An inverted ankle joint orientation at foot strike could incite ankle inversion sprain: Comparison between injury and non-injured cutting motions of a tennis player

Ankle sprain is very common in sports. Research on its prevention is as important as on its treatment as recommended in the 2016 consensus statement of the International Ankle Consortium. Successful prevention depends on the understanding of its mechanism, which has been presented with quantities in some recent case reports. Inciting event was suggested to be an inverted ankle joint at foot strike, however, is still lacking evidence from comparison with non-injury trials. This study investigated the ankle joint orientation at foot strike in successful non-injury cases and compared them with a previously analysed ankle sprain injury case. Two injury-free cutting motions with similar movement approach to a previously analysed ankle sprain injury performed by the same athlete were collected from an online search and were trimmed from 0.05 s before until 0.30 s after the foot strike. The video sequences were then processed by video editing software and then analysed by a model-based image-matching motion analysis technique. Ankle joint orientation at foot strike and the profiles were presented in inversion, plantarflexion and rotation planes, for both the previously analysed injury case and the two non-injury cases. The ankle joint orientation at foot strike was 0–1 degree inverted and 10–21° dorsiflexed in the two non-injury cases, compared to 14° inverted and 16° plantarflexed in the previously analysed injury case. From the case comparison, it can be observed that an inverted ankle joint orientation at foot strike in an inciting event of ankle inversion sprain.     

Simultaneous bilateral versus unilateral tibial tubercle fractures

PurposeTibial tubercle/tuberosity fractures are rare injuries in young patients accounting for less than one percent of physeal fractures. Bilateral simultaneous fractures are even rarer, with only a few case reports in literature. The purpose of our study was to describe the largest case series of bilateral simultaneous tibial tuberosity avulsion fractures and compare it with unilateral fractures. We also wanted to compare our bilateral fractures case series with all the cases reported in the last 65 years.MethodsIRB approved retrospective study involving patients under age 18 years with tibial tuberosity avulsion fractures. Bilateral simultaneous fractures were compared to a unilateral group including demographic data, mechanism of injury, clinical exam findings, complication rates, and outcomes including return to function. Statistical analysis was performed using Mann-Whitney and Fisher Exact tests to compare the different groups.Results138 patients (131 males, 7 females) from a tertiary children’s hospital between 2012 and 2019 with tibial tuberosity avulsion fractures were included. 11 bilateral simultaneous fractures (BL Group) were identified and compared to age matched cohort from the 127 unilateral fracture patients (UL group). There was no significant difference found in BMI, height, weight, age, sex, mechanism of injury, return to functional range of motion, and return to sports between the groups. 7/11 (63%) of the patients in the BL group who sustained simultaneous fractures had to be home bound and could not attend school for an average of 8.3 weeks. There was a higher rate of complications in the BL group (63.3%) compared to the UL group (21.1%), which was statistically significant. The most common complications in the bilateral group were hardware removal and wound dehiscence.ConclusionThis first case series comparing unilateral versus bilateral simultaneous tibial tuberosity avulsion fractures suggests that the final outcomes of the two groups are similar, however it shows a significantly higher complication rate and hardware removal rate in the BL group. This study is also the first to highlight the significant initial morbidity in the BL fracture group with issues with regards to early mobility and loss of school-days. Keeping in mind the profound initial impact the bilateral injury poses to the patient; surgeons can possibly plan for rigid fixation for early mobilization to better prepare bilateral fracture patients for the early post-operative recovery process.     

3种抗肿瘤有毒蒙药的研究进展

随着社会发展和生活水平的提高,恶性肿瘤已经成为影响人类健康的重大疾病之一。有毒蒙药在治疗疾病及救治疑难杂症中具有重要作用。多种有毒蒙药有一定的抗肿瘤作用,且有着良好的治疗效果,但由于其本身的毒性,使其在临床上的应用受到很大的限制。蒙医在实践中不断摸索出有毒蒙药的多种减毒方法,如采用配伍、炮制等减毒手段进行处理,以达到降低毒性、提高疗效的作用。通过对3种代表性有毒蒙药斑蝥Mylabris、草乌Aconiti Kusnezoffii Radix、瑞香狼毒Stellerae Chamaejasmes Radix的抗肿瘤作用、毒性机制及减毒策略进行综述,为其临床用药及新药开发提供依据。     

基于网络药理学探究防风中生物活性成分及对类风湿关节炎的作用机制

目的 通过以网络药理学为基础的策略研究防风治疗类风湿关节炎（rheumatoid arthritis,RA）的分子生物学机制。方法 采用网络药理学方法收集防风活性成分和治疗RA的潜在靶点,并评估活性成分的药理和毒理学等相关参数;构建蛋白质相互作用网络筛选核心靶点,并通过生物信息学方法进一步验证核心靶点和疾病的关联;对核心成分和相应靶点进行分子对接。体外通过CCK-8实验、细胞迁移和侵袭、细胞凋亡、qRT-PCR和Western blotting分析,阐明别欧前胡素对MH7A细胞磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase,PI3K）/蛋白激酶B（protein kinase B,Akt）通路的调控作用。结果 从防风中共鉴定出18种活性成分和66个与筛选出的RA疾病靶基因相交的潜在靶基因,最终获得了汉黄芩素、β-谷甾醇、5-O-甲基维斯阿米醇和别欧前胡素等核心成分。防风治疗RA的潜在机制可能是通过调控PI3K/Akt、白细胞介素-17（interleukin-17,IL-17）、凋亡等信号通路和多种生物过程来实现,以发挥抗炎和免疫调节作用。分子对接证实了所有的核心成分和关键靶点均具有很好的对接活性。别欧前胡素抑制MH7A细胞的活力、迁移和侵袭（P＜0.05、0.01）,诱导细胞凋亡（P＜0.01）,并显著下调IL-1β、IL-6、IL-8、基质金属蛋白酶-1（matrix metalloproteinase-1,MMP-1）和MMP-3的基因表达（P＜0.01）。分子分析表明别欧前胡素通过抑制PI3K/Akt通路发挥对MH7A的调控作用。结论 成功预测了防风治疗RA的有效成分和潜在靶点,为进一步探究其分子机制提供了新的理论基础。揭示了别欧前胡素通过PI3K/Akt通路抑制RA成纤维样滑膜细胞的活力、迁移、侵袭及细胞因子和MMPs的表达,并诱导细胞凋亡。     

有机溶液环境下中药成分的纳滤分离机制及适用性研究策略

随着有机溶液在中药制药领域应用的逐渐普遍,涉及到提取、醇沉、树脂洗脱剂成分制备等环节,从而衍生出衔接性的热处理精制引起中药成分转化、溶剂污染等问题。纳滤具有常温化分离优势,但适用于水溶液的分离模型在有机溶液中存在明显的局限性。通过综述纳滤分离机制,结合复杂溶液体系下中药成分的真实状态和传质行为,以期发现适用于有机溶液环境的中药成分纳滤分离研究策略,提升纳滤技术在中药制药领域的适用性,推动中药资源的合理化利用。     

Fifty years of the mitochondrial pyruvate carrier: New insights into its structure,function, and inhibition

The mitochondrial pyruvate carrier (MPC) resides in the mitochondrial inner membrane, where it links cytosolic and mitochondrial metabolism by transporting pyruvate produced in glycolysis into the mitochondrial matrix. Due to its central metabolic role, it has been proposed as a potential drug target for diabetes, non-alcoholic fatty liver disease, neurodegeneration, and cancers relying on mitochondrial metabolism. Little is known about the structure and mechanism of MPC, as the proteins involved were only identified a decade ago and technical difficulties concerning their purification and stability have hindered progress in functional and structural analyses. The functional unit of MPC is a hetero-dimer comprising two small homologous membrane proteins, MPC1/MPC2 in humans, with the alternative complex MPC1L/MPC2 forming in the testis, but MPC proteins are found throughout the tree of life. The predicted topology of each protomer consists of an amphipathic helix followed by three transmembrane helices. An increasing number of inhibitors are being identified, expanding MPC pharmacology and providing insights into the inhibitory mechanism. Here, we provide critical insights on the composition, structure, and function of the complex and we summarize the different classes of small molecule inhibitors and their potential in therapeutics.     

基于网络药理学的三仙汤治疗骨质疏松症作用机制研究

目的通过网络药理学方法探讨三仙汤干预骨质疏松症(OP)的有效成分、作用靶点及信号通路等,从而明确其作用机制。方法应用中药系统药理学数据库与分析平台(TCMSP)检索获得三仙汤中3味药物的化学成分,通过Uniprot数据库,将已筛选出的靶点名称进行标准化。通过Genecards、OMIM数据库检索骨质疏松症的相关靶基因。将药物靶点与疾病靶点取交集,筛选得到疾病-药物成分共同靶蛋白在String网站构建蛋白-蛋白相互作用(PPI)网络模型。在Cytoscape软件中绘制药物、疾病、靶基因网络图,并进行基因GO功能和KEGG通路富集分析,探讨三仙汤治疗骨质疏松症的作用机制。结果通过数据库筛选得到三仙汤的28种有效成分以及与骨质疏松症相关的靶点127个,其中蛋白激酶、白介素6、血管内皮生长因子等基因为PPI网络中的核心基因; GO富集分析显示靶点主要影响核受体活性、转录因子活性、类固醇激素受体活性、细胞因子受体结合、蛋白质异二聚活性、血红素结合等生物过程;以及影响AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化通路、IL-17信号通路、前列腺癌通路、肿瘤坏死因子信号通路、乙型肝炎等信号通路。结论三仙汤中的有效成分通过关键信号通路作用于核心基因,影响细胞分化、凋亡、炎症、氧化应激等多种生物学过程发挥抗骨质疏松的作用,为其后续研究提供了科学依据。     

生信分析肾阴虚型绝经后骨质疏松症分子机制及熟地黄靶向治疗

目的基于生信数据挖掘探究肾阴虚型绝经后骨质疏松症的病理机制及熟地黄的治疗靶点。方法通过GEO数据库挖掘阴虚型绝经后骨质疏松症患者差异表达基因,运用GeneCards及OMIM数据库预测骨质疏松症相关基因,采用R软件对阴虚靶点与骨质疏松靶点映射匹配。借助String数据库在线平台进行蛋白互作网络构建。分子对接预测熟地黄治疗阴虚型骨质疏松症的靶点。采用DAVID数据库进行生物过程及通路注释。结果通过分析得到差异表达基因1 272个,骨质疏松症靶点662个,阴虚型骨质疏松症相关靶点45个,主要涉及细胞凋亡调节、雌激素应答、骨骼肌系统发育等生物过程,并由PI3K-Akt、Wnt信号通路、MAPK信号通路、卵巢类固醇生成等信号通路调节。熟地2种有效成分能够作用于核心蛋白IGF1、VEGFA等。结论熟地黄可能靶向IGF1、VEGFA等核心蛋白,通过PI3K-Akt、MAPK等信号通路调节细胞凋亡及雌激素应答过程,从而实现防治阴虚型骨质疏松症的疗效。     

基于辨证论治结合网络药理学探析六味地黄丸治疗绝经后骨质疏松症作用机制

目的 基于临床试验结合网络药理学探析六味地黄丸治疗绝经后骨质疏松症的作用机制。方法 ①将60例肾阴虚证绝经后骨质疏松症患者随机分为治疗组和对照组,两组患者在口服维生素D和钙剂的同时,治疗组口服六味地黄丸、对照组口服雷洛昔芬,治疗6个月后测定并比较两组患者腰椎（L1～4）、右侧股骨颈骨密度值、血清骨钙素(OCN)及血清抗酒石酸酸性磷酸酶-5b（TRAP-5b）水平。②依据TCMSP数据库筛选出六味地黄丸活性成分及其对应的靶点,通过GeneCards、OMIM、Drugbank 3个数据库获取绝经后骨质疏松症相关靶点,将活性成分靶点与绝经后骨质疏松症相关靶点取交集所得靶点即为六味地黄丸治疗绝经后骨质疏松症靶点。采用Cytoscape3.7.2软件构建活性成分、靶点以及蛋白间的相互作用网络,使用STRING数据库进行PPI网络分析,运用Metascape数据分析平台进行GO生物过程富集以及KEGG通路富集分析。结果 与治疗前比较两组均可提升骨密度,反映骨形成指标的OCN值明显升高,骨吸收指标的TRAP-5b值则明显降低,且治疗组优于对照组（P＜0.05）。而通过网络药理学预测显示六味地黄丸作用于绝经后骨质疏松症的活性成分有36个,位居前三位的活性成分为槲皮素、山奈酚、儿茶素,主要靶点为干扰素调节因子-1（IRF1）、抑瘤素M（OSM）、白介素6（IL-6）。GO富集分析显示,生物过程主要涉及到细胞因子介导的信号通路、细胞凋亡信号通路等;细胞组成主要包括蛋白激酶复合物、质膜蛋白复合物等;分子功能主要包括转录因子结合、核受体活性等。KEGG富集分析获取相关信号通路为JAk-STAT、Wnt及NF-κB信号通路。结论 六味地黄丸可显著增加骨密度、促进骨形成、抑制骨吸收,而其作用机制在于应用槲皮素、山奈酚、儿茶素等活性成分,以IRF1、OSM及IL-6为主要靶点,通过JAk-STAT、Wnt及NF-κB等信号通路发挥改善绝经后骨质疏松症的作用。