目的 探讨缺氧环境下缺氧诱导因子1α(HIF-1α)和细胞因子C-X-C基序趋化因子6(CXCL6)在髓核细胞中的特异性调控机制.方法 在缺氧条件下(2％O2)分别培养髓核细胞0、3、6、12、24 h,分别采用Western blot法、荧光定量PCR(qPCR)法及ELISA法检测缺氧条件下髓核细胞HIF-1α和CXCL6蛋白表达、mRNA表达及细胞上清液中CXCL6水平.将髓核细胞分为A组(正常氧培养组)、B组(2％O2培养组)和C组(2％O2+HIF-1α抑制剂KC7F2 50 μmol/L培养),24 h后采用Western blot法、qPCR法及ELISA法检测缺氧条件下髓核细胞HIF-1α和CXCL6蛋白表达、mRNA表达及细胞上清液中CXCL6水平.将髓核细胞随机分为D组(正常氧培养)、E组(2％O2 培养)、F 组(2％O2 培养+siNC)、H 组(2％O2 培养+siCXCL6#1)和 L 组(2％O2 培养+siCXCL6#2),且E、F、H、L组同时接受NF-κB抑制剂吡咯烷二硫代氨基甲酸铵25 μmol/L处理,24 h后采用Western blot法检测缺氧条件下沉默CXCL6表达对C-X-C基序趋化因子受体1(CXCR1)、CXCR2、Bax和Bcl-2蛋白表达的影响,采用流式细胞术检测五组细胞凋亡情况.结果 缺氧条件下,髓核细胞HIF-1α和CXCL6蛋白表达、mRNA表达及细胞上清液中CXCL6水平呈时间依赖性升高(P＜0.05).与A组比较,B组髓核细胞HIF-1α和CXCL6蛋白表达、mRNA表达及细胞上清液中CXCL6水平均升高(P＜0.05);与B组比较,C组上述指标表达均降低(P＜0.05).流式细胞术检测显示,与E、F组相比,H、L组细胞凋亡率降低(P＜0.05).结论 缺氧诱导CXCL6通过NF-κB信号通路促进髓核细胞凋亡.

OBJECTIVE:Low back pain (LBP) is a worldwide health issue primarily attributed to intervertebral disc degeneration (IVDD). Qiangjin Zhuang Qufeng mixture (QJZG), an approved hospital-based formula with years of clinical application, has demonstrated notable therapeutic effects in the treatment of LBP. Nevertheless, the underlying mechanism by which it alleviates LBP remains uncertain.METHODS:The bioactive constituents of QJZG were initially identified using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Subsequently, network pharmacology was employed to explore the core components and targets. In vivo and in vitro experiments were then conducted to validate the specific mechanism of action of QJZG based on the identified targets and pathways. Following that, ultra-high-performance liquid chromatography/mass spectrometry combined with 16S rRNA gene sequencing of blood and faecal samples was utilized to assess the impact of gut microbiota on faecal and serum metabolites subsequent to QJZG administration in intervertebral disc degeneration (IVDD) rats.RESULTS:The principal constituents of QJZG were identified using UPLC-Q-TOF-MS/MS, revealing a substantial enrichment of flavonoids and triterpenes. Network pharmacology analysis indicated the potential inhibitory effects of QJZG on the NLRP3 inflammasome and downstream inflammatory factors. Furthermore, investigations demonstrated that intervertebral disc degeneration may be attributed to pyroptotic cell death within the nucleus pulposus. In vitro experiments were performed utilizing LPS to induce the inflammatory response in nucleus pulposus cells (NPC), and it was observed that QJZG-containing serum significantly suppressed key pyroptosis-related genes and downstream inflammatory factors. Additionally, in vivo experiments substantiated the capacity of QJZG to preserve disc height and ameliorate the progression of disc degeneration. Concurrently, oral pharmacotherapy in animal studies prominently involved the effects of Enterobacteriaceae and Clostridium, closely intertwined with lipid metabolism.CONCLUSIONS:QJZG exhibited a delaying effect on IVDD by preserving the equilibrium between extracellular matrix (ECM) synthesis and degradation in NPCs. This effect was achieved through the suppression of NLRP3 inflammasome expression and the prevention of pyroptosis in NPCs.

To construct an injectable fibrin glue system loaded with kaempferol (FG@F) to improve the bioavailability of kaempferol and observe its efficacy in the treatment of intervertebral disc degeneration (IVDD). Kaempferol-loaded fibrin glue was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Then, nucleus pulposus cells (NPCs) were stimulated with lipopolysaccharide (LPS) to establish a degenerative cell model, and the corresponding intervention treatment was conducted to observe the effect in vitro. Finally, the tail disc of rats was punctured to establish a model of IVDD, and the therapeutic effect of the material in vivo was observed after intervertebral disc injection. The FG@F system has good injectability, sustained release and biocompatibility. This treatment reduced the inflammatory response associated with IVDD and regulated matrix synthesis and degradation. Animal experimental results showed that the FG@F system can effectively improve needle puncture-induced IVDD in rats. The FG@F system has better efficacy than kaempferol or FG alone due to its slow release and mechanical properties. The drug delivery and biotherapy platform based on this functional system might also serve as an alternative therapy for IVDD.

Abstract Purpose To construct an injectable, sustained-release hydrogel containing rhein to solve the problem of low bioavailability of rhein, and observe its efficacy in the treatment of intervertebral disc degeneration. Methods The fibrin gel containing rhein was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Secondly, the degenerative cell model was constructed by stimulating nucleus pulposus cells with lipopolysaccharide (LPS), and the corresponding intervention treatment was carried out to observe the effect in vitro. Finally, the rat tail intervertebral disc was acupunctured by needles to establish the intervertebral disc degeneration model, and the effect of the material was observed through intradiscal injection. Results The fibrin glue containing rhein (rhein@FG) showed good injectability, sustained release and biocompatibility. Rhein@FG can improve the LPS-induced inflammatory microenvironment, regulate ECM metabolic disorders of nucleus pulposus cells and aggregation of the NLRP3 inflammasome in vitro, and inhibit cell pyroptosis. Furthermore, in vivo experiments, rhein@FG effectively prevented needle puncture-induced intervertebral disc degeneration in rats. Conclusions Rhein@FG has better efficacy than rhein or FG alone due to its slow release and mechanical properties, which can be used as a potential replacement therapy for intervertebral disc degeneration.

To construct an injectable, sustained-release fibrin gel containing rhein to solve the problem of low bioavailability of rhein, and observe its efficacy in the treatment of intervertebral disc degeneration. The fibrin gel containing rhein was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Secondly, the degenerative cell model was constructed by stimulating nucleus pulposus cells with lipopolysaccharide (LPS), and the corresponding intervention treatment was carried out to observe the effect in vitro. Finally, the rat tail intervertebral disc was acupunctured by needles to establish the intervertebral disc degeneration model, and the effect of the material was observed through intradiscal injection. The fibrin glue containing rhein (rhein@FG) showed good injectability, sustained release and biocompatibility. Rhein@FG can improve the LPS-induced inflammatory microenvironment, regulate ECM metabolic disorders of nucleus pulposus cells and aggregation of the NLRP3 inflammasome in vitro, and inhibit cell pyroptosis. Furthermore, in vivo experiments, rhein@FG effectively prevented needle puncture-induced intervertebral disc degeneration in rats. Rhein@FG has better efficacy than rhein or FG alone due to its slow release and mechanical properties, which can be used as a potential replacement therapy for intervertebral disc degeneration.

腰椎间盘髓核摘除术是治疗腰椎间突出症(lumbar?disc?herniation,LDH)的一种有效方法.但术后不可避免会在纤维环遗留破口,破口若愈合不良,可能会导致椎间盘突出复发.纤维环缝合是预防腰椎髓核摘除术后复发的有效方法之一[1].由于椎间盘镜手术系统(microendoscopic?discectomy, MED)技术在空气介质下操作,解剖结构辨认较困难,易导致缝合失败.而经皮椎间孔镜技术(percutaneous?endoscopic?lumbar?discectomy,PLED)在单通道下视野及操作空间有限,对合打结存在困难,单侧双通道脊柱内镜(unilateral?biportal?endoscopy,UBE)技术的出现弥补了经皮椎间孔镜技术的不足,该技术观察通道与操作通道独立,术者可在直视下操作,视野清晰且缝合效率高.现对UBE下腰椎纤维环缝合技术进行病例研究,以评估该技术在脊柱外科领域的安全性及有效性.

单侧双通道内镜(unilateral biportal endoscopy, UBE)技术是近年来兴起的一种微创脊柱内镜技术.UBE技术与传统的脊柱微创技术相比,手术视野更加清晰、开阔,操作更加精准灵活,器械使用限制更少,可以解决单通道内镜技术在治疗中央型腰椎管狭窄症或游离型腰椎间盘突出症等复杂腰椎疾病时所面临的问题[1-2].但随着 UBE技术的推广应用,相关手术并发症也不断被报道,如硬脊膜撕裂、硬脊膜外血肿、神经根损伤等[3],但目前尚无UBE术后并发类脊髓高压综合征的报道.

Objective The purpose of this study was to investigate the learning curve and complications of unilateral biportal endoscopy (UBE) in the treatment of lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS). Methods This was a retrospective cohort analysis of 197 consecutive patients who received UBE unilateral laminotomy bilateral decompression (UBE-ULBD) or lumbar discectomy (UBE-LD) surgery, including 107 males and 90 females with an average age of 64.83±14.29 years. Cumulative sum (CUSUM) and risk-adjusted cumulative sum analysis (RA-CUSUM) were used to evaluate the learning curve, with the occurrence of complications defined as surgical failure, and variables of different phase of the learning curve were compared. Results The cutoff point of learning curve of UBE surgery was 54 cases according to CUSUM analysis. The learning curve of UBE-ULBD and UBE-LD were divided into 3 phases. The first cutoff points were 31 and 12 cases, and the second cutoff point were 67 and 32 cases respectively. With the progress of the learning curve, the operation time and postoperative hospital stays decreased. The visual analogue scale and Oswestry Disability Index at the last follow-up were significantly lower than that before surgery. The incidence of surgical failure was 6.11% and began to decrease after the 89th case based on RA-CUSUM analysis. The surgical failure rate decreased from 10.11% to 2.78 after the 89th case with significant different. Conclusion UBE surgery is effective in the treatment of LDH and LSS with low incidence of complications. But a learning curve of at least 54 cases still required for mastering UBE surgery.

腰椎间盘囊肿临床上较为少见,囊肿可突入椎管内,压迫硬膜囊和(或)神经根,引起腰痛及神经根性疼痛,极易与腰椎间盘突出症混淆,常被误诊或漏诊.国内外现有文献多为临床个案报道,尚未有系统性研究.本文从腰椎间盘囊肿的流行病学、发病机制、临床表现、影像学诊断、鉴别诊断及治疗方法6个方面对腰椎间盘囊肿的研究进展进行了综述.

膝骨关节炎(knee osteoarthritis,KOA)是临床上常见的一种慢性退行性骨关节疾病,其最主要的临床表现是膝关节疼痛.目前,KOA在临床上尚无根治办法,其治疗以控制膝关节疼痛、延缓疾病进展为主要目的.对于轻中度KOA,目前临床上常采用口服非甾体抗炎药、氨基葡萄糖及关节腔内注射透明质酸钠等治疗,但其疗效不甚理想.膝动脉栓塞术(genicular artery emboliza-tion,GAE)具有创伤小、精准度高、起效快等优点,可以有效缓解膝关节疼痛.目前,该技术在KOA治疗中的应用潜力已得到了众多学者的关注.本文概述了GAE,介绍了GAE的适应证与禁忌证,重点阐述了GAE治疗KOA的机制、GAE所用栓塞剂的选择、GAE治疗KOA的临床应用及GAE术后常见的并发症,为非手术治疗无效的KOA疼痛患者提供了新的治疗选择.

Breast cancer (BC), the most common cancer in women, is caused by the uncontrolled proliferation of mammary epithelial cells under the action of a variety of carcinogenic factors. Cuproptosis-related targets have been found to be closely associated with breast cancer development. TCGA obtained 1226 tumor samples, 1073 clinical data, and 37 lncRNAs during univariate Cox multivariate analysis. We used nonnegative matrix factoring (NMF) agglomeration to spot thirty-three potential molecular subsets with totally different cuproptosis-related lncRNA expression patterns. The least absolute shrinkage and selection operator (LASSO) formula and variable Cox multivariate analysis were not used to construct the best prognostic model. The variations in neoplasm mutation burden and factor gene ontology (GO) and gene set enrichment analysis (GSEA) within the high- and low-risk teams were analyzed, and therefore, the potential mechanism of the development of carcinoma was analyzed. We created a prognostic profile consisting of nineteen cuproptosis-related genes (NFE2L2, LIPT1, LIPT2, DLD, etc.) and their connected targets. The correlation between tumor mutational burden (TMB) and clinical manifestations of tumors demonstrates the importance of high- and low-expression bunch data on the incidence of clinical manifestations of tumors. The area under the curve (AUC) shows moderate prophetic power for copper mortality. GO enrichment analysis showed that immunorelated responses were enriched. Correlation analysis of immune cells showed that pathology could play an important role in the prevalence and prognosis of tumors, and there were variations in immune cells between the probable and low-risk groups. Our study suggests that the prognostic characteristic genes associated with cuproptosis can be used as new biomarkers to predict the prognosis of breast cancer patients. In addition, we found that immunotherapy may play a key role in breast cancer treatment regimens. Levels of immune-associated cells and pathways vary significantly among risk groups of breast cancer patients.

OBJECTIVE:To investigate the clinical effect of percutaneous endoscopic lumbar discectomy (PELD) through bone tunnel in the treatment of migrated lumbar intervertebral disc herniation.METHODS:The clinical data of 42 patients with migrated lumbar intervertebral disc herniation treated through PELD techniques were retrospectively analyzed from October 2015 to December 2018. There were 26 males and 16 females, aged from 39 to 71 years old with a mean of(58.55±7.16) years. There were 7 cases where the affected segment was L3,4, 24 cases of L4,5, and 11 cases of L5S1. According to modified free nucleus pulposus classification, 3 cases of type A1, 6 cases of type A2, 8 cases of type B1, 8 cases of type B2, 6 cases of type C1, and 11 cases of C2. Among these 42 cases, 22 patients were treated with transpedicular approach (transpedicular approach group), 6 cases were type A2, 6 cases were type B2 and 10 cases were type C2, and 20 cases with translaminar approach(translaminar approach group), 3 cases were type A1, 8 cases were type B1, 6 cases were type C1, 2 cases were type B2 and 1 case was type C2. The operation time, intraoperative and postoperative complications of the two groups were recorded, and the pain visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to assess the improvement of the clinical symptoms before surgery, immediately after surgery, and 12 months after surgery, and the modified Macnab evaluation system was used to evaluate the clinical efficacy.RESULTS:The operative time was from 69 to 105 min with a mean of (88.29±9.85) min;and no intraoperative complications such as neurovascular injury or dural tear were occurredin all patients. One case in the transpedicular approach group was changed to general anesthesia and translaminar approach due to local anesthesia intolerance. All the patients were followed up from 13 to 34 months, with a mean of (13.71±3.56) months. VAS and ODI were significantly improved in two groups immediately after surgery and 12 months after surgery (P<0.05). According to modified Macnab criteria, 27 cases obtained excellent results, 11 good, 3 fair, and 1 poor. There were no postoperative complications such as lumbar fractures and postoperative infections in the follow-up patients.CONCLUSION:For migrated intervertebral disc herniation, the modified nucleus pulposus classification can be used to estimate the precise target before operation, and the reasonable bone tunnel approach can be selected to obtain good results.

退行性腰椎椎管狭窄症(degenerative lumbar spinal stenosis,DLSS)是临床常见腰椎退行性疾病.近年来,单侧入路双侧减压术(unilateral laminotomy for bilateral decompression,ULBD)逐渐成为治疗DLSS的主要方式.随着脊柱外科微创技术的发展,目前在显微镜、单通道内镜及双通道内镜下均可行ULBD治疗DLSS.该术式减压充分、临床疗效显著,但仍存在发生硬脊膜撕裂、硬脊膜外血肿、脊柱不稳、头痛等并发症的风险.为了提高临床医师对ULBD治疗DLSS的相关并发症的认识,本文对其研究进展进行了综述.