腕部痛风性关节炎的临床分型与治疗体会

目的探讨腕部痛风性关节炎的临床特点、临床分型及相应治疗方法和疗效。方法回顾性分析2011年4月—2020年8月24例明确诊断为腕部痛风性关节炎并有完整随访资料的患者。男21例，女3例；首次发病年龄21～72岁，中位年龄50岁。单纯腕关节发病15例，合并其他关节（手、膝、踝、跖趾关节）受累9例；首发部位为腕关节者19例。排除1例有21年病史患者，其余23例患者发病至确诊时间为7 d～9 年，中位时间2个月。依据腕部痛风性关节炎的临床表现、影像学表现、病损范围和术中腕关节镜表现由轻至重分为5型，24例患者中Ⅰ型13例，ⅡA型2例，ⅡB型3例，ⅢA型2例，Ⅳ型3例，Ⅴ型1例。Ⅰ、Ⅱ型患者首次发病至确诊时间为（12.7±40.1）个月，Ⅲ～Ⅴ型患者为（152.0±88.5）个月，差异有统计学意义（t=−4.355，P=0.001）。13例Ⅰ型患者采用保守治疗（包括饮食、运动和生活方式的干预治疗以及药物治疗），11例Ⅱ～Ⅴ型患者接受手术治疗（包括关节镜下滑膜、痛风结晶清理术 1 例，韧带修复术 1 例，病灶清理/人工骨植骨填充术 5 例，腕关节融合术3例，痛风石切除术1例）。治疗前后采用疼痛视觉模拟评分（VAS）评价腕关节疼痛改善情况；评估腕关节掌屈、背伸、桡偏、尺偏活动度。 结果13例保守治疗患者获随访，随访时间10个月～9年，平均2.2年。治疗前及末次随访时VAS评分分别为（6.8±0.7）分和（2.9±0.9）分，差异有统计学意义（t=12.309，P=0.000）。随访期间无1例出现腕骨与腕关节破坏；腕关节活动度基本达到正常, 患者末次随访时腕关节掌屈、背伸、桡偏、尺偏活动度均较治疗前显著改善（P<0.05）。11例手术治疗患者获随访，随访时间5个月～9年，平均4.9年。所有患者肿胀、疼痛充分缓解，术前、术后1个月及末次随访时VAS评分分别为（7.3±0.8）、（2.7±0.6）、（2.5±0.6）分，术后较术前显著改善（P<0.05）；术后1个月与末次随访间差异无统计学意义（P>0.05）。排除3例接受腕关节融合术患者，其余8例患者末次随访时腕关节掌屈、背伸、桡偏、尺偏活动度均较术前显著改善（P<0.05）。患者对手术结果主观满意度达100%。 结论腕部痛风性关节炎容易漏诊而严重影响腕关节的稳定性和功能，早期诊断和治疗可有效遏制病情发展，晚期患者可依据病变分型予以相应手术治疗。     

五味子乙素通过抑制TLR4-MyD88信号通路减轻脂多糖诱导的小鼠巨噬细胞凋亡

[目的]研究五味子乙素(schisandrin B,Sch B)对脂多糖(lipopolysaccharide,LPS)诱导的小鼠巨噬细胞损伤的保护作用及其潜在分子机制。[方法]以小鼠巨噬细胞(RAW 264.7)为研究对象,建立LPS细胞炎症损伤模型,通过比色法测定细胞乳酸脱氢酶(lactate dehydrogenase,LDH)释放量、细胞存活率、细胞内炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)表达,以检测Sch B对LPS诱导的炎症的保护作用;荧光定量PCR检测Toll样受体4(Toll like receptor4,TLR4)、髓样分化因子88(myeloid differentiation factor88,MyD88)及TNF-α的mRNA表达。[结果]LPS显著诱导RAW 264.7细胞损伤(P＜0.05),而Sch B能减轻LPS诱导的RAW 264.7细胞损伤,且呈剂量依赖关系(P＜0.05)。Sch B能显著下调TNF-α、IL-6的表达(P＜0.05),此外Sch B能显著抑制TLR4、MyD88及TNF-α的mRNA表达(P＜0.05),减轻LPS诱导的细胞炎症反应。[结论]Sch B能够显著改善LPS诱导的RAW 264.7细胞炎症反应,具有潜在防治非酒精性脂肪肝炎的作用,TLR4-MyD88信号通路参与Sch B对细胞损伤的保护作用。     

高原红细胞增多症与消化性溃疡出血的关系

目的探讨高原红细胞增多症(high altitude polycythemia，HAPC)与消化性溃疡出血的关系，以期为我国西藏地区消化性溃疡的临床诊治提供依据。方法选择2015年1月1日—2021年4月30日因消化性溃疡出血在西藏自治区人民医院消化内科住院的患者为病例组，以同一时期在泌尿外科住院的无消化性溃疡、无消化道出血病史的患者作为对照组，进行回顾性病例对照研究，按照性别、年龄(±2岁)、民族(藏族、汉族)，以及居住地海拔高度(分为＜4 000 m和≥4 000 m两组)进行1 ∶ 1病例匹配，病例组与对照组各纳入393例。两组间针对消化性溃疡出血的危险因素(居住地，吸烟，饮酒，服用NSAIDs/抗凝药物，合并HAPC、高血压、糖尿病、心脏病、高脂血症、脑血管病、慢性肺病、关节病等慢性疾病)进行比较分析。结果病例组中合并HAPC患者28例(7.1%)，对照组为5例(1.3%)，组间差异有统计学意义(OR=5.953，P＜0.001)。多因素Logistic回归分析发现HAPC(OR=5.270，95%CI: 1.806~15.380)、居住在城镇(OR=2.369，95%CI: 1.559~3.602)、饮酒(OR=3.238，95%CI: 1.973~5.317)及服用非甾体抗炎药(non-steroidal anti-inflammatory drugs, NSAIDs)/抗凝药物(OR=20.584，95%CI: 2.639~160.545)是我国西藏地区消化性溃疡出血的独立危险因素。在调整了居住在城镇、饮酒、服用NSAIDs/抗凝药物等可能的混杂因素后，HAPC与我国西藏地区消化性溃疡出血风险增加有关(OR=5.270)。结论我国西藏地区合并HAPC的患者可显著增加消化性溃疡出血风险。     

计算机模拟亚甲基蓝与牙龈卟啉单胞菌部分蛋白的分子对接

目的使用计算机模拟的靶点预测与分子对接的方法，研究抗菌光动力疗法中光敏剂与细菌结合的靶点，并计算结合能。方法在Uniprot数据库和RCSB PDB数据库中获取并汇总牙龈卟啉单胞菌(Porphyromonas gingivalis，Pg)的蛋白名称；在SciFinder数据库、PubChem数据库、ChemSpider数据库和Chemical Book中筛选并对比亚甲基蓝的结构图，并用ChemBioDraw软件绘制确认；在PharmMapper数据库对亚甲基蓝三维结构进行靶点预测，并用Cytoscape软件构建可视化网络图；在String数据库中构建亚甲基蓝靶点与Pg蛋白交集的相互作用网络；选择FimA、Mfa4、RgpB、Kgp K1蛋白，使用AutoDock软件计算亚甲基蓝与上述蛋白的对接能量，并进行分子对接。结果靶点预测结果显示，268个亚甲基蓝潜在靶点和1 865个Pg的蛋白之间有19个共同的靶点，这19个靶点为：groS、radA、rplA、dps、fabH、pyrG、thyA、panC、RHO、frdA、ileS、bioA、def、ddl、TPR、murA、lepB、cobT、gyrB。分子对接结果显示，亚甲基蓝能与FimA蛋白的9个位点结合，结合能-6.26 kcal/mol；与Mfa4蛋白的4个位点和氢键形成位点GLU47结合，结合能-5.91 kcal/mol；与RgpB蛋白的氢键形成位点LYS80结合，结合能-5.14 kcal/mol；与Kgp K1蛋白的6个位点和氢键形成位点GLY1114结合，结合能-5.07 kcal/mol。结论计算机模拟的靶点预测与分子对接技术可以初步揭示亚甲基蓝与Pg部分蛋白发生结合、结合程度及结合位点，为将来研究光敏剂与细胞、细菌结合位点的筛选提供参考。     

Effect of curcumin on regulatory B cells in chronic colitis mice involving TLR/MyD88 signaling pathway

Curcumin (Cur) is a natural active phenolic compound extracted from the root of Curcuma Longa L. It has anti-inflammatory, anti-tumor and other pharmacological activities, and is commonly used to treat ulcerative colitis (UC). However, it is not clear whether curcumin regulates the function and differentiation of Breg cells to treat UC. In this study, mice with chronic colitis were induced by dextran sulfate sodium (DSS), and treated with curcumin for 12 days. Curcumin effectively improved the body weight, colonic weight, colonic length, decreased colonic weight index and pathological injury score under colonoscopy in mice with chronic colitis, and significantly inhibited the production of IL-1β, IL-6, IL-33, CCL-2, IFN-γ, TNF-α, and promoted the secretion of IL-4, IL-10, IL-13 and IgA. Importantly, curcumin markedly upregulated CD3⁻CD19⁺CD1d⁺, CD3⁻CD19⁺CD25⁺, CD3⁻CD19⁺Foxp3⁺Breg cells level and significantly down-regulated CD3⁻CD19⁺PD-L1⁺, CD3⁻CD19⁺tim-1⁺, CD3⁻CD19⁺ CD27⁺ Breg cells level. In addition, our results also showed that curcumin observably inhibited TLR2, TLR4, TLR5, MyD88, IRAK4, p-IRAK4, NF-κB P65, IRAK1, TRAF6, TAB1, TAB2, TAK1, MKK3, MKK6, p38MAPK, p-p38MAPK and CREB expression in TLR/MyD88 signaling pathway. These results suggest that curcumin can regulate the differentiation and function of Breg cell to alleviate DSS-induced colitis, which may be realized by inhibiting TLR/MyD88 pathway.     

原发性中枢神经系统淋巴瘤的临床特征及预后分析

目的:探讨原发性中枢神经系统淋巴瘤（primary central nervous system lymphoma，PCNSL）患者的临床病理和分子学特征及预后影响因素。方法:收集2013年03月至2021年05月山西省人民医院35例PCNSL患者的临床资料及组织标本，总结其临床病理特征并应用二代测序技术检测淋巴瘤相关基因，分析年龄、病灶部位、乳酸脱氢酶（lactate dehydrogenase，LDH）、免疫组化等指标对预后的影响，比较不同基因突变组及治疗方案之间的总生存（overall survival，OS）差异。结果:最常见的基因突变为MYD88（66.7%，12/18），IGLL5、PIM1（38.9%，7/18）；PIM1突变组、IGLL5突变组OS差于未突变组，差异均有统计学意义（P=0.019和0.021）；多因素Cox回归分析显示LDH、不同的治疗方案是PCNSL患者独立的预后影响因素（P=0.007和0.002）；接受大剂量甲氨蝶呤（methotrexate，MTX）、利妥昔单抗（rituximab，R）治疗组OS明显优于未接受组，差异均有统计学意义（P=0.005和＜0.001）；使用布鲁顿酪氨酸激酶抑制剂（broughton tyrosine kinase inhibitor，BTKi）组与未接受组相比，有生存获益的趋势，但未显示出统计学差异。结论:血清LDH升高与不良预后显著相关，PIM1及IGLL5突变患者生存较差，含MTX、R治疗方案可改善患者生存。     

Prognostic impact of MYD88 and CXCR4 mutations assessed by droplet digital polymerase chain reaction in IgM monoclonal gammopathy of undetermined significance and smouldering Waldenström macroglobulinaemia

Waldenström macroglobulinaemia (WM) is characterized by recurrent somatic mutations in MYD88 and CXCR4 genes. However, limitations arise when analysing these mutations in IgM monoclonal gammopathy of undetermined significance (MGUS) or smouldering WM (SWM) given the lower tumour load. Here, we used droplet digital polymerase chain reaction (ddPCR) to analyse MYD88 L265P and CXCR4 S338* mutations (C1013G and C1013A) in unsorted bone marrow (BM) or cell-free DNA (cfDNA) samples from 101 IgM MGUS and 69 SWM patients. ddPCR was more sensitive to assess MYD88 L265P compared to allele-specific PCR, especially in IgM MGUS (64% vs 39%). MYD88 mutation burden correlated with other laboratory biomarkers, particularly BM infiltration (r = 0.8; p < 0.001). CXCR4 C1013G was analysed in MYD88-mutated samples with available genomic DNA and was detected in 19/54 (35%) and 18/42 (43%) IgM MGUS and SWM cases respectively, also showing correlation with BM involvement (r = 0.9; p < 0.001). ddPCR also detected 8 (38%) and 10 (63%) MYD88-mutated cfDNA samples in IgM MGUS and SWM respectively. Moreover, high BM mutation burden (≥8% MYD88 and ≥2% CXCR4) was associated with an increased risk of progression to symptomatic WM. We show the clinical applicability of ddPCR to assess MYD88 and CXCR4 in IgM MGUS and SWM and provide a molecular-based risk classification.     

Lycopene abolishes palmitate-mediated myocardial inflammation in female Wistar rats via modulation of lipid metabolism,NF-κB signalling pathway,and augmenting the antioxidant systems

Background and aimsObesity-related heart failure is exacerbated by excessive intake of saturated fats such as palmitate (PA). Lycopene (LYC) possesses anti-lipidemic, antioxidant, cytoprotective, and anti-inflammatory effects. This study, therefore, evaluated the impact of LYC against PA-invoked cardiotoxicity.Methods and resultsThirty-six female rats were equally divided into six groups: control; PA (5 mM); PA + LYC (24 mg/kg); PA + LYC (48 mg/kg); LYC (24 mg/kg); and LYC (48 mg/kg). The PA was administered five times weekly for seven weeks, while the LYC was given for the last two weeks. Lipids in the blood and the heart were estimated, as were oxidative stress and antioxidant indices, cardiac function, inflammation, and histology. Palmitate overload occasioned a significant (p < 0.05) increase in cardiac cholesterol (50%), phospholipids (19%), and non-esterified fatty acids (40%). However, triglyceride levels decreased (38%). Furthermore, malondialdehyde (45%), hydrogen peroxide (33%) levels and myeloperoxidase activity increased (79%). Also, cardiac gamma-glutamyl transferase (50%), serum creatine kinase activities (1.34 folds), NF-kB, interleukin1β, and interleukin-6 mRNA expression increased in the PA group relative to the control. In contrast, reduced glutathione (13%) and nitric oxide levels (22%), interleukin-10 mRNA expression, cardiac creatine kinase (35%), lactate dehydrogenase (33%), aspartate, and alanine transaminase activities decreased markedly (15- and 10%, respectively). Also, PA caused hyperemia, congestion of the cardiac interstitium, and infiltration of inflammatory cells. However, treatment with LYC reversed the features of cardiotoxicity and histological complications caused by PA. These observations are likely because LYC has anti-inflammatory, antioxidant, and cytoprotective properties.ConclusionThus, LYC might be an appropriate remedy to manage PA-induced cardiotoxicity in female rats.     

The role of extracellular ATP in homeostatic immune cell migration

Antigen stimulation induces adenosine triphosphate (ATP) release from naïve lymphocytes in lymphoid tissues. However, previous studies indicated that the non-lytic release of ATP also occurs in most tissues and cell types under physiological conditions. Here, we show that extracellular ATP (eATP) is indeed constitutively produced by naïve T cells in response to lymphoid chemokines in uninflamed lymph nodes and is involved in the regulation of immune cell migration. In this review, we briefly summarize the homeostatic role of extracellular ATP in immune cell migration in vivo.