生脉养心颗粒对老年人心功能干预的临床观察

目的:通过对生脉养心颗粒的临床观察,探讨生脉养心颗粒治疗老年慢性心力衰竭(Chronic Heart Failure,CHF)患者的治疗效果,并预测其远期临床获益。方法:将120例中医辨证分型为气阴两虚型的老年慢性心力衰竭患者随机分为两组,治疗组60例,对照组60例。对照组给予单纯的常规西药治疗,治疗组在常规西药治疗的基础上加用生脉养心颗粒治疗,两组治疗时间均为24个月。观察两组患者临床疗效,检测用药不同时间(分别于第3、12、24个月末)治疗前后B型脑钠肽(BNP)、左室射血分数(Left Ventricular Ejection Fracfion,LVEF)、6分钟步行试验(6-minute walk Test,6MWT)等疗效指标的变化,并且随访两组患者再入院率与病死率。结果:24个月后治疗组总有效率为86.7%(52/60),优于对照组的68.3%(41/60),两组差异比较有统计学意义(P<0.05)。治疗后两组BNP、LVEF、6MWT较治疗前均有明显改善(P<0.01)。组间比较:治疗3、12、24个月后BNP比较,治疗组优于对照组,差异有统计学意义(P<0.01)或(P<0.05)。治疗3个月后LVEF比较,两组间差异无统计学意义(P>0.05);治疗12、24个月后,治疗组LVEF优于对照组,两组差异有统计学意义(P<0.05)。治疗3、12、24个月后,治疗组6MWT优于对照组,比较差异有统计学意义(P<0.01)。随访2年,治疗组的再入院率和病死率显著低于对照组,组间差异有统计学意义(P<0.05)。结论:生脉养心颗粒能够改善老年慢性心力衰竭患者心功能及预后,提高其临床疗效,值得在临床推广应用。     

羌活中的香豆素类成分及其抑制脂多糖诱导的RAW 264.7细胞NO生成活性的研究

目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7～10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50～35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。     

Chronic inflammation and risk of lung cancer in older adults in the health,aging and body composition cohort study

Objectives

We examined the association between three inflammatory markers (Interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α) and incident lung cancer using baseline, updated, and averaged inflammatory measures in older adults.

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.