Review/overview of pain in sickle cell disease

Sickle cell disease (SCD) is a highly complex inherited disorder of hemoglobin structure. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of the disease. Its manifestations could be acute, chronic, nociceptive, neuropathic that could occur singly or in various combinations. Pain continues to be the major factor of SCD phenotypic complications and the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing curative therapies such as hematopoietic stem cell transplantation and gene therapy, effective pain management continues to lag behind. Palliative therapies continue to be the major approach to the management of SCD and its complications. The advent of hydroxyurea made partial success in preventing the frequency of vaso-occlusive crises and l-glutamine awaits post-trial confirmation of benefits. The search for additional pharmacotherapeutic agents that could be used singly or in combination with hydroxyurea and/or l-glutamine awaits their dawn hopefully in the near future. The purpose of this review is to describe the various manifestations of SCD, their pathophysiology and their current management. Recent impressive advances in understanding the pathophysiology of pain promise the determination of agents that could replace or minimize the use of opioids.     

a-1, 2岩藻糖基转移酶II在肺鳞癌组织中的表达及对肺鳞癌细胞增殖的影响

目的：探讨a-1，2岩藻糖基转移酶II（FUT2）在肺鳞癌中的表达情况及其对肺鳞癌细胞增殖的影响。方法：应用UALCAN数据库分析FUT2在临床肺鳞癌患者组织中的差异表达及其与肺鳞癌患者临床TNM分期、年龄及性别因素的相关性；采用瞬时转染技术，将FUT2的shRNA质粒转染进H226细胞株中构建FUT2低表达的肺鳞癌细胞模型；利用CCK-8、平板克隆及Western blot实验检测FUT2对肺鳞癌细胞的生长、单克隆细胞团形成及PCNA蛋白表达的影响。结果：FUT2在肺鳞癌尤其是肺鳞癌TNM早中期呈现高表达趋势（P＜0.05），而与年龄和性别无关。低表达FUT2可以抑制肺鳞癌细胞的生长速率和单克隆细胞团的形成数，同时，可以抑制肺鳞癌细胞PCNA蛋白的表达水平，差异均有统计学意义（P＜0.05）。结论：FUT2在肺鳞癌中高表达且促进肺鳞癌细胞的增殖能力，有望成为肺鳞癌的早期诊断指标。     

Prognostic and clinicopathological utility of programmed death-ligand 1 in malignant pleural mesothelioma: A meta-analysis

ObjectiveProgrammed death ligand 1 (PD-L1) has been reported to be connected to prognosis in individuals with malignant pleural mesothelioma (MPM), although there is no consensus based on data from previous studies. Accordingly, this quantitative meta-analysis investigated prognostic and clinicopathological utility of PD-L1 in patients with MPM.MethodsA comprehensive search of the PubMed, Web of Science, Embase, and Cochrane Library databases for articles published up to October 4, 2019 was performed. Studies using immunohistochemical techniques to detect/quantify the expression of PD-L1 in MPM tissue were enrolled in the analysis. The combined hazard ratio (HR) and corresponding 95% confidence interval (CI) was applied to assess the association between PD-L1 expression and overall survival (OS).ResultsA total of 11 studies comprising 1606 patients was included in the present meta-analysis. For OS, pooled data revealed an HR of 1.50 (95% CI 1.32–1.70; p < 0.001), suggesting that patients with PD-L1 overexpression experience inferior OS. Subgroup analysis revealed that elevated PD-L1 remained a significant prognostic indicator for worse OS, irrespective of sample size, cut-off value, ethnicity, and Newcastle-Ottawa Scale score. Moreover, PD-L1 overexpression was associated with non-epithelioid histology (odds ratio 4.30 [95% CI 1.89–9.74]; p < 0.001).ConclusionsResults of this meta-analysis show that elevated expression of PD-L1 could be a factor predicting poorer survival in patients with MPM.     

乌司他丁辅助治疗重症感染性休克的价值分析

目的探究临床用乌司他丁辅助治疗重症感染性休克的治疗效果。方法90例重症感染性休克患者,随机分为观察组与对照组,每组45例。对照组患者采用西医常规治疗,观察组患者在对照组基础上联合乌司他丁治疗。比较两组患者治疗效果、体温情况、感染情况以及治疗前后白细胞计数、白细胞介素-6(IL-6)水平、格拉斯哥昏迷量表(GCS)评分、急性生理功能和慢性健康状况评分系统Ⅱ(APACHEⅡ)评分。结果治疗后,观察组白细胞计数(7.34±1.32)×10^9/L低于对照组的(9.41±1.16)×10^9/L,差异具有统计学意义(P<0.05)。治疗后,观察组高热、感染体征发生率分别为97.78%、86.67%,均高于对照组的82.22%、62.22%,差异具有统计学意义(P<0.05);观察组体温恢复时间、感染消失时间分别为(7.19±1.39)、(3.88±0.89)d,均短于对照组的(9.81±1.88)、(10.76±1.57)d,差异具有统计学意义(P<0.05)。观察组患者血清IL-6为(4.27±0.95)μg/L低于对照组的(9.58±1.07)μg/L,差异具有统计学意义(P<0.05)。观察组患者GCS评分和APACHEⅡ评分较治疗前均有所改善,GCS评分(8.19±1.59)分、APACHEⅡ评分(8.83±0.82)分均优于对照组的(6.81±1.82)、(14.71±3.52)分,差异均具有统计学意义(P<0.05)。观察组患者治疗总有效率95.56%明显高于对照组的77.78%,差异具有统计学意义(χ^2=6.154,P<0.05)。结论乌司他丁具有较好的抗炎效果,与西医治疗相结合可以提高临床疗效,加快重症感染性休克患者退热速度,缩短感染时间,降低白细胞计数及血清IL-6水平,改善GCS评分和APACHEⅡ评分,临床疗效较好。     

Compositional analyses reveal correlations between taxon-level gut bacterial abundance and peripheral T cell marker expression in African infants

ABSTRACT

Although exclusive breastfeeding has been linked to lower rates of postnatal HIV transmission compared to nonexclusive breastfeeding, mechanisms underlying this are unclear. Across a longitudinally sampled cohort of South African infants, we showed that exclusively breastfed (EBF) infants had altered gut bacterial communities when compared to nonexclusively breastfed (NEBF) infants, as well as reduced peripheral CD4 + T cell activation and lowered chemokine and chemokine receptor expression in the oral mucosa. We further demonstrated that the relative abundance of key taxa was correlated with peripheral CD4 + T cell activation. Here, we supplement those findings by using compositional data analyses to identify shifts in the abundance of several Bifidobacteria strains relative to select strains of Escherichia, Bacteroides, and others that are associated with the transition to NEBF. We illustrate that the abundance ratio of these taxa is tightly correlated with feeding modality and is a strong predictor of peripheral T cell activation. More broadly, we discuss our study in the context of novel developments and explore future directions for the field.