Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

补阳还五汤加伸筋草治疗脑梗死后痉挛型偏瘫疗效研究

目的:探讨补阳还五汤重用伸筋草治疗脑梗死后痉挛型偏瘫的作用。方法:收集脑梗死后痉挛型偏瘫患者共88例,分为两组,对照组44例,西医治疗加康复训练和补阳还五汤治疗; 研究组44例,西医治疗加康复训练及补阳还五汤重用伸筋草治疗。比较治疗前后患者患侧上下肢肌张力、临床疗效、NIHSS、日常生活能力Barthel指数以及上下肢运动功能和不良反应发生率。结果:治疗后,两组患者患侧上下肢肌张力≤1级者占比均升高,且研究组中≤1级者占比均高于对照组,组间比较有统计学意义(P<0.05)。两组临床疗效等级分布和总有效率比较,差异有统计学意义(P<0.05)。治疗后两组患者NIHSS评分均降低,且研究组NIHSS评分低于对照组,治疗后两组患者Barthel指数和患侧上下肢FMA评分均升高,且研究组均高于对照组,组间比较有统计学意义(P<0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:补阳还五汤重用伸筋草能够显著降低患者患侧上下肢肌张力,改善临床疗效和神经功能缺损,提高患者日常生活能力和患侧运动功能,且安全性良好。     

双眼外直肌后徙术与常规疗法治疗斜视临床疗效比较

目的:比较双眼外直肌后徙术与常规疗法治疗斜视的临床疗效。方法:选取2016年6月-2017年6月笔者医院收治的128例斜视患者,按治疗方式不同分成对照组和研究组,每组各64例。其中对照组患者行常规单眼外直肌后徙联合内直肌缩短术(R&R),研究组患者行双眼外直肌后徙术(BLR-rec)。术后对患者随访1年,观察术后眼位正位率、欠矫率、过矫率,视觉功能恢复情况以及并发症发生率。结果:研究组患者正位率为89.06%高于对照组的68.75%,差异有统计学意义(P<0.05)。术前,对照组和研究组患者视近度、视远度和平均斜视度比较,两组患者融合功能和立体视功能占比比较,差异均无统计学意义(P>0.05)。术后,两组患者的斜视度较治疗前均出现了明显下降(P<0.05),且研究组治疗后斜视度下降幅度明显大于对照组(P<0.05);两组患者视觉功能恢复率均明显增加(P<0.05),且研究组恢复率明显大于对照组(P<0.05)。研究组并发症发生率明显低于对照组(P<0.05)。结论:双眼外直肌后徙术较单眼外直肌后徙联合内直肌缩短术有更好地临床效果,且安全性更高,值得临床推广。     

细胞因子白细胞介素-4对认知功能改善的研究进展

白细胞介素4(IL-4)是T辅助2(Th2)介导的免疫反应的基本免疫调节细胞因子,IL-4具有复杂的信号系统和多效的功能,但在脑组织中,诸多研究发现IL-4可在炎症中保护认知功能。该文总结了关于IL-4保护认知功能的证据及机制,以及在阿尔茨海默病、缺血性脑血管病以及手术后认知功能障碍中IL-4保护认知功能的途径及证据。     

The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I² = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I² = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I² = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I² = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I² = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I² = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I² = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I² = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I² = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I² = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.     

Patient-reported Upper Limb Function After Sentinel Lymph Node Biopsy for Breast Cancer: A Prospective Observational Study

IntroductionSentinel lymph node biopsy (SLNB) is the standard procedure for axillary staging in breast cancer. There is a lack of consistency in studies reporting on upper limb morbidity after SLNB. We present a prospective study evaluating upper limb function after SLNB using the validated quickDASH questionnaire.Materials and MethodsConsecutive patients who underwent wide local excision and SLNB were included in the study. Arm function was assessed using the quickDASH questionnaire at 3 time points – prior to surgery and 2 weeks and 3 months after SLNB. The scores obtained were labeled as A, B, and C respectively. The mean and median scores were compared using the paired t test and Wilcoxon signed rank test.ResultsNinety-nine patients met all inclusion criteria and were included in the final analysis. The mean A, B, and C scores were 8.46, 16.05, and 13.36. The median A, B, and C scores were 2.27, 7.5, and 4.54. There was a statistically significant difference between mean and median A and B scores, B and C scores, and A and C scores. A similar trend was observed in patients with better preoperative upper limb function. Patients with a higher body mass index had significantly worse B and C scores.ConclusionThere is a significant deterioration in upper limb function following SLNB. This improves at 3 months but does not reach baseline levels. Larger studies with long-term follow-up are required to establish the extent of upper limb functional morbidity and natural course of functional recovery after SLNB.     

miR-451a suppresses the development of breast cancer via targeted inhibition of CCND2

Extensive research has indicated that miRNAs are crucial for the occurrence and progression of cancers. miR-451a, involved in breast cancer (BC), is one of the miRNAs. This study focused on the mechanism by which miR-451a regulates BC. The levels of miR-451a in BC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan‒Meier analysis showed that this was intimately related to the patient's overall survival rate. Functional experiments revealed the negative effects of miR-451a on the abilities of BC cells to multiply (tested by Cell Counting Kit-8), migrate (tested by wound healing assay), and invade (tested by Transwell assay) and its positive effects on apoptosis (tested by flow cytometry). Western blotting indicated that the expression of tumor-related proteins was affected by miR-451a. Moreover, in vivo experiments suggested that tumor growth was clearly restrained by an miR-451a agonist in a xenograft tumor model. Bioinformatic analysis indicated that miR-451a directly targeted Cyclin D2 (CCND2), as demonstrated by the luciferase reporter assay. An opposite change in the level of CCND2 and miR-451a in BC was indicated by qRT-PCR, western blotting, and immunohistochemistry. Subsequently, functional experiments and western blotting analysis confirmed that CCND2 accelerated BC progression, which was regulated by miR-451a. Cumulatively, research on miR-451a may be valuable for BC treatment.     

不同剂量地佐辛术后镇痛对老年患者肝功能的影响

目的 探讨地佐辛术后镇痛对高龄患者围术期肝功能的影响。方法 选择2018 年1 月～2020 年6 月吉安市中心人民医院麻醉科收治的ASA 分级Ⅱ～Ⅲ级高龄患者80 例，按照随机数字表法，分为A 组、B 组、C 组、D 组，每组各20 例。分别给予0.4 mg/kg、0.5 mg/kg、0.6 mg/kg、0.7 mg/kg 地佐辛进行术后镇痛，评估术后1、2、6、12、24、48 h 患者的疼痛程度[视觉模拟评分法（VAS）]、术后镇静效果（Ramsay 评分法）及肝功能指标（ALT、AST）水平，评价不同剂量的地佐辛术后镇痛对高龄患者围术期肝功能的影响。结果 C 组术后患者不同时间段VAS 疼痛评分低于A 组、B 组、D 组，差异有统计学意义（P＜0.05）；四组患者术后1、2、6 h Ramsay 镇静评分比较，差异有统计学意义（P＜0.05）；但术后12、24、48 h Ramay 镇痛评分比较，差异无统计学意义（P＞0.05）。C 组肝功能指标ALT、AST优于A 组、B 组、D 组，差异有统计学意义（P＜0.05）。结论 高龄患者术后镇痛应用0.6 mg/kg地佐辛对围术期肝功能的影响最小。