基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

Comparison study of patient demographics and patient-related risk factors for peri-prosthetic joint infections following primary total shoulder arthroplasty

BackgroundWhile studies have demonstrated favorable outcomes in utilization of primary total shoulder arthroplasty (TSA) for the treatment of glenohumeral osteoarthritis (OA), adverse events such as infections can still occur. Periprosthetic joint infections (PJIs) are associated with worse outcomes and patient morbidity. The purpose of this study was to: (1) compare patient demographics amongst TSA patients with and without PJIs following primary TSA; and (2) identify patient-related risk factors for PJIs following primary TSA.MethodsPatients undergoing primary TSA for the treatment of glenohumeral OA were identified using the Mariner administrative claims database by CPT code 23,472. Laterality modifiers were utilized to ensure PJIs were developing in the correct laterality as those patients undergoing primary TSA. Inclusion for the study group consisted of patients who developed PJIs within 2-years after the index procedure, whereas patients who did not develop PJIs served as the comparison cohort. Primary outcomes analyzed included patient demographics and patient-related risk factors for PJIs following primary TSA. A stepwise backwards elimination multivariate binomial logistic regression analyses was performed to determine the odds (OR) of PJIs in patients undergoing primary TSA. A P value less than .05 was considered statistically significant.ResultsThe query yielded 15,396 patients who underwent primary TSA for glenohumeral OA, of which 191 patients developed PJIs and 15,205 did not develop PJIs. The study found statistically significant differences amongst patients who did and did not develop PJIs following primary TSA with respect to age, sex, and presence of comorbid conditions. Risk factors associated with developing PJIs following primary TSA included: pathologic weight loss (OR: 2.06, P < .0001), obesity (OR: 1.56, P = .0001), male sex (OR: 1.52, P = .007), and peripheral vascular disease (OR: 1.46, P = .022).ConclusionAs the number of primary TSAs for the treatment of glenohumeral OA increase worldwide, identifying modifiable risk-factors to reduce the incidence of infection is critical. The study found various modifiable and non-modifiable risk factors associated with developing PJIs following primary TSA. This study is valuable to orthopedists in order to identify and risk-stratify patients with regard to PJI in the setting of primary TSA for OA.Level of EvidenceLevel III; Case-Control Study     

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies

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Feasibility of a method for low contrast CT image quality assessment using difference detail curves for abdominal scans

This work describes a measurement method for assessing dose-related image-quality of CT scans based on the difference detail curve (DDC) method, and showcases its use in a low contrast setting. The method is based on a phantom consisting of elliptical slices of different sizes into which contrast object modules can be inserted. These modules contain contrast objects based on (synthetic) resin mixtures with sucrose (native) or sodium iodine (contrast medium). Mixing ratios are provided to achieve a range of clinically relevant CT-numbers with these materials. The phantom is characterized in terms of contrast accuracy, energy dependency and long-term drift with satisfying results. Contrast accuracy and energy dependency are similar to that of water or soft tissue. Image quality of 655 scans of the phantom acquired at 30 different clinical institutions and with 16 different CT scanner models from 4 manufacturers was assessed by calculating a difference detail curve (DDC) from evaluation of up to 5 human observers using a custom-made software (RadiVates) described in this work. Based on these measurements, inter-observer variability was quantified using a bootstrap method and was shown to be a large contributor to the overall variability. This work demonstrates that assessment of CT image quality is feasible with the aforementioned phantom and DDC method.     

The infant health effects of starting universal child benefits in pregnancy: Evidence from England and Wales

Child benefits are typically paid from birth. This paper asks whether starting universal child benefits in pregnancy leads to improvements in infant health. Leveraging administrative birth registry and hospital microdata from England and Wales, I study the effects of the Health in Pregnancy Grant, a universal conditional cash transfer equivalent to three months of child benefit (190 GBP) as a lump sum to pregnant mothers from 2009 to 2011. I exploit quasi-experimental variation in eligibility with a regression discontinuity design in the date of birth of the baby. I find that the policy increased birth weight by 8–12 grams on average, reduced low birth weight ($<$2500 g) by 3-6 percent and decreased prematurity by 9–11 percent. Younger mothers, particularly those living in deprived areas, benefit the most. I present evidence that the mechanisms are unlikely to be antenatal care, nutrition or smoking, with reductions in stress remaining a possible explanation.     

Effectiveness and safety of extracorporeal shock wave treatment for low back pain：a systematic review and meta-analysis of RCTs

This meta-analysis was designed to assess the effectiveness and safety of extracorporeal shock wave therapy (ESWT) for patients with low back pain (LBP). Pubmed, Embase, Cochrane's library, PEDro (Physiotherapy Evidence Database), China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched until December 2019 to identify studies assessing the effectiveness and safety of EPSW for LBP. The prime outcome is pain intensity measured by Visual Analog Scale (VAS) or numeric rating scale (NRS). Other outcomes included functional status, quality of life, psychological outcomes measured by Oswestry Disability Index (ODI), as well as the adverse events. Mean differences (MD) were calculated for continuous outcomes, while odd ratios (OR) were calculated for binary outcomes. Revman 5.3 software was used for statistical analysis. Five randomized controlled trials (RCTs) were finally included in this meta-analysis. The pooled mean difference in post-treatment pain scores was −2.37 (P ＜0.0001), indicating that post-treatment pain scores was significantly higher by 2.37 in control group than in ESWT group. At a mean follow-up time of 4–6 weeks, the pooled mean difference in ODI scores was −14.10 (P ＜0.00001), indicating that the pooled mean difference of post-treatment ODI scores was 14.10 higher in control group than in ESWT group. The use of ESWT is effective in alleviating pain and improving the general functional state for patients with LBP. However, more evidence was needed to verify its safety.     

An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Update on adrenal cortical neoplasia

The adrenal cortex gives rise to a biologically heterogenous group of neoplasms, each with a distinct morphology, antigen expression and molecular profile. Adrenal cortical adenomas have excellent prognosis and are usually cured by surgical resection alone, while adrenal cortical carcinomas are very aggressive tumors with a poor prognosis regardless of therapy. These tumors are rare and often challenging for a pathologist to diagnose, as significant overlap exists between benign and malignant lesions in some cases. In this review, we attempt to summarize most important histologic and clinical features of adrenal cortical adenomas and carcinomas, clarify the use of different grading systems, the use of special stains and the differential diagnosis for practicing pathologists. Most relevant hereditary syndromes associated with adrenal cortical tumors are listed. Updates in molecular alterations in adrenal cortical neoplasms and hyperplastic diseases as well as their clinical significance and potential therapeutic implications are also discussed.