背景:研究发现,淫羊藿苷可促进小鼠前成骨细胞增殖分化.核因子κB信号通路和细胞自噬在成骨细胞分化调节中发挥重要作用,两者是否参与调节淫羊藿苷对小鼠前成骨细胞增殖分化的影响尚不清楚.目的:探讨淫羊藿苷对小鼠前成骨细胞增殖分化的影响以及核因子κB信号通路和细胞自噬在其中的作用.方法:①筛选出淫羊藿苷的最佳干预浓度:将小鼠前成骨细胞MC3T3-E1细胞分为空白对照组及不同浓度(0.01,0.1,1,10,100μmol/L)的淫羊藿苷组,MTS检测淫羊藿苷干预后各组小鼠前成骨细胞增殖活性;茜素红染色评估成骨分化水平;Western blot检测淫羊藿苷干预后各组小鼠前成骨细胞成骨分化能力和自噬活性;②加入3-甲基腺嘌呤抑制自噬:实验设置4组,对照组、3-甲基腺嘌呤组、淫羊藿苷组、3-甲基腺嘌呤+淫羊藿苷组,茜素红染色观察细胞矿化结节;Western blot检测细胞碱性磷酸酶、Runx2、p62、LC3、NF-κB p65、p-NF-κB p65蛋白的表达情况.结果 与结论:①淫羊藿苷能促进小鼠前成骨细胞增殖,浓度为10μmol/L时效果最明显(P<0.05);10μmol/L淫羊藿苷组矿化结节形成明显多于空白对照组,碱性磷酸酶、Runx2蛋白表达显著增加(P<0.05);与空白对照组相比,10μmol/L淫羊藿苷组Beclin1、LC3Ⅱ/LC3Ⅰ表达显著增加,p62表达减少(P<0.05);②予3-甲基腺嘌呤抑制自噬后,与淫羊藿苷组相比,3-甲基腺嘌呤+淫羊藿苷组碱性磷酸酶、Runx2、LC3Ⅱ/LC3Ⅰ表达减少,p62表达增加(P<0.05);③与对照组相比,淫羊藿苷组p-p65/p65表达减少(P<0.05);④结果提示,淫羊藿苷可能通过抑制核因子κB信号通路和增强自噬促进MC3T3-E1细胞成骨分化.

目的 观察补肾活血协定方治疗膝关节骨性关节炎(knee osteoarthritis,KOA)(肾虚血瘀证)的疗效.方法 选取2018年2月—2020年2月医院收治的KOA患者186例,按照随机数字表法将患者分为对照组(n=93例)和观察组(n =93例).对照组给予依托考昔片口服,观察组在对照组基础上加用补肾活血协定方口服,连续治疗2个月.分别以疼痛视觉模拟评分法(visual analogue scale,VAS)、美国特种外科医院量表(hospital for special surgery scores,HSS)评价膝关节疼痛程度与膝关节功能,用膝关节高频超声检查软骨厚度、滑膜厚度,检测关节液中肿瘤坏死因子-α(tumor necro-sis factor-α,TNF-α)、Toll样受体-4(Toll-like receptor 4,TLR-4)、P物质(Substance P,SP)含量及血清中脂联素(ad-iponectin,APN)、低氧诱导因子1α(hypoxic induction factor-1α,HIF-1α)水平,对比两组治疗效果.结果:观察组的有效率93.55％ (87/93),与对照组82.79％ (77/93)的有效率比较,以观察组显著升高(x2 =5.155,P＜0.05);两组患者的VAS评分在治疗治疗2周、治疗4周后均降低,HSS评分在治疗2周、治疗4周后均升高,以观察组VAS评分显著高于对照组,HSS评分显著高于对照组(P＜0.05);治疗后,两组在增加关节软骨厚度、降低滑膜厚度等方面均具有一定效果,以观察组软骨厚度增加程度、滑膜厚度降低程度更明显(P＜0.05);观察组患者经治疗后关节液中TNF-α、TLR-4、P物质水平均显著低于对照组(P＜0.05);血清APN水平显著升高,HIF-1α水平显著降低(P＜0.05).结论 补肾活血协定方利于减轻膝骨性关节炎患者的关节疼痛,提高膝关节功能,其机制可能与调节关节液、血清中相关因子水平以减轻滑膜炎症、调节软骨代谢有关,值得进行临床推广.

Background: Microendoscopic discectomy (MED) and percutaneous transforaminal endoscopic discectomy (PTED), as two alternative surgical techniques in minimally invasive spine surgery (MISS), are widely conducted in the treatment of upper lumbar disc herniation (ULDH). This study will systematically assess and compare the clinical outcomes of MED and PTED in treating ULDH combining with the meta-analysis. Methods: All the randomized controlled trials (RCTs) will be searched at the databases including PubMed, EMBASE, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP), and WANFANG Database from inception to December 2025. The primary outcome will involve Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and visual analog scale (VAS) scores. The secondary outcomes will be the short-form 36-item (SF-36) health survey questionnaire and themodifiedMacNab criterion. Wewill perform data synthesis, subgroup analysis, sensitivity analysis, meta-regression analysis, and the assessment of reporting bias using RevMan 5.3 software. Results: This systematic review will comprehensively evaluate the clinical outcomes of comparison of MED and PTED in the treatment of ULDH and provide a reliable and high-quality evidence. Conclusion: The conclusion of this study will elucidate the clinical outcomes of MED compared with PTED and clarify whether PTED generates better clinical effects than MED in treating ULDH. PROSPERO registration number: CRD 42021244204 Abbreviations: CI= confidence interval, MED=microendoscopic discectomy, PTED= percutaneous transforaminal endoscopic discectomy, RCTs = random control trials, SMD = standardized mean difference, ULDH = upper lumbar disc herniation, WMD = weighted mean difference.

目的 观察益气活血通脉方预防膝关节置换术(TKA)后深静脉血栓(DVT)的有效性.方法 将90 例TKA 术后患者随机分为中药组和利伐沙班组,每组45 例.2 组患者均行TKA 治疗,术后均进行抗凝干预.中药组于术后第1 天给予益气活血通脉方口服治疗,利伐沙班组则给予利伐沙班口服治疗,疗程为14 d.观察2 组患者术后下肢DVT 发生情况及术后24 h 引流量、皮下瘀斑、皮下浅表感染的发生情况,评价2 组患者手术前后的运动范围和中医证候积分情况,比较2组患者术前和术后2、7、14 d血浆D-二聚体水平和关节疼痛视觉模拟量表(VAS)评分的变化情况.结果 (1)治疗14 d 后,中药组和利伐沙班组的下肢DVT发生率分别为15.55％(7/45)和20.00％(9/45),以中药组的防治效果相对较好,但差异无统计学意义(P＞0.05).(2)中药组术后24h引流量明显低于利伐沙班组(P＜0.05);中药组术后皮下瘀斑、皮下浅表感染发生率分别为6.67％(3/45)和4.44％(2/45),明显低于利伐沙班组的22.22％(10/45)和20.00％(9/45),差异均有统计学意义(P＜0.05).(3)术后14 d,2组患者的运动范围均有所提高,中医证候积分均有降低,差异均有统计学意义(P＜0.05);且中药组术后14 d 与利伐沙班组比较,运动范围明显提高,中医证候评分明显降低,差异均有统计学意义(P＜0.01).(4)术后2d,2组患者血浆D-二聚体水平和关节疼痛VAS评分均较术前明显升高(P＜0.05);术后7d和14d,2组患者血浆D-二聚体水平和关节疼痛VAS评分均逐渐下降,与术后2d比较,差异均有统计学意义(P＜0.05);组间比较,术后各观察时点,中药组患者的血浆D-二聚体水平和关节疼痛VAS评分均明显低于对照组,差异均有统计学意义(P＜0.05).结论 TKA术后早期口服益气活血通脉方预防DVT发生的临床效果与利伐沙班相当,可明显减少患者双下肢皮下瘀斑、皮下浅表感染的发生率,提高运动范围,缓解临床症状,减轻痛感,更利于促进患者TKA 后的康复.

背景:淫羊藿苷是用于防治骨质疏松疗效比较确切的中药活性成分,但其具体的机制尚未完全明确.研究表明自噬能够参与调控骨代谢,淫羊藿苷是否能够通过改变自噬防治骨质疏松尚未可知.目的:研究淫羊藿苷是否通过调节自噬促进成骨细胞分化防治骨质疏松.方法:①体外实验:选取对数生长期小鼠前体成骨细胞株(MC3T3-E1),用不同浓度的淫羊藿苷(10-6-10-3 mmol/L)干预,通过观察细胞活力、细胞凋亡率、碱性磷酸酶活性、矿化结节数量、成骨分化标志物表达水平确定淫羊藿苷的最佳作用浓度;用最佳浓度淫羊藿苷处理MC3T3-E1细胞,将细胞分为3组:对照组、淫羊藿苷组及淫羊藿苷+3-MA组(自噬抑制剂),MDC染色检测自噬体数量,实时荧光定量聚合酶链反应检测成骨分化标志物及自噬相关基因的表达水平,免疫印迹法检测自噬相关蛋白的表达水平;②体内实验:通过构建去势大鼠模型,将动物分为4组:假手术组、病理模型组、淫羊藿苷组、戊酸雌二醇组,显微CT检测各组骨显微参数,免疫印迹法检测各组自噬相关蛋白表达水平.结果与结论:①淫羊藿苷能促进成骨细胞的增殖以及分化,同时抑制细胞凋亡,以10-5 mmol/L淫羊藿苷能力最强(P<0.05);②淫羊藿苷能够增加自噬体的数量,同时可上调成骨分化标志物及自噬相关基因、蛋白的表达(P<0.05),3-MA能够拮抗这些效应(P<0.05);③淫羊藿苷能够改善去势大鼠骨微结构相关参数,同时上调自噬相关蛋白的表达(P<0.05);④结果提示,淫羊藿苷能够通过提高自噬促进成骨细胞分化防治骨质疏松.

Abstract Background: Microendoscopic discectomy (MED) and percutaneous transforaminal endoscopic discectomy (PTED), as two alternative surgical techniques in minimally invasive spine surgery (MISS), are widely conducted in the treatment of upper lumbar disc herniation (ULDH). This study will systematically assess and compare the clinical outcomes of MED and PTED in treating ULDH combining with the meta-analysis. Methods: All the randomized controlled trials (RCTs) will be searched at the databases including PubMed, EMBASE, Cochrane Library and Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP), and WANFANG Database from inception to December 2025. The primary outcome will involve Japanese Orthopedic Association (JOA), Oswestry disability index (ODI), and visual analog scale (VAS) scores. The secondary outcomes will be the short-form 36-item (SF-36) health survey questionnaire and the modified MacNab criterion. We will perform data synthesis, subgroup analysis, sensitivity analysis, meta-regression analysis, and the assessment of reporting bias using RevMan 5.3 software. Results: This systematic review will comprehensively evaluate the clinical outcomes of comparison of MED and PTED in the treatment of ULDH and provide a reliable and high-quality evidence. Conclusion: The conclusion of this study will elucidate the clinical outcomes of MED compared with PTED and clarify whether PTED generates better clinical effects than MED in treating ULDH. PROSPERO registration number: CRD 42021244204

Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first‑line treatment is cisplatin‑based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy‑induced senescence can act as a 'back‑up' response to chemotherapy in cancer types that are resistant to apoptosis‑based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)‑induced senescence in cisplatin‑resistant bladder cancer cells. Cisplatin‑resistant bladder cancer cells were established via long‑term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA‑β‑Gal staining, but this was not observed in the cisplatin‑resistant cells. The cisplatin‑resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin‑resistant cells, and that CRY1 knockdown restored PTX‑induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto‑oncogene. These data suggested that the accumulated CRY1 in cisplatin‑resistant cells could prevent PTX‑induced senescence by promoting p53 degradation.

目的 研究牛膝甾酮(IS)对小鼠成骨细胞系(MC3T3-E1细胞)增殖、分化的影响及其可能的分子机制.方法 将MC3T3-E1细胞分为对照组及IS不同浓度组(10-4～10-1 ng/μL),24、48 h后采用细胞计数(CCK8)试剂盒检测细胞增殖,7、14天后采用碱性磷酸酶(ALP)活性试剂盒检测ALP活性,茜素红染色检测矿化结节,原位末端标记(TUNEL)试剂盒检测细胞凋亡情况,实时荧光定量PCR(RT-qPCR)检测成骨分化相关标志物Ⅰ型胶原(Collagen Ⅰ)、骨保护素(OPG)、骨桥蛋白(OPN)、骨钙素(OCN)、ALP以及雌激素受体alpha(ERα)、雌激素受体beta(ERβ) mRNA的表达水平.结果 与对照组比较,在干预48 h后,10-3、10-2、10-1 ng/μL IS能抑制细胞的增殖(P＜0.05),但对细胞凋亡无明显影响.10-4、10-3、10-2、10-1 ng/μL IS均能够促进ALP活性及矿化结节的形成(P＜0.05),亦能促进ERα、OPG、Collagen Ⅰ、ALP mRNA表达(P＜0.05);10-3、10-2、10-1 ng/μL IS均能促进OPN、OCN mRNA表达(P＜0.05),10-1ng/μL IS能够促进ERp mRNA表达(P＜0.05).结论 IS能促进MC3T3-E1细胞的成骨分化,其可能机制与上调成骨分化标志物及提高ERα mRNA表达有关.

目的 观察用补肝肾活血协定方治疗肝肾亏虚型膝关节病的临床效果.方法 选择该院收治的90例膝关节病患者为研究对象,随机分为对照组45例和观察组45例.对照组患者给予玻璃酸钠关节腔注射+硫酸氨基葡萄糖片口服,观察组在对照组基础上加用补肝肾活血协定方口服,连续治疗8周.通过观察膝关节痛感、功能、肿胀程度变化评价临床效果,监测治疗前后血清中致痛因子[β-内啡肽(β-endorphin,β-EP)、环氧合酶(Cyclooxygenase-2,COX-2)、前列腺素E2(Prostaglandin E2,PGE2)]、炎症相关因子[肿瘤坏死因子-α[(Tumor necrosis factor-α[,TNF-α)、基质金属蛋白酶-3(Matrix metalloproteinase-3,MMP-3)、白细胞介素-1β(Interleukin-1β,IL-1β)]水平,评价用药安全性.结果 观察组的临床有效率高达93.33％(42/45),相比对照组的75.56％(34/45)明显升高(x2=5.414,P＜0.05).两组患者治疗后的膝关节疼痛程度均有所缓解,观察组患者从坐位站立时疼痛、行走时疼痛、起床后疼痛、夜卧休息疼痛等视觉模拟评分(VAS评分)显著低于对照组(P＜0.05).两组患者治疗后膝关节功能均有所提高,肿胀程度有所减轻,观察组膝关节功能评分(Lyshom评分)、肿胀评分均显著高于对照组(P＜0.05).观察组治疗后血清中致病因子β-EP水平显著高于对照组,COX-2、PGE2水平显著低于对照组(P＜0.05).两组患者治疗后血清中炎症相关因子TNF-α、MMP-3、IL-1 β水平较治疗前有所降低(P＜0.05),观察组显著低于对照组(P＜0.05).观察组患者的不良反应相对较少,仅出现便秘1例,不良反应率为2.22％,但与对照组的不良反应率8.89％相比,差异无统计学意义(x2=1.906,P=0.167＞0.05).结论 加用补肝肾活血协定方治疗膝关节病有确切的疗效,在减轻关节疼痛、肿胀程度及恢复患膝关节功能方面优于常规西药治疗,其作用机制可能是通过调控血清中致痛因子水平、降低关节的炎性反应状态而实现的,本法安全可靠,值得进一步研究.

生酮饮食是一种高脂、低碳水化合物的饮食,1920年,生酮饮食开始被用来治疗癫痫,尤其作为耐药性癫痫的一种非药物治疗方式,尽管生酮饮食是安全、有效的,仍需关注其对骨骼生长带来的不利影响.生酮饮食导致骨质疏松症的最早临床报道见于1979年,在治疗难治性癫痫时患者出现了显著的骨矿物质丢失,近年来,基础研究提示生酮饮食能够导致实验小鼠松质骨以及皮质骨骨量的减少,提示在应用生酮饮食治疗的过程中应该辅助应用一些促成骨类药物,研究表明中药及其有效成分促成骨效能明确,课题组前期的研究表明中药能够正向调节骨代谢,因此有必要对生酮饮食负向调节骨代谢的研究进展做一详尽的综述,以期用传统中药干预,弘扬祖国医学的潜在优势.

目的 探讨针刺四关联合塞来昔布在全膝关节置换(TKA)患者围术期中超前镇痛的临床疗效.方法 行人工TKA患者60例,随机分为针药组及对照组各30例,分别在手术前2 d及术后2 w对患者进行镇痛治疗,并用疼痛视觉模拟评分(VAS)及膝关节协会评分(KSS)评定,观察治疗后的近远疗效.结果 治疗后,手术前1 d、术后1、2 d及术后7 d的静息/活动VAS评分,两组差异有统计学意义(P<0.05);术后7 d及术后14 d两组KSS评分差异有统计学意义(P<0.05);针药组总体镇痛满意度明显高于对照组(P<0.05).结论 针刺四关联合塞来昔布用于全膝关节置换术患者,可以获得比单用塞来昔布更好的镇痛效果.