A dysbiotic subpopulation of alcohol-dependent subjects

The vast majority of studies that assessed the importance of biological factors for the development of psychiatric disorders focused on processes occurring at the brain level. Alcohol-dependence is a very frequent psychiatric disorder where psycho-pharmacological interventions are only of moderate efficacy. Our laboratory has recently described that a subpopulation of alcohol-dependent subjects, that accounted for approximately 40% of individuals tested, presented with an increased intestinal permeability, with a dysbiosis, with alterations in the metabolomic content of faeces - that could play a role in the increased permeability - and finally with a more severe profile of alcohol-dependence than the other non-dysbiotic subpopulation. In this addendum, we discuss the implications of our observations for the pathophysiology of alcohol dependence where we try to discriminate which addiction dimensions are likely related to the gut microbiota alterations and whether these alterations are the cause or the consequence of drinking habits.     

Differences in knee adduction moment between healthy subjects and patients with osteoarthritis depend on the knee axis definition

ObjectiveThis study, firstly, investigates the effect of using an anatomical versus a functional axis of rotation (FAR) on knee adduction moment (KAM) in healthy subjects and patients with knee osteoarthritis (KOA). Secondly, this study reports KAM for models with FAR calculated using weight-bearing and non-weight-bearing motion.DesignThree musculoskeletal models were created using OpenSim with different knee axis of rotation (AR): transepicondylar axis (TEA); FAR calculated based on SARA algorithm using a weight-bearing motion (wFAR) and a non-weight-bearing motion (nwFAR). KAM were calculated during gait in fifty-nine subjects (n = 20 healthy, n = 16 early OA, n = 23 established OA) for all models and groups.ResultsSignificant differences between the three groups in the first peak KAM were found when TEA was used (p = 0.038). However, these differences were no longer present when using FAR. In subjects with established OA, KAMs were significantly reduced when using nwFAR compared to TEA models but also compared to wFAR models.ConclusionThe presence of excessive KAM in subjects with established KOA showed to be dependent on the definition of the AR: anatomical versus functional. Therefore, caution should be accounted when comparing KAM in different studies on KOA patients. In patients with end-stage knee OA where increased passive knee laxity is likely to exist, the use of weight-bearing motions should be considered to avoid increased variability in the location and orientation of a FAR obtained from activities with only limited joint loading.     

化痰通络汤对脑缺血/再灌注大鼠“肠-脑”轴的干预作用

目的 基于“肠-脑”轴探讨化痰通络汤（HTTLD）对大鼠脑缺血再灌注后脑组织和肠道形态和功能的影响。方法 将60只SPF级雄性大鼠随机分为假手术组，模型组，HTTLD高、中、低剂量组（28.66，14.33，7.16 g·kg^-1），依达拉奉（4 g·kg^-1）+丁酸梭菌（5.0×10⁸ cfu·mL^-1）组，采用大鼠局灶性脑缺血再灌注模型，灌胃给药HTTLD，神经功能缺损评分和2，3，5-氯化三苯四氮唑（TTC）染色法测定脑组织损伤，小肠推进率观察脑缺血再灌注对肠道动力的影响，十二指肠黏膜的病理形态学检测评价肠黏膜细胞损伤，酶联免疫吸附测定法（ELISA）测定血清D-乳酸（D-LAC），二胺氧化酶（DAO），细菌内毒素（LPS）含量，蛋白免疫印迹法（Western blot）检测十二指肠的闭合蛋白（Occludin），紧密连接蛋白-5（Claudin-5），闭锁小带蛋白-1（ZO-1）蛋白的表达。结果 脑缺血再灌注后，大鼠出现神经功能缺损症状，与假手术组比较，模型组神经功能缺损评分显著升高（P<0.01）；与模型组比较，HTTLD中、高剂量组能显著减少神经功能缺损症状，降低神经功能缺损评分（P<0.01）。与假手术组比较，模型组大鼠脑组织出现明显梗死灶，脑梗死率显著升高（P<0.01）；与模型组比较，各给药组脑梗死体积明显减少（P<0.01），以HTTLD高剂量组的效应最佳，且效应具有剂量依赖性。小肠推进率结果显示，与假手术组比较，模型组小肠推进率显著降低（P<0.01）；与模型组比较，各给药组能显著升高小肠推进率（P<0.01），以HTTLD高剂量效应最佳，且效应具有剂量依赖性。十二指肠黏膜组织病理学检测显示，脑缺血再灌注后十二指肠黏膜可见明显损伤，各给药组黏膜损伤情况明显减轻。与假手术组比较，模型组ZO-1，Occludin，Claudin-5蛋白表达均显著降低（P<0.01）；与模型组比较，HTTLD低、中、高剂量组能不同程度上调ZO-1，Occludin，Claudin-5蛋白表达（P<0.05，P<0.01），以高剂量组的效应最为显著。与假手术组比较，模型组血清D-LAC，DAO，LPS蛋白含量均显著升高（P<0.01）；与模型组比较，各给药组D-LAC，DAO含量均明显降低（P<0.05，P<0.01），HTTLD中、高剂量组明显降低LPS含量（P<0.05，P<0.01），且HTTLD高剂量组的作用最明显。结论 脑缺血再灌注后，大鼠脑组织受损、出现神经功能障碍，同时肠道黏膜损伤、肠道蠕动减弱和肠道黏膜屏障破坏。HTTLD能减少脑组织和胃肠道黏膜损伤，减轻神经功能缺损症状，提高胃肠道动力、改善肠道屏障功能、减少肠道细菌代谢产物和毒物的释放，从而发挥对脑缺血再灌注后“脑-肠”轴损伤的保护作用。     

基于“脑-肠轴”学说论治慢性乙型肝炎合并肠易激综合征

慢性乙型肝炎合并肠易激综合征的发病机制尚未完全清楚,西医疗效亦不容乐观,但"脑-肠轴异常"理论被认为是本病发病的关键,此恰与中医理论不谋而合,且中医理论认识更深、更广。基于"脑-肠轴"学说,以针刺头针胃区和头针肠区作为切入点,运用"调神针法"调节"脑神"进而调节"五脏神",以达到阴平阳秘,百病不生的状态,从而治愈本病。     

促性腺激素释放激素类似物激发试验尿检法对儿童促性腺激素释放激素类似物疗效的判断价值

目的 探讨促性腺激素释放激素类似物(GnRHa)激发试验时免疫化学发光分析法(ICMA)检测的无创性尿促性腺激素(UGn)可否用于儿童GnRHa的疗效判断.方法 患儿23例(男4例,女19例).中枢性性早熟17例(均为女童),予GnRHa治疗.青春期预测终身高矮小6例(男4例,女2例),予GnRHa联合生长激素治疗.在治疗前和治疗3个月均行GnRHa激发试验,留激发试验0～3.5 h尿,其中18例留取了激发试验前1d同一时段的日间自发性尿,应用ICMA检测促黄体生成素(LH)和卵泡刺激素(FSH).结果 1.治疗前后GnRHa激发试验时UGn显著性检验:治疗前后的尿促黄体生成素(ULH)水平分别为(1.27±1.63) IU和(0.07±0.06) IU,尿卵泡刺激素(UFSH)水平分别为(6.38±3.85)IU和(0.54±0.30) IU.2.GnRHa激发试验时血清Gn峰值和UGn对GnRHa疗效评估:当血清LH峰值(PLH)和FSH峰值(PFSH)分别≤2.30IU·L-1和2.39 IU·L-时,其判断疗效的灵敏度分别为95.45％和100％,特异度均为100％；当ULH水平和UFSH水平分别≤0.083 IU和1.089 IU时,其灵敏度分别为90.91％和100％,特异度均为100％.3.GnRHa激发试验时血清Gn和UGn分别与其激发试验前的比值对GnRHa疗效评估:当血清PLH/日间自发性血清LH、血清PFSH/日间自发性血清FSH分别≤5.40和2.16时,其灵敏度和特异度均为100％；当其激发试验时ULH水平/日间自发性ULH水平、激发试验时UFSH水平/日间自发性UFSH水平分别≤6.076和2.480时,其灵敏度和特异度也均达100％.结论 GnRHa激发试验时ICMA检测的无创性3.5 h UGn水平、激发试验时3.5 h UGn水平/日间自发性UGn水平指标可能对儿童GnRHa疗效具有判断价值,其中UFSH水平及其与日间自发性UFSH水平比值指标价值可能更大.     

Are Cushing's disease patients curable?

Treatment of Cushing's disease remains a challenge. Whereas pituitary surgery can “cure” the patient and restore a completely normal pituitary adrenal axis, there are immediate failures and late recurrences which ultimately require alternate therapeutic approaches. These are numerous, but so are their drawbacks, and all appear to be “default options”. For the future, pituitary adenoma has to remain the “reasonable obsession” of efficient and optimistic therapists…