论中药工业中的中试放大验证

本文对中药制药工程技术的四要素之一-中药施工与验证进行探讨,从中药研究成果转化为大规模生产的过程中一般都将发生质的变化,许多重大工程技术问题也往往出现在这一阶段。因此,中试放大验证至关重要,也中药现代化的关键。本文论述了在实现中药大规模生产过程中进行中试放大验证的必要性,主要技术内容,应达到的目标,并就中试放大验证平台的建设,基本功能与任务,运行等进行了详细介绍。     

升麻甙与5-O甲基维斯阿米醇甙对血管内皮细胞分泌细胞因子的影响

目的:观察升麻甙与5-O甲基维斯阿米醇甙对氧化低密度脂蛋白(ox-LDL)致心脏微血管内皮细胞损伤,引起IL-6和TNF-α分泌的影响。方法:采用体外培养的乳鼠心脏微血管内皮细胞,测定其生长曲线及药物的最大无毒浓度后,经升麻甙(50、100、200μg/ml)与5-O甲基维斯阿米醇甙(50、100、200μg/ml)预处理24h,再与ox-LDL(MDA含量为3nmol/ml)共同孵育24h,用ELISA法和放免法分别检测细胞培养液中IL-6和TNF-α的水平。结果:升麻甙与5-O甲基维斯阿米醇甙在50、100、200μg/ml时能够明显抑制ox-LDL引起的内皮细胞IL-6、TNF-α分泌,且呈剂量依赖性。结论:升麻甙与5-O甲基维斯阿米醇甙能够抑制血管内皮细胞产生炎性细胞因子IL-6和TNF-α。     

Prospective pricing system by diagnosis-related groups: comparison of federal diagnosis-related groups with high-risk obstetric care groups

Of 468 diagnosis-related groups identified by the federal government for Medicaid reimbursement, 15 are related to obstetric hospital care. Each diagnosis-related group is considered a distinct group in which cases are homogeneous with respect to resource consumption. Because the diagnosis-related group system is based primarily on data from community and secondary care hospitals, it does not differentiate sufficiently among high-risk obstetric patients seen at tertiary care institutions, such as Florida's Regional Perinatal Intensive Care Centers. We developed an alternative scheme for diagnosis-related groups, called obstetric care groups, using the federal diagnosis-related groups as the model from which to depart. Data collected for 4192 women during a 2 1/2-year period indicate that obstetric care groups provide more homogeneous groups than diagnosis-related groups for our population of high-risk patients. The obstetric care groups differentiate between no complications, one complication, and two or more complications, while the diagnosis-related groups differentiate only between no complications and one or more complications. Also, complications for obstetric care groups are based on only 19 diagnoses that contribute significantly to resource consumption, while the list of possible complications exceeds 200 for diagnosis-related groups. Although the obstetric care group classification system is simpler than that for diagnosis-related groups, it results in a more accurate reimbursement of hospitalization charges for high-risk obstetric care.     

Chorionic villus sampling by rigid forceps: experience with 300 cases at risk for thalassemia major

In this article we report the results of chorionic villus sampling by a biopsy forceps inserted via the cervix under ultrasonic guidance in 300 pregnancies at risk for thalassemia major. A sufficient amount of chorionic villi for deoxyribonucleic acid analysis by oligonucleotide hybridization was obtained in all cases tested but one, with a success rate of 99.7%. The percentage of fetal loss, expressed as proportion of continuing pregnancies, was 4.8%. To verify the results, we carried out amniocyte deoxyribonucleic acid analysis in all the continuing pregnancies for the first 100 cases and in those in which trophoblast deoxyribonucleic acid analysis showed the heterozygous state for beta-thalassemia for the second 200 cases. At the beginning we had two cases of decidual contamination in such an amount to cause misdiagnosis. Successively more careful elimination of decidual tissue from villi avoided avoided this pitfall. These results indicate that chorionic villus sampling by a rigid forceps is a reliable and relatively safe method for fetal diagnosis of genetic diseases by deoxyribonucleic acid analysis.     

不同发育天数囊胚冻融移植后妊娠结局分析

目的比较不同发育天数冻融囊胚移植后的妊娠结局。方法回顾性分析1 176例行冻融囊胚移植患者的临床资料,其中植入前遗传学诊断(preimplantation genetic diagnosis,PGD)周期135例,比较第5日单囊胚移植(single embryo transfer,SET)组、双囊胚移植(double embryo transfer,DET)组与第6日SET组和DET组的妊娠结局。结果同是优质囊胚级别的条件下,第5日DET组的生化妊娠率(56.91%)、临床妊娠率(53.25%)以及多胎妊娠率(1.20%)显著高于其他组(P0.05);第5日DET组与SET组的胚胎着床率无统计学差异(P0.05),但均显著高于第6日DET组和SET组(P0.05);同级别以及PGD周期中第5日和第6日SET组相比较,第5日组的生化妊娠率、胚胎着床率均显著高于第6日组(P0.05)。结论在同是优质囊胚的条件下,第5日SET、DET及经PGD诊断的SET妊娠结局均优于第6日。     

雷公藤单体对大鼠睾丸间质细胞及支持细胞毒性与其抗生育作用不相关

本文用体外培养的睾丸间质细胞和支持细胞筛选了２２种从雷公藤根、皮中分离、纯化的单体，并选择其中对两种细胞杀伤作用强、弱不同的化合物ＴＷ－９，ＴＷ－５，ＴＷ－２８和ＴＷ－２７进行抗生育试验以及体外杀精试验。结果发现对两种细胞毒性作用最弱的ＴＷ－１９对大鼠有明显的抗生育作用；而毒性作用较强的ＴＷ－５，ＴＷ－２８和最强的ＴＷ－２７则无明显的抗生育作用。然而这四种化合物的体外杀精强度则依次为：ＴＷ－２７，ＴＷ－５，ＴＷ－１９，ＴＷ－２８。与它们的抗生育作用不相关。     

膈肌深呼吸训练辅助药物治疗支气管哮喘慢性持续期患儿的效果

目的探讨膈肌深呼吸训练辅助药物治疗支气管哮喘慢性持续期患儿的临床疗效。方法选取2018年6月—2020年1月咸宁市某医院收治的200例支气管哮喘慢性持续期患儿,采用随机数字表法分为观察组与对照组,每组100例。对照组患儿给予药物雾化吸入治疗,观察组患儿在对照组基础上给予膈肌深呼吸训练辅助治疗。比较2组患儿的临床疗效,治疗前后实验室指标、肺功能及家属满意度。结果观察组患儿治疗总有效率为95.00%,高于对照组的79.00%,差异有统计学意义(χ²=11.317,P<0.05)。2组患儿治疗后血清免疫球蛋白E(Ig E)、白介素-4(IL-4)及肿瘤坏死因子α(TNF-α)水平低于治疗前,且观察组低于对照组,差异均有统计学意义(P<0.05)。2组患儿治疗后FEV1、FVC及PEF水平高于治疗前,且观察组高于对照组,差异均有统计学意义(P<0.05)。观察组患儿家属满意度为94.00%,高于对照组的77.00%,差异有统计学意义(χ²=11.656,P<0.05)。结论膈肌深呼吸训练辅助药物治疗慢性持续期支气管哮喘患儿疗效...     

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

Background/AimsBinge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).MethodsSerum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.ResultsA marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.ConclusionsFormation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.     

抑郁障碍患者楔前叶功能连接与抗抑郁药物早期疗效的相关性

背景 默认网络内楔前叶功能活动与抗抑郁药物的疗效有关。然而,楔前叶功能网络与抗抑郁药物早期疗效的关系仍不清楚。 目的 探索抑郁障碍患者楔前叶功能连接（FC）与抗抑郁药物早期疗效的关系,以期寻找预测抗抑郁药物早期疗效的神经生物标志物。 方法 连续纳入2017年7月—2019年2月在四川大学华西医院心理卫生中心就诊的、符合《精神障碍诊断与统计手册（第5版）》（DSM-5）诊断标准的47例抑郁障碍患者。采集患者基线期静息态功能磁共振（rs-fMRI）数据及临床信息。患者接受2周抗抑郁药物治疗,根据治疗2周时16项抑郁症状快速自评量表（QIDS-SR16）评分减分率是否≥20%,将患者分为早期改善组（ n=27）和未改善组（ n=20）。以双侧楔前叶为种子点,计算楔前叶与全脑FC值,比较两组基线期楔前叶FC的差异。采用Pearson相关分析考查差异有统计学意义的脑区的FC值与QIDS-SR16评分及其减分率之间的相关性。 结果 早期改善组左侧楔前叶与左侧中央前回的FC值、右侧楔前叶与右侧梭状回的FC值均高于未改善组（GRF校正, P<0.01）。抑郁障碍患者左侧楔前叶与左侧中央前回的FC值、右侧楔前叶与右侧梭状回的FC值与QIDS-SR16总评分减分率均呈正相关（ r=0.475、0.297, P均<0.05）。 结论 基线期较低的左侧楔前叶与左侧中央前回、右侧楔前叶与右侧梭状回的FC与较差的抗抑郁药物早期疗效有关,楔前叶FC可能是预测抗抑郁药物早期疗效的潜在指标。