High mobility group box-1-toll-like receptor 4-phosphatidylinositol 3-kinase/protein kinase B-mediated generation of matrix metalloproteinase-9 in the dorsal root ganglion promotes chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutics. The mechanisms of CIPN remain substantially unidentified, although inflammation-induced peripheral sensitization has been indicated as an important factor. Here, we aimed to illustrate the role of the matrix metalloproteinase (MMP)-9-related signaling pathway in the process of CIPN. Oxaliplatin (L-OHP) was administered to mice to establish the CIPN model. Gelatin zymography was used to measure MMP-9/2 activities. Western blotting and immunohistochemistry were used to measure the expression of high-mobility group box-1 (HMGB-1), calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1. Mechanical withdrawal was measured by von Frey hairs testing. Raw 264.7 cells and SH-SY5Y cells were cultured to investigate cell signaling in vitro. Here, we report that L-OHP-induced mechanical pain in mice with significant MMP-9/2 activation in dorsal root ganglion (DRG) neurons. MMP-9 inhibition or knockout alleviated the occurrence of CIPN directly. MMP-9/2 were released from macrophages and neurons in the DRG via the HMGB-1-toll-like receptor 4 (TLR4)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) axis, because MMP-9/2 activities could be reduced by macrophage scavengers or PI3Kγ knockout in CIPN mice. The in vitro data revealed that induced MMP-9 activity by recombinant HMGB-1 could be abolished by TLR4, PI3K or Akt inhibitors. Finally, it was shown that N-acetyl-cysteine (NAC) could reduce MMP-9/2 activities and attenuate CIPN effectively and safely. The HMGB-1-TLR4-PI3K/Akt-MMP-9 axis is involved in the crosstalk between macrophages and neurons in the pathological process of CIPN in mice. Direct inhibition of MMP-9 by NAC may be a potential therapeutic regimen for CIPN treatment.     

基于微信平台的翻转课堂在神经病学教学中的应用

目的　探讨基于微信平台的翻转课堂在神经病学教学中的应用及其效果。方法　以浙江中医药大学滨江学院2014级临床医学专业学生为教学对象，设一班、三班共74名学生为实验组，二班38名学生为对照组。选择周围神经病、神经肌肉-接头疾病为教学内容，实验组采用翻转课堂教学，并利用微信平台进行课前预习、课后复习和互动交流；对照组采用传统教学。两组学生课前和课后分别进行微测试、不记名问卷调查；课程结束后统一进行期末考试，其中包含病例分析题，记录并分析每组学生期末考试和病例分析题成绩。所有数据用SPSS 20.0处理，行t 检验或卡方检验。结果　实验组学生的课后微测试成绩明显高于对照组（P=0.038）；期末考试成绩高于对照组（P=0.046），且期末考试中病例分析题得分高于对照组（P=0.026）。课前问卷调查显示，在学习内容了解程度和预习情况的评价上，实验组选择“良”的学生比例高于对照组（P<0.05）。课后问卷调查显示，实验组在学习兴趣的评价中选择“优”“良”的学生比例均高于对照组（P<0.05）；自学能力评价中选择“良”的学生比例、临床思维能力和教学满意度评价中选择“优”的学生比例均高于对照组（P<0.05）；且实验组在所有项目评价中选择“优”“良”的学生总体比例均高于对照组（P<0.05）。课后实验组学习兴趣评价中选择“优”“良”的学生总体比例高于课前（P<0.01）。结论　基于微信平台的翻转课堂在神经病学教学中的应用可行且有效，可弥补传统教学的不足，有助于提高学生的学习兴趣和自主学习能力、锻炼学生的临床思维，值得推广。     

互动平台在膝关节置换手术护理培训中的应用

目的探讨基于优慕网(UMU)互动平台下的混合式教学在膝关节置换手术(TKA)护理培训中的应用价值。 方法选取广州医科大学附属第一医院参加TKA护理培训计划的手术室护士，根据培训批次，将2020年11月至12月参加培训的护士30人作为对照组，采用传统培训模式；将2021年5月至6月参加培训的护士30人作为观察组，采用基于UMU互动平台下的混合式教学模式。完成培训1周后，进行理论与操作考核；两组培训成员的6个月单独配合率比较采用卡方检验；两组理论成绩、操作成绩、与同一组医生进行TKA的平均手术用时比较采用t检验；两组手术的配合能力满意度采用非参数检验。 结果观察组的理论考核分数、操作考核分数均显著高于对照组(t＝3.870、5.142，均为P<0.05)。培训结束后6个月内，观察组单人器械护士的单独配合率为84.9%，显著高于对照组的46.9%(χ²＝16.516, P<0.05)。观察组的手术配合能力满意度明显优于对照组(Z＝5.138, P<0.05)。观察组的平均手术时间为(152±10)min，显著短于对照组的(160±11)min(t＝3.542, P<0.05)。 结论将基于UMU互动平台下的混合式教学应用于TKA护理培训中效果较优，值得进一步推广。     

Association of heart rate and diabetes among 0.5 million adults in the China Kadoorie biobank: Results from observational and Mendelian randomization analyses

Background and aimsObservational studies have associated resting heart rate with incident diabetes. Whether the associations are causal remains unclear. We aimed to examine the shape and strength of the associations and assessed the causal relevance of such associations in Chinese adults.Methods and resultsThe China Kadoorie Biobank enrolled 512,891 adults in China. Cox proportional hazard regression models was conducted to estimate hazard ratios (HRs) for the associations of resting heart rate with type 2 diabetes and total diabetes. Among 92,724 participants, 36 single-nucleotide polymorphisms (SNPs) related to resting heart rate were used to construct genetic risk score. We used Mendelian randomization analyses to make the causal inferences. During a median follow-up of 9 years, 7872 incident type 2 diabetes and 13,349 incident total diabetes were documented. After regression dilution bias adjustment, each 10 bpm higher heart rate was associated with about a 26% higher risk of type 2 diabetes (HR, 1.26 [95% CI, 1.23, 1.29]) and 23% higher risk of total diabetes (HR, 1.23 [95% CI, 1.20, 1.26]). Instrumental variable analyses showed participants at top quintile compared with those at bottom quintile had 30% higher risk for type 2 diabetes (HR, 1.30 [95% CI, 1.17, 1.43]), and 10% higher risk for total diabetes (HR, 1.10 [95% CI, 1.02, 1.20]).ConclusionsThis study provides evidence that resting heart rate is an important risk factor for diabetes risk. The results suggest that novel treatment approaches targeting reduction of high heart rate for incidence of diabetes may be worth further investigation.     

Recognition of moyamoya disease and its hemorrhagic risk using deep learning algorithms:sourced from retrospective studies

Although intracranial hemorrhage in moyamoya disease can occur repeatedly, predicting the disease is difficult. Deep learning algorithms developed in recent years provide a new angle for identifying hidden risk factors, evaluating the weight of different factors, and quantitatively evaluating the risk of intracranial hemorrhage in moyamoya disease. To investigate whether convolutional neural network algorithms can be used to recognize moyamoya disease and predict hemorrhagic episodes, we retrospectively selected 460 adult unilateral hemispheres with moyamoya vasculopathy as positive samples for diagnosis modeling, including 418 hemispheres with moyamoya disease and 42 hemispheres with moyamoya syndromes. Another 500 hemispheres with normal vessel appearance were selected as negative samples. We used deep residual neural network(Res Net-152) algorithms to extract features from raw data obtained from digital subtraction angiography of the internal carotid artery, then trained and validated the model. The accuracy, sensitivity, and specificity of the model in identifying unilateral moyamoya vasculopathy were 97.64 ± 0.87%, 96.55 ± 3.44%, and 98.29 ± 0.98%, respectively. The area under the receiver operating characteristic curve was 0.990. We used a combined multi-view conventional neural network algorithm to integrate age, sex, and hemorrhagic factors with features of the digital subtraction angiography. The accuracy of the model in predicting unilateral hemorrhagic risk was 90.69 ± 1.58% and the sensitivity and specificity were 94.12 ± 2.75% and 89.86 ± 3.64%, respectively. The deep learning algorithms we proposed were valuable and might assist in the automatic diagnosis of moyamoya disease and timely recognition of the risk for re-hemorrhage. This study was approved by the Institutional Review Board of Huashan Hospital, Fudan University, China(approved No. 2014-278) on January 12, 2015.     

冠状动脉临界病变血管内超声检查参数与定量血流分数的相关性研究

目的探讨冠状动脉临界病变血管内超声(IVUS)检查参数与定量血流分数(QFR)的相关性。方法前瞻性连续入选2018年9月至2019年9月于同济大学附属东方医院接受QFR和IVUS检查的116例患者(117处冠状动脉临界病变)。根据QFR评估结果,将患者分为QFR≤0.80组(25处病变)和QFR>0.80组(92处病变),比较两组IVUS检查参数的差异。应用Poisson线性相关性分析以及受试者工作特征(ROC)曲线评估IVUS与QFR的相关性,应用logistic多元回归分析QFR≤0.80的预测因素。结果IVUS检查发现,QFR≤0.80组最小管腔面积(MLA)[(3.1±0.8)mm²比(3.6±1.1)mm²,P=0.040]、最小管腔直径(MLD)[(1.8±0.3)mm比(2.0±0.3)mm,P=0.012]显著小于QFR>0.80组,而斑块负荷[(73.5±5.6)%比(68.0±8.4)%,P=0.002]、面积狭窄率[(69.8±8.8)%比(63.8±9.8)%,P=0.007]、斑块偏心指数[(0.83±0.12)比(0.73±0.19),P=0.008]及回声消减斑块比例(52.0%比23.9%,P=0.003)显著高于QFR>0.80组,差异均有统计学意义。Poisson线性相关分析显示,MLA(r=0.259,P=0.005)、MLD(r=0.300,P=0.001)与QFR正相关,而斑块负荷(r=–0.357,P<0.001)以及斑块偏心指数(r=–0.247,P=0.008)与QFR负相关。logistic多因素回归分析表明斑块负荷>70%(OR 4.531,95%CI 1.443~14.222,P=0.010)和斑块偏心指数(OR 1.066,95%CI 1.014~1.121,P=0.012)为QFR≤0.80的独立预测因素。结论冠状动脉临界病变IVUS检查结果中斑块负荷>70%以及斑块偏心指数是QFR≤0.80的独立预测因子。     

生化汤加味促进剖宫产后子宫复旧随机对照试验的系统评价及Meta分析＊

目的 对生化汤加味促进剖宫产后子宫复旧的有效性与安全性进行系统评价，为其在临床应用提供循证医学证据。方法 检索中国生物医学文献数据库（CBM）、中国知网（CNKI）、万方资源数据库（WanFang）、维普期刊数据库（VIP）、Cochrane Library、PubMed、Web of Science等，检索时限为建库至2020年7月，选择生化汤加味促进剖宫产后子宫复旧的随机对照试验（RCT），采用Cochrane系统评价员手册提供的偏倚风险评估工具进行文献质量评价，应用RevMan5.3软件进行Meta分析。结果 共纳入12篇RCT文献，共计1804例剖宫产产妇；Meta分析结果显示，生化汤加味联合缩宫素组在产后第1、3、5天子宫底高度［MD = -0.75，95%CI（-1.35， -0.15），P < 0.00001；MD = -1.92，95%CI（-3.13， -0.72），P < 0.00001；MD = -1.92，95%CI（-3.79， -0.06），P < 0.00001］低于单用缩宫素组，联合用药组血性恶露时间［MD = -1.52，95%CI（-2.71，-0.34），P < 0.00001］和产后恶露持续时间［MD = -4.47，95%CI（-6.20，-2.75），P < 0.00001］均短于单用缩宫素组。结论 生化汤加味联合缩宫素与单用缩宫素比较，更能促进产后子宫复旧；不良反应少，报道的仅有4例出现轻微腹泻，安全性较高；但由于纳入文献质量较低，上述结论尚需更多的随机对照临床研究加以证实。     

基于红外热成像技术的膝骨性关节炎患者穴位体表温度规律研究＊

目的 观察膝骨性关节炎患者穴位体表温度分布规律。方法 以256例膝骨性关节炎患者和256例健康受试者为观察对象。使用Fotric 226红外热像仪检测患者和健康受试者腧穴的温度值，每名患者每周固定时间检测1次，共检测4次，健康人检测1次，比较患者组与健康受试者组穴位温度值的差异，比较不同时间点不同部位、经脉温度值的差异。结果 膝骨性关节炎患者血海穴、鹤顶穴、梁丘穴、曲泉穴、内膝眼穴、犊鼻穴、委阳穴、阴陵泉穴、膝关穴、阳陵泉穴、大杼穴、悬钟穴、足三里穴、命门穴、腰阳关穴温度值高于健康受试者（P < 0.05）；患者组胃经的4次皮温均较高（P < 0.05），腰背部的4次皮温均较高（P < 0.05）；KOA相关腧穴4次温度值变化趋势不显著（P > 0.05）。结论 膝关节骨性关节炎患者部分腧穴皮温升高；膝骨性关节炎患者的穴位升温现象具有规律性，与经络、部位相关；膝关节骨性关节炎相关穴位升温效应具有稳定性。     

Turning duration and steps predict future falls in poststroke hemiplegic individuals: A preliminary cohort study

ABSTRACT

Introduction: Turning was reported as one of the activities that most frequently leads to falling among stroke patients. This study investigated whether the duration and steps of a 180° turn while walking can distinguish retrospective fallers from non-fallers and predict future falls in a 1-year period in patients with poststroke hemiplegia.

Methods: Thirty stroke patients were recruited. They were instructed to get up from a chair, walk straight 3 m, turn around, and return to seated position to assess the 180° walking-turn task. Turning performance was measured by two inertial sensor units of Physilog. Turn duration and steps were recorded for analysis. The numbers of retrospective and prospective falls were also obtained.

Results: No significant difference was observed between retrospective stroke fallers and non-fallers in turn duration and steps. Turn duration and steps were significantly greater in prospective stroke fallers than in non-fallers. The cutoff turn duration of 4 s (area under the curve 0.75, 95% CI: 0.56–0.93, sensitivity 67%, specificity 80%, p =.04) and turn step of 7 steps (area under the curve 0.73, 95% CI: 0.51–0.94, sensitivity 56%, specificity 85%, p =.05) were found to most accurately predict prospective stroke fallers from non-fallers.

Conclusions: Turn duration and steps were unable to discriminate between retrospective fallers and non-fallers but could predict prospective falls in patients with stroke. More than 4 s or 7 steps to complete a 180° turn while walking can be a predictor for patients with stroke at an increased risk of falling.