股直肌斜切在复杂人工全膝关节置换术中的应用

目的探讨复杂人工全膝关节置换术（total knee arthroplasty，TKA）中采用股直肌斜切辅助显露的安全性及有效性。方法回顾分析 2016 年 1 月—2017 年 5 月，采用股直肌斜切辅助显露的 19 例（29 膝）复杂 TKA 患者临床资料。其中男 9 例（13 膝），女 10 例（16 膝）；年龄 34～66 岁，平均 50.2 岁。强直性脊柱炎 4 例（8 膝），类风湿性关节炎 5 例（7 膝），膝关节骨关节炎 10 例（14 膝）。病程 8～15 年，平均 10.9 年。Kellgren-LawrenceⅢ级 12 膝，Ⅳ级 17 膝。患者膝关节活动度为（19.86±7.23）°，膝关节学会评分系统（KSS）临床评分（47.86±11.26）分、功能评分（15.52±11.21）分。术后随访纳入并发症、膝关节活动度、KSS 评分、伸膝迟滞发生情况及假体松动情况。结果术后切口均Ⅰ期愈合，无感染及心脑血管意外等并发症发生。患者均获随访，随访时间 25～39 个月，平均 30.3 个月。末次随访时，患者膝关节活动度为（91.03±7.30）°，KSS 临床评分为（83.62±9.99）分、功能评分为（66.38±7.89）分，均较术前明显改善，差异有统计学意义（P<0.05）。3 膝出现伸膝迟滞，分别迟滞 10°、10°、15°。X 线片复查未见假体位置不良、松动及病理性透亮线。 结论复杂 TKA 中采用股直肌斜切能有效显露膝关节术野，减少髌腱撕脱、髌骨骨折以及股四头肌肌腱损伤等并发症的发生；采用 Krackow 肌腱缝合法修复切断的股直肌有利于术后早期膝关节功能锻炼及恢复，而且不会增加并发症发生风险。     

2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione,isolated from the root of Averrhoa carambola L., protects against diabetic kidney disease by inhibiting TLR4/TGFβ signaling pathway

ObjectiveDiabetic kidney disease (DKD) is the leading cause of death and disability of diabetes mellitus. However, there is still a lack of specific drugs for the treatment of DKD. The chief aim of this research is to investigate the role and mechanism of 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) for DKD.MethodsWild type and TLR4 knockout mice were induced to diabetes. After 4-week treatment with DMDD, blood sugar, renal function, blood lipid and pathological changes were assessed. Real-time PCR, western blotting, and immunohistochemistry were employed to detect the expressions of TLR4, TGFβ1 and Smad2/3 in the renal tissue.ResultsDMDD improved the serum lipid and decreased fasting blood glucose levels in diabetic mice. CysC and urinary albumin levels increased markedly in the diabetic group, and they were obviously decreased after 4 weeks of DMDD treatment. Compared with the WT diabetic mice, the urinary albumin and CysC in the TLR4^-/- mice were expressed at lower levels. HE and Masson’s staining revealed that DMDD clearly ameliorated pathological changes and renal fibrosis. When TLR4 gene was knock out, the pathological was improved. Mechanistically, TLR4, TGF-β1 and Smad2/3 were obvious up-regulation in the renal tissues of diabetic mice. The expressions of these proteins were significantly down-regulated after DMDD treatment (p < 0.05). In the TLR4^-/- mice, mRNA and protein levels of TGF-β1 and Smad2/3 were obviously lower than those in the WT mice. In addition, IHC revealed that a strong in situ expressions of TLR4, TGF-β1 and Smad2/3 were seen in the kidney tissues of diabetic mice, which were distinctly weakened in the DMDD-treated mice. In the TLR4^-/- mice, however, expressions of TGF-β1 and Smad2/3 were not remarkable increase in the diabetic mice compared with normal mice.ConclusionsThese results strongly indicate that TLR4 is essential for DMDD protection against renal dysfunction in diabetic mice. Its hypoglycemic and anti-fibrosis effects were likely mediated by the TLR4/TGFβ signaling pathway.     

PTPN6通过抑制SP1/p38 MAPK信号通路促进前列腺癌细胞的化疗敏感性

目的:研究PTPN6对前列腺癌细胞PC3的作用及其作用机制。方法:RT-PCR和Western blot实验检测前列腺癌组织和细胞以及癌旁组织和人前列腺上皮细胞中PTPN6的表达量；CCK-8和EDU染色实验检测PTPN6对前列腺癌细胞PC3增殖的影响；Western blot实验检测耐药相关蛋白P-gp和MRP-1的蛋白表达水平。结果:RT-PCR和Western blot结果显示，PTPN6在前列腺癌组织和细胞中的表达量显著低于癌旁组织和人前列腺上皮细胞中的表达量；过表达PTPN6显著抑制前列腺癌PC3细胞的增殖，并降低PC3细胞的耐药性；进一步的研究结果表明PTPN6可通过抑制SP1，并抑制p38 MAPK通路抑制PC3细胞的增殖和耐药。结论:PTPN6能够抑制前列腺癌细胞PC3的增殖和耐药，提高其化疗敏感性，作用机制是通过调控SP1/p38 MAPK信号通路来实现的，这一结果能够为临床上前列腺癌的诊断和治疗提供分子基础。     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

SDF-1α/CXCR4 信号通路在轴向应力刺激促进骨再生中的作用研究

目的通过轴向应力刺激促进骨再生，观察基质细胞衍生因子 1α/趋化因子 CXC 亚族受体 4（stromal cell-derived factor 1α/cysteine X cysteine receptor 4，SDF-1α/CXCR4）信号通路变化，探讨轴向应力刺激促进骨再生的机制。方法取 72 只雄性新西兰大白兔，于右后肢胫骨近端内侧制备直径 8 mm 圆形皮质骨缺损并脱蛋白松质骨支架修复模型，随机分为 3 组（n=24）。A 组腹腔注射 PBS，B 组术肢给予应力刺激治疗+腹腔注射 PBS，C 组术肢给予应力刺激治疗+腹腔注射 CXCR4 拮抗剂（AMD3100）。术后 2、4、8、12 周，摄 X 线片并采用 Lane-Sandhu X 线评分标准评价骨愈合情况，取标本行 HE 染色观察新生骨组织及支架降解，免疫组织化学染色观察 VEGF、CXCR4 表达水平；4、8 周取标本 Western blot 检测 SDF-1α 及 CXCR4 蛋白表达水平；12 周行 Micro-CT 检查，计算新生骨体积及新生骨密度。 结果X 线片检查示，除术后 2 周各组骨缺损区及支架无明显变化外，4、8 及 12 周时 B 组骨愈合评分均高于 A、C 组（P<0.05）。12 周时 Micro-CT 扫描可见 B 组骨缺损修复、髓腔再通，新生骨体积及骨密度均高于 A、C 组（P<0.05）。HE 染色显示，术后 4 周开始 B 组骨再生及支架降解均明显快于 A、C 组。免疫组织化学染色示，各组 VEGF 及 CXCR4 阳性表达均在 4 周达峰值；各时间点 B 组 VEGF 及 CXCR4 表达量均显著高于 A、C 组（P<0.05）。Western blot 检测显示，4、8 周时 B 组 SDF-1α 与 CXCR4 表达量均显著高于 A、C 组（P<0.05）。 结论轴向应力刺激促进骨再生可能与其促进骨缺损区组织高表达 SDF-1α，激活与其下游调控 BMSCs 募集的 CXCR4 信号有关。