基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

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??Objective    To observe the effects of lithium chloride pretreatment on cognitive ability of aged rats after oral and maxillofacial surgery. Methods    A total of 48 aged male SD rats??18 ~ 20 months old??weight 550 ~ 700 g?? were bought from the Experimental Animal Center of China Medical University . These rats were randomly divided into three groups??including the normal control group??group C??n=16????surgery and anesthesia group??group O??n=16????and lithium chloride preconditioning group??group L??n=16??.Rats in each group were randomly divided into two parts??one part was given Morris water maze test three days after the surgery and its characteristics of behavior tested. Another part was decapitated 24 h after the surgery and extracted and the hippocampus brain separated at the same time. Test expression content of IL-1β GSK-3β p-GSK-3β??ser9??in the hippocampus by Elisa and Western blotting detection method respectively. Results    Morris water maze test showed that??the first day after surgery??latencies of group L and O were significantly longer than group C??compared with group C in swimming distance?? latency and swim distances of group L were shorter than group O. With the comparison of multiple analysis of variance??differences were statistically significant??P??0.05??. Groups L and O in the second day were slightly shortened compared to the first day??on the third day after surgery it has also improved over the second day. Space exploration experiments in rats showed that??the dwell time of group C was significantly longer in the platform quadrant and the frequency of crossing the platform also increased compared with groups L and O. In addition??group L and group O were higher in IL-β levels than group C??the difference being statistically significant by analysis of variance??P??0.05????but group L was significantly lower compared with group O??the difference being statistically significant??P??0.05??. The content of GSK-3β of three groups were of no significant difference??P > 0.05????but p-GSK-3β??ser9??content was significantly lower in group L and O than in group C. The content of GSK-3β of group L was higher than in group O??the difference being statistically significant??P??0.05??. Conclusion    Pretreatment with lithium chloride in postoperative aged rats can inhibit the expression of inflammatory cytokines and increase GSK-3β phosphorylation in the hippocampus cells??so p-GSK-3β??ser9??upregulates and inhibites  the apoptosis of brain cells??thereby improved cognitive abilities after the cavity and maxillofacial surgery.     

Incidence of pressure ulcers in intensive care units and direct costs of treatment: Evidence from Iran

Background and objective

Pressure ulcer (PU) is one of the important and frequent complications of hospitalization, associated with high treatment costs. The present study was conducted to determine the incidence of PU and its direct treatment costs for patients in intensive care unit (ICU) in Iran.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists

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Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study

Abstract

Objective

The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT₂R₂) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT₂G₂) Score; and the so-called modified SAMe-TT₂R₂ scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT₂R₂ and SAMe-TT₂G₂ scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control.     

Current status of peptic ulcer disease in Port Harcourt metropolis,Nigeria

BackgroundEpidemiological studies on peptic ulcer disease (PUD) have shown a recent decrease in hospital admissions in Western countries.ObjectiveThis paper aimed to study the current status and risk factors of PUD in a Nigerian metropolis.MethodsA cross-sectional study of symptomatic patients at upper gastrointestinal (GI) endoscopy diagnosed with PUD from February 2014 to September 2019 at a referral endoscopy facility in Port Harcourt, Niger delta region of Nigeria. The variables studied included demographics, symptoms and duration, blood group, chronic non-steroidal anti-inflammatory (NSAID) use, smoking, endoscopic and histology findings. Statistical analysis was performed using SPSS version 20.ResultsA total of 434 upper GI endoscopies were performed during the study period with thirty-one diagnosis of PUD made. The mean age of gastric ulcer (GU) and duodenal ulcer (DU) cases were 54.4 ± 20.2yrs and 48.1 ± 14.5yrs respectively (p = 0.367). GU to DU ratio was 1.4:1. H. pylori infection, chronic NSAID use and blood group O were seen in 7(22.5%), 8(25.8%) and 18(72.0%) respectively. Major indication in 21(67.7%) cases was gastrointestinal bleeding.ConclusionThere is a low diagnostic rate of PUD (6.7%) with pre-pyloric antral gastric ulcers as most common type and multifactorial aetiology.     

Medical practitioners’ educational competence about oral and oropharyngeal carcinoma: a systematic review and meta-analysis

Medical practitioners’ (MP) role is pivotal in primary prevention, early diagnosis, prompt referral and effective management of oral and oropharyngeal carcinomas (OC/OPC), which raises the importance of their effective OC/OPC education at all levels of medical education. The purpose of this systematic review was to summarise the available scientific evidence about their educational competence in dealing with OC/OPC. We made a systematic search of papers in the English language in MEDLINE, Scopus, Cochrane Library CENTRAL and CINAHL databases from their inception until December 2018. Overall, 23 cross-sectional and three interventional studies have been selected for the systematic review and 18 of these were included in the meta-analyses. Excluding tobacco use (synthesised estimate of 95% of respondents identified tobacco as an OC/OPC risk factor, 95% CI of synthesised estimate 92% to 97%) and alcohol consumption (65%, 95%CI 52% to 77%), less than half of MP (approximately) were knowledgeable about important OC/OPC risk factors including human papilloma virus (42%, 95% CI 30% to 54%), poor diet (34%, 95% CI 17% to 54%), and advancing age (45%, 95% CI 21% to 70%). There was a low to moderate level of awareness among MP regarding common precancerous oral lesions involving leukoplakia (56%, 95% CI 32% to 79%), erythroplakia (30%, 95% CI 8% to 58%), and oral lichen planus (13%, 95% CI 0 to 41%). Moderate knowledge was also recorded about frequent sites of OC development involving the tongue (48%, 95% CI 33% to 64%) and floor of the mouth (37%, 95% CI 19% to 57%). Most MP enquired about tobacco use (86%, 95% CI 74% to 96%), and alcohol consumption (73%, 95% CI 47% to 94%) during history taking, and expressed willingness to be given supplementary OC/OPC education (78%, 95% CI 54% to 96%), as well. With regard to the incidence of intraoral screening, 27% of MP (95% CI 12% to 46%) make an intraoral examination as a routine. Interestingly, studies from each continent yielded significantly different outcomes to some research questions in the review. From the MP’s perspective, clinical time restrictions and deficiencies in organised training were recognised as the main barriers towards their OC/OPC educational competence. The findings of this systematic review indicated the existence of deficiencies in knowledge and misconceptions, neglected preventive responsibilities, and associated barriers towards OC/OPC. A need for improved OC/OPC training at all levels of medical education is required to increase competence worldwide.     

Direct oral anticoagulants (DOACs) and neck of femur fractures: Standardising the perioperative management and time to surgery

Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC.