葶苈大枣泻肺汤加减对慢性心力衰竭患者尿液白蛋白/肌酐比值及炎症因子的影响

目的：探索葶苈大枣汤对慢性心力衰竭患者微量尿白蛋白及血浆炎症因子IL-6,C反应蛋白的影响。方法：70例诊断为慢性心力衰竭的患者（心功能Ⅱ~Ⅳ级）按心功能分级并随机分为中药＋心衰基础治疗组（治疗组）和心衰基础治疗对照组（对照组）,每组35例;在进行积极控制感染,改善心功能的基础上,对照组患者给予心衰的基础治疗（利尿剂＋β受体阻断剂＋ARB或ACEI）;治疗组在心衰基础治疗的基础上给予葶苈大枣汤加减进行治疗,每2周随访1次,观察周期为3月。治疗前后观察患者的心功能变化,尿微量白蛋白的变化,炎症因子IL-6,CRP的变化。结果：基线资料比较,两组患者无显著性差异;经3月的治疗后,治疗组患者心功能改善情况要好于对照组患者,P〈0.05;与对照组比较,葶苈大枣汤加减可显著降低慢性心力衰竭患者血浆IL-6,CRP水平,降低尿微量白蛋白水平,P均〈0.05,且与对照组比较,不良反应事件未见显著增加,P〉0.05。结论：对于慢性心力衰竭患者,在心衰基础治疗的基础上结合葶苈大枣汤加减治疗可显著提高对慢性心力衰竭患者的临床疗效,且安全性良好,值得临床推广。     

Newly discovered insect RNA viruses in China

Insects are a group of arthropods and the largest group of animals on Earth,with over one million species described to date.Like other life forms,insects suffer from viruses that cause disease and death.Viruses that are pathogenic to beneficial insects cause dramatic economic losses on agriculture.In contrast,viruses that are pathogenic to insect pests can be exploited as attractive biological control agents.All of these factors have led to an explosion in the amount of research into insect viruses in recent years,generating impressive quantities of information on the molecular and cellular biology of these viruses.Due to the wide variety of insect viruses,a better understanding of these viruses will expand our overall knowledge of their virology.Here,we review studies of several newly discovered RNA insect viruses in China.     

δ-Opioid Receptor Activation Modified MicroRNA Expression in the Rat Kidney under Prolonged Hypoxia

Hypoxic/ischemic injury to kidney is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs are differentially involved in hypoxic/ischemic events and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering the microRNA (miRNA) expression in kidney under hypoxic condition. We selected 31 miRNAs based on microarray data for quantitative PCR analysis. Among them, 14 miRNAs were significantly altered after prolonged hypoxia, DOR activation or a combination of both. We found that 1) DOR activation alters miRNA expression profiles in normoxic conditions; 2) hypoxia differentially alters miRNA expression depending on the duration of hypoxia; and 3) DOR activation can modify hypoxia-induced changes in miRNA expression. For example, 10-day hypoxia reduced the level of miR-212 by over 70%, while DOR activation could mimic such reduction even in normoxic kidney. In contrast, the same stress increased miR-29a by >100%, which was reversed following DOR activation. These first data suggest that hypoxia comprehensively modifies the miRNA profile within the kidney, which can be mimicked or modified by DOR activation. Ascertaining the targeted pathways that regulate the diverse cellular and molecular functions of miRNA may provide new insights into potential therapies for hypoxic/ischemic injury of the kidney.     

Pulmonary Tuberculosis Incidence and Risk Factors in Rural Areas of China: A Cohort Study

The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies.     

The NHV Rehabilitation Services Program Improves Long-Term Physical Functioning in Survivors of the 2008 Sichuan Earthquake: A Longitudinal Quasi Experiment

Background

Long-term disability following natural disasters significantly burdens survivors and the impacted society. Nevertheless, medical rehabilitation programming has been historically neglected in disaster relief planning. ‘NHV’ is a rehabilitation services program comprised of non–governmental organizations (NGOs) (N), local health departments (H), and professional rehabilitation volunteers (V) which aims to improve long-term physical functioning in survivors of the 2008 Sichuan earthquake. We aimed to evaluate the effectiveness of the NHV program.

Methods/Findings

510 of 591 enrolled earthquake survivors participated in this longitudinal quasi-experimental study (86.3%). The early intervention group (NHV–E) consisted of 298 survivors who received institutional-based rehabilitation (IBR) followed by community-based rehabilitation (CBR); the late intervention group (NHV–L) was comprised of 101 survivors who began rehabilitation one year later. The control group of 111 earthquake survivors did not receive IBR/CBR. Physical functioning was assessed using the Barthel Index (BI). Data were analyzed with a mixed-effects Tobit regression model. Physical functioning was significantly increased in the NHV–E and NHV–L groups at follow-up but not in the control group after adjustment for gender, age, type of injury, and time to measurement. We found significant effects of both NHV (11.14, 95% CI 9.0–13.3) and sponaneaous recovery (5.03; 95% CI 1.73–8.34). The effect of NHV-E (11.3, 95% CI 9.0–13.7) was marginally greater than that of NHV-L (10.7, 95% CI 7.9–13.6). It could, however, not be determined whether specific IBR or CBR program components were effective since individual component exposures were not evaluated.

Conclusion

Our analysis shows that the NHV improved the long-term physical functioning of Sichuan earthquake survivors with disabling injuries. The comprehensive rehabilitation program benefitted the individual and society, rehabilitation services in China, and international rehabilitation disaster relief planning. Similar IBR/CBR programs should therefore be considered for future large-scale rehabilitation disaster relief efforts.     

Occurrence of Regulated and Emerging Iodinated DBPs in the Shanghai Drinking Water

Drinking water chlorination plays a pivotal role in preventing pathogen contamination against water-borne disease. However, chemical disinfection leads to the formation of halogenated disinfection by products (DBPs). Many DBPs are highly toxic and are of health concern. In this study, we conducted a comprehensive measurements of DBPs, including iodoacetic acid (IAA), iodoform (IF), nine haloacetic acids and four trihalomethanes in drinking waters from 13 water plants in Shanghai, China. The results suggested that IAA and IF were found in all the water treatment plants, with maximum levels of 1.66 µg/L and 1.25 µg/L for IAA and IF, respectively. Owing to deterioration of water quality, the Huangpu River has higher IAA and IF than the Yangtze River. Our results also demonstrated that low pH, high natural organic matter, ammonia nitrogen, and iodide in source waters increased IAA and IF formation. Compared to chlorine, chloramines resulted in higher concentration of iodinated DBP, but reduced the levels of trihalomethanes. This is the first study to reveal the widespread occurrence of IAA and IF in drinking water in China. The data provide a better understanding on the formation of iodinated disinfection byproducts and the findings should be useful for treatment process improvement and disinfection byproducts controls.     

δ-Opioid Receptor Activation Rescues the Functional TrkB Receptor and Protects the Brain from Ischemia-Reperfusion Injury in the Rat

Objectives

δ-opioid receptor (DOR) activation reduced brain ischemic infarction and attenuated neurological deficits, while DOR inhibition aggravated the ischemic damage. The underlying mechanisms are, however, not well understood yet. In this work, we asked if DOR activation protects the brain against ischemic injury through a brain-derived neurotrophic factor (BDNF) -TrkB pathway.

Methods

We exposed adult male Sprague-Dawley rats to focal cerebral ischemia, which was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (60 nmol), antagonist Naltrindole (100 nmol) or artificial cerebral spinal fluid was injected into the lateral cerebroventricle 30 min before MCAO. Besides the detection of ischemic injury, the expression of BDNF, full-length and truncated TrkB, total CREB, p-CREB, p-ATF and CD11b was detected by Western blot and fluorescence immunostaining.

Results

DOR activation with TAN-67 significantly reduced the ischemic volume and largely reversed the decrease in full-length TrkB protein expression in the ischemic cortex and striatum without any appreciable change in cerebral blood flow, while the DOR antagonist Naltrindole aggregated the ischemic injury. However, the level of BDNF remained unchanged in the cortex, striatum and hippocampus at 24 hours after MCAO and did not change in response to DOR activation or inhibition. MCAO decreased both total CREB and pCREB in the striatum, but not in the cortex, while DOR inhibition promoted a further decrease in total and phosphorylated CREB in the striatum and decreased pATF-1 expression in the cortex. In addition, MCAO increased C11b expression in the cortex, striatum and hippocampus, and DOR activation specifically attenuated the ischemic increase in the cortex but not in the striatum and hippocampus.

Conclusions

DOR activation rescues TrkB signaling by reversing ischemia/reperfusion induced decrease in the full-length TrkB receptor and reduces brain injury in ischemia/reperfusion     

Synergistic Effects of GhSOD1 and GhCAT1 Overexpression in Cotton Chloroplasts on Enhancing Tolerance to Methyl Viologen and Salt Stresses

In plants, CuZn superoxide dismutase (CuZnSOD, EC l.15.1.1), ascorbate peroxidase (APX, EC 1.11.1.11), and catalase (CAT, EC l.11.1.6) are important scavengers of reactive oxygen species (ROS) to protect the cell from damage. In the present study, we isolated three homologous genes (GhSOD1, GhAPX1, and GhCAT1) from Gossypium hirsutum. Overexpressing cassettes containing chimeric GhSOD1, GhAPX1, or GhCAT1 were introduced into cotton plants by Agrobacterium transformation, and overexpressed products of these genes were transported into the chloroplasts by transit peptide, as expected. The five types of transgenic cotton plants that overexpressed GhSOD1, GhAPX1, GhCAT1, GhSOD1 and GhAPX1 stack (SAT), and GhSOD1 and GhCAT1 stack (SCT) were developed. Analyses in the greenhouse showed that the transgenic plants had higher tolerance to methyl viologen (MV) and salinity than WT plants. Interestingly, SCT plants suffered no damage under stress conditions. Based on analyses of enzyme activities, electrolyte leakage, chlorophyll content, photochemical yield (Fv/Fm), and biomass accumulation under stresses, the SCT plants that simultaneously overexpressed GhSOD1 and GhCAT1 appeared to benefit from synergistic effects of two genes and exhibited the highest tolerance to MV and salt stress among the transgenic lines, while the SAT plants simultaneously overexpressing GhSOD1 and GhAPX1 did not. In addition, transgenic plants overexpressing antioxidant enzymes in their chloroplasts had higher tolerance to salt stress than those expressing the genes in their cytoplasms, although overall enzyme activities were almost the same. Therefore, the synergistic effects of GhSOD1 and GhCAT1 in chloroplasts provide a new strategy for enhancing stress tolerance to avoid yield loss.     

Promoter Hypermethylation of ARID1A Gene Is Responsible for Its Low mRNA Expression in Many Invasive Breast Cancers

ARID1A (AT-rich interactive domain 1A) has recently been identified as a tumor suppressor gene. Its mRNA expression is significantly low in many breast cancers; this is often associated with more aggressive phenotypes. However, the underlying molecular mechanism for its low expression has not been fully understood. This study was undertaken to evaluate the contribution of gene copy number variation, mutations, promoter methylation and histone modification to ARID1A’s low expression. 38 pairs of breast invasive ductal carcinomas and their normal breast tissue counterparts from the same patients were randomly selected for gene expression and copy number variation detection. Promoter methylation and histone modification levels were evaluated by MeDIP-qPCR and ChIP-qPCR, respectively. PCR product Sanger sequencing was carried out to detect the exon mutation rate. Twenty-two out of 38 invasive ductal carcinomas in the study (57.9%) revealed ARID1A mRNA low expression by realtime RT-PCR. The relative promoter methylation level was, significantly higher in ARID1A mRNA low expression group compared with its high expression group (p<0.001). In the low expression group, nineteen out of 22 invasive ductal carcinomas (86.4%) exhibited ARID1A promoter hypermthylation. In addition, the promoter hypermethylation was accompanied with repressive histone modification (H3K27Me3). Although five out of 38 invasive ductal carcinomas (13.2%) exhibited loss of ARID1A gene copy number by realtime PCR and nine exon novel mutations are seen from eight out of 33 invasive ductal carcinomas (24.2%), there was no statistically significant difference in both ARID1A mRNA low and high expression groups (p = 0.25,and p = 0.68, respectively). We demonstrate that promoter hypermethylation was the main culprit for ARID1A mRNA low expression in invasive ductal carcinomas. The influence of mutation and copy number variation on the expression were statistically insignificant at mRNA level, and were, therefore, not considered the main causes for ARID1A mRNA low expression in invasive breast cancer.