Personal comorbidities and their subsequent risks for liver,gallbladder and bile duct cancers

Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers.     

基于全基因组测序的耐碳青霉烯类抗生素鲍曼不动杆菌耐药基因、毒力因子及同源性分析

摘要：目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株，通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型，并应用MORPHEUS在线制作 热图，应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子，应用MLST软件检测菌 株的ST型，应用Kaptive软件检测荚膜型，应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药，而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因，11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66，β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主，大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子，包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等，如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型，同源性分析结果显示C组内同源性关系相近，存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样，同源性分析显示该院存在1种优势克隆株，该克隆株有医 院内传播的风险。     

Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

Diabetic foot ulcers: A devastating complication of diabetes mellitus continues non-stop in spite of new medical treatment modalities

Diabetic foot ulcer is a devastating complication of diabetes mellitus and significant cause of mortality and morbidity all over the world and can be complex and costly. The development of foot ulcer in a diabetic patient has been estimated to be 19%-34% through their lifetime. The pathophysiology of diabetic foot ulcer consist of neuropathy, trauma and, in many patients, additional peripheral arterial disease. In particular, diabetic neuropathy leads to foot deformity, callus formation, and insensitivity to trauma or pressure. The standard algorithms in diabetic foot ulcer management include assessing the ulcer grade classification, surgical debridement, dressing to facilitate wound healing, off-loading, vascular assessment (status and presence of a chance for interventional vascular correction), and infection and glycemic control. Although especially surgical procedures are sometimes inevitable, they are poor predictive factors for the prognosis of diabetic foot ulcer. Different novel treatment modalities such as nonsurgical debridement agents, oxygen therapies, and negative pressure wound therapy, topical drugs, cellular bioproducts, human growth factors, energy-based therapies, and systematic therapies have been available for patients with diabetic foot ulcer. However, it is uncertain whether they are effective in terms of promoting wound healing related with a limited number of randomized controlled trials. This review aims at evaluating diabetic foot ulcer with regard to all aspects. We will also focus on conventional and novel adjunctive therapy in diabetic foot management.     

Immunohistochemical analysis of von Willebrand factor expression in myocardial tissues from autopsies of patients with ischemic heart disease

von Willebrand factor (VWF) plays a crucial role in hemostasis and thrombosis. VWF is involved in platelet attachment to the subendothelium, serving as a carrier protein for coagulation factor VIII. In this study, myocardial tissues from deceased patients with ischemic heart disease and a mouse model of acute myocardial infarction were subjected to immunohistochemistry to determine VWF expression. We examined 28 neutral formalin-fixed, paraffin-embedded myocardial tissue samples obtained from the autopsies of patients who were diagnosed with ischemic heart disease within 48 h postmortem. Most myocardial cells were negative for VWF, although some cells showed nonspecific positivity. Elevated VWF expression was observed around myocardial cells undergoing remodeling, suggesting that endothelial proliferation occurred at these sites. In contrast, completely fibrotic myocardial foci did not show upregulated VWF expression. Positivity in fibrin deposition and hemorrhagic sites was observed. The same VWF expression characteristics as those observed in the human samples were observed in the mouse model. VWF immunostaining as an endothelial marker may be a useful supplementation to conventional staining techniques that are currently used in the diagnosis of ischemic heart disease in terms of examining the timing of myocardial remodeling in detail and highlighting the remodeling process.     

重组人表皮生长因子凝胶联合CO2点阵激光治疗增生性瘢痕的效果观察

目的观察重组人表皮生长因子凝胶联合CO₂点阵激光治疗烧伤及创伤后增生性瘢痕的临床效果。 方法选择2020年12月至2021年10月安徽医科大学第一附属医院烧伤与创面修复外科收治的20例增生性瘢痕患者，按照随机数字表法将患者分为联合治疗组及单纯激光治疗组，每组10例。术前均对2组患者术区进行拍照存像、消毒、擦干，局部均匀涂抹5%复方利多卡因乳膏后以无菌薄膜封闭保护60 min，擦去乳膏后再次消毒术区。术中使用CO₂点阵激光治疗仪对患者瘢痕部位进行扫描，根据患者增生性瘢痕厚度选定合适的机器参数，维持机器频率300 Hz及密度5%，在20～30 J调整能量参数的大小，时间间隔1 s，保证点阵矩形完全覆盖增生瘢痕，允许2次激光形成的热损伤矩阵之间存在25%面积的重叠。术后即刻冷敷创面60 min，冷敷结束至术后1周，单纯激光治疗组不外用任何药物，联合治疗组术区加用重组人表皮生长因子凝胶外用，3次/d。术后3 d治疗部位不碰水，若出现感染情况，可以加用抗生素软膏，点状损伤创面外痂皮未掉落完全时禁止擦洗创面，禁止直接剥除痂皮，禁止术区涂抹化妆品等，避免接受阳光直射。于第1次激光治疗后2个月进行第2次激光治疗，以2次CO₂点阵激光治疗为1个疗程，1个疗程治疗后间隔2个月待术区稳定后行疗效判断，计算2组患者治疗的总有效率；根据温哥华瘢痕量表(VSS)与患者与观察者瘢痕评估量表(POSAS)对患者治疗前、第1次激光治疗后2个月、第2次激光治疗后2个月瘢痕的各项指标进行评分。数据比较采用重复测量方差分析和χ²检验。 结果(1)治疗1个疗程后2个月，单纯激光治疗组与联合治疗组患者治疗的总有效率分别为80%(8/10)、90%(9/10)，2组间比较差异无统计学意义(χ²＝2.40，P＝0.49)。(2)对2组VSS评分的各项指标进行比较，其中疼痛、瘙痒、柔软度及厚度评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中色泽评分分别为(1.9±0.7)、(1.9±0.1)、(1.8±1.0)分，联合治疗组分别为(2.9±0.7)、(2.8±0.6)、(1.9±0.7)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.143，P<0.05)；2组组间不同时相点比较，差异有统计学意义(F＝6.753，P＝0.018)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组VSS评分中血管分布评分分别为(1.8±1.0)、(1.7±0.7)、(1.5±1.0)分，联合治疗组分别为(2.6±0.5)、(2.5±0.5)、(1.7±0.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝17.603，P<0.05)，2组组间不同时相点比较，差异无统计学意义(F＝ 2.538，P＝0.129)。(3)对2组POSAS评分的各项指标进行比较，其中厚度、粗糙度、柔软度和表面积评分的组内及组间各时相点比较，差异均无统计学意义(P>0.05)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中色泽评分分别为(4.9±2.6)、(4.1±0.8)、(3.5±2.0)分，联合治疗组分别为(7.6±1.1)、(6.8±1.4)、(5.4±1.8)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 26.509，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 8.973，P＝0.008)。治疗前、第1次激光治疗后2个月及第2次激光治疗后2个月，单纯激光治疗组POSAS评分中血管分布评分分别为(4.4±2.1)、(3.9±0.9)、(3.5±1.6)分，联合治疗组分别为(6.3±1.1)、(5.7±2.0)、(4.5±1.6)分，2组在不同时相点组内比较，差异有统计学意义(F＝ 20.118，P<0.05)，2组组间不同时相点比较，差异有统计学意义(F＝ 5.744，P＝0.028)。 结论重组人表皮生长因子凝胶联合CO₂点阵激光及单独使用CO₂点阵激光治疗增生性瘢痕均效果明确，但联合使用重组人表皮生长因子凝胶能有效促进创面愈合、改善瘢痕组织血管分布和减少局部色素沉着。     

丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床研究

目的 探讨丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床疗效.方法 选取2019年6月—2021年6月在天津市职业病防治院门诊皮肤科就诊治疗的114例银屑病患者,根据随机数字法分为对照组和治疗组,每组各57例.对照组患者给予他扎罗汀倍他米松乳膏,洗净患处,待皮肤干爽后,将适量本品均匀涂抹于患处,1次/d.治疗组患者在对照组治疗基础上口服丹青胶囊,4粒/次,3次/d.两组患者均连续治疗7 d.观察两组患者的临床疗效和临床症状好转时间,比较两组治疗前与治疗1、4、8周的皮损面积和严重程度指数(PASI)评分和血清炎性因子水平.结果 治疗后,治疗组总有效率是98.25％,显著高于对照组的82.46％(P<0.05).治疗后,治疗组患者皮损暗红、皮损肥厚、皮肤瘙痒、皮肤疼痛等症状好转时间均显著短于对照组(P<0.05).治疗后,两组PASI评分均较治疗前显著降低(P<0.05);治疗1、4、8周治疗组PASI评分显著低于对照组(P<0.05).治疗后,两组患者血清炎性因子白细胞介素6(IL-6)、白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)、干扰素-γ(IFN-γ)水平均较治疗前显著降低(P<0.05);治疗后,治疗组血清炎性因子水平显著低于对照组(P<0.05).结论 丹青胶囊联合他扎罗汀倍他米松治疗银屑病效果明显,能显著降低炎性因子水平,并有助于改善皮损情况,值得临床推广应用.     

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.     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。