TENG Zezhong, CHEN Nan, WANG Yuqing, LUO Zuomei, CHEN Gangwen, LI Liqun, LIU Lijian, ZHAO Xueping, YANG Chengning
摘要:OBJECTIVETo investigate the molecular mechanism of Tiaozhong Huashi Decoction in regulating endoplasmic reticulum autophagy of rat esophageal interstitial cells of Cajal (ICC) mediated by p62 signaling pathway to improve gastroesophageal reflux disease (GERD). METHODS A total of 52 SPF SD rats were selected, and 10 rats were randomly selected as the blank group. The remaining rats were used to construct GERD model by weak acid gavage method and improper diet. After successful modeling, the model rats were randomly divided into model group, western medicine group (mosapride citrate dispersible tablets 1.56 mg/(kg·d), lansoprazole enteric-coated tablets 3.125 mg/(kg·d) and Tiaozhong Huashi Decoction low [9.425 g/(kg·d)], medium [18.85 g/(kg·d)], high [37.70 g/(kg·d)] dose groups, twice a day, continuous intervention for 14 days. During the intervention, the general condition of rats was observed. After the intervention, the pathological changes of esophageal tissue were observed by light microscopy, the ultrastructure of ICC and the morphological changes of endoplasmic reticulum autophagy were observed by transmission electron microscopy, and the protein expression of P62, ATG8, FIP200 and ULK1 was detected by Western blot and immunohistochemistry.RESULTSCompared with the blank group, the rats in the model group were depressed, the esophageal basal layer was thickened, the lamina propria nipple was prolonged with inflammatory cell infiltration, the endoplasmic reticulum was significantly expanded into a round vesicle pool, accompanied by ribosome degranulation, and a small amount of autophagy was observed. Small volume accumulation, suggesting that endoplasmic reticulum autophagy clearance is blocked ; the expression of P62, ATG8, FIP200 and ULK1 protein was significantly decreased (P<0.05). Compared with the model group, the above macroscopic and pathological damage of the rats in the western medicine group and the Chinese medicine intervention group were significantly improved, the endoplasmic reticulum structure was repaired, and no small volume of autophagy was observed, suggesting the recovery of autophagy function ; the expression of P62, ATG8, FIP200 and ULK1 protein in the middle dose group of Tiaozhong Huashi Decoction was significantly up-regulated (P<0.05).CONCLUSIONSTiaozhong Huashi Decoction can improve the esophageal mucosal injury of GERD in rats, and its mechanism may be related to the activation of P62 signaling pathway, the repair of endoplasmic reticulum structure and autophagy ability of ICC cells.
关键词:gastroesophageal reflux disease;endoplasmic reticulum autophagy;p62 signaling pathway;interstitial cells of Cajal
YANG Jing, ZHANG Xinyu, ZHENG Lei, GUAN Yuyao, CHANG Wenlai, LIN Zhongkun, ZHANG Yahui, FU Zheng
摘要:ObjectiveTo investigate the effect of gene polymorphism on adverse reactions(ADR) of constipation induced by opioids.Methods We first conducted evidence-based medical data analysis on the research of genes related to opioid adverse reactions, and selected target genes; Then 50 patients with severe constipation and 50 patients with cancer pain without adverse drug reactions after taking opioid drugs were included as the test group and the control group for 1:1 matched case study; The target gene was detected by polymerase chain reaction (PCR) or in situ hybridization and correlation analysis was performed. Finally, combined with the clinical data of patients such as age, sex, dosage and duration of medication, we used multivariate logistic regression analysis to explore the relevant predictive factors affecting the occurrence of opioid constipation adverse reactions.ResultsCYP2D6, CYP3A5*3, ABCB1 and OPRM1 were selected as target genes for detection; SNPStats genetic model analysis showed that CYP3A5*3 (058rs776746, A>G), OPRM1 (047rs1799971, A>G) polymorphisms were associated with opioid induced constipation, among which CYP3A5*3 (058rs776746) GG, AG, OPRM1 (047rs1799971) AA, AG were risk factors for opioid induced constipation. At the same time, combined with clinical data, logistic regression analysis showed that the duration of drug use, CYP3A5*3 and OPRM1 gene polymorphisms could all be used as predictors of constipation in patients using opioids.ConclusionCYP3A5*3 (058rs776746, A>G), OPRM1 (047rs1799971, A>G) polymorphisms are associated with opioid induced constipation, which is expected to become a clinical predictor of adverse drug reactions of opioids, and more attention should be paid to the occurrence of severe constipation in patients who have been taking opioids for a long time.
关键词:Pharmacogenomics;Adverse drug reactions;constipation;individualized medication
摘要:To provide prevention and control strategies of occupational exposure risks for cytotoxic drugs in medical institutions, improve the awareness of protection among medical staff, and reduce potential occupational exposure risks, the “Guidelines for Occupational Exposure Risk Protection of Cytotoxic Drugs in Medical Institutions” was developed. Based on the World Health Organization (WHO) guidelines development manual, we collected the exposure risk issues in seven stages after the cytotoxic drugs entered the hospital, such as transportation, receipt, storage, unpacking, dispensing, used of finished products, and waste disposal. The Delphi method was used to construct identify clinical issues, and evidence-based research methods were used to develop relevant evidences. Quality evaluation was conducted using the GRADE method, and consensus was reached on the recommendation opinions and evidence levels through expert consensus method. By combining engineering controls, administrative controls and personal protective equipment at different levels, a graded control approach was established. A total of 37 clinical issues were identified, resulting 36 recommendations. This guideline provides reference and supplementation for the formulation of cytotoxic drugs prevention and control measures in medical institutions.
XU Feifei, BIAN Yuan, HAN Yong, YAN Junfeng, TONG Rongsheng
摘要:At present, there is a lack of unified and standardized management for the rational use of national key monitoring drugs. According to the relevant requirements of the state, in order to make the national key monitored drugs more reasonable use and standardized management in medical institutions at all levels, the Clinical pharmacy Branch of the Chinese Medical Association, the Pharmaceutical Epidemiology Special Committee of the Chinese Pharmaceutical Association and the Pharmaceutical Epidemiology Special Committee of the Sichuan Pharmaceutical Association organized experts to fully discuss, based on the relevant literature published at home and abroad in recent years and combined with the management practice of many medical institutions across the country on the national key monitored drugs, Form this management standard. This standard mainly provides relevant opinions and suggestions on the basic principles of rational use of key monitored drugs and the regulatory measures for key monitored drugs, especially on how to strengthen the pharmaceutical management and use management of key monitored drugs.