Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial

Aim: Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. Methods: Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. Results: As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case  group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). Conclusion: The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.     

硫酸核糖霉素分子式中硫酸数目的确定及控制方法的比较

目的：为了确定硫酸核糖霉素分子式中硫酸的数目,并选择适合的方法控制其硫酸盐的含量。方法：建立了高效液相色谱-蒸发光散射法（HPLC-ELSD）对硫酸核糖霉素的硫酸盐（SO4）含量进行测定,并开发出了同样适用的离子色谱电导法（HPIC-CD）进行结果比对。同时采用《中国药典》方法测定硫酸核糖霉素的酸碱度。结果：HPLC-ELSD法,硫酸盐（SO4）在15～250 μg·mL-1范围内线性良好,检测限和定量限分别为0.16 μg和0.25 μg,回收率为101.1%;HPIC-CD法,硫酸盐（SO4）在20～180 μg·mL-1范围内线性良好,检测限和定量限分别为0.17 ng和0.50 ng,回收率为99.8%。结论：两种硫酸盐测定方法,专属性强,灵敏度高,重复性好,测定结果无显著性差异,分子式中硫酸的数目约为1.5,进一步发现,硫酸盐含量和溶液pH值呈显著负相关,并具有一定的线性关系,酸碱度检查可以控制硫酸盐的含量。     

川芎清脑颗粒联合硫酸软骨素治疗偏头痛的临床研究

目的探讨川芎清脑颗粒联合硫酸软骨素治疗偏头痛的临床疗效。方法选取2017年3月—2018年3月在陕西省核工业二一五医院治疗的偏头痛患者76例,根据用药的差别分为对照组(38例)和治疗组(38例)。对照组口服硫酸软骨素钠片,0.6 g/次,3次/d;治疗组在对照组基础上口服川芎清脑颗粒,10 g/次,3次/d。两组患者均治疗4周。观察两组患者临床疗效,同时比较治疗前后两组患者临床症状评分、血清学指标和脑血流情况。结果治疗后,对照组临床有效率为81.58%,显著低于治疗组的97.37%,两组比较差异具有统计学意义(P0.05)。治疗后,两组头痛发作次数、头痛发作持续时间和头痛发作程度评分均明显降低(P0.05),且治疗组患者临床症状评分明显低于对照组(P0.05)。治疗后,两组患者血清高敏C反应蛋白(hs-CRP)、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)和溶血磷脂酸(LPA)水平均显著降低(P0.05),且治疗后治疗组这些血清学指标明显低于对照组(P0.05)。治疗后,两组患者大脑前动脉(ACA)、大脑中动脉(MCA)、大脑后动脉(PCA)、基底动脉(BA)、椎动脉(VA)的平均血流速度(Vm)均显著降低(P0.05),且治疗后治疗组脑血流情况明显优于对照组(P0.05)。结论川芎清脑颗粒联合硫酸软骨素治疗偏头痛可有效改善患者临床症状,降低血清hs-CRP、MMP-9、VEGF、LPA水平,有利于脑血流速度改善。     

新疆医科大学附属肿瘤医院门诊患者麻醉药品使用情况分析

目的 分析新疆医科大学附属肿瘤医院门诊麻醉药品的使用现状,为促进合理用药提供参考依据,促进癌症镇痛药物合理使用和科学规范管理。方法 收集2019—2022年新疆医科大学附属肿瘤医院门诊患者麻醉药品用药相关数据,对麻醉药品的处方数量、总消耗量、销售总金额、用药频度(DDDs)、限定日费用(DDC)、排序比(B/A)等进行数据分析。结果 2019—2022年新疆医科大学附属肿瘤医院门诊麻醉药品共涉及12个品规。盐酸羟考酮缓释片(10 mg)、盐酸吗啡片的处方量较多;麻醉药品的总消耗量显现逐年递减现象,盐酸羟考酮缓释片(40 mg)和硫酸吗啡缓释片(30 mg)总体用药量较多;销售金额总体上出现递增趋势,其中盐酸羟考酮缓释片(40 mg)与盐酸吗啡缓释片(30 mg)销售金额连续4年位居前3名,并且2者的DDDs连续3年排在前3名。结论 新疆医科大学附属肿瘤医院门诊患者麻醉药品总消耗量逐渐减少,销售金额逐年增长,麻醉药品的使用基本合理,管理方式科学有序符合标准。但是,仍需加强临床规范化用药,药师需要进一步提高业务能力并加强监督和干预,倡导麻醉药品个体化用药。     

离子色谱-抑制电导法测定硫酸镁钠钾口服用浓溶液中镁、钠、钾离子

目的 建立离子色谱–抑制电导法同时测定硫酸镁钠钾口服用浓溶液中镁、钠、钾离子的方法。方法 采用Dionex IonPac^TM CS12A色谱柱（250 mm×4 mm）,Dionex IonPac^TM CG12A保护柱（50 mm×4 mm）;以甲烷磺酸溶液为洗脱液,梯度洗脱,体积流量为1.0 mL/min,柱温30 ℃,检测池温度35 ℃,电导检测器,抑制器为Dionex CDRS 600 4 mm,电流值117 mA,进样体积为25 μL。结果 镁在0.72～1.08μg/mL、钠在12.80～19.20 μg/mL、钾在3.20～4.80 μg/mL线性关系良好,平均回收率分别为101.0%、100.7%、102.9%,RSD值分别为1.4%、1.4%、0.7%。结论 该方法简单、快速、准确,能够有效地控制硫酸镁钠钾口服用浓溶液中镁、钠、钾离子。     

舒筋活络丸联合硫酸羟氯喹治疗类风湿性关节炎的临床研究

目的 探讨舒筋活络丸联合硫酸羟氯喹片治疗类风湿性关节炎的临床疗效。方法 选取2020年3月—2022年3月在聊城市第二人民医院诊治的90例类风湿性关节炎患者,依据用药区别分为对照组和治疗组,每组各45例。对照组口服硫酸羟氯喹片,0.1 g/次,4次/d;治疗组在对照组的基础上口服舒筋活络丸,2丸/次,2次/d。两组患者治疗4周。观察两组患者临床疗效,比较治疗前后两组患者症状改善时间,DAS-28评分、HAQ指数、VAS评分和HSS评分,及血清肽聚糖识别蛋白-1（PGLYRP-1）、抗环瓜氨酸多肽抗体（ACCP）、胰岛素样生长因子结合蛋白-6（IGFBP-6）、中粒细胞集落刺激因子（GM-CSF）、白细胞介素-17（IL-17）和金属蛋白酶-3（MMP-3）水平。结果 经治疗,治疗组有效率为97.78%,明显高于对照组（82.22%,P＜0.05）。经治疗,治疗组症状改善时间均早于对照组（P＜0.05）。经治疗,两组患者DAS-28评分、HAQ指数、VAS评分均明显降低,而HSS评分明显升高（P＜0.05）,且治疗组评分较对照组改善更明显（P＜0.05）。经治疗,两组患者血清PGLYRP-1、ACCP、IGFBP-6、GM-CSF、IL-17、MMP-3水平均明显下降（P＜0.05）,且治疗组患者比对照组降低更明显（P＜0.05）。结论 舒筋活络丸联合硫酸羟氯喹片治疗类风湿性关节炎可有效改善患者症状,减轻患者疼痛,促进细胞因子水平改善。     

补肺活血胶囊联合沙丁胺醇治疗缓解期慢性肺心病的临床研究

目的 探讨补肺活血胶囊联合沙丁胺醇治疗缓解期慢性肺心病的临床疗效。方法 选择2018年6月—2021年6月濮阳市中医医院收治的86例缓解期慢性肺心病患者,按照随机数字表法分为对照组（43例）和治疗组（43例）。对照组口服硫酸沙丁胺醇片,2片/次,3次/d。治疗组在对照组的基础上口服补肺活血胶囊,4粒/次,3次/d。两组用药14 d观察效果。观察两组患者临床疗效,比较治疗前后两组患者症状改善时间,肺功能第1秒用力呼气量（FEV1）、用力肺活量（FVC）和FEV1/FVC指标,心功能心脏每搏量（SV）、心脏心输出量（CO）、心脏指数（CI）指标,血清炎性因子肿瘤坏死因子-α（TNF-α）、转化生长因子-β1（TGF-β1）、白细胞介素-8（IL-8）、血管内皮素（ET-1）水平及不良反应情况。结果 治疗后,治疗组患者总有效率（95.35%）明显高于对照组（81.40%,P＜0.05）。治疗后,治疗组患者症状改善时间比对照组明显缩短（P＜0.05）。治疗后,两组患者FEV1、FVC、FEV1/FVC、SV、CO、CI比治疗前明显升高,而血清炎性因子TGF-β1、ET-1、TNF-α和IL-8水平比治疗前明显降低（P＜0.05）,且治疗后治疗组肺功能和心功能指标明显高于对照组（P＜0.05）,血清炎性因子水平明显低于对照组（P＜0.05）。治疗后,治疗组不良反应总发生率为9.30%,明显低于对照组（16.28%,P＜0.05）。结论 补肺活血胶囊联合沙丁胺醇治疗缓解期慢性肺心病效果确切,能显著提高心肺功能,减弱机体炎性反应,且不良反应低。     

盐酸曲马多与硫酸镁注射液在氯化钠注射液中的配伍稳定性研究

目的 考察盐酸曲马多注射液与硫酸镁注射液配伍的稳定性,为临床用药安全提供依据。方法 模拟临床用药方案,观察盐酸曲马多与硫酸镁注射液在0.9%氯化钠注射液配伍后,在168 h内的外观、pH值及不溶性微粒变化,并采用高效液相色谱法测定盐酸曲马多质量浓度的变化。结果 配伍液在室温条件下外观、pH值及不溶性微粒均无明显变化,两药配伍后盐酸曲马多相对质量浓度>99%。结论 盐酸曲马多注射液与硫酸镁注射液在0.9%氯化钠注射液配伍后,在室温条件下168 h可保持稳定。     

The development and validation of methods for evaluating the immune system in preweaning piglets

The preweaning piglet has been found to be a valuable research model for testing ingredients used in infant formula. As part of the safety assessment, the neonates' immune system is an important component that has to be evaluated. In this study three concurrent strategies were developed to assess immune system status. The methods included (1) immunophenotying to assess circulating innate immune cell populations, (2) monitoring of circulating cytokines, particularly in response to a positive control agent, and (3) monitoring of localized gastrointestinal tissue cytokines using immunohistochemistry (IHC), particularly in response to a positive control agent. All assays were validated using white papers and regulatory guidance within a GLP environment. To validate the assays precision, accuracy and sample stability were evaluated as needed using a fit for purpose approach. In addition animals were treated with proinflammtory substances to detect a positive versus negative signal. In conclusion, these three methods were confirmed to be robust assays to evaluate the immune system and GIT-specific immune responses of preweaning piglets.     

Epitope-Dependent Selective Targeting of Thrombomodulin Monoclonal Antibodies to Either Surface or Intracellular Compartment of Endothelial Cells

Abstract

Internalization of antibodies to thrombomodulin (TM) may provide a mechanism for intraendothelial targeting of drugs or genes. This study characterized three monoclonal antibodies against human TM (mAb 1009,1029, and 1045) and examined their internalization by human umbilical vein endothelial cells (HUVEC). It assessed binding of antibodies to recombinant human TM containing chondroitin sulfate (complete, cTM) and TM lacking chondroitin sulfate (incomplete, iTM). Direct RIA, indirect RIA, and ELISA and competitive ELISA show that (1) mAb 1009 binds to both cTM and iTM independently of divalent cations; (2) binding of mAb 1029 to iTM requires divalent cations, while binding to cTM is cation-independent; (3) mAb 1045 binds selectively to cTM independently of divalent cations. Binding of all three antibodies to the surface TM in HUVEC at 4°C was similar by indirect immunostaining. In permeabilized HUVEC, however, mAb 1009 and 1029 provide brighter intracellular staining than mAb 1045. Uptake of ¹²⁵I-mAb 1009 by HUVEC at 37°C was significantly higher than that of ¹²⁵I-mAb 1045. Low temperature markedly suppresses binding of ¹²⁵I-mAb 1009 to HUVEC, but has no effect on ¹²⁵I-mAb 1045 binding. About 80% of radiolabeled mAb 1045 bound to HUVEC at 37°C could be eluted by acidic buffer from the cell surface, but only 40% of mAb 1009 and 1029 was elutable at these conditions. About 70-80 % of ¹²⁵I in cell lysates was TCA-soluble after HUVEC incubation with either mAb 1009 and 1029, but only 10 and 2.5% of ¹²⁵I was TCA-soluble in cell lysates and medium after 90 min incubation with ¹²⁵I-mAb 1045 at 37°C. Therefore, HUVEC internalize and degrade an mAb that reacts with iTM, yet do not internalize an mAb that reacts selectively with cTM (mAb 1045). This result implies that either HUVEC do not internalize cTM constitutively or mAb 1045 suppresses TM internalization. Therefore, antibodies recognizing different TM epitopes might provide targeting of drugs to different cellular compartments.