Immunohistochemical analysis of von Willebrand factor expression in myocardial tissues from autopsies of patients with ischemic heart disease

von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.     

丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床研究

目的 探讨丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床疗效.方法 选取2019年6月—2021年6月在天津市职业病防治院门诊皮肤科就诊治疗的114例银屑病患者,根据随机数字法分为对照组和治疗组,每组各57例.对照组患者给予他扎罗汀倍他米松乳膏,洗净患处,待皮肤干爽后,将适量本品均匀涂抹于患处,1次/d.治疗组患者在对照组治疗基础上口服丹青胶囊,4粒/次,3次/d.两组患者均连续治疗7 d.观察两组患者的临床疗效和临床症状好转时间,比较两组治疗前与治疗1、4、8周的皮损面积和严重程度指数(PASI)评分和血清炎性因子水平.结果 治疗后,治疗组总有效率是98.25％,显著高于对照组的82.46％(P<0.05).治疗后,治疗组患者皮损暗红、皮损肥厚、皮肤瘙痒、皮肤疼痛等症状好转时间均显著短于对照组(P<0.05).治疗后,两组PASI评分均较治疗前显著降低(P<0.05);治疗1、4、8周治疗组PASI评分显著低于对照组(P<0.05).治疗后,两组患者血清炎性因子白细胞介素6(IL-6)、白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)、干扰素-γ(IFN-γ)水平均较治疗前显著降低(P<0.05);治疗后,治疗组血清炎性因子水平显著低于对照组(P<0.05).结论 丹青胶囊联合他扎罗汀倍他米松治疗银屑病效果明显,能显著降低炎性因子水平,并有助于改善皮损情况,值得临床推广应用.     

Role of site-directed mutagenesis and adjuvants in the stability and potency of anthrax protective antigen

Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation.     

Systemic immune inflammation index in patients with recurrent aphthous stomatitis

ObjectivesRecurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII).MethodsPatients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019–2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as <0.05.ResultsThere was no statistically significant difference between the control and RAS groups in terms of sex and age distributions (p = 0.566 and p = 0.173, respectively). SII, NLR and PLR values were significantly higher in the RAS group compared to the controls (p < 0.001, p < 0.001 and p = 0.001, respectively). A very strong correlation between SII and NLR, moderately strong correlation between SII and PLR and moderate correlation between NLR and PLR values were detected (respectively ρ: 0.813, 0.719, 0.532; p-values <0.001).ConclusionSII, NLR and PLR has significantly higher levels in the RAS group compared to the control group, that it supports the role of systemic inflammation in the etiopathogenesis of RAS. In addition, the results show that SII is a valuable marker for inflammation.Level of evidence4.     

一测多评法在中药质量控制中的应用及研究进展＊

一测多评法（quantitative analysis of multi-components by single marker，QAMS）已成熟应用于中药材、中药提取物及中成药领域等中药复杂体系的质量评价研究中，有效解决了因对照品缺乏而导致的多指标质控技术推广难问题。本文查阅近五年的国内外研究文献，重点总结了高效液相色谱、气相色谱和质谱等技术在QAMS法中药质量控制中的应用。高效液相色谱联用紫外检测器（UV）技术应用最为广泛，最适合于中药QAMS法定量，结果稳定、准确；而高效液相色谱联用蒸发光检测器在中药QAMS法应用中，其测定准确性和适用性仍然需进一步探索和验证。液质联用技术虽然具有灵敏度高、线性范围宽等优点，但易受仪器参数、基质效应等的影响。进一步发展HPLC-UV技术在中成药制剂质量评价中的应用，是QAMS法多成分定量值得关注的方向；探索LC-MS和GC技术在中药QAMS质量评价中的稳定性和普适性是未来将面临的挑战。     

血清和尿液中外泌体miRNAs的表达水平对肾细胞癌的诊断价值

目的:研究血清和尿液中外泌体miRNAs的表达水平对肾细胞癌(RCC)的诊断价值。方法:选择本院2018年11月至2020年08月诊治的68例RCC患者（RCC组）进行前瞻性分析，并将RCC患者根据临床分期进行分组，以本院同期收治的60例肾脏良性病变患者作为对照组。检测患者血清和尿液中外泌体miRNAs相对表达量，分析血清和尿液中外泌体miRNAs在肾细胞癌中的诊断价值。结果:RCC组患者血清、尿液中miR-210、miR-21、miR-153、miR-1233和miR-221表达量均明显高于对照组，miR-34a表达量均明显低于对照组（P＜0.05）；血清中ROC曲线显示AUC最大的为miR-221，其诊断敏感度为79.40%，特异度为95.00%；尿液中最大的为miR-34a，其敏感度为85.30%，特异度为88.30%；不同临床分期RCC患者的血清miR-210、miR-153表达量以及尿液miR-153表达量无显著差异（P＞0.05），但血清和尿液中的miR-21、miR-34a、miR-1233、miR-221表达量以及尿液miR-210表达量在不同分期RCC患者中存在显著差异（P＜0.05）；血清中，miR-210、miR-153与临床分期无相关性（P＞0.05），miR-21、miR-1233、miR-221与临床分期呈正相关，miR-34a与临床分期呈负相关（P＜0.05）；尿液中，miR-210、miR-153与临床分期无相关性（P＞0.05），miR-21、miR-1233、miR-221与临床分期呈正相关，miR-34a与临床分期呈负相关（P＜0.05）。结论:RCC患者血清、尿液外泌体miR-210、miR-21、miR-34a、miR-153、miR-1233和miR-221表达量较良性肾脏病变患者存在显著差异，同时miR-21、miR-34a、miR-1233、miR-221表达量均与RCC患者病理分期存在显著相关性，可为疾病进展评估提供参考。     

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。     

硫氧还蛋白还原酶在肺癌疗效监测中的应用

目的探讨血浆硫氧还蛋白还原酶(TR)在肺癌化疗疗效监测中的价值。方法将482例肺癌患者依据化疗疗效分为治疗未获益组(211例)和治疗获益组(271例),检测所有患者TR、癌胚抗原(CEA)、鳞状上皮细胞癌抗原(SCC-Ag)、细胞角蛋白19片段(CYFRA 21-1)、神经元特异性烯醇化酶(NSE)及胃泌素释放肽前体(ProGRP)水平。采用受试者工作特征(ROC)曲线评估各项指标单项及联合检测判断化疗疗效的价值。结果治疗未获益组TR、CEA及NSE水平均高于治疗获益组(P<0.05),2个组之间SCC-Ag、CYFRA21-1及ProGRP水平差异均无统计学意义(P>0.05)。治疗未获益组TR阳性率为56.40%,显著高于治疗获益组(13.16%)(P<0.05)。ROC曲线分析结果显示,TR、CEA、CYFRA 21-1、SCCAg、NSE及ProGRP单项检测判断肺癌化疗疗效的曲线下面积(AUC)分别为0.759、0.667、0.579、0.530、0.619、0.544。将各项指标进行组合,TR+CEA、TR+CEA+CYFRA21-1、TR+CEA+CYFRA21-1+NSE及TR+CEA+CYFRA 21-1+NSE+ProGRP联合检测判断肺癌化疗疗效的AUC分别为0.757、0.749、0.752和0.788。TR与CEA、NSE、SCC-Ag、CYFRA 21-1及ProGRP均无相关性(r值分别为0.05、0.02、-0.15、0.05、0.10,P>0.05)。结论TR或可作为更有效的肺癌疗效监测的生物标志物。     

补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响＊

目的 探讨补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响。方法 选取90例2019年1月-2020年3月因kummell病住院手术治疗的患者，随机分为试验组45例和对照组45例。对照组给予骨水泥分期灌注椎体后凸成形术，术后口服阿仑膦酸钠治疗，试验组术后加用补肾壮督方口服治疗。记录两组术中骨水泥注入量。采用VAS疼痛评分标准评估术后疼痛改善情况，采用ODI评分评估功能障碍改善情况。采用伤椎前缘高度比值和伤椎椎体楔形角评估脊柱稳定性。采用碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）评估治疗前后血清骨形成情况。结果 与对照组比较，试验组术后第3天VAS疼痛评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后第3天、术后6个月和术后12个月ODI评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎前缘高度比值明显高于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎椎体楔形角明显低于对照组，差异有统计学意义（P<0.05）。试验组术后6个月和术后12个月碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）明显高于对照组，差异有统计学意义（P<0.05）。结论 补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术治疗kummell病可加快术后患者疼痛改善和功能恢复，促进骨形成，有效抑制患者中远期椎体压缩塌陷，维持脊柱稳定性。