芫根调节免疫功能的小肠转录组学研究

利用生物信息学技术初步探索芫根调控肠道免疫功能的分子生物学机制。方法 选择雄性SPF级BALB/c小鼠18只，随机分为3组，每组6只。SC1组小鼠每只每次灌胃芫根提取液150 μL，SC2组小鼠每只每次灌胃绞碎芫根原浆悬液150 μL，NC组小鼠每只每次灌胃生理盐水150 μL，连续7 d每日灌胃一次。分别取每组小鼠小肠组织样品提取RNA，总RNA的质检合格后，进行转录组测序。按GO功能和KEGG信号通路对差异表达基因聚类分析揭示差异表达高度富集的免疫相关通路。从免疫角度分析芫根灌胃小鼠小肠组织的基因表达变化情况。结果 转录组测序共检测到27733条 mRNA的表达，SC1组与NC组比较，显著差异表达基因1635个，其中上调差异表达基因1236个，下调差异表达基因399个；SC2组与NC组比较，显著差异表达基因2872个，其中上调差异表达基因2233个，下调差异表达基因639个（P＜0.05）。按GO功能和KEGG信号通路聚类分析显示差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路及维生素和脂肪消化吸收等途径的富集度在两个芫根组中均居于前20位（P＜0.01），肠黏膜趋化因子CCL20和巨噬细胞极化标志物CD274等免疫蛋白编码基因差异表达显著且同属于上述多个免疫通路。结论 芫根灌胃小鼠小肠的差异表达基因在白介素分泌、干扰素反应、T细胞受体信号通路、营养物质消化吸收等途径高度富集，提示芫根对肠道免疫系统及肠黏膜功能的调节，其中CD274的表达上调和CCL20的表达下调提示诱导M1型巨噬细胞极化和T细胞活化可能是芫根调控免疫和维护肠道正常结构功能的重要途径。     

靶向MLL1-WDR5蛋白-蛋白相互作用抑制剂的研究进展

Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平，对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白，MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物，故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结，并结合已报道数据对该领域进行了展望，以期为后续研究提供参考。     

26所基层民营口腔诊所医务人员手卫生现况调查

 目的 调查十堰市区基层民营口腔诊所医务人员手卫生现况。方法 2019年9—11月采用便利抽样法对十堰市区民营口腔诊所医务人员手卫生现况进行隐蔽式调查,分析并比较不同岗位类别医务人员的手卫生依从率及正确率。结果 共调查民营口腔诊所26所,设有专用洗手设施的仅17所(占65.38%),配有快速手消毒剂的12所(46.15%)。隐蔽式观察102名医务人员,观察有效手卫生时机2 183次,医务人员实际执行572次,手卫生依从率26.20%,正确率25.52%(146次)。不同岗位类别医务人员的手卫生依从率、正确率比较,差异均有统计学意义(均P＜0.001)。护士的手卫生依从率(30.80%)、正确率(31.85%)较其他岗位人员高。医务人员在接触患者体液后的依从率(76.24%)和正确率(40.26%)较其他手卫生时刻高,接触患者前后的手卫生依从率最低,仅为15.38%、24.72%。医务人员不同手卫生时刻的依从率、正确率比较,差异均有统计学意义(均P＜0.001)。结论 基层民营口腔诊所医务人员手卫生依从率和正确率均较低,急需相关部门加强对基层民营口腔诊所的手卫生管理。     

Assessing the Effects of Geniculate Artery Embolization in a Nonsurgical Animal Model of Osteoarthritis

PurposeTo create a nonsurgical animal model of osteoarthritis (OA) to evaluate the effects of embolotherapy during geniculate artery embolization (GAE).Materials and MethodsFluoroscopy-guided injections of 700 mg of sodium monoiodoacetate were performed into the left stifle in 6 rams. Kinematic data were collected before and after induction. At 10 weeks after induction, Subjects 1 and 4–6 underwent magnetic resonance (MR) imaging with dynamic contrast enhancement (DCE) and Subjects 1, 3, and 4–6 underwent angiography with angiographic scoring to identify regions with greatest disease severity for superselective embolization (75–250-μm microspheres). Target vessel size was measured. At 24 weeks after angiography, DCE-MR imaging, angiography, and euthanasia were performed, and bilateral stifles were harvested. Medial/lateral tibial and femoral condylar, patellar, and synovial samples were cut, preserved, decalcified, and scored using the Osteoarthritis Research Society International criteria. The stifle and synovium Whole-Organ Magnetic Resonance Imaging Score and Multicenter Osteoarthritis Study score were determined. The volume transfer constant (K_trans) and extracellular volume fraction (v_e) were calculated from DCE-MR imaging along the lateral synovial regions of interest.ResultsThe mean gross and microscopic pathological scores were elevated at 38 and 61, respectively. Mean synovitis score was elevated at 9.2. Mean pre-embolization and postembolization angiographic scores were 5 and 3.8, respectively. Mean superior, transverse, and inferior geniculate artery diameters were 3.1 mm ± 1.21, 2.0 mm ± 0.50, and 1.6 mm ± 0.41 mm, respectively. Mean pre-embolization and postembolization cartilage and synovitis scores were elevated at 35.13 and 73.3 and 5.5 and 9.2, respectively. The K_trans/v_e values of Subjects 4, 5, and 6 were elevated at 0.049/0.38, 0.074/0.53, and 0.065/0.51, respectively. Altered gait of the hind limb was observed in all subjects after induction, with reduced joint mobility. No skin necrosis or osteonecrosis was observed.ConclusionsA nonsurgical ovine animal knee OA model was created, which allowed the collection of angiographic, histopathological, MR imaging, and kinematic data to study the effects of GAE.     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

The hidden aspect of carotid lesions in traffic accidents: A little-known phenomenon

Vascular injuries that occur during traffic accidents are a commonly neglected aspect that can add more detail to the framework of a case. In this study, we analysed a case series of 150 traffic accidents, 39 of which were marked by microscopically identifiable vascular lesions. The purpose was to identify the presence of carotid injuries in individuals who died due to traffic accidents and had nonpenetrating trauma of the neck. We focused on the discrepancies regarding the macroscopical aspect and the histology and demonstrated how histological analysis of the carotids in cases of trauma can reveal injuries that are attributable to the trauma itself. We conducted a histological analysis of the lesions to describe their distribution and type and investigate potential correlations. The study offers insight on how to examine road accidents that involve traumatic injury of the carotid arteries. Indeed the main task of the forensic pathologist in the case of death is to establish the existence of a causal relationship between the micro- or macroscopic alterations observed in the autopsy and the traumatic event that led to the death of the subject. Thus, further morphological elements were provided to the forensic practitioners that may reveal injuries attributable to the trauma itself and should be evaluated in cases of trauma in traffic accidents.     

The effect of trans arterial chemoembolization in the management of intrahepatic cholangiocarcinoma. A systematic review and meta-analysis

BackgroundA comprehensive re-evaluation on the role of trans-arterial chemoembolization (TACE) in patients with intrahepatic cholangiocarcinoma.MethodsA thorough database searching was performed in PubMed, EMBASE, and the Cochrane Library. Eligible studies were restricted to comparative studies between TACE and non-TACE cohorts. RevMan5.3 software and Stata 13.0 software were used for statistical analyses. The primary endpoint of our study was long-term survival.ResultsA total of 11 studies with 2036 patients were finally identified. Pooled results revealed that patients receiving TACE had a significantly better overall survival (OS) versus those without TACE (P < 0.05). Subgroup analyses were performed according to different types of TACE. Prophylactic post-surgical TACE (PPTACE) was associated with a significantly better OS versus those without PPTACE (P < 0.05). Palliative TACE (PTACE) also achieved a significantly better OS compared with those with supportive treatment (ST) only (P < 0.00001). However, TACE had no impact on disease-free survival (P = 0.87) and was less effective than surgical resection (P = 0.003).ConclusionPPTACE has a remarkable impact on OS versus those with surgical resections only and should be regularly performed. Regarding patients with unresectable disease, apart from conventional ST, adjuvant PTACE is also recommended. Upcoming prospective randomized controlled trials are warranted for further validation.     

Prospective Study of Radial Artery Occlusion Following Transradial Arterial Access during IR Procedures

PurposeTo prospectively determine the rate of radial artery occlusion (RAO) in patients undergoing transradial access for intra-arterial interventions.Materials and MethodsSeventy-seven patients undergoing transradial access from August 2019 to March 2021 for 120 intra-arterial procedures (yttrium-90 mapping [n = 39] and radioembolization [n = 38], uterine artery embolization [n = 19], transarterial chemoembolization [n = 10], active bleed embolization [n = 8], angiomyolipoma embolization [n = 4], and other [n = 2]) were enrolled. The average patient age was 59 years ± 13.1 (range, 30–90 years), and 43 (55.8%) of the 77 patients were men. The patients underwent radial artery (RA) palpation, ultrasound evaluation, the Barbeau test, and the reverse Barbeau test prior to and following the intervention. Verapamil, nitroglycerin, and heparin were administered in a total of 114 (95%) of the 120 procedures prior to starting the procedure. The incidence of RAO and radial artery spasm (RAS) was calculated, and univariate logistic regression was performed to analyze the predictors of RAS.ResultsThe preprocedural RA diameter (3.0 mm ± 0.67) was not significantly different from the postprocedural RA diameter (3.0 mm ± 0.65, P = .904). The RAO rate was determined to be 0.8% (1/120), and this artery recanalized within 1 week. Due to the small number of occlusions, statistical analysis of predictors of RAO was not performed. The rate of RAS was 22.7% (27/119). None of the variables tested—including age, sex, RA diameter, initial versus repeat access, operator experience, and artery puncture technique—showed significant prediction for RAS. Patients were seen for follow-up after 111 (92.5%) of the 120 procedures.ConclusionsTransradial access resulted in a <1% rate of RAO.