基于NF-κB相关信号通路探讨常用中药治疗溃疡性结肠炎研究进展

核转录因子-κB(NF-κB)相关信号通路在溃疡性结肠炎的形成与发展中起到很大的作用。研究显示中药单体及单药可以通过NF-κB信号通路介导减少黏膜炎症反应、抑制肠道上皮细胞凋亡、增强肠道黏膜屏障、调节肠道内菌群丰度等抑制溃疡性结肠炎的发展,但具体的作用机制尚不明确。可能与调节TLR4/NF-κB信号通路、JAK2/STAT3/NF-κB信号通路、PI3K/AKT/NF-κB信号通路、NF-κB/NLRP3信号通路等有关。涉及到的常用药物包括黄连、干姜、鸦胆子、黄芪、肉桂、青黛、雷公藤、黄芩、蒲公英、马齿苋、苦参、青蒿等及其提取物小檗碱、6-姜烯酚、鸦胆子苦醇、黄芪多糖、肉桂醛、雷公藤多苷、黄芩苷、苦参总碱、双氢青蒿素等。故围绕NF-κB相关信号通路对常用治疗UC的中药及其单体作一综述,旨在为进一步深入研究提供思路和参考。     

Effect of commercially available green and black tea beverages on drug-metabolizing enzymes and oxidative stress in Wistar rats

The effect of commercially available green tea (GT) and black tea (BT) drinks on drugmetabolizing enzymes (DME) and oxidative stress in rats was investigated. Male Wistar rats were fed a laboratory chow diet and GT or BT drink for 5 weeks. Control rats received de-ionized water instead of the tea drinks. Rats received the GT and BT drinks treatment for 5 weeks showed a significant increase in hepatic microsomal cytochrome P450 (CYP) 1A1 and CYP1A2, and a significant decrease in CYP2C, CYP2E1 and CYP3A enzyme activities. Results of immunoblot analyses of enzyme protein contents showed the same trend with enzyme activity. Significant increase in UDP-glucuronosyltransferase activity and reduced glutathione content in liver and lungs were observed in rats treated with both tea drinks. A lower lipid peroxide level in lungs was observed in rats treated with GT drink. Electrophoretic mobility shift assay revealed that both tea drinks decreased pregnane X receptor binding to DNA and increased nuclear factor-erythroid 2 p45-related factor 2 binding to DNA. These results suggest that feeding of both tea drinks to rats modulated DME activities and reduced oxidative stress in liver and lungs. GT drink is more effective on reducing oxidative stress than BT drink.     

Nanodelivery of immunogenic cell death-inducers for cancer immunotherapy

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PI3K/PKB信号通路在TGF-β_1诱导人肝星状细胞表达骨桥蛋白中的作用

目的:研究磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/PKB)信号通路在转化生长因子β1(TGF-β1)诱导人肝星状细胞表达骨桥蛋白(OPN)的调控作用。方法:体外培养LX-2人肝星状细胞株,予TGF-β1(终浓度2.5、5、10、20μg/L)刺激24 h或予TGF-β1(终浓度10μg/L)刺激12 h、24 h、48 h;先经PI3K/PKB信号通路特异性抑制剂wortmannin(0.1μmol/L)预处理1 h,再予10μg/L TGF-β1刺激24 h,收集细胞,采用real-time PCR及Western blotting法检测OPN表达情况。结果:TGF-β1能够促进LX-2细胞表达OPN,在一定浓度和时间范围内,其表达量随着TGF-β1浓度和时间的增加而增加,呈剂量和时间依赖性关系;经wortmannin预处理再予TGF-β1刺激的LX-2细胞,与对照组相比,OPN表达受到明显抑制(P0.01)。结论:TGF-β1对LX-2人肝星状细胞OPN表达具有诱导作用,此作用可能受PI3K/PKB信号通路的调控。     

新型冠状病毒影响下对药物Ⅰ期临床试验受试者管理的思考

2019年末至今新型冠状病毒肺炎疫情在全球蔓延,造成严重的经济冲击和社会影响,对药物临床试验的开展也带来诸多困难与挑战。基于药物I期临床试验受试人群和流程的特殊性,引发了对在新型冠状病毒肺炎疫情影响下药物I期临床试验受试者管理的一些思考。提出从受试者招募、筛选、入住的不同阶段,到受试者宣教、饮食管理及不良事件观察等多方面的应对策略,旨在探讨如何在疫情防控常态化情况下,更好地保护受试者安全与权益,加强临床试验的风险控制,确保试验的顺利完成。     

FLNA基因变异致额骨干骺端发育不良1型一例

目的探讨FLNA基因变异所致额骨干骺端发育不良1型(frontometaphyseal dysplasia 1,FMD1)的临床及遗传学特点。方法分析患儿的临床表型,应用全外显子测序技术对先证者进行致病基因变异筛查,用Sanger测序法对其父母进行验证。结果先证者男性,2岁9个月,表现为特殊面容:眉弓轻度突出、眼睑下斜、眼距宽,骨骼畸形:双下肢弯曲、右膝外翻、左膝内翻、双手食指及中指轻度畸形、小指屈曲挛缩,左肘关节活动受限。基因测序发现患儿FLNA基因存在错义变异c.3527G>A,p.Gly1176Glu(半合子),父母均未携带该变异。结论FLNA基因变异引起的FMD1在婴幼儿时期即可出现关节挛缩、长骨发育不良,并随年龄增长进展,需要长期随访治疗。本例患儿FLNA基因变异位点尚未见文献报道。     

Changes of mesenchymal stromal cells mobilization and bone turnover in an experimental bone fracture model in ovariectomized mice

Objective: The aim of this study was to characterize the mesenchymal stromal cells (MSCs) and endothelial progenitor cells (EPCs) mobilization, and bone turnover in osteoporotic fracture healing in ovariectomized mice. Methods: In total, 112 female C57/BL mice were divided into two groups. The first group was sham-operated (SO), and the other group was ovariectomized (OVX). After three weeks, the right femora of the mice were fractured under anesthesia and internally fixed with steel pin. Peripheral blood and bone marrow were was collected for flow cytometry analysis, at 0 hours (h), 12 h, 24 h, 72 h and 168 h after fracture. MSCs and EPCs levels were assessed using cell surface antigens in different combinations (CD44+ CD34-CD45-, and CD34+ KDR+CD45-) by flow cytometry. At 0, 14, 28 and 42 days after fracture, sera were assayed for circulating levels of procollagen type I-N-terminal propeptide (P1NP) and C-terminal telopeptide of type I-collagen (CTX) by ELISA. Femurs were harvested at 2 weeks and 6 weeks after fracture for X-ray radiography, micro-computed tomography (micro-CT) and histology. Results: Our results showed that bone marrow and peripheral blood MSCs numbers of the OVX mice were significantly lower than the SO mice, at 12 h, 24 h and 72 h after fracture. In addition, circulating P1NP and CTX levels of the OVX mice were significantly higher than the SO mice, at 2 and 4 weeks. Conclusion: Results of the present study revealed disorders of bone marrow MSCs mobilization and bone turnover may partially account for the delay of osteoporotic fracture healing.     

术前不同糖化血红蛋白水平对成人心脏手术患者预后影响的Meta分析

背景 对于术前糖化血红蛋白（HbA1c）水平对成人心脏手术预后所造成的影响,目前已经引起了国内外学者的重视。但各研究参考标准不同,导致对HbA1c分界值的划定也不尽相同。 目的 通过Meta分析方法系统评价术前不同HbA1c水平对成人心脏手术患者预后的影响。 方法 计算机检索中国知网、万方数据知识服务平台、Medline、EMBase、The Cochrane Library,搜集有关术前HbA1c水平对成人心脏手术预后影响的病例-对照、前瞻性或回顾性队列研究,检索时限为2000年1月1日至2021年9月10日。由2名研究人员独立进行文献筛选、数据提取,评价纳入研究的偏倚风险后,采用RevMan 5.4.1软件进行Meta分析。 结果 最终纳入35篇文献,均为队列研究,共计35 826例患者。根据血糖控制程度将研究分层,相同HbA1c分界值的归入同一亚组合并分析。Meta分析结果显示：术前HbA1c<5.5%组患者成人心脏术后早期死亡率低于HbA1c≥5.5%组〔相对危险度（RR）=0.39,95%CI（0.18,0.84）,P=0.02〕。术前HbA1c<6.0%、6.5%、7.0%、7.5%、8.0%组患者成人心脏术后胸骨感染率分别低于HbA1c≥6.0%、6.5%、7.0%、7.5%、8.0%组〔RR=0.47,95%CI（0.24,0.91）,P=0.02;RR=0.48,95%CI（0.34,0.69）,P<0.000 1;RR=0.37,95%CI（0.26,0.52）,P<0.000 01;RR=0.22,95%CI（0.13,0.35）,P<0.000 01;RR=0.23,95%CI（0.14,0.38）,P<0.000 01〕。术前HbA1c<6.5%、7.0%、7.5%、8.0%组患者成人心脏术后脑血管事件发生率分别低于HbA1c≥6.5%、7.0%、7.5%、8.0%组〔RR=0.70,95%CI（0.52,0.94）,P=0.02;RR=0.52,95%CI（0.39,0.69）,P<0.000 01;RR=0.50,95%CI（0.32,0.80）,P=0.003;RR=0.47,95%CI（0.29,0.75）,P=0.002〕。术前HbA1c<6.0%、6.5%、7.0%、7.5%、8.0%组患者成人心脏术后急性肾损伤发生率分别低于HbA1c≥6.0%、6.5%、≥7.0%、≥7.5%、≥8.0%组〔RR=0.40,95%CI（0.18,0.92）,P=0.03;RR=0.78,95%CI（0.71,0.84）,P<0.000 01;RR=0.66,95%CI（0.55,0.78）,P<0.000 01;RR=0.73,95%CI（0.65,0.82）,P<0.001;RR=0.75,95%CI（0.67,0.84）,P<0.000 01〕。术前HbA1c<6.0%、6.5%、7.0%组患者成人心脏术后住院时间分别短于HbA1c≥6.0%、6.5%、7.0%组〔均数差（MD）=-0.61,95%CI（-1.23,0.00）,P=0.05;MD=-0.93,95%CI（-1.58,-0.29）,P=0.005;MD=-0.81,95%CI（-1.11,-0.51）,P<0.000 01〕。 结论 现有证据表明,术前HbA1c<5.5%能有效降低成人心脏手术患者术后早期死亡率,患者术前血糖控制越好,术后发生并发症的风险越小、预后越好。因此,成人心脏手术前应关注患者HbA1c,对处于高值者,应结合临床表现和脏器功能,对是否需要进行术前血糖优化干预进行权衡。     

单孔机器人辅助单纯前列腺切除术的初步体会

目的:探讨单孔机器人辅助单纯前列腺切除术（spRASP）治疗良性前列腺增生（BPH）的可行性及临床应用价值。方法:回顾性分析2020年11月—2021年6月上海中医药大学附属曙光医院泌尿中心7例采用spRASP治疗BPH患者的临床资料。平均年龄（67±9）岁。经估算的平均前列腺体积（78.3±12.9） mL;平均残余尿（PVR）(58.0±24.8) mL;平均国际前列腺症状评分（IPSS）(20.9±5.9)分,平均生活质量评分（QOL）(4.7±1.5)分,平均最大尿流率(Q_max)（7.9±3.6） mL/s。比较患者术前和术后3个月的IPSS评分、QOL评分、PVR、Q_max、IIEF等差异,分析评价手术疗效。结果:7例手术均顺利完成。平均手术时间（85.5±25.5） min,平均估计出血量（75.5±25.5） mL,平均留置引流管时间（3.4±0.8） d,平均留置尿管时间（7.5±1.2） d,术后平均住院时间（5.1±3.1） d。术后3个月患者平均IPSS评分（10.8±3.1）分、平均QOL评分（1.6±0.9）分、平...