温阳、解郁及温阳解郁方对母婴分离结合慢性神经疼痛应激小鼠疼痛敏感性及抑郁样行为的调节作用

目的 观察母婴分离小鼠给予慢性神经疼痛应激后的行为、痛阈改变，以及血清和中枢抑郁、疼痛相关指标的变化，以温阳方、解郁方、及温阳解郁方进行干预探讨温阳解郁法抗抑郁、改善疼痛敏感的可能机制。方法 以小鼠出生日为PD0，小鼠在出生后随机分为对空白组和母婴分离组，母婴分离组在PD5~14进行8 h·d^-1的母婴分离，离乳后将其分为母婴分离组、温阳组、解郁组、温阳解郁组和氟西汀组，每组15只，同时以15只未经母婴分离的同期雄性仔鼠作为空白组。空白组、母婴分离组小鼠于PD21~90以普通发育饲料喂养，余组分别以温阳方二仙汤、解郁方逍遥散、温阳解郁方及氟西汀药混饲料喂养（用药剂量分别为5.84、12.00、16.68 g·kg^-1及2.60 mg·kg^-1）。于PD91行坐骨神经结扎手术，建立母婴分离+慢性神经病理性疼痛模型。采用旷场实验观察各组小鼠抑郁样行为，测量机械痛阈和温度痛阈检测各组小鼠疼痛敏感性，酶联免疫吸附测定法（ELISA）检测血清皮质酮（CORT）、P物质及β-内啡肽（β-EP）含量，免疫组化检测杏仁核糖皮质激素受体（GR）和下丘脑β-EP蛋白表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测杏仁核糖皮质激素受体基因（Nr3c1）、FK506结合蛋白5基因（FKBP5）、代谢型谷氨酸受体5基因（GRM5）及脑源性神经营养因子（BDNF）mRNA的表达量。结果 与空白组比较，母婴分离组小鼠5 min旷场中心停留时间和运动总距离均显著减少（P<0.01），机械痛阈显著降低（P<0.01）。血清CORT和β-EP均显著上升（P<0.01），FKBP5 mRNA表达显著下降（P<0.01）。下丘脑β-EP表达上升，差异具有明显统计学意义（P<0.05）。与母婴分离组比较，各给药组5 min旷场中心停留时间均明显增加（P<0.05，P<0.01），温阳组、温阳解郁组和氟西汀组小鼠在5 min旷场运动总距离明显增加（P<0.05，P<0.01），各给药组痛阈均不同程度上调。解郁组小鼠血清CORT显著下降（P<0.01），β-EP明显下降，但差异无统计学意义；BDNF mRNA显著上升（P<0.01）。温阳组小鼠Nr3c1及GRM5 mRNA均明显下降（P<0.05，P<0.01）。温阳解郁组小鼠血清CORT明显下降（P<0.05），Nr3c1、GRM5及BDNF mRNA均下降（P<0.05，P<0.01），差异具有明显统计学意义，各给药组下丘脑β-EP表达水平均有不同程度提升，但差异无统计学意义。温阳组、解郁组和温阳解郁组小鼠杏仁核GR表达水平均明显上升，差异具有明显统计学意义（P<0.05）。结论 温阳解郁方可通过增强杏仁核GR表达、抑制杏仁核区神经可塑性及兴奋性达到抑制中枢疼痛敏化和调节下丘脑-垂体-肾上腺（HPA）轴功能，缓解抑郁行为和改善躯体疼痛过敏的作用。     

High enhancer,downer, withdrawal helper: Multifunctional nonmedical benzodiazepine use among young adult opioid users in New York City

BackgroundBenzodiazepines are a widely prescribed psychoactive drug; in the U.S., both medical and nonmedical use of benzodiazepines has increased markedly in the past 15 years. Long-term use can lead to tolerance and dependence, and abrupt withdrawal can cause seizures or other life-threatening symptoms. Benzodiazepines are often used nonmedically in conjunction with other drugs, and with opioids in particular—a combination that can increase the risk for fatal and non-fatal overdose. This mixed-methods study examines nonmedical use of benzodiazepines among young adults in New York City and its relationship with opioid use.MethodsFor qualitative analysis, 46 90-minute semi-structured interviews were conducted with young adult opioid users (ages 18–32). Interviews were transcribed and coded for key themes. For quantitative analysis, 464 young adult opioid users (ages 18–29) were recruited using Respondent-Driven Sampling and completed structured interviews. Benzodiazepine use was assessed via a self-report questionnaire that included measures related to nonmedical benzodiazepine and opioid use.ResultsParticipants reported using benzodiazepines nonmedically for a wide variety of reasons, including: to increase the high of other drugs; to lessen withdrawal symptoms; and to come down from other drugs. Benzodiazepines were described as readily available and cheap. There was a high prevalence (93%) of nonmedical benzodiazepine use among nonmedical opioid users, with 57% reporting regular nonmedical use. In bivariate analyses, drug-related risk behaviours such as polysubstance use, drug binging, heroin injection and overdose were strongly associated with regular nonmedical benzodiazepine use. In multivariate analysis, growing up in a middle-income household (earning between $51,000 and $100,000 annually), lifetime overdose experience, having ever used cocaine regularly, having ever been prescribed benzodiazepines, recent drug binging, and encouraging fellow drug users to use benzodiazepines to cope with opioid withdrawal were consistently strong predictors of regular nonmedical benzodiazepine use.ConclusionNonmedical benzodiazepine use may be common among nonmedical opioid users due to its drug-related multi-functionality. Harm reduction messages should account for the multiple functions benzodiazepines serve in a drug-using context, and encourage drug users to tailor their endorsement of benzodiazepines to peers to include safer alternatives.     

Informing the design of clinical decision support services for evaluation of children with minor blunt head trauma in the emergency department: A sociotechnical analysis

Integration of clinical decision support services (CDSS) into electronic health records (EHRs) may be integral to widespread dissemination and use of clinical prediction rules in the emergency department (ED). However, the best way to design such services to maximize their usefulness in such a complex setting is poorly understood. We conducted a multi-site cross-sectional qualitative study whose aim was to describe the sociotechnical environment in the ED to inform the design of a CDSS intervention to implement the Pediatric Emergency Care Applied Research Network (PECARN) clinical prediction rules for children with minor blunt head trauma. Informed by a sociotechnical model consisting of eight dimensions, we conducted focus groups, individual interviews and workflow observations in 11 EDs, of which 5 were located in academic medical centers and 6 were in community hospitals. A total of 126 ED clinicians, information technology specialists, and administrators participated. We clustered data into 19 categories of sociotechnical factors through a process of thematic analysis and subsequently organized the categories into a sociotechnical matrix consisting of three high-level sociotechnical dimensions (workflow and communication, organizational factors, human factors) and three themes (interdisciplinary assessment processes, clinical practices related to prediction rules, EHR as a decision support tool). Design challenges that emerged from the analysis included the need to use structured data fields to support data capture and re-use while maintaining efficient care processes, supporting interdisciplinary communication, and facilitating family-clinician interaction for decision-making.     

乌梅丸治疗更年期崩漏的临床观察

目的探究乌梅丸治疗更年期崩漏的临床疗效。方法选择2017年3月—2019年11月收治的52例更年期崩漏患者,以随机数字表法分为治疗组和对照组,每组26例。对照组给予乙烯雌酚2 mg/d和醋酸甲羟孕酮片10 mg/d,治疗组给予乌梅丸治疗。观察2组患者治疗效果及治疗前后汉密尔顿焦虑量表(HAMA)及汉密尔顿抑郁量表(HAMD)评分变化情况。结果治疗组的治疗总有效率高于对照组(P<0.05),且治疗组治疗后的HAMA、HAMD评分均低于对照组(P<0.05)。结论乌梅丸可有效改善更年期崩漏患者的临床症状,缓解患者负面情绪,临床应用价值较高,值得推广。     

桑白皮及其相关方剂治疗呼吸系统疾病的研究进展

桑白皮味甘、辛，性寒，归肺经，具泻肺平喘、利水消肿之功，主治肺热喘咳、尿少水肿、面目肌肤肿胀等证，是临床最常用的草药之一，用桑白皮配伍的方剂如桑白皮汤、清金化痰方和清肺化痰汤等被广泛使用于临床。桑白皮的主要活性成分是发挥其功效的物质基础，现代中药药效物质分析鉴定手段已较成熟，对桑白皮化学成分的研究已经非常深入系统，该文查阅了近些年来关于桑白皮化学成分、药理作用及其相关方剂治疗呼吸系统疾病的文献报道，结合桑白皮已分离鉴定出的主要药效成分及主要药理作用，对桑白皮及其相关方剂治疗呼吸系统疾病的作用和机制进行综述；该文通过总结并分析现临床常用桑白皮方剂的组方配伍思路和常用量，为桑白皮治疗呼吸系统疾病提供参考。该文为桑白皮及其相关方剂治疗呼吸系统疾病的深入研究提供思考，有利于桑白皮及其相关方剂在临床上发挥更广泛的治疗作用。     

Trends in adolescent alcohol use in the Netherlands, 1992–2015: Differences across sociodemographic groups and links with strict parental rule-setting

BackgroundFrom an international perspective, studying trends in adolescent alcohol use in the Netherlands is an important case study. Whereas Dutch adolescents topped the international rankings of alcohol consumption in the beginning of this century, they are nowadays found more toward the bottom of these rankings. This study examines time trends in adolescent alcohol use between 1992 and 2015, and tests whether these trends differ according to gender, age group, and educational track. Moreover, it examines to what extent the strictness of parental rule-setting can explain the identified trends.MethodsUsing data from ten waves of two nationally representative studies with a repeated cross-sectional design, trends were examined for eight different alcohol measures. Interaction analyses were conducted to test for subgroup differences. All analyses were controlled for educational track, family structure, and ethnicity. For the period 2007–2015, trends in parental alcohol-specific rule-setting were included as a predictor of the trends in adolescent alcohol use.ResultsAdolescent alcohol use increased substantially between 1992 and 2003, and decreased sharply thereafter. Trends were stronger for 12- to 15-year olds, compared to the 16-year olds, and for adolescents attending higher educational tracks, compared to adolescents attending lower educational tracks. Overall, gender differences remained constant over time. Between 2007 and 2015, strict parental alcohol-specific rule-setting increased substantially, and this (partly) explained the strong decline in adolescent alcohol use during this period.ConclusionThis study shows clear time trend changes in alcohol use among Dutch adolescents. The phenomenal decrease in adolescent alcohol use since 2003 appears to be closely related to a radical change in parenting behaviours surrounding the alcohol use of their children. While national prevention programs may have encouraged stricter parenting behaviours, the decline in alcohol use should be interpreted in a broader context of internationally changing sociocultural norms regarding adolescent alcohol use.