2型糖尿病患者血清SUA和CysC水平与糖尿病视网膜病变的关系

目的：探讨血清尿酸(SUA)、胱抑素C(CysC)水平与糖尿病视网膜病变(DR)的关系。

方法：前瞻性研究。选取2019-05/2021-05本院收治无DR的2型糖尿病(T2DM)患者53例和DR患者83例，DR患者中包括非增殖型糖尿病视网膜病变(NPDR)47例、增殖型糖尿病视网膜病变(PDR)36例。另选取同期体检中心体检健康者48人作为对照组。比较受试者血清学指标，尿酸氧化酶法检测SUA水平，免疫比浊法检测血清CysC含量，Spearman相关性分析血清SUA、CysC与其他血清学指标的相关性，多因素线性逐步回归法分析血清SUA、CysC的影响因素，使用受试者工作特征曲线(ROC)分析血清SUA、CysC对DR预测效能。

结果：T2DM组、NPDR组和PDR组的体质量指数(BMI)、收缩压(SBP)均明显高于对照组(均P<0.05)，PDR组的SBP均明显高于T2DM组和NPDR组(均P<0.05)，NPDR组和PDR组糖尿病病程均明显高于T2DM组(均P<0.05)，PDR组糖尿病病程明显高于NPDR组(P<0.05)。对照组、T2DM组、NPDR组、PDR组纳入对象中空腹血糖(FPG)、糖化血红蛋白(HbA1c)、SUA、CysC水平呈逐渐明显升高趋势(均P<0.001)，PDR组的低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)水平明显高于对照组(均P<0.05)，而高密度脂蛋白胆固醇(HDL-C)水平明显低于对照组(P<0.05)。血清SUA水平与FPG、HbA1c、TC、TG水平呈正相关(r_s=0.564、0.631、0.513、0.408，P<0.001)，与HDL-C、LDL-C无相关性(r_s=-0.061、0.035，P>0.05)； 血清 CysC水平与FPG、HbA1c、TC、TG水平呈正相关(r_s=0.524、0.692、0.395、0.435，P<0.001)，与HDL-C、LDL-C无相关性(r_s=-0.012、0.049，P>0.05)，FPG、HbA1c、TC、TG是血清SUA、CysC水平影响因素(P<0.001)。SUA、CysC联合检测时曲线下面积(AUC)(0.892，95%CI：0.840～0.944，敏感性71.1%，特异性94.3%)显著高于其单独检测AUC\〖SUA(0.807，95%CI：0.735～0.879，敏感性69.9%，特异性75.5%)、CysC(0.763，95%CI：0.684～0.841，敏感性69.9%，特异性75.5%)\〗(均P<0.05)。

结论：随着DR病情严重程度加重而血清SUA、CysC水平逐渐升高。血清SUA、CysC联合检测可提高DR诊断预测效能。     

Zhang Weishen: A Pioneer in the Development and Industrial Production of Penicillin in New China

The research and development of penicillin started with difficulty before 1949 and achieved certain results. In 1951, after the founding of the People's Republic of China, Zhang Weishen, as the only Chinese scientist who had been trained and worked in a penicillin research and development center in the United States for many years, overcame many difficulties and returned to China. In 1953, with the efforts of Zhang Weishen and his colleagues, China realized the industrialized production of penicillin, alleviating the urgent needs of the masses. Antibiotics has also become the first discipline to achieve major scientific and technological achievements after the founding of the New China. In the mid-1950s, the technical breakthrough in the localization of lactose substitutes marked the localization of the raw materials of the penicillin-producing culture medium, which paved the way for the industrialized production of penicillin with Chinese characteristics. Antibiotics have become one of the most widely used and affordable drugs for hundreds of millions of patients in China, and China has since ended the humiliating history of the “Sick Man of East Asia".     

外伤性晶状体脱位合并周边隐匿性视网膜病变的临床特征及预后分析

目的观察分析眼球钝挫伤合并外伤性晶状体脱位患者周边隐匿性视网膜病变的临床特点及预后。 方法本研究纳入2013年1月至2020年1月在柳州市人民医院眼科住院诊断为眼球钝挫伤合并外伤性晶状体脱位，并行23G微创玻璃体切割联合白内障摘除手术的72例（72眼）患者。根据裂隙灯和超声生物显微镜（UBM）检查，将患者分为晶状体不全脱位组和全脱位组，详细记录2组患者的术中周边视网膜病变情况，并分析其临床特征及疗效。 结果眼球钝挫伤合并外伤性晶状体脱位患者中有周边隐匿性视网膜病变的占72.22%，其中晶状体不全脱位组发生率高达80.95%，显著大于晶状体全脱位组的60.00%（P＜0.05）。2组患者的周边隐匿性视网膜病变均以隐匿性视网膜裂孔、变性和出血为最常见。所有患者术后视网膜情况稳定，视力预后较好。 结论眼球钝挫伤合并外伤性晶状体脱位患者常出现周边隐匿性视网膜病变，最常见的是视网膜裂孔、出血、变性。23G微创玻璃体切割联合白内障摘除手术是有效治疗手段，具有创伤小、并发症少的优势。     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

miR-145调控肝癌腹水模型Th9细胞升高的机制研究

目的:探讨miR-145调控肝癌腹水模型Th9细胞升高的作用机制。方法:构建小鼠H22肝癌腹水模型。造模两周后处死小鼠并分离出脾脏组织，流式细胞术分析肝癌腹水组（MA组）与正常对照组（Control 组）小鼠脾脏Th9细胞表达水平。ELISA法检测脾脏IL-9表达水平。RT-PCR法检测脾脏miR-145表达水平。Western Blot法检测脾脏中PI3K/Akt/mTOR/P70S6K/HIF-1α相关蛋白表达水平。分选小鼠脾脏CD4+T细胞，随机分为miR-145 mimics组和NC组，分别应用miR-145-5P mimics、阴性对照寡核苷酸（negative control，NC）进行转染，RT-PCR检测各组miR-145、HIF-1α mRNA及IL-9 mRNA表达水平。结果:与Control 组相比，MA组Th9细胞及其细胞因子IL-9表达均升高（P<0.05），miR-145表达降低（P<0.05），p-PI3K、p-Akt、mTOR、p-mTOR、p-P70S6K、HIF-1α蛋白均升高（P<0.05）。与NC组相比，miR-145 mimics组miR-145显著升高，HIF-1α mRNA及IL-9 mRNA表达下降。结论:肝癌腹水中Th9细胞升高可能与miR-145下降导致的PI3K/Akt/mTOR/P70S6K/HIF-1α通路激活有关。     

七氟烷预处理对大鼠骨髓间充质干细胞在缺氧复氧环境下的作用和机制初探

目的:研究七氟烷预处理对大鼠骨髓间充质干细胞（MSCs）在缺氧复氧环境下的作用和机制初探。方法:分离培养SD大鼠骨髓间充质干细胞，通过流式细胞仪和诱导分化培养鉴定其免疫表型和分化潜能。细胞随机分为3组:组1空白对照组；组2缺氧复氧组（缺氧24 h，复氧24 h）；组3七氟烷预处理组（2%七氟烷预处理2 h后，缺氧24 h，复氧24 h）。处理后收集各组细胞，用流式细胞仪测定其凋亡率，线粒体膜电位变化及细胞周期。Western blot测定细胞外调节蛋白激酶（ERK）的蛋白表达。结果:与组2相比，组3 MSCs凋亡率明显下降，处于S期细胞增多，细胞增殖能力增强。Western blot结果显示:与组2相比，组3磷酸化ERK蛋白表达上升。结论:七氟烷预处理能提高缺氧复氧环境下骨髓间充质干细胞存活率，降低MSCs凋亡数量，并能增强MSCs的增殖能力，这一机制与七氟烷促进MSCs细胞p-ERK蛋白表达相关。