Activity-dependent targeting of TRPV1 with a pore-permeating capsaicin analog

The capsaicin receptor TRPV1 is the principal transduction channel for nociception. Excessive TRPV1 activation causes pathological pain. Ideal pain mangement requires selective inhibition of hyperactive pain-sensing neurons, but sparing normal nociception. We sought to determine whether it is possible to use activity-dependent TRPV1 agonists to identify nerves with excessive TRPV1 activity, as well as exploit the TRPV1 pore to deliver charged anesthetics for neuronal silencing. We synthesized a series of permanently charged capsaicinoids and found that one, cap-ET, efficaciously evoked TRPV1-dependent entry of Ca(2+) or the large cationic dye YO-PRO-1 comparably to capsaicin, but far smaller electrical currents. Cap-ET-induced YO-PRO-1 transport required permeation of both the agonist and the dye through the TRPV1 pore and could be enhanced by kinase activation or oxidative covalent modification. Moreover, cap-ET reduced capsaicin-induced currents by a voltage-dependent block of the pore. A low dose of cap-ET elicited entry of permanently charged Na(+) channel blockers to effectively suppress Na(+) currents in sensory neurons presensitized with oxidative chemicals. These results implicate therapeutic potential of these unique TRPV1 agonists exhibiting activity-dependent ion transport but of minimal pain-producing risks.     

131Ⅰ治疗对甲状腺功能亢进患者心率变异性的影响

目的 观察甲状腺功能亢进(简称甲亢)患者心率变异性,探讨131Ⅰ治疗对甲亢患者自主神经功能的影响.方法 以哈尔滨医科大学附属第二医院和哈尔滨市第二医院就诊的56例甲亢患者作为观察对象,于131Ⅰ治疗前和治疗6个月后,进行12导联同步24 h动态监测,同时选取49例健康体检人员作对照组.观察指标包括24 h连续窦性R-R间期标准差(SDNN)、24 h连续5 min节段的窦性R-R间期标准差(SDANN)、24 h内两个相邻窦性R-R间期差>50 ms心率数占所分析信息期内的心率数的百分比(PNN50)、24 h连续窦性R-R间期差值的均方根(rMSSD)、极低频段功率(VLF)、低频段功率(LF)、高频段功率(HF)、低频段功率与高频段功率比值(LF/HF).结果 甲亢组治疗前SDNN[(85.25±13.59)ms]、SDANN[(95.47±33.15)ms]、PNN50[(15.26±4.84)%]、rMSSD[(14.47±3.49)ms]、LF[(435.57±75.74)ms2/Hz]、HF[(129.81±63.21)ms2/Hz]均明显低于对照组[(155.24±15.87)ms、(134.02±24.15)ms、(29.41±6.21)%、(26.64±6.11)ms、(515.69±74.83)ms2/Hz、(265.93±58.84)ms2/Hz,P均<0.05],VLF[(1765.21±315.22)ms2]、LF/HF(3.95±1.89)明显高于对照组[(374.25士54.47)ms2,2.94±1.55,P均<0.05],而甲亢组治疗后SDNN[(126.91±16.32)ms]、SDANN[(125.20±43.22)ms]、PNN50[(26.34±7.56)%]、rMSSD[(24.85±7.85)ms]、LF[(489.35-i-91.49)ms2/Hz]、HF[(209.45±75.32)ms2/Hz]均明显高于治疗前(P均<0.05),VLF[(571.80±97.41)ms2]、LF/HF比值(2.41±0.93)明显低于治疗前(P均<0.05),但与对照组相比较,SDNN、PNN50、HF仍明显降低,VLF明显增高,组间比较差异有统计学意义(P均<0.05).结论 甲亢患者心率变异性总体表现为降低,以交感神经活性占优势,应用131Ⅰ治疗可部分纠正心脏自主神经异常的病理生理现象.

Abstract：

Objective To observe the heart rate variability in patients with hypothyroidism, and to analyze the effect of 131Ⅰ therapy on autonomic nervous system of patients with the diseases. Methods A total of 56 cases of hyperthyroidism from the Second Affiliated Hospital of Harbin Medical University and the Second Hospital of Harbin City were enrolled as research subjects. 12-synchronous dynamic 24-hour monitoring and man-machine dialogue were used 6 months before and after 131Ⅰ treatment, and 49 cases of healthy volunteers were selected as controls.Heart rate variability indicators observed included 24 h consecutive sinus standard deviation of R-R interval (SDNN), standard deviation of sequential five-minute R-R interval (SDANN), percentage of differences between adjacent NN intervals that > 50 ms(PNN50), root mean square standard deviation from adjacent R-R interval (rMSSD), very low frequency power(VLF), low frequency power(LF), high frequency power(HF), and low frequency power/high frequency power(LF/HF). Results In hyperthyroidism group before 131Ⅰ therapy, SDNN[(85.25 ± 13.59)ms], SDANN [( 95.47 ± 33.15)ms], PNN50 [( 15.26 ± 4.84) %], rMSSD [( 14.47 ~ 3.49) ms], LF [(435.57 ± 75.74)ms2/Hz], and HF[(129.81 ± 63.21 )ms2/Hz] were significantly lower than those of the control group [(155.24 ±15.87), ( 134.02 ± 24.15)ms, (29.41 ± 6.21 )%, (26.64 ± 6.11 )ms, (515.69 ± 74.83)ms2/Hz, and (265.93 ± 58.84)ms2/Hz, all P < 0.05], VLF[(1765.21 ± 315.22)ms2] and LF/HF(3.95 ± 1.89) were significantly higher than that of the control group[(374.25 ± 54.47)ms2, 2.94 ± 1.55, all P < 0.05]. In hyperthyroidism group after treatment,SDNN [(126.91 ± 16.32)ms], SDANN[(125.2 ± 43.22)ms], PNN50[(26.34 ~ 7.56)%], rMSSD[(24.85 ± 7.85)ms],LF [(489.35 ± 91.49)ms2/Hz], and HF [(209.45 ± 75.32)ms] were also significantly higher than those before 131Ⅰ therapy, VLF[(571.80 ± 97.41)ms] and LF/HF(2.41 ± 0.93) were lower than that before 131Ⅰ therapy,but SDNN, PNN50 and HF were lower and VLF was higher than those of the control group (all P < 0.05). Conclusions The heart rate variability in patients with hyperthyroidism is lower in the overall performance, sympathetic activity is dominate, 131Ⅰ therapy partly corrects abnormal autonomic nerve function.     

肛裂切除黏膜下移术治疗陈旧性肛裂的前瞻性多中心随机对照试验

背景：肛裂是常见肛肠科疾病之一,约10%陈旧性肛裂患者最终需要手术治疗。如何通过技术改良减轻手术痛苦和预防功能损伤是肛肠外科医师关注的热点。目的：评价肛裂切除黏膜下移术治疗陈旧性肛裂的疗效和安全性。设计、场所、对象和干预措施：采用前瞻性、多中心、随机、对照临床试验设计方案,纳入2009年1月～2010年4月来自上海中医药大学附属岳阳中西医结合医院和上海市中医医院、上海交通大学医学院附属第九人民医院肛肠科住院的陈旧性肛裂患者120例,采用各分中心随机分层,随机分为试验组（肛裂切除黏膜下移术）和对照组（肛裂切除术）各60例。两组均采取手术治疗,术后观察期为2周,短期随访6周。主要结局指标：以治愈率、创面愈合时间和临床症状为主要观察指标,观察术后并发症以及手术前后肛管张力变化进行安全性评价。结果：3例患者（试验组1例,对照组2例）因术后1周内提早出院而退出试验。术后第6周,试验组疗效优于对照组（P〈0.05）。试验组创面愈合时间为（17.22±4.41）d,对照组为（21.24±7.44）d,两组比较差异有统计学意义（P〈0.05）。术后第3天、第14天和第6周时试验组肛门疼痛程度轻于对照组（P〈0.05）;术后第3天和第14天,试验组肛门出血情况优于对照组（P〈0.05）,术后6周试验组与对照组出血情况比较,差异无统计学意义（P=0.051）。术后两组肛管张力比较,差异无统计学意义（P〉0.05）。术后2周内两组患者并发症（排尿障碍、创缘水肿、术后发热、术后感染、肛门失禁、肛门变形）比较,差异无统计学意义（P〉0.05）。两组均随访6周,所有随访患者未见术后并发症,未见复发。结论：陈旧性肛裂患者采用肛裂切除黏膜下移术能提高手术疗效,缩短疗程,改善患者术后痛苦,同时具有较好的安全性。     

Odors from proximal species reverse the stress-decreased neurogenesis via main olfactory processing

Unconditioned foot shock followed by restraint in water was used as a stress regimen to induce decreases in neurogenesis in mouse dentate gyrus (DG). Presence of conspecific odors has been known to reverse the stress-induced decrease in DG neurogenesis. In this study, we found that the conspecific odors did not produce these protective effects in mice whose MOE was impaired by nasal zinc sulfate lavage. Moreover, we observed that the presence of odors from rats, hamsters, and guinea pigs throughout the stress procedure reversed the stress-induced decrease in cell proliferation and neurogenesis in mouse dentate gyrus, while these odors alone did not affect mouse dentate cell proliferation or neurogenesis. In contrast, the presence of rabbit, sugar glider, hedgehog, beetle odors did not affect cell proliferation, neurogenesis, the stress-decreased cell proliferation or neurogenesis in DG. Finally, the presence of fox urine odors decreased mouse dentate cell proliferation and neurogenesis but did not affect the stress-induced decrease in cell proliferation or neurogenesis. Taken together, we conclude that olfactory processing via activation of sensory neurons in MOE is responsible for the conspecific odor-produced protective effect against the stress-decreased cell proliferation and neurogenesis. Phylogenetic distances of the odor-generating species and mice might contribute to the odors’ protective effects against the stress-induced decreases in cell proliferation and neurogenesis.     

Mental Health Law of the People's Republic of China

The following document is a translation of the first national mental health law of the People''s Republic of China, which was adopted by the National People''s Congress on October 26, 2012. The original Chinese version of the law is available at the official government website: http://www.gov.cn/jrzg/2012-10/26/content_2252122.htm. The translation was completed by a team of translators at the Shanghai Mental Health Center at the Shanghai Jiao Tong University School of Medicine. The translators have added footnotes at the end of the document that explain their choices in sections where alternative translations are possible and that provide background information for sections that may be confusing to readers unfamiliar with China. This translation should be cited as follows:ChenHH, Phillips MR, Cheng H, Chen QQ, Chen XD, Fralick D, Zhang YE, Liu M, Huang J, Bueber M. Mental Health Law of the People''s Republic of China (English translation with annotations). Shanghai Archives of Psychiatry. 2012; 24(6):305-321. doi:10.3969/j.issn.1002-0829.2012.06.001Shanghai Archives of Psychiatry     

血液透析护理环节质量评价指标的研究

目的:建立血液透析护理环节质量评价指标体系,科学评价血液透析专科护理质量。方法:通过临床调研和查阅文献资料初步确立护理环节质量评价指标体系,再采用德尔菲法咨询护理专家28名,对评价指标进行论证。结果:经过2轮专家咨询确立了5项一级指标和20项二级指标及相应的权重值。结论:应用德尔菲法建立的血液透析护理环节质量评价指标体系体现了血液透析专科护理质量的内涵,为制定专科护理质量评价量表和专科护理管理工作提供了一定的参考依据。     

Clinical characteristics of essential tremor in Taiwan: an exploratory‐comparative study

Background: There are few large‐scale clinical analyses of essential tremor (ET) in Asia. We studied the detailed clinical profile with emphasizing the age of onset, tremor location, specific tremor patterns, and rate of progression (ROP) to delineate the characteristics of Taiwanese ET patients and found the difference between the Taiwanese and the Caucasians ET patients. Methods: All ET patients fulfilled the Movement Disorders Society diagnosis criteria were investigated with a standardized assessment protocol, which including clinical evaluation, uniform severity scoring, self‐reported questionnaires, accelerometry, surface electromyography, and videotaped tremor examination. Results: Of 219 patients recruited from July 2008 to October 2009, 153 completed the study protocol. Their mean age was 58.9 years and 47% were women, and 33.3% had family history (FH). There was bimodal distribution in age of tremor onset in patients without but not in those with FH. Head tremor (HT) was present in 48 of 153 (31%) patients. Patients with HT showed slower tremor frequency and less ROP than those without HT. Sixty‐seven (44%) patients presented with intention tremor (IT). Male gender and voice tremor were predictive factors of IT occurrence. Conclusions: Comparing with the Caucasians, Taiwanese ET patients have different patterns of onset‐age distribution and lack of female predominance in ET with HT. However, patients with IT and without HT also progressed more rapid as found in the Caucasian.     

Predisposing factors of pituitary hemorrhage

Background and purpose: The clinical features of pituitary adenomas were retrospectively analyzed, focusing on the factors that contribute to the development of pituitary hemorrhage. Although many causes of pituitary adenoma hemorrhage have been identified, it is difficult to distinguish which conditions are truly causative. We determined the independent variables that contribute to pituitary hemorrhage in pituitary adenoma. Methods: Two hundred and eighty‐eight consecutive patients diagnosed as pituitary adenoma were enrolled. These patients underwent tumor removal through endoscopic transsphenoidal approach. The subjects were divided into hemorrhagic and non‐hemorrhagic groups, based on magnetic resonance images and histological findings. The predisposing factors were reviewed in the medical records for all patients. Univariate and multivariate analyses were performed to assess the relationships between variables of pituitary adenoma hemorrhage. Results: We investigated 81 patients in whom hemorrhage from pituitary adenoma occurred. The incidence of pituitary hemorrhage was 28.1% (81/288). The predisposing factors surveyed for pituitary hemorrhage were significantly associated with macroadenoma, non‐functional adenomas, anticoagulation therapy, end‐stage renal disease, dopamine agonist treatment, and underlying malignant disease (all P < 0.05). Sex, age, hypertension, diabetes mellitus, and previous radiation therapy were not related to pituitary hemorrhage. Conclusions: In this pooled cohort, the predisposing factors of pituitary adenoma characteristic for pituitary hemorrhage were macroadenoma and non‐functional adenoma. Patients who received dopamine agonist and anticoagulation therapy are implicated as precipitating factors. Underlying end‐stage renal disease and malignant disease are also factors that contribute to pituitary adenoma hemorrhage.