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预混地塞米松的高分子自交联透明质酸水凝胶抑制软骨细胞凋亡缓解早期创伤性骨关节炎的作用机制

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中华医学杂志 2024年第9期104卷 695-703页

作者：张志伟赵静雅冯毅尹崑李鹏翠卫小春山西医科大学第二医院骨科骨与软组织损伤修复山西省重点实验室，太原030001 太原市人民医院内分泌科，太原030001

目的探究预混有地塞米松(Dex)的高分子自交联透明质酸(cHA)水凝胶(cHA-Dex水凝胶)抑制软骨细胞凋亡缓解早期创伤性骨关节炎(PTOA)的作用机制。方法取2月龄雄性SD大鼠140只分两组,70只进行前交叉韧带切断(ACLT)手术制造PTOA动物模型,以... 详细信息

目的探究预混有地塞米松(Dex)的高分子自交联透明质酸(cHA)水凝胶(cHA-Dex水凝胶)抑制软骨细胞凋亡缓解早期创伤性骨关节炎(PTOA)的作用机制。方法取2月龄雄性SD大鼠140只分两组,70只进行前交叉韧带切断(ACLT)手术制造PTOA动物模型,以假手术组(70只)为对照,在术后不同时间点(1~14 d,每组每个时间点5只大鼠)检测关节灌洗液中白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)、基质金属蛋白酶3(MMP-3)及MMP-13等炎性指标的变化趋势。将cHA-Dex(0.5 mg/ml)水凝胶(实验组,n=70)及预混有Dex的普通低分子透明质酸(HA)水凝胶,即HA-Dex(0.5 mg/ml)水凝胶(对照组,n=70)注入PTOA大鼠关节腔,检测每个时间点(1~14 d,每组每个时间点5只大鼠)大鼠关节液中的Dex的释放量及累计释放量,揭示cHA-Dex水凝胶的缓释机制。取2020年1月至2022年12月在山西医科大学第二医院关节科进行膝关节置换术后的骨关节炎(OA)患者(胫骨平台上Outbridge评分1~2分,n=18)膝关节软骨进行体外组织块培养,将预混有0.1、0.2、0.5 mg/ml三种梯度Dex浓度的cHA-Dex水凝胶处理软骨组织块后,检测关节软骨组织块中IL-1β、IL-6、TNF-α、MMP-3以及MMP-13的mRNA表达水平变化。运用酶解法分离出OA软骨细胞并进行体外原代培养(来自18例OA患者,分6次重复实验,每次3例患者的软骨细胞提取后混合均匀培养),软骨细胞贴壁后分为4组,分别进行下列干预:生理盐水干预组、cHA水凝胶干预组、Dex(0.5 mg/ml)干预组、cHA-Dex(0.5 mg/ml)水凝胶干预组,检测不同干预对软骨细胞增殖及凋亡的影响。结果大鼠PTOA组和假手术组膝关节番红O固绿染色国际骨关节炎协会(OARSI)评分分别为(3.34±0.35)分和(1.17±0.21)分(P=0.010);PTOA大鼠膝关节骨赘Meachim评分相对于假手术组增高[(2.66±0.41)分比(0.22±0.17)分,P=0.010],大鼠PTOA造模成功。与PTOA大鼠关节内炎症因子早期出现峰值变化规律相对应的cHA-Dex水凝胶中Dex也在早期释放,并在后期长期缓释。预混0.1、0.2、0.5 mg/ml Dex的cHA-Dex水凝胶处理OA关节软骨组织块后,组织块中的IL-1β、IL-6、TNF-α、MMP-3及MMP-13的mRNA表达均下降(均P<0.05)。体外培养OA软骨细胞,与Dex(0.5 mg/ml)水凝胶干预组相比,cHA-Dex(0.5 mg/ml)水凝胶干预组凋亡率明显减少(0.60±0.07比6.63±0.98,P=0.010)。相对生理盐水干预组或单纯cHA水凝胶干预组,cHA-Dex(0.5 mg/ml)水凝胶干预组细胞增殖明显,各时间点差异均有统计学意义(均P<0.05)。结论针对PTOA的早期炎症,cHA-Dex水凝胶可能通过缓释Dex,既可抑制软骨炎症,又可逆转Dex导致的软骨细胞凋亡增加、增殖率降低,最终缓解PTOA进展。

关键词：骨关节炎创伤性骨关节炎地塞米松高分子自交联透明质酸水凝胶软骨炎症因子凋亡增殖

屏风生脉胶囊联合单硝酸异山梨酯治疗冠心病心绞痛的临床研究

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现代药物与临床 2024年第5期39卷 1227-1231页

作者：吴裕勇张红媛韦晓春黄杏媚张宏亮河池市宜州区人民医院药剂科广西河池546300 河池市宜州区人民医院心血管内科广西河池546300 广西医科大学第一附属医院药学部广西南宁530021

目的探讨屏风生脉胶囊联合单硝酸异山梨酯片治疗冠心病心绞痛的临床疗效。方法选取2022年1月—2023年6月河池市宜州区人民医院共计120例冠心病心绞痛患者,以计算机随机排列法分为对照组(60例)和治疗组(60例)。对照组口服单硝酸异山梨酯... 详细信息

目的探讨屏风生脉胶囊联合单硝酸异山梨酯片治疗冠心病心绞痛的临床疗效。方法选取2022年1月—2023年6月河池市宜州区人民医院共计120例冠心病心绞痛患者,以计算机随机排列法分为对照组(60例)和治疗组(60例)。对照组口服单硝酸异山梨酯片,1片/次,2次/d。治疗组在对照组治疗的基础上口服屏风生脉胶囊,3粒/次,3次/d。两组治疗1个月。观察两组的心绞痛和心电图疗效,比较两组的心绞痛症状、心功能指标、血清指标。结果治疗后,治疗组的心绞痛总有效率比对照组高,差异显著(93.33%vs 80.00%,P<0.05)。治疗后,治疗组心电图总有效率比对照组高,差异显著(85.00%vs 70.00%,P<0.05)。治疗后,两组疼痛程度、持续时间、发作频率显著降低(P<0.05),治疗组的心绞痛症状低于对照组(P<0.05)。治疗后,两组的射血分数(EF)、心指数(CI)、每搏输出量(SV)比治疗前大(P<0.05),治疗组的EF、CI、SV比对照组大(P<0.05)。治疗后,两组的血清肌钙蛋白Ⅰ(c TnI)、心型脂肪酸结合蛋白(H-FABP)、肿瘤坏死因子受体相关因子6(TRAF6)、脂蛋白磷脂酶A2(Lp-PLA2)水平比治疗前小(P<0.05),治疗组的血清指标比对照组小(P<0.05)。结论冠心病心绞痛患者经屏风生脉胶囊联合单硝酸异山梨酯治疗,明显提高心绞痛和心电图疗效,降低心绞痛症状,改善心功能,降低心肌炎症损伤。

关键词：屏风生脉胶囊单硝酸异山梨酯片冠心病心绞痛疼痛程度持续时间发作频率射血分数心指数每搏输出量肌钙蛋白Ⅰ 心型脂肪酸结合蛋白肿瘤坏死因子受体相关因子6 脂蛋白磷脂酶A2

基底硬度介导IL-1β调控软骨细胞炎症响应

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太原理工大学学报 2024年第2期55卷 384-389页

作者：孟楠王笑笑张艳君陈维毅卫小春张全有太原理工大学生物医学工程学院山西晋中030600 山西医科大学第二医院骨与软骨组织损伤修复山西省重点实验室太原030001

【目的】基质力学微环境异常是导致骨性关节炎(osteoarthritis,OA)的关键因素之一。然而,软骨细胞在基质力学微环境发生变化过程中的炎症响应目前尚不清楚。【方法】利用聚二甲基硅氧烷(polydimethylsiloxane,PDMS)模拟正常和OA软骨细... 详细信息

【目的】基质力学微环境异常是导致骨性关节炎(osteoarthritis,OA)的关键因素之一。然而,软骨细胞在基质力学微环境发生变化过程中的炎症响应目前尚不清楚。【方法】利用聚二甲基硅氧烷(polydimethylsiloxane,PDMS)模拟正常和OA软骨细胞周基质(pericellular matrix,PCM)硬度,制备不同硬度的细胞培养基底,定量分析基底硬度和炎症因子白细胞介素-1β(interleukin-1β,IL-1β)协同作用对软骨细胞形态、炎症介质和基质重塑蛋白表达的影响。首先,定量分析了不同基底硬度和IL-1β对软骨细胞前列腺素E2(prostaglandin,PGE2)和一氧化氮(NO)分泌水平的影响;其次,采用免疫荧光技术分析了IL-1β对不同硬度基底上软骨细胞铺展面积和核面积的影响;最后,采用Western blot分析了不同硬度基底上软骨细胞Ⅱ型胶原(typeⅡcollagen,COLⅡ)和基质金属蛋白酶13(matrix metalloproteinase-13,MMP13)蛋白水平的表达。【结果】实验结果表明,基底硬度介导软骨细胞对炎症信号IL-1β的响应。软基底显著增强PGE2和NO释放量(P<0.0001)及MMP-13的蛋白表达水平(P<0.05),而IL-1β能进一步增强这一调控作用;硬基底能显著促进软骨细胞铺展面积、核面积(P<0.0001)和Ⅱ型胶原蛋白表达水平(P<0.01),IL-1β加入后同样能进一步增强这种调控作用。【结论】有助于揭示软骨细胞感受基质力学微环境的力学生物学调控机制,同时也为优化细胞诱导性生物材料的设计提供了参考。

关键词：软骨细胞基底硬度白细胞介素1β 细胞周基质 Ⅱ型胶原基质金属蛋白酶13

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六价铬对牛蛙心脏、骨骼肌和坐骨神经干生理功能的影响

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太原理工大学学报 2024年第2期55卷 365-375页

作者：张艳君张敬张全有李明臻李鹏翠卫小春陈维毅太原理工大学生物医学工程学院山西晋中030600 太原理工大学机械与运载工程学院太原030024 山西医科大学第二医院骨与软组织损伤修复山西省重点实验室太原030001

【目的】从电生理学角度研究六价铬对牛蛙心脏、腓肠肌和坐骨神经干动作电位的影响,探讨六价铬的毒性作用机制。【方法】将不同浓度重铬酸钾溶液通过腹腔注射和离体心脏灌流法处理牛蛙心脏,测定六价铬对在体和离体心脏心率和收缩力的影... 详细信息

【目的】从电生理学角度研究六价铬对牛蛙心脏、腓肠肌和坐骨神经干动作电位的影响,探讨六价铬的毒性作用机制。【方法】将不同浓度重铬酸钾溶液通过腹腔注射和离体心脏灌流法处理牛蛙心脏,测定六价铬对在体和离体心脏心率和收缩力的影响。用重铬酸钾溶液浸润好的纱布包裹腓肠肌,测定腓肠肌收缩力变化。采用细胞外电极引导法,测定六价铬对坐骨神经干动作电位传导速度的影响。【结果】结果显示:重铬酸钾对心率和收缩力具有抑制作用,机制分别与六价铬抑制T型钙通道活性和L型钙通道活性有关;然而1 mg/L铬对在体蛙心作用15 min至30 min后,心率增加,可能是“毒物兴奋效应”所致;0.001 mg/L至10 mg/L六价铬对腓肠肌收缩力具有浓度依赖性增强作用,表现为正性变力效应,可能是“毒物兴奋效应”的结果;100 mg/L六价铬抑制了腓肠肌收缩力,表现为负性变力效应,机制与六价铬对兰尼碱受体(Ryanodine receptor,RyR)的抑制作用有关;六价铬以质量浓度和时间依赖性降低了神经干动作电位传导速度,机制与六价铬对电压门控Na+通道产生的失活作用有关。【结论】六价铬对心肌、骨骼肌和神经均具有毒性作用,结果可为六价铬的毒性作用研究提供一定的电生理实验依据。

关键词：六价铬收缩力电位传导速度心脏骨骼肌坐骨神经干

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The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

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Neural Regeneration Research 2014年第2期9卷 171-178页

作者： Yongping Li Jie Lao Xin Zhao Dong Tian Yi Zhu xiaochun wei Department of Hand Surgery of HuaShan Hospital Fudan University Key Laboratory of Hand Reconstruction Ministry of Healthy Shanghai Key Laboratory of Peripheral Nerve and Microsurgery Department of Orthopedics the Second Hospital of Shanxi Medical University

The distance between the two electrode tips can greatly influence the parameters used for record- ing compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spac- ings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance be- tween two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed significantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no significant change. Different distances between recording and stimulating sites did not produce significant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference （however also required a higher threshold and higher supramaximal stimulus）, was found to be superior to the antidromic compound action potential.

关键词： nerve regeneration peripheral nerve injury compound nerve action potential mediannerve electrodes amplitude supramaximal stimulus intensity recording electrode the Project 211in China neural regeneration

Sr-Nd isotope stratification along water depth:An example from Datong hydrological station of Yangtze River

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Chinese Science Bulletin 2012年第34期57卷 4482-4490页

作者： LUO Chao ZHENG HongBo WU weiHua WANG Ping CHEN YuLiang wei xiaochun Key Laboratory of Surficial Geochemistry School of Earth Sciences and EngineeringNanjing UniversityNanjing 210093China School of Geography Nanjing Normal UniversityNanjing 210000China

This study examines the effects of hydrologic sorting and mixing of sources on the Sr-Nd isotopic compositions of suspended sediments at different water depths. The samples were collected from three layers (surface, middle and bottom) at Datong hydrological station of Yangtze River during the flood season of 2010. Our results show that, 87 Sr/ 86 Sr values decrease from surface to bottom, ranging from 0.730332 to 0.720857. ε Nd (0) values range from 14.75 to 10.09, with surface sediments being the most negative. The isotope composition at the middle layer can best represent the mean isotopic composition of the total suspended sediments transported by a river. It is believed that the stratification of Sr-Nd isotope is attributable to mixing of sediments from different sources due to hydrological sorting. Sediments from the upper stream are found to be coarser, and tend to contribute more to the lower water column. Although Sr-Nd isotope is a well acknowledged tool to trace sediment provenance, the current study suggests that the grain size of the samples and the sampling locations should be taken into consideration when applying this method to provenance study.

关键词： Sr-Nd同位素水文站长江水深悬浮沉积物同位素组成个例大通

A fluid flow model in the lacunar-canalicular system under the pressure gradient and electrical field driven loads

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Applied Mathematics and Mechanics(English Edition) 2022年第6期43卷 899-916页

作者： Xiaogang WU Xiyu WANG Chaoxin LI Zhaowei WANG Yuqin SUN Yang YAN Yixian QIN Pengcui LI Yanqin WANG xiaochun wei weiyi CHEN College of Biomedical Engineering Taiyuan University of TechnologyTaiyuan 030024China Shanxi Provincial Key Laboratory for Repair of Bone and Soft Tissue Injury Taiyuan 030001China

The lacunar-canalicular system(LCS)is acknowledged to directly participate in bone tissue *** fluid flow in the LCS is synergic driven by the pressure gradient and electric field loads due to the electro-mechanical properties of *** this paper,an idealized annulus Maxwell fluid flow model in bone canaliculus is established,and the analytical solutions of the fluid velocity,the fluid shear stress,and the fluid flow rate are *** results of the fluid flow under pressure gradient driven(PGD),electric field driven(EFD),and pressure-electricity synergic driven(P-ESD)patterns are compared and *** effects of the diameter of canaliculi and osteocyte processes are *** results show that the P-ESD pattern can combine the regulatory advantages of single PGD and EFD patterns,and the osteocyte process surface can feel a relatively uniform shear stress *** the bone canalicular inner radius increases,the produced shear stress under the PGD or P-ESD pattern increases slightly but changes little under the EFD *** increase in the viscosity makes the flow slow down but does not affect the fluid shear stress(FSS)on the canalicular inner wall and osteocyte process *** increase in the high-valent ions does not affect the flow velocity and the flow rate,but the FSS on the canalicular inner wall and osteocyte process surface increases *** this study,the results show that the shear stress sensed by the osteocyte process under the P-ESD pattern can be regulated by changing the pressure gradient and the intensity of electric field,as well as the parameters of the annulus fluid and the canaliculus size,which is helpful for the osteocyte mechanical *** established model provides a basis for the study of the mechanisms of electro-mechanical signals stimulating bone tissue(cells)growth.

关键词： bone canaliculi osteocyte process pressure gradient electricity fluid shear stress(FSS)

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

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Journal of Pharmaceutical Analysis 2024年第2期14卷 225-243页

作者： Bingjia Zhao Qian Zhang Yiqian He weifang Cao wei Song xiaochun Liang Department of Traditional Chinese Medicine Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China Institute of Basic Medicine Sciences Chinese Academy of Medical SciencesBeijing100005China Medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

关键词： Diabetic peripheral neuropathy JinMaiTong Energy metabolism Targeted metabolomics Adenosine monophosphate-activated protein kinase

激光治疗膝骨关节炎多途径生物效应的可能机制

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中国组织工程研究 2024年第34期28卷 5521-5527页

作者：娄鑫奇钟浩王熹宇冯皓宇李鹏翠卫小春王艳芹武晓刚陈维毅薛艳茹太原理工大学生物医学工程学院山西省太原市030024 山西白求恩医院(山西医学科学院同济山西医院) 山西医科大学第三医院山西省太原市030032 骨与软组织损伤修复山西省重点实验室山西省太原市030001

背景:激光疗法是一种无创、无痛的治疗手段,由于它操作简单和非侵入性的特点,被认为是治疗骨关节炎的适用方法。目前,激光疗法对组织的作用机制尚不明确,并且其临床应用的研究结果仍存在争议。目的:回顾总结激光疗法治疗膝骨关节炎在细... 详细信息

背景:激光疗法是一种无创、无痛的治疗手段,由于它操作简单和非侵入性的特点,被认为是治疗骨关节炎的适用方法。目前,激光疗法对组织的作用机制尚不明确,并且其临床应用的研究结果仍存在争议。目的:回顾总结激光疗法治疗膝骨关节炎在细胞水平、动物实验和临床疗效方面的最新研究进展,探讨激光介导多途径生物效应的可能机制,从而为进一步研究激光治疗膝骨关节炎提供理论基础。方法:在中国知网、万方数据、维普和PubMed数据库对2018-2023年发表的有关激光疗法治疗膝骨关节炎的文献进行检索,以“激光疗法,低强度激光疗法,高强度激光疗法,光生物调节,膝关节骨关节炎,软骨细胞”为中文检索词,以“laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes”为英文检索词。加上手工检索的14篇文献,最终纳入70篇文献进行综述。结果与结论:(1)激光疗法治疗膝骨关节炎主要分为高强度激光和低强度激光两种类型,激光参数和治疗方案的不同会对激光疗效产生直接影响;在使用适当的参数时,低强度激光在细胞实验、动物模型以及临床疗效方面都显示出积极的作用;高强度激光在膝骨关节炎治疗中的研究较少,但一些初步的临床研究结果显示出积极的效果;(2)细胞实验表明,低强度激光可促进软骨细胞增殖和软骨基质合成,从而降低炎症反应;(3)动物实验表明,低强度激光可以减少促炎症因子的释放,促进软骨基质合成,抑制基质降解,有效改善软骨组织的修复过程;低强度激光还能减轻膝骨关节炎过程中的氧化应激损伤,缓解疼痛;(4)在临床试验中,低强度激光和高强度激光均可以减轻患者疼痛,改善功能活动;激光疗法与运动治疗方式联合使用可能会提高治疗效果;(5)激光可能通过光生物效应或热力学效应影响细胞内的信号传导和细胞功能,为激光促进关节软骨再生提供了直接证据。

关键词：激光疗法低强度激光高强度激光膝关节骨关节炎软骨修复软骨细胞