Effects of traditional herbal medicine, Hwaotang, on atherosclerosis using the spontaneous familial hypercholesterolemia model, Kurosawa and Kusanagi-hypercholesterolemic rabbits and the venous thrombosis rats

Hwaotang (HOT), a traditional Korean medicinal formulation, is a dried decoctum of a mixture of seven herbal medicines, consisting of Angelica gigantis Radix, Rehmanniae Radix, Paeoniae Radix, Ciniamomi Cortex, Cnidii Rhizoma, Persicae Semen and Carthami Flos. In the present study, the inhibitory effects and anti thrombic properties of HOT on the progression of atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits and rats. Changes in blood chemistry, pathology and low-density lipoprotein (LDL) oxidation were measured in a control and HOT group. In the control group, the area of atheromatous plaques of the aorta progressed between week 12 (36.65%) and week 14 (46.22%). This progression of atherosclerotic lesions did not occur in the HOT-treated group after 12 (24.24%) and 14 (23.34%) weeks. Antioxidative effects on LDL were seen in the HOT in weeks 12 and 14. HOT improved the hypercholesterolemia in the KHC rabbits. On the other hand, HOT and five of the seven herbs, except Cnidii Rhizoma and Carthami Flos, inhibited the endotoxin-induced hepatic venous thrombosis in high cholesterol diet-treated rats. However, Ciniamomi Cortex showed a very weak inhibitory effect on the endotoxin-induced hepatic venous thrombosis. The extract also inhibited the endotoxin-induced decrease in blood platelets and fibrinogen, and endotoxin-induced increase in fibrin degradation products (FDP) on disseminated intravascular coagulation in normal rats. In conclusion, these results suggest that HOT has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH rabbits. It is also suggested that the antioxidative effects of HOT on LDL led to the beneficial effects observed in this study. The protection by HOT and its herbs on the artificially induced ischemic infarction might be related to their inhibitory effects on disseminated intravascular coagulation, platelet coagulation and thrombotic action.     

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure. Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14–25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength. Results: Groups did not differ for age. Median baseline BMI z-scores were −1.13 (−1.58, −0.38) in AN-E+ vs. 0.08 (−0.40, 0.84) in HC (p < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased (p = 0.01; p = 0.02; p = 0.004 respectively) over 12 months in AN-E+ compared to HC. Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.     

Spleen stiffness-spleen size-to-platelet ratio risk score as noninvasive predictors of esophageal varices in patients with hepatitis B virus-related cirrhosis

This study was conducted to evaluate the predictive value of spleen stiffness-spleen size-to-platelet ratio risk score (SSPS) as a noninvasive predictor of esophageal varices (EVs) and to compare it with others.In this retrospective study, from April 2017 to October 2018, a total of 65 patients with hepatitis B virus-related cirrhosis who underwent the liver and spleen stiffness (LS, and SS) measurements by 2 dimensional-shear wave elastography and endoscopic evaluation for EVs were enrolled. Liver stiffness-spleen size-to-platelet ratio risk score (LSPS) and SSPS were calculated. The prognostic values were assessed by the area under the receiver operating characteristic curve (AUC).Twenty-six patients had no EV on endoscopy. Among 39 patients who had EVs, 12 patients had high risk EVs. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting EVs were 0.72, 0.77, 0.80, and 0.85, respectively. The AUCs of the LS value, SS value, LSPS, and SSPS for predicting high-risk EVs were 0.55, 0.78, 0.67, and 0.80, respectively. SSPS had the highest specificity, at 96.15%, for predicting EVs.SSPS may be beneficial to exclude from having EVs and it is expected that the frequency of performing endoscopies for screening EVs can be reduced.     

KIF23 is a potential biomarker of diffuse large B cell lymphoma: Analysis based on bioinformatics and immunohistochemistry

Diffuse Large B Cell Lymphoma (DLBCL), the most common form of blood cancer. The genetic and clinical heterogeneity of DLBCL poses a major barrier to diagnosis and treatment. Hence, we aim to identify potential biomarkers for DLBCL.Differentially expressed genes were screened between DLBCL and the corresponding normal tissues. Kyoto Encyclopedia of Genes and Genomes and Gene oncology analyses were performed to obtain an insight into these differentially expressed genes. PPI network was constructed to identify hub genes. survival analysis was applied to evaluate the prognostic value of those hub genes. DNA methylation analysis was implemented to explore the epigenetic dysregulation of genes in DLBCL.In this study, Kinesin family member 23 (KIF23) showed higher expression in DLBCL and was identified as a risk factor in DLBCL. The immunohistochemistry experiment further confirmed this finding. Subsequently, the univariate and multivariate analysis indicated that KIF23 might be an independent adverse factor in DLBCL. Upregulation of KIF23 might be a risk factor for the overall survival of patients who received an R-CHOP regimen, in late-stage, whatever with or without extranodal sites. Higher expression of KIF23 also significantly reduced 3, 5, 10-year overall survival. Furthermore, functional enrichment analyses (Kyoto Encyclopedia of Genes and Genomes, Gene oncology, and Gene Set Enrichment Analysis) showed that KIF23 was mainly involved in cell cycle, nuclear division, PI3K/AKT/mTOR, TGF-beta, and Wnt/beta-catenin pathway in DLBCL. Finally, results of DNA methylation analysis indicated that hypomethylation in KIF23''s promoter region might be the result of its higher expression in DLBCL.The findings of this study suggested that KIF23 is a potential biomarker for the diagnosis and prognosis of DLBCL. However, further studies were needed to validate these findings.     

High-Dose Dual Therapy Versus Bismuth-Containing Quadruple Therapy for the Treatment of Helicobacter pylori Infection: A Systematic Review with Meta-Analysis

Background:This study aimed to evaluate the efficacy and safety of high-dose dual therapy for Helicobacter pylori (H. pylori) eradication compared to bismuth-containing quadruple therapy.Methods:The electronic database of PubMed, Embase, and Cochrane Library were searched from inception to March 18, 2021. Randomized, controlled trials that evaluated high-dose dual therapy versus bismuth-containing quadruple therapy for H. pylori infection were included.Results:We included 6 studies containing 1677 patients with H. pylori infection. This meta-analysis demonstrated that high-dose dual therapy achieved similar eradication rate compared with bismuth-containing quadruple therapy (intention-to-treat: 84.6% vs 83.7%, relative risk (RR) = 1.01, 95% CI: 0.97-1.06, P = .49; per-protocol = 88.4% vs 89.0%, RR = 1.00, 95% CI: 0.97-1.04, P = .99). However, high-dose dual therapy showed fewer side effects (13.1% vs 32.0%, RR = 0.51, 95% CI: 0.34-0.78, P = .002) and better compliance (96.1% vs 93.3%, RR = 1.03, 95% CI: 1.00-1.05, P = .03) compared to bismuth-containing quadruple therapy.Conclusion:This meta-analysis demonstrated that high-dose dual therapy is equally effective with bismuth-containing quadruple therapy in eradicating H. pylori, with fewer side effects and better compliance.     

小儿尿道下裂尿道板组织中雌激素受体及微血管密度的表达及临床意义

目的 探讨尿道下裂患儿尿道板组织和尿道部皮肤组织中雌激素受体(ER)和微血管密度(MVD)的表达及意义.方法 选取2013年6月-2015年1月天津儿童医院收治的尿道下裂手术患儿30例,术中分别取部分尿道板和尿道部皮肤组织,检测不同组织中ER及MVD的表达及分布情况.结果 2组均检测到ER及MVD的表达.尿道板组织与尿道部皮肤组织中ER表达水平比较差异无统计学意义(P＞0.05),尿道板组织中MVD低于尿道部皮肤组织(P＜0.05).结论 尿道板组织和尿道部皮肤组织ER含量接近,可能与尿道发育异常有关;尿道板组织中存在微血管分布,为保留尿道板的尿道成形术提供了理论依据;尿道板组织内MVD显著降低,可能为术后发生尿瘘的原因之一.     

两种指标计算住院病人抗菌药物使用强度的适用性比较

目的：比较采用实际占用总床日数和收治病人人数天数计算住院病人抗菌药物使用强度（antibacterial use density, AUD）的准确性,以确定一个适用性更高的AUD计算方法。方法：分别使用实际占用总床日数和收治病人人数天数（即抽样时间段内出院人数×平均住院天数）计算上海市公共卫生临床中心2009-2011年每年,以及2012年1-3月每月住院病人的AUD,记为AUD1和AUD2,比较月度AUD1和AUD2、年度AUD1和AUD2的离散度。结果：月度AUD1的离散度显著小于月度AUD2离散度,年度AUD1和年度AUD2的离散度相差不大。结论：与收治病人人数天数相比,使用实际占用总床日数计算AUD适用性更佳,更能真实反映住院病人抗菌药物使用水平。     

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

Aim： Paeonol （2＇-hydroxy-4＇-methoxyacetophenone） from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells （VECs） in vitro.
Methods： VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 （miR-21） and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA.

Results： Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners （the value of IC50 was about 20 mg/L at 24 h）. Furthermore, ox-LDL （20 mg/L） significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL （20 mg/L） significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol （120 μmol/L） prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN＇s 3＇-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment.

Conclusion： miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis.     

银杏叶提取物体外对铜离子诱导的人血清低密度脂蛋白氧化修饰的抑制作用(英文)

本文在体外对EGb761能否抑制钢离子诱导的人血清低密度脂蛋白氧化修饰进行了研究。低密度脂蛋白（LDL）用EGb76140,80,160mg·L(-1)‘预处理1h,然后用CuSO410μmol·(-1)氧化修饰10h。结果表明LDL被钢离子氧化修饰后低密度脂蛋白中维生素E（VE）被耗竭,丙二醛（MDA）及自身荧光物质（LF）含量升高,载脂蛋白B（apoB）的电泳迁移速率加快。EGb761剂量依赖性地抑制VE的含量降低和MDA及自身荧光物质的含量升高,载脂蛋白B的电泳迁移速率依次减慢。可见在体EGb761能抑制钢离子诱导的人血清低密度脂蛋白氧化修饰。     

右旋兰索拉唑的药理学特点及在胃食管反流病治疗中的应用

虽然质子泵抑制剂(PPI)在胃食管反流病(GERD)治疗方面取得了很大的成功,但是抑酸时间不足、患者依从性差等挑战仍然存在。近期,美国FDA批准了一种新的PPI药物右旋兰索拉唑(dexlanso-prazole,日本武田公司开发,商品名:DexliantTM),目前主要用于糜烂性食管炎急性期及维持期的治疗,以及非糜烂性胃食管反流疾病烧心症状的控制。该药物采用独特的双层缓释技术,可以维持更长的作用时间,达到更好的抑酸效果,且安全性和耐受性良好。