Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

上海市黄浦区社会办医疗美容机构《医疗美容管理办法》知晓情况调查

目的了解上海市黄浦区社会办医疗美容机构的管理人员和医师对《医疗美容管理办法》相关内容的掌握情况,发现存在的问题并提出改善建议.方法采用现场调查与现场问卷调查相结合的方式,对在上海市黄浦区开展医疗美容科目的所有社会办医疗机构(共计38家)进行全覆盖现场调查,并对其中的管理人员41人、相关医师31人进行问卷调查.结果38家社会办医疗美容机构中,美容外科和美容皮肤科的开展率较高,分别为96.8%和97.2%,而美容牙科开展率为52.4%,美容中医科开展率最低(25.0%).管理人员关于非主诊医师可在主诊医师指导下工作的知晓率仅68.3%.关于美容外科、皮肤科、中医科、牙科主诊医师应具备的工作年限,管理人员答对率为90.2%,医师答对率为72.0%,二者有显著性差异(P<0.05).结论社会办医疗美容机构中的二级科目设置需进一步优化,以减少资源空置.应加强对医疗机构管理人员和医师的法律培训,改变经营模式,制定明确的准入与退出机制,从而减少违法违规行为的发生.     

四方联动防跌护理在社区跌倒高危老年人中的应用

目的探讨专科护士-社区护士-个体-家庭四方联动防跌护理模式在社区跌倒高危老年人中的应用与效果。方法选取深圳市龙岗区的2个社区,随机分为观察组和对照组,从两个社区登记建档的跌倒高风险老年居民中分别随机抽选45名进行干预。观察组采用"专科护士-社区护士-个体-家庭"四方联动推进的综合干预方案。对照组接受社区防跌倒常规护理。于干预前及干预后12个月使用修订版社区老年人跌倒危险评估量表、步态和平衡测试量表对两组老年人进行评测,记录两组1年内跌倒发生例次。结果干预期间跌倒发生情况:观察组1人次,对照组6人次。观察组步态和平衡测试得分提高,跌倒危险评估表得分降低,与对照组比较,差异有统计学意义(均P0.01)。结论四方联动的综合干预方案应用于社区居家老年人,能有效降低老年人跌倒风险,提升其防跌能力,对预防社区老年人跌倒的发生有积极作用。     

HPLC法同时测定健儿膏中8种成分

目的建立HPLC法同时测定健儿膏(党参、山药、甘草等)中白术内酯Ⅲ、白术内酯Ⅰ、党参炔苷、紫丁香苷、去氢土莫酸、土莫酸、去氢茯苓酸、茯苓酸的含有量。方法该药物甲醇提取液的分析采用Diamonsil Plus C18色谱柱(4.6 mm×250 mm,5μm);流动相乙腈-0.05%磷酸,梯度洗脱;体积流量1.0 mL/min;柱温30℃;检测波长210、220、266 nm。结果 8种成分在各组范围内线性关系良好(r≥0.999 1),平均加样回收率96.99%~100.01%,RSD 0.83%~1.47%。结论该方法准确可靠,重复性好,可用于健儿膏的质量控制。     

新形势下八年制医学教育的再思考

新形势下，健康中国建设和我国卫生事业发展迫切需要具有国际竞争力的医学科学家和领军人才。在现行医学教育体系中，培养具有国际竞争力的未来医学科学家和领军人才是八年制医学教育的必然选择。创新八年制医学人才培养模式应汲取长学制试办经验，直面现存问题，聚焦创新能力和创新精神，构建以研究为基础的八年制医学人才培养模式，确立“目标引领、厚植基础、面向临床、聚集创新”的办学原则，为我国卫生事业培养具有国际竞争力的未来领军人才。     

植入物乳房重建一步法和二步法临床对比研究

目的:探讨即刻乳房假体重建（一步法）和应用扩张器的假体重建（二步法）两种不同手术方式在术后并发症、美容效果和成本效益的差异。方法:回顾性分析我院乳腺外科2015年5月至2018年5月收治的285例乳腺癌植入物重建患者，依据手术方式不同分为一步法组（145例）和二步法组（140例），比较两组患者临床资料的差异。结果:一步法组术后出血发生率（6.8%）高于二步法组（1.4%），差异有统计学意义（P=0.021）。一步法组术后伤口皮瓣坏死率（6.2%）高于二步法组（1.4%），差异有统计学意义（P=0.036）。二步法组乳房满意度评分（81.5±7.1）分高于1步法组（78.6±6.2）分，差异有统计学意义（P=0.035）。二步法组住院总花费（80 334.8±6 149.8）元高于一步法组（60 966.5±5 544.9）元，差异有统计学意义（P=0.049）。二步法组住院天数（34.3±3.2）天多于一步法组（17.5±3.9）天，差异有统计学意义（P=0.014）。结论:在植入物乳房重建两种手术方式中，二步法相较于一步法，其并发症少，美容效果好，但在成本效益上并不优于一步法。     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

非霍奇金淋巴瘤侵犯骨髓时Cx43表达情况

目的:研究非霍奇金淋巴瘤(non-Hodgkin' s lymphoma,NHL)骨髓侵犯患者骨髓病灶中间隙连接蛋白（connexin，Cx）43表达情况。 方法:选取我院确诊的非霍奇金淋巴瘤骨髓侵犯患者26例，骨髓组织中查见呈灶性分布且已通过免疫组化证实为反应性淋巴细胞增生的患者9例，正常骨髓组织10例行免疫组化染色，根据阳性率及阳性程度评分后进行统计学分析。 结果:Cx43在NHL样本中的阳性率（30.8%）低于在反应性淋巴细胞增生样本（88.9%）及正常样本（100%）中的阳性率，差异有统计学意义（P<0.05）。而反应性淋巴细胞增生样本和正常样本间Cx43阳性率无统计学意义（P>0.05），但反应性淋巴细胞增生样本的阳性积分明显低于正常样本（P<0.05）。结论:非霍奇金淋巴瘤骨髓侵犯时病灶处Cx43表达情况显著低于反应性淋巴细胞增生及正常骨髓组织。