Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke: a systematic review and network meta-analysis

Transcranial magnetic stimulation, a type of noninvasive brain stimulation, has become an ancillary therapy for motor function rehabilitation. Most previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS) on motor function in stroke patients. There have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with stroke. The MEDLINE, Embase, Cochrane Library, ISI Science Citation Index, Physiotherapy Evidence Database, China National Knowledge Infrastructure Library, and ClinicalTrials.gov databases were searched. Parallel or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke, published from inception to November 28, 2019, were included. Standard pairwise meta-analysis was conducted using R version 3.6.1 with the "meta" package. Bayesian network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol interventions. Network meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham stimulation. Network meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency r TMS or sham stimulation. These findings suggest that rTMS can improve motor function in patients with stroke, and that low-frequency rTMS mainly affects motor function, whereas high-frequency rTMS increases the amplitudes of motor evoked potentials. More highquality randomized controlled trials are needed to validate this conclusion. The work was registered in PROSPERO(registration No. CRD42020147055) on April 28, 2020.     

Pro-caspase-3 is constitutively expressed in luteinized granulosa cells from women undergoing controlled ovarian stimulation for in vitro fertilization

Apoptosis regulation in luteinized granulosa cells (LGC) during assisted reproduction procedures is still controversial. Caspase-3 is a major apoptosis mediator encoded by CASP3 and formed through cleavage of its precursor pro-caspase-3. The aim of this study was to investigate the expression patterns of pro-caspase-3 (mRNA and protein) and cleaved caspase-3 in human LGC. Thirty-five women undergoing controlled ovarian stimulation for in vitro fertilization were prospectively enrolled in the study. LGC were isolated from follicular fluid during oocyte pickup and evaluated by immunocytochemistry for pro-caspase-3 and cleaved caspase-3, and by real-time PCR for CASP3 mRNA expression. We found a positive staining of pro-caspase-3 in 77 % of the LGC (95 % confidence interval [CI] 60%–84%), whereas cleaved caspase-3 was found in only 4% of the cells (95 % CI 3%–6%). The abundance of cells expressing pro-caspase-3 was independent from CASP3 mRNA levels (r = 0.24, p = 0.255) and did not correlate with the amount of cleaved caspase-3 (r = -0.24, p = 0.186). Multivariable logistic regression showed that pro-caspase-3 positivity was not influenced by clinical characteristics such as age, cause or length of infertility, antral follicle count or hormonal drugs used to induce ovulation. These findings suggest that pro-caspase-3 is constitutively expressed in LGC, allowing quick cleavage into active caspase-3 and apoptosis triggering whenever needed in the course of gonadotropin-induced follicular development.     

Cold urticaria – What we know and what we do not know

Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold-induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold-induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work-up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off-label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.     

鼻腔内机械振荡刺激对健康人群静息态脑电图相对功率及有效连接的影响

鼻腔内机械振荡刺激(iMVS)是一种新型的无创神经刺激技术, 可提升边缘系统内在功能活性从而改善自主神经平衡。通过分析iMVS对健康人群脑电图(EEG)相对功率以及EEG有效连接的影响,探索iMVS的神经生理机制。将22名健康成年被试随机均分为刺激组与对照组,并对11名刺激组被试两侧鼻腔各进行10 min的iMVS,11名对照组被试进行假刺激。在iMVS前和iMVS结束30 min后记录被试的静息态脑电图。采用Welch变换进行相对功率分析;采用直接定向传递函数(dDTF)进行有效连接分析;采用独立样本t检验、配对t检验以及FDR方法进行统计学分析。结果显示,iMVS后刺激组被试的alpha、beta频段EEG相对功率显著提升。刺激组alpha频段相对功率从51.57%±5.93%上升至57.33%±4.59%,其中C3、C4、T8、O1、O2导联的alpha频段相对功率提升显著(P<0.05);刺激组beta频段相对功率从7.28%±0.11%上升至8.36%±0.44%,其中C3、C4、T7、T8、O2导联的beta频段相对功率提升显著(P<0.05); iMVS后刺激组被试的alpha频段dDTF值显著提升,刺激组alpha频段dDTF值由0.052±0.0017提升至0.0592±0.0028,其中F4至F3、O2至F3、C4至F4、O2至F4、F3至C3、C4至C3、F3至T7、C4至T8、O2至O1方向的dDTF值显著提升(P<0.05)。刺激前后对照组的EEG相对功率以及EEG有效连接未见显著变化。大脑边缘系统的内在功能活性与alpha、beta频段EEG相对功率以及alpha频段EEG有效连接呈正相关。研究结果表明,在刺激结束30 min后iMVS技术对于边缘系统的内在功能活性具有提升作用。研究首次从脑电分析角度阐释iMVS改善自主神经平衡的相关机制,并为采用EEG相对功率和EEG有效连接作为iMVS效用评价的生物标记物提供证据。     

载荷作用下骨细胞分泌因子对成骨细胞和破骨细胞的调节

骨细胞是骨组织主要的力学感受及转导细胞,它们通过众多突触结构相互连接,形成庞大的骨稳态细胞调控网络,联系着成骨细胞、破骨细胞等骨基质表面细胞。骨细胞通过旁分泌途径影响成骨细胞骨形成和破骨细胞骨吸收来调节骨代谢,维持骨更新。针对骨细胞在受到力学刺激后分泌或释放的一些信号分子或蛋白因子对成骨细胞和破骨细胞生长分化的影响,本文综述近年来关于受力学刺激的骨细胞如何与成骨/破骨细胞进行通讯,为骨细胞生物力学研究提供新思路。     

Time efficiency of direct anterior hip arthroplasty compared to postero-lateral approach in elderly patients

IntroductionPrimary arthroplasty of the hip joint is currently one of the most commonly performed procedures in orthopedics. In Poland we are observing significant changes in the age structure. With the prolonged life more and more elderly patients require musculoskeletal surgery to maintain comfortable and painless mobility. Reducing the duration of the procedure reduces the costs of anesthesiology, surgical and instrument teams, as well as the operating room technical team. The aim of the study was to compare the time required to perform hip joint arthroplasty by the direct anterior approach (DAA) with the postero-lateral approach (PLA) in our hospital.Material and methodsA retrospective analysis of 559 total and bipolar cemented and cementless hip replacement procedures based on two operative approaches – the minimally invasive DAA over the course of 2 years, and the standard PLA over the course of 3 years – was performed.ResultsStatistically significant differences were observed between the approaches used for cementless total arthroplasty with regard to the mean treatment times: 51.9 min for the 272 DAA cases, and 78.3 min for the 190 PLA cases (p < 0.0001). For the cementless hemi-arthroplasty procedure, the mean treatment times were 46.9 min in 36 patients for DAA, and 48.2 min for 61 patients for PLA (p = 0.57).ConclusionsMinimally invasive DAA significantly shortens the time of the procedure in elderly patients compared to PLA. Further study is needed to analyze other aspects of those two approaches.     

基于经食管超声心动图的卵圆孔未闭形态与隐源性卒中的关系研究

目的 应用经食管超声心动图（tran s e so p h ageal e ch o card iograp hy,TEE）检查评估隐源性卒中 （cryptogenic stroke,CS）患者卵圆孔未闭（patent foramen ovale,PFO）的形态学特征,探讨PFO形态与 CS发生的关系。 方法 回顾性选取2015年3月-2020年1月于大连医科大学附属大连市中心医院行PFO封堵治疗的患 者95例,其中CS患者52例（CS组）,偏头痛患者43例（偏头痛组）。所有患者均于术前行TEE检查,静 息状态测量PFO宽度、PFO通道长度,评估PFO合并房间隔膨出瘤、永存下腔静脉瓣情况,Valsalva状态 测量PFO宽度,根据TCD发泡实验（contrast-enhanced transcranial Doppler,c-TCD）判断PFO右向左分流量, 以c-TCD双侧微泡栓子信号成帘状或淋浴型为大量右向左分流。比较CS和偏头痛患者PFO上述指标的 差异。 结果 CS组静息状态PFO宽度[1.6（1.1～2.0）mm]与偏头痛组[1.6（0.9～2.0）mm]比较,差异无统计学 意义,Valsalva状态PFO宽度（2.18±0.64 mm）大于偏头痛组（1.84±0.82 mm）（P =0.026）。CS组静息状 态PFO通道长度（9.63±4.42 mm）与偏头痛组（10.15±4.06 mm）比较差异无统计学意义,PFO合并房 间隔膨出瘤患者比例（44.2%）高于偏头痛组（20.9%）（P =0.017）,PFO合并永存下腔静脉瓣患者比 例（36.5%）高于偏头痛组（16.3%）（P =0.027）。CS组c-TCD大量右向左分流患者比例（90.4%）与偏 头痛组（76.7%）比较差异无统计学意义。logistic回归分析结果显示,Valsalva状态PFO宽度（OR 2.261, 95%CI 1.191～4.291,P =0.013）是CS发生的独立预测因子。 结论 Valsalva状态PFO宽度与CS发生有关,Valsalva状态PFO宽度是识别CS的有效参数。     

等位基因特异荧光PCR法检测CYP2C19基因型

目的了解人群CYP2C19基因型的分布,评价等位基因特异荧光PCR法检测CYP2C19基因型。方法等位基因特异荧光PCR法和金标准Sanger DNA直接测序法检测356名供者外周血CYP2C19基因型,实验采用同步盲法。结果 CYP2C19*1/*1型、CYP2C19*1/*2型、CYP2C19*2/*3型、CYP2C19*3/*3型、CYP2C19*2/*2型及CYP2C19*1/*3型的频率分布:使用PCR荧光法检测时分别为46.6%(166/356)、33.2%(118/356)、2.0%(7/356)、0.8%(3/356)、10.7%(38/356)及6.7%(24/356);采用DNA测序法时分别为46.3%(165/356)、33.4%(119/356)、2.0%(7/356)、0.8%(3/356)、11.0%(39/356)及6.5%(23/356)。两种方法检测CYP2C19基因型具有一致性(P=0.392),且一致性较好(Kappa=0.987);两种方法基因型检测结果一致率为99.2%。结论为保障医疗安全,临床需开展CYP2C19基因型检测;等位基因特异荧光PCR法检测CYP2C19基因型简便可靠。     

Theta-burst stimulation entrains frequency-specific oscillatory responses

BackgroundBrain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3–8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity.ObjectiveOur study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture.MethodsWe recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity.ResultsWe found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain.ConclusionsBy demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks.     

Neuromodulatory treatments for psychiatric disease: A comprehensive survey of the clinical trial landscape

BackgroundNumerous neuromodulatory therapies are currently under investigation or in clinical use for the treatment of psychiatric conditions.Objective/hypothesisWe sought to catalogue past and present human research studies on psychiatric neuromodulation and identify relevant trends in this field.MethodsClinicalTrials.gov (https://www.clinicaltrials.gov/) and the International Clinical Trials Registry Platform (https://www.who.int/ictrp/en/) were queried in March 2020 for trials assessing the outcome of neuromodulation for psychiatric disorders. Relevant trials were categorized by variables such as neuromodulation modality, country, brain target, publication status, design, and funding source.ResultsFrom 72,086 initial search results, 1252 unique trials were identified. The number of trials registered annually has consistently increased. Half of all trials were active and a quarter have translated to publications. The largest proportion of trials involved depression (45%), schizophrenia (18%), and substance use disorders (14%). Trials spanned 37 countries; China, the second largest contributor (13%) after the United States (28%), has increased its output substantially in recent years. Over 75% of trials involved non-convulsive non-invasive modalities (e.g., transcranial magnetic stimulation), while convulsive (e.g., electroconvulsive therapy) and invasive modalities (e.g., deep brain stimulation) were less represented. 72% of trials featured approved or cleared interventions. Characteristic inter-modality differences were observed with respect to enrollment size, trial design/phase, and funding. Dorsolateral prefrontal cortex accounted for over half of focal neuromodulation trial targets. The proportion of trials examining biological correlates of neuromodulation has increased.Conclusion(s)These results provide a comprehensive overview of the state of psychiatric neuromodulation research, revealing the growing scope and internationalism of this field.