A genetic adaptive pattern＊low hemoglobin concentration in the himalayan highlanders

Mean hemoglobin （Hb） concentration of about 3 500 subjects derived from 17 studies of Himalayan highlanders （Tibetans, Sherpas, and Ladakhis） was compared with lowlanders （Chinese Han, Indian Tamils） lived in the Himalayas, and European climbers during Everest expeditions as well as Andean natives. The results found that Hb concentration in Himalayan highlanders was systemically lower than those reported for Andean natives and lowland immigrants. These comparative data demonstrated that a healthy native population may successfully reside at high altitude without a significant elevation in Hb, and the lower Hb levels of Himalayan highlanders than those of migrated lowlanders and Andean natives are an example of favourable adaptation over the generations. In addition, excessive polycythemia has frequently been used as a marker of chronic mountain sickness （CMS）. Altitude populations who have a higher Hb concentration also have a higher incidence of CMS. The low Hb in Himalayans suggested as showing adaptation over many generations in Tibetan stock. Recent work in Tibet, suggested that Tibetans there may have adapted to high altitude as a result of evolutionary pressure selecting for genes which give an advantage at altitude. All of the population genomic and statistical analysis indicated that EPAS1 and EGLN1 are mostly likely responsible for high altitude adaptation and closely related to low Hb concentration in Tibetans. These data supported the hypothesis that Himalayan highlanders have evolved a genetically different erythropoietic response to chronic hypoxia by virtue of their much longer exposure to high altitude.     

注射小针刀联合奥施康定治疗癌性疼痛的临床疗效研究

目的:观察注射小针刀联合奥施康定治疗癌性疼痛的临床疗效。方法:选择我院收治的66例癌性疼痛患者,根据随机方法将入选病例分为注射针刀组(针刀配合奥施康定)、奥施康定组(单纯西药奥施康定),每组各33例。针刀组每日给予口服药物、隔日给予针刀治疗;奥施康定组每日给予口服药物,14日为1个观察周期。治疗前后测定疼痛程度(NRS)并分析疼痛缓解度(PAR)。结果:治疗组临床总有效率为90.9%,对照组为84.9%,两组比较差异无统计学意义(P0.05)。治疗后,两组NRS评分均较治疗前显著降低(P0.05),且治疗组比对照组改善更为显著(P0.01)。结论:注射小针刀联合奥施康定对癌性疼痛的治疗疗效较单用奥施康定更好。     

小儿慢性胃炎的消化道外表现(附864 例报道)

目的:分析和总结小儿慢性胃炎的消化道外表现。方法:选择2008年1月~2008年10月哈尔滨医科大学附属第二医院儿科门诊诊治的经腹部胃区叩诊法确诊为慢性胃炎的患儿864例,建立随访卡片,分析和总结其消化道内及消化道外的临床表现。结果:864例患儿常见的消化道症状依次为腹痛、恶心呕吐、便秘、上腹压痛。消化道外表现依次为头痛、刀枪刺、鼻出血、胸痛、多动抽动、手足搐搦。消化道外表现的发病率并不低于消化道表现,特别是头痛的发病率高达58.54%。腹痛、恶心呕吐症状缓解得最快,其次是头痛、头晕、胸闷、胸痛,多动症状较晚缓解,腹部叩痛的消失时间最晚。结论:小儿慢性胃炎的胃肠道外表现广泛存在,且极易与脑炎、心肌炎误诊,值得关注。头痛、胸痛的产生原因可能与内脏-内脏之间的牵涉痛有关。     

Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL

In 10–20% of the cases of chronic lymphocytic leukemia of B-cell phenotype (B-CLL), the IGHV1-69 germline is utilized as VH gene of the B cell receptor (BCR). Mouse G6 (MuG6) is an anti-idiotypic monoclonal antibody discovered in a screen against rheumatoid factors (RFs) that binds with high affinity to an idiotope expressed on the 51p1 alleles of IGHV1-69 germline gene encoded antibodies (G6-id⁺). The finding that unmutated IGHV1-69 encoded BCRs are frequently expressed on B-CLL cells provides an opportunity for anti-idiotype monoclonal antibody immunotherapy. In this study, we first showed that MuG6 can deplete B cells encoding IGHV1-69 BCRs using a novel humanized GTL mouse model. Next, we humanized MuG6 and demonstrated that the humanized antibodies (HuG6s), especially HuG6.3, displayed ～2-fold higher binding affinity for G6-id⁺ antibody compared to the parental MuG6. Additional studies showed that HuG6.3 was able to kill G6-id⁺ BCR expressing cells and patient B-CLL cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Finally, both MuG6 and HuG6.3 mediate in vivo depletion of B-CLL cells in NSG mice. These data suggest that HuG6.3 may provide a new precision medicine to selectively kill IGHV1-69-encoding G6-id⁺ B-CLL cells.     

Intra-host mathematical model of chronic wasting disease dynamics in deer (Odocoileus)

Bioassays of native cervid hosts have established the presence of infectious chronic wasting disease (CWD) prions in saliva, blood, urine, and feces of clinically diseased and pre-clinical infected deer. The intra-host trafficking of prions from the time of initial infection to shedding has been less well defined. We created a discrete-time compartmentalized model to simulate the misfolding catalysis, trafficking, and shedding of infectious prions throughout the organ systems of CWD-infected cervids. Using parameter values derived from experimental infections of North American deer (Odocoileus spp.), the exponential-based model predicts prion deposition over time with: 1) nervous tissues containing the highest deposition of prions at 20 months post-infection and 2) excreted fluids containing low levels of prions throughout infection with the highest numbers of prions predicted to be shed in saliva and feces (as high as 10 lethal doses (1.34 × 10²⁹ prions) in 11–15 months). These findings are comparable to prion deposition described in literature as assayed by conventional and ultrasensitive amplification assays. The comparison of our model to published data suggests that highly sensitive assays (sPMCA, RT-QuIC, and bioassay) are appropriate for early prion detection in bodily fluids and secretions. The model provides a view of intra-host prion catalysis leading to pre-clinical shedding and provides a framework for continued development of antemortem diagnostic methods.     

Cross-species transmission of CWD prions

Prions cause fatal neurodegenerative diseases in humans and animals and can be transmitted zoonotically. Chronic wasting disease (CWD) is a highly transmissible prion disease of wild deer and elk that affects cervids over extensive regions of the United States and Canada. The risk of cross-species CWD transmission has been experimentally evaluated in a wide array of mammals, including non-human primates and mouse models expressing human cellular prion protein. Here we review the determinants of cross-species CWD transmission, and propose a model that may explain a structural barrier for CWD transmission to humans.     

Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease

COPD (chronic obstructive pulmonary disease) is characterized by airway inflammation and increases the likelihood of the development of atherosclerosis. Recent studies have indicated that FABP4 (fatty-acid-binding protein 4), an intracellular lipid chaperone of low molecular mass, plays an important role in the regulation of inflammation and atherosclerosis. We carried out a preliminary clinical study aiming at investigating the relationships between circulating FABP4 levels in patients with COPD and inflammation and lung function. We enrolled 50 COPD patients and 39 healthy controls in the study. Lung function tests were performed in all subjects. Plasma levels of FABP4 and adiponectin, TNFα (tumour necrosis factor α) and CRP (C-reactive protein) were measured. The correlations between FABP4 and lung function, adipokine (adiponectin), inflammatory factors and BMI (body mass index) were analysed. Compared with both males with COPD and healthy females, plasma FABP4 levels in females with COPD were significantly increased. Adiponectin and CRP levels were significantly higher in patients with COPD. Furthermore, we found that FABP4 levels were inversely correlated with FEV₁% predicted (FEV₁ is forced expiratory volume in 1 s) and positively correlated with adiponectin and TNFα in COPD patients. In addition, a positive correlation between plasma FABP4 and CRP was found in females with COPD. However, FABP4 levels were not correlated with BMI. Our results underline a gender difference in FABP4 secretion in stable COPD patients. Further studies are warranted to clarify the exact role of FABP4 in the pathogenesis of COPD.     

Community mental health care worldwide: current status and further developments

This paper aims to give an overview of the key issues facing those who are in a position to influence the planning and provision of mental health systems, and who need to address questions of which staff, services and sectors to invest in, and for which patients. The paper considers in turn: a) definitions of community mental health care; b) a conceptual framework to use when evaluating the need for hospital and community mental health care; c) the potential for wider platforms, outside the health service, for mental health improvement, including schools and the workplace; d) data on how far community mental health services have been developed across different regions of the world; e) the need to develop in more detail models of community mental health services for low‐ and middle‐income countries which are directly based upon evidence for those countries; f) how to incorporate mental health practice within integrated models to identify and treat people with comorbid long‐term conditions; g) possible adverse effects of deinstitutionalization. We then present a series of ten recommendations for the future strengthening of health systems to support and treat people with mental illness.     

辛伐他汀联合运动训练治疗COPD稳定期合并代谢综合征患者的临床研究

目的:探讨辛伐他汀联合运动训练治疗慢性阻塞性肺疾病(COPD)稳定期合并代谢综合征患者的临床疗效,为临床治疗提供指导。方法:按照随机数字表法将2013年9月-2015年3月我院收治的COPD稳定期合并代谢综合征患者分为A、B组和对照组,A组患者在常规治疗的基础上联合辛伐他汀和运行训练,B组患者在常规治疗的基础上以辛伐他汀治疗,对照组患者仅以常规治疗。治疗后6个月,比较三组患者的临床治疗效果。结果:A、B组治疗后的血清白细胞介素-6(IL-6)白细胞介素-8(IL-8)以及肿瘤坏死因子-α(TNF-α)水平低于治疗前,差异有统计学意义(P0.05),对照组治疗后的IL-6、IL-8及TNF-α水平与治疗前差异无统计学意义(P0.05),治疗后A组的IL-6、IL-8及TNF-α水平明显低于B组,差异有统计学意义(P0.05)。A组的胰岛素抵抗指数(HOMA-IR)低于B组、对照组,差异有统计学意义(P0.05);A、B组的颈-股动脉脉搏波速度(CFPWV)低于对照组,差异有统计学意义(P0.05)。A、B组治疗后的改良医学研究委员会量表(m MRC)低于对照组,A组m MCR低于B组,差异有统计学意义(P0.05),A、B组治疗后的6 min步行距离(6MWD)高于对照组,A组6MWD高于B组,差异有统计学意义(P0.05)。结论:辛伐他汀联合运动训练能明显降低COPD稳定期合并代谢综合征患者的炎症性反应,改善患者的胰岛素抵抗和大动脉弹性,提高临床治疗效果。