能的差异。     

Age-related changes in mouse taste bud morphology, hormone expression, and taste responsivity

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact.     

Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population

Aim: Our aim was to provide a quantitative analysis of the changes in the principal determinants of insulin sensitivity and secretion in relation to fasting plasma glucose (FPG) or 2‐h plasma glucose (2h PG) in a Chinese population with a wide range of glucose tolerance. Methods: A total of 5728 adults spanning the entire range of glucose tolerance were included. Insulin sensitivity was measured by Matsuda insulin sensitivity index (ISI_M) and homeostasis model assessment of 1/homeostasis model assessment of insulin resistance (HOMA‐IR). β‐Cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at early‐phase DI₃₀ and total DI₁₂₀. The exponential curve was established as the best fit for the relationship between insulin sensitivity or β‐cell function and FPG or 2h PG. Results: Relative to the trend classified as increasing 2h PG, hepatic insulin sensitivity and insulin secretion showed a decreasing trend to a substantial degree as FPG increased. A 1 mmol/l increase in FPG and 2h PG concentration was associated with a ?22 and ?21% decline in ISI_M, ?16 and ?4% in 1/HOMA‐IR, ?38 and ?35% in DI₃₀ and ?36 and ?26% in DI₁₂₀. The decay constant of ISI_M and DI₃₀ in IFG or ISI_M, 1/HOMA‐IR, DI₃₀ and DI₁₂₀ in IGT was lower than that in normal glucose tolerance. Significant interactions between sex and glucose levels determining DI were found. Conclusions: We conclude that impairment of insulin sensitivity and insulin secretion contributes to both FPG or 2h PG hyperglycaemia in a Chinese population, but that the decline in insulin secretion is more pronounced with increasing fasting than 2h PG.     

Prevalence of syphilis infection in different tiers of female sex workers in China: implications for surveillance and interventions

Background

Streptococcus pneumoniae is a leading cause of invasive infection in young children causing morbidity and mortality. Active surveillance systems of invasive pneumococcal disease (IPD) are recommended worldwide. The aim of this study was to estimate the current incidence of IPD and to describe the serotype distribution and the antimocrobial susceptibility of S. pneumoniae isolates in children aged less than 5?years residing in North-West Lombardy, Italy.

Methods

A twelve-month prospective active surveillance system recruited all children aged less than 5?years admitted for suspicion of IPD at emergency room of ten hospitals located in the monitored area. Blood samples were taken in all participants for confirmation of IPD based on isolation of S. pneumoniae from blood. Pneumococcal meningitis and sepsis were additionally confirmed by cerebrospinal fluid analysis. Serotyping and antimicrobial susceptibility testing were performed on isolates from blood.

Results

A total of 15 confirmed cases of IPD were detected among 135 recruited children, including pneumonia (n?=?8), bacteremia (n?=?4), sepsis (n?=?2) and meningitis (n?=?1). The annual IPD incidence rate was 50.0/100,000 (95%CI, 30.5-82.5/100,000). Incidence was 58.3/100,000 (28.8-120.1/100,000) among children aged less than 2?years and 44.4/100,000 (22.9-87.5/100,000) among children aged 2?C4?years. Thirteen isolates were typified. The most common serotype was 19A (23.1%) that together with serotypes 1, 7F and 19F accounted for 69.2% of typified isolates. Serotypes 14, 23F, 12B and 15C were also identified. The 7- and 13-valent pneumococcal conjugate vaccines covered respectively 30.8% and 84.6% of typified IPD cases. One isolate (serotype 15C) was penicillin-resistant and caused meningitis.

Conclusions

The inclusion of the 13-valent pneumococcal conjugate vaccine in immunization programs of young children might be considered to reduce incidence and morbidity of invasive pneumococcal disease in this surveilled population.     

Leber's Hereditary Optic Neuropathy Arising From the Synergy Between ND1 3635G>A Mutation and Mitochondrial YARS2 Mutations

PurposeTo investigate the mechanism underlying the synergic interaction between Leber''s hereditary optic neuropathy (LHON)-associated ND1 and mitochondrial tyrosyl-tRNA synthetase (YARS2) mutations.MethodsMolecular dynamics simulation and differential scanning fluorimetry were used to evaluate the structure and stability of proteins. The impact of ND1 3635G>A and YARS2 p.G191V mutations on the oxidative phosphorylation machinery was evaluated using blue native gel electrophoresis and enzymatic activities assays. Assessment of reactive oxygen species (ROS) production in cell lines was performed by flow cytometry with MitoSOX Red reagent. Analysis of effect of mutations on autophagy was undertaken via flow cytometry for autophagic flux.ResultsMembers of one Chinese family bearing both the YARS2 p.191Gly>Val and m.3635G>A mutations exhibited much higher penetrance of optic neuropathy than those pedigrees carrying only the m.3635G>A mutation. The m.3635G>A (p.Ser110Asn) mutation altered the ND1 structure and function, whereas the p.191Gly>Val mutation affected the stability of YARS2. Lymphoblastoid cell lines harboring both m.3635G>A and p.191Gly>Val mutations revealed more reductions in the levels of mitochondrion-encoding ND1 and CO2 than cells bearing only the m.3635G>A mutation. Strikingly, both m.3635G>A and p.191Gly>Val mutations exhibited decreases in the nucleus-encoding subunits of complex I and IV. These deficiencies manifested greater defects in the stability and activities of complex I and complex IV and overproduction of ROS and promoted greater autophagy in cell lines harboring both m.3635G>A and p.191Gly>Val mutations compared with cells bearing only the m.3635G>A mutation.ConclusionsOur findings provide new insights into the pathophysiology of LHON arising from the synergy between ND1 3635G>A mutation and mitochondrial YARS2 mutations.     

High Rates of Viral Suppression After Long-term Entecavir Treatment of Asian Patients With Hepatitis B e Antigen-Positive Chronic Hepatitis B

There are limited data on the effects of long-term entecavir therapy in Asian patients with chronic hepatitis B (CHB). We performed a post hoc analysis of 94 Asian hepatitis B e antigen-positive (HBeAg+), nucleos(t)ide analogue-naive patients who received 5 years of therapy with entecavir (up to 2 years in study ETV-022 and the remainder in study ETV-901). Among patients completing week 240, 95% (63 of 66) had levels of hepatitis B virus DNA <300 copies/mL, and 76% (50 of 66) had normalized levels of alanine aminotransferase. In addition to patients who achieved a serologic response during ETV-022, a further 40% (26 of 65) achieved HBeAg loss, and 18% (12 of 65) underwent HBeAg seroconversion through year 5 of entecavir therapy. No resistance to entecavir was detected, and the safety profile was consistent with previous reports. The long-term efficacy and safety of entecavir are therefore comparable between Asians and the overall population of HBeAg+ patients with CHB.     

干性年龄相关性黄斑变性免疫学机制的研究进展

干性年龄相关性黄斑变性(ARMD)是一种发病机制尚不完全明确的退行性眼底病变,可造成中心视力不可逆的损失,以黄斑部色素紊乱、玻璃膜疣生成及地图样萎缩为主要眼底表现。免疫与炎性反应在本病的发展过程中起到关键作用,免疫分子中的补体系统、模式识别受体、炎症小体及多种细胞因子等均与干性ARMD的发生密切相关。现将这些免疫分子与干性ARMD的最新研究进展做一综述。