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.     

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。     

(Re)organisation of the somatosensory system after early brain lesion: A lateralization index fMRI study

ObjectiveTo evaluate the relationship between neural (re)organization of the somatosensory cortex and impairment of sensory function (2-point discrimination [2PD]) in individuals with unilateral cerebral palsy.MethodsWe included 21 individuals with unilateral cerebral palsy. 2PD thresholds were evaluated on thumb pads, and activation of the somatosensory cortex was recorded by functional MRI (fMRI) during passive movements of the affected hand. A lateralization index (LI) was calculated for the primary sensory (S1) and secondary sensory (S2) cortices and the correlation between the LI and 2PD thresholds was analysed.ResultsWe found a significant negative correlation between the 2PD thresholds and the S2 LI (r = −0.5, one-tailed P-value = 0.01) and a trend towards a negative correlation with the S1 LI (r = −0.4, one-tailed P-value = 0.05).ConclusionHigh levels of activation in the contralesional hemisphere were associated with high levels of sensory impairment in individuals with unilateral cerebral palsy. The interhemispheric (re)organization of the somatosensory system may not effectively compensate for somatosensory impairment.     

The transition between turning and sitting in patients with Parkinson's disease: A wearable device detects an unexpected sequence of events

BackgroundWhen older adults turn to sit, about 80% of the subjects complete the turn before starting to sit i.e., a distinct-strategy, while in about 20%, part of the turning and sitting take place concurrently, i.e., an overlapping-strategy. A prolonged duration of the separation between tasks in the distinct-strategy (D-interval) and a prolonged duration of the overlap interval in overlapping-strategy (O-interval) are related to worse motor symptoms and poorer cognition. In the present study, we evaluated what strategy is employed by patients with Parkinson’s disease (PD) when they transition from turning to sitting.Methods96 participants with PD performed turn to sit as part of the Timed Up and Go test, both with and without medications, while wearing a body-fixed sensor. We quantified the turn-to-sit transition and determined which strategy (distinct or overlapping) was employed. We then stratified the cases and used regression models adjusted for age, gender, height, and weight to examine the associations of the D-interval or O-interval with parkinsonian features and cognition.ResultsMost patients (66%) employed the overlapping-strategy, both off and on anti-parkinsonian medications. Longer O-intervals were associated with longer duration of PD, more severe PD motor symptoms, a higher postural-instability-gait-disturbance (PIGD) score, and worse freezing of gait. Longer D-intervals were not associated with disease duration or PD motor symptoms. Neither the D- nor O-intervals were related to cognitive function. Individuals who employed the overlapping-strategy had more severe postural instability (i.e., higher PIGD scores), as compared to those who used the distinct-strategy.SignificanceIn contrast to older adults without PD, most patients with PD utilize the overlapping strategy. Poorer postural and gait control are associated with the strategy choice and with the duration of concurrent performance of turning and sitting. Additional work is needed to further explicate the mechanisms underlying these strategies and their clinical implications.     

支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系

目的探讨支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系。方法选取本院2017年9月-2018年9月支气管哮喘患者80例作为观察组,并以同期健康体检的30例儿童作为对照组,采用pico Green dsDNA荧光染色定量检测支气管哮喘患者NETs水平,采用T淋巴细胞亚群评价患者免疫功能,对比不同NETs水平患者免疫功能及临床特点,采用Logistic回归分析探讨小儿支气管哮喘急性发作的风险因素。结果观察组白细胞、中性粒细胞、单核细胞、Cf-DNA/NETs水平均高于对照组(P <0. 05),而淋巴细胞水平低于对照组,差异均有统计学意义(P <0. 05)。Logistic回归分析显示,哮喘家族史、呼吸道感染、Cf-DNA/NETs水平上升、有害气体接触、被动吸烟均是支气管哮喘急性发作的独立危险因素(P <0. 05)。结论中性粒细胞胞外诱捕网水平与支气管哮喘患者免疫功能及预后密切相关,值得临床重点关注。     

逐瘀止血汤加减治疗慢性子宫内膜炎气虚血瘀证的疗效观察

目的 评价逐瘀止血汤加减对慢性子宫内膜炎（CE）气虚血瘀证患者妊娠结局的影响及对免疫炎症因子的调节作用。方法 将144例患者随机按数字表法分为观察组和对照组各72例。观察组脱落、失访4例，剔除2例，完成66例；对照组脱落、失访3例，剔除5例，完成65例。两组均给予抗感染治疗14 d。对照组口服妇科千金片，6片/次，3次/d。观察组内服逐瘀止血汤加减，1剂/d。两组疗程均为3个月，并随访6个月。记录治疗前后月经经量、经期和周期变化情况；进行治疗前后宫腔镜和阴道彩色多普勒超声检查，评价子宫内膜形态、子宫内膜容受性（CP）［子宫内膜厚度、阻力指数（RI），搏动指数（PI）和血流指数（FI）］等，并进行子宫内膜病理检查；进行治疗前后气虚血瘀证评分；检测治疗前后月经血白细胞介素-1β（IL-1β），IL-6和肿瘤坏死因子-α（TNF-α）水平和外周血测T淋巴亚群（CD3⁺，CD4⁺，CD8⁺）水平；随访记录妊娠情况和流产情况。进行安全性评价。结果 治疗后观察组经量、经期、周期和月经完全正常率均高于对照组（P<0.05）；观察组子宫内膜厚度和FI均高于对照组（P<0.01），RI和PI均低于对照组（P<0.01）；观察组月经血IL-1β，IL-6和TNF-α水平均低于对照组（P<0.01）；观察组CD3⁺，CD4⁺水平和CD4⁺/ CD8⁺均高于对照组（P<0.01），CD8⁺水平低于对照组（P<0.01）；在6个月随访期间，观察组妊娠率46.97%（31/66），高于对照组的27.69%（18/65）（χ²=5.197，P<0.05）；观察组子宫内膜形态疗效总有效率为96.97%（64/66），高于对照组的86.15%（56/65）（χ²=4.981，P<0.05）；观察组子宫内膜病理组织疗效总有效率为95.45%（63/66），高于对照组的84.62%（55/65）（χ²=4.304，P<0.05）；观察组综合临床疗效总有效率为93.94%（62/66），高于对照组的81.54%（55/65）（χ²=4.696，P<0.05）；两组治疗期间均未发现与中药相关不良反应。结论 逐瘀止血汤加减治疗CE气虚血瘀证患者，可调经月经、减轻临床症状，改善宫腔镜下内膜形态，调节全身和局部的免疫炎症反应，提高了CP，从而改善了妊娠结局，有着较好的综合疗效，且安全。     

How does measurement of platelet P-selectin compare with other methods of measuring platelet function as a means of determining the effectiveness of antiplatelet therapy?

Measurement of P-selectin on activated platelets as a means of measuring platelet function utilizing the technology described here has the advantage of not requiring immediate access to specialist equipment and expertise. Blood samples are activated, fixed, stored, and transported to a central laboratory for flow cytometric analysis. Here we have compared P-selectin with other more traditional approaches to measuring platelet function in blood and/or platelet-rich plasma (PRP) from patients with acute coronary syndromes on treatment for at least 1 month with either aspirin and clopidogrel or aspirin with prasugrel. The comparators were light transmission aggregometry (LTA), VerifyNow and Multiplate aggregometry (for determining the effects of aspirin) and LTA, VerifyNow and Multiplate together with the BioCytex VASP phosphorylation assay (for the P2Y₁₂ antagonists). The P-selectin Aspirin Test revealed substantial inhibition of platelet function in all but three of 96 patients receiving aspirin with clopidogrel and in none of 51 patients receiving aspirin and prasugrel. The results were very similar to those obtained using LTA. There was only one patient with high residual platelet aggregation and low P-selectin expression. The same patients identified as “non-responders” to aspirin also presented with the highest residual platelet activity as measured using the VerifyNow system, although not quite as well separated from the other values. With the Multiplate test only one of these patients clearly stood out from the others. The results obtained using the P-selectin P2Y₁₂ Test in 102 patients taking aspirin and clopidogrel were similar to the more traditional approaches in that a wide scatter of results was obtained. Generally, high values seen with the P-selectin P2Y₁₂ Test were also high with the LTA, VerifyNow, Multiplate, and BioCytex VASP P2Y₁₂ Tests. Similarly, low residual platelet function using the P2Y₁₂ test was seen irrespective of the testing procedure used. However, there were differences in some patients. Prasugrel was always more effective than clopidogrel in inhibiting platelet function with none of 56 patients (P-selectin and VerifyNow), only 2 of 56 patients (Multiplate) and only 3 of 56 patients (Biocytex VASP) demonstrating high on-treatment residual platelet reactivity (HRPR) defined using previously published cut-off values. The exception was LTA where there were 11 of 56 patients with HRPR. It remains to be seen which experimental approach provides the most useful information regarding outcomes after adjusting therapies in treated patients.