A molecular perspective for the use of type IV tyrosine kinase inhibitors as anticancer therapeutics

Tyrosine kinases are enzymes that can transfer a phosphate group from ATP to a specific protein tyrosine, serine or threonine residue within a cell, operating as a switch that can turn ‘on’ and ‘off’ causing different physiological alterations in the body. Mutated kinases have been shown to display an equilibrium shift toward the activated state. Types I–III have been studied intensively leading to drugs like imatinib (type II), cobimetinib (type III), among others. It is the same scenario for types V–VII; however, there is a lacuna in information regarding type IV inhibitors, although recently some advances have surfaced. This review aims to accumulate the knowledge gained so far about type IV inhibitors.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

异牡荆素对非小细胞性肺癌细胞自我更新和凋亡的影响

目的研究异牡荆素(ISO)对非小细胞性肺癌(NSCLC)细胞的影响和潜在的机制。方法将A549和H1650细胞分别分为空白组、低剂量实验组(4μmol·L^-1 ISO)和高剂量实验组(16μmol·L^-1 ISO)。用噻唑蓝法检测NSCLC细胞活性,用肿瘤球形成实验检测NSCLC细胞的细胞球形成率,用Western blot法检测NSCLC细胞凋亡、自我更新、无翅型MMTV整合位点家族/β-连环蛋白(Wnt/β-catenin)信号通路相关蛋白的表达水平。结果与空白组比较,低、高剂量实验组中A549和H1650细胞在24,48和72 h的细胞活性均显著降低。低、高剂量实验组和空白组中A549细胞的细胞球形成率分别为(4.18±0.45)%,(2.01±0.67)%和(6.02±0.57)%,切割的半胱氨酸蛋白酶-3相对表达量分别为0.24±0.08,1.25±0.13和0.06±0.07,SRY相关高迁移率族盒蛋白-2相对表达量分别为0.49±0.04,0.25±0.03和1.00±0.09,Kruppel样因子4相对表达量分别为0.68±0.04,0.44±0.03和1.01±0.06,Wnt1相对表达量分别为0.63±0.06,0.28±0.04和1.00±0.06,β-catenin相对表达量分别为0.41±0.05,0.22±0.03和1.01±0.09;与空白组比较,低、高剂量实验组中A549细胞的上述指标的差异均有统计学意义(P<0.05,P<0.01)。上述3组中H1650细胞的上述指标也呈现一致的现象。结论ISO可能通过抑制Wnt/β-catenin信号通路来抑制NSCLC细胞活性和自我更新,并促进其凋亡。     

红外光谱数据融合对栽培滇重楼产地鉴别*

目的 多样的环境因素使得不同产地栽培滇重楼的化学成分也丰富多样，不同居群栽培滇重楼的甾体皂苷类成分具有很大的差异，多源数据融合分析能更全面的表征药材化学信息，建立一个高效而准确的产地鉴别模型，为其资源合理开发利用提供依据。方法 以来自云南和四川的8个产地（保山、楚雄、大理、红河、丽江、成都、文山、玉溪）共366份栽培滇重楼根茎为实验材料，采集其傅里叶变换近红外光谱（FT-NIR）和衰减全反射-傅里叶变换中红外光谱（ATR-FTMIR）数据。采用Kennard-Stone算法将不同产地的样品分为2/3的训练集和1/3的预测集，基于4种特征变量提取方法（CARS、VIP、SPA、SO-Covsel）结合2种数据融合策略（低级数据融合和中级数据融合），建立偏最小二乘产地判别分析模型。根据模型参数交叉验证均方根误差（RMSECV）和预测均方根误差（RMSEP）评估模型的稳定性，模型训练集和预测集准确率（ACC）评估模型分类性能。结果 近红外光谱和中红外光谱均能反应不同产地栽培滇重楼的化学成分差异，在中级数据融合中，基于VIP和SPA提取的特征变量建立的模型正确率均大于94%。相较于中级数据融合，低级数据融合模型得到了最为满意的结果，其预测集分类正确率达到100%。结论 根据近红外和中红外数据建立的低级数据融合PLS-DA模型，能够用于栽培滇重楼的产地鉴别分析。     

Asymptomatic or mildly symptomatic COVID-19 patients with craniomaxillofacial injuries have an increased risk of surgical site infection

The aim of this paper was to evaluate the association between ‘asymptomatic or mildly symptomatic’ severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (AS/MS-COVID) and surgical site infection (SSI) after repair of craniomaxillofacial injury (CMFI). Using a case-control study design with a match ratio of 1:4, we enrolled a cohort of AS/MS-COVID cases with immediately treated CMFI during a one-year period. The main predictor variable was SARS-CoV-2 infection (yes/no), and the outcome of interest was SSI (yes/no). The other variables were demographic, clinical, and operative. Appropriate statistics were computed, and p<0.05 was considered statistically significant. The study group comprised 257 cases (28.8% female; 13.2% aged ≥ 60 years; 10.5% with fractures; 39.7% with involvement of nasal/oral/orbital tissue [viral reservoir organs, VROs]; 81.3% with blunt trauma; 19.1% developed an SSI [vs 6.8% in the control group]) with a mean (SD) age of 39.8 (16.6) years (range 19–87). There was a significant relation between SARS-CoV-2 infection and SSI events (p<0.0001; odds ratio 3.22; 95% confidence interval 2.17 to 4.78). On subgroup analysis, SSIs significantly increased with age ≥ 60 years, presence and treatment of fracture, contact with VROs, and prolonged antibiotic use (PAU). However, multivariate logistic regression analysis confirmed a positive effect only from old age, contact with VROs, and PAU (relative risk = 1.56, 2.52, and 2.03, respectively; r = 0.49; p = 0.0001). There was a significant 2.8-fold increase in SSIs among AS/MS-COVID cases, especially in those aged ≥ 60 years, or those with injuries to VROs, or both, who therefore required PAU.     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

基于患者出射EPID剂量验证的在体调强放疗质控技术研究

背景与目的：调强放疗（intensity-modulated radiation therapy，IMRT）中剂量投照失误可导致严重后果，而目前常用的治疗前计划验证方法并不能反映患者真实投照剂量。实现一种评估患者在体剂量执行准确度的方法，能够在分次治疗中及时发现较大剂量错误，避免发生患者投照剂量过高或不足。方法：复旦大学附属肿瘤医院收治的患者首次实施治疗前行锥形束计算机断层成像（cone beam computed tomography，CBCT）扫描，与定位CT图像进行配准保证治疗体位与模拟定位时一致，实时治疗中使用电子射野影像装置（electronic portal imaging device，EPID）获取患者出射剂量影像，并把首次出射EPID影像作为剩余分次治疗的基准值，后续分次实时治疗野结束后快速将其出射EPID影像与对应基准影像进行γ分析比较，以验证治疗计划是否准确执行于患者身上。设计模体实验对治疗部位错误和摆位误差情况进行分析，来评估本方法识别放疗差错的准确性。结果：本方法可有效地识别出IMRT放疗中患者治疗部位错误和非平行于射野角度方向的摆位误差，但对平行于射野角度方向的摆位误差并不敏感，30例鼻咽癌患者临床应用结果中能够直观显示分次治疗间摆位重复性情况。结论：基于EPID实现的一种在体剂量验证方法能够对调强放疗中患者实时剂量的准确性进行评估，在单个治疗野结束后可快速检测出较大治疗错误。     

推拿手法安全性的研究进展

中医推拿疗法是一种传统的、有效的理疗方法。在临床实践中具有独特的优势。它可以弥补许多疾病和损伤的药物治疗的不足,具有不可替代的疗效。推拿是部位和手法的综合作用,意外事件的发生主要是因为有的医者求效心切,不关注治疗部位和手法,疗效不明显,而且增加了患者的痛苦并危及患者的健康。本文试从施术部位和手法的不同,分析推拿操作中的意外事件,总结产生损伤的原因,并厘清操作要点,以期指导临床推拿操作的安全实施。     

Model Setting and Interpretation of Results in Research Using Structural Equation Modeling: A Checklist with Guiding Questions for Reporting

PurposeThis study develops a checklist with guidelines for the methods and important factors to consider in research using structural equation modeling (SEM).MethodThe paper discusses the factors to consider in the process across the three stages of 1) model setting, 2) model evaluation and modification, and 3) interpretation and reporting of SEM-based studies.ResultsThe authors present a checklist for researchers during the stages of model setting, model evaluation and modification, result analysis, and reporting, along with examples of figures and tables with explanations.ConclusionA checklist will help to improve the reporting quality of SEM-based studies.