Optimization of voriconazole dosage regimen to improve the efficacy in patients with invasive fungal disease by pharmacokinetic/pharmacodynamic analysis

Invasive fungal disease (IFD) is a significant cause of morbidity and mortality in hospitalized patients. To maximize the efficacy of voriconazole treatment, the study established the relationship between voriconazole pharmacokinetic/pharmacodynamic (PK/PD) and probability of response and optimized voriconazole dosage regimen in patients with IFD based on Monte Carlo simulation. Forty‐four patients proven with IFD were involved in this study. Among them, the overall cure rate was 75% (33/44) and there was a significant difference between C_min/MIC values in patients with lack of response (n = 11) and those with successful response (n = 33) (mean value: 1.91 vs. 11.33; P < 0.05). Logistic regression model showed a high correlation between voriconazole C_min/MIC ratio and clinical response (P = 0.044, OR = 1.349). According to Monte Carlo simulation results under different voriconazole dosing regimens, we could draw a conclusion that 200 mg voriconazole administered intravenously or orally twice daily for Candida infections and 300 mg administered orally or with 200 mg administered intravenously twice daily for Aspergillus infections were rational, which could achieve a value of the cumulative fraction of response >90%. This study built the relationship between voriconazole PK/PD and clinical response and obtained the reasonable empirical dosage regimen, which can be used to customize individual dosage regimen and improve the efficacy of voriconazole treatment.     

Melatonin enhances cold tolerance in drought‐primed wild‐type and abscisic acid‐deficient mutant barley

Melatonin is involved in multiple plant developmental processes and various stress responses. To explore the roles of melatonin played as well as its association with abscisic acid (ABA) in a process of drought priming‐induced cold tolerance (DPICT), a wild‐type barley and its ABA‐deficient mutant Az34 counterpart were selected for comparison, in which the effects of melatonin application (either foliarly or rhizospherically) and/or drought priming on the cold tolerance of both types of barleys were systematically investigated. It was demonstrated that the early drought priming induced an increase of endogenous melatonin production, which is not ABA dependent. In addition, exogenously applied melatonin resulted in higher ABA concentration in the drought‐primed plants than in the nonprimed plants when exposed to cold stress, indicating that ABA responded in a drought‐dependent manner. The interplay of melatonin and ABA leads to plants maintaining better water status. Drought priming‐induced melatonin accumulation enhanced the antioxidant capacity in both chloroplasts and mitochondria, which sustained the photosynthetic electron transport in photosynthetic apparatus of the plants under cold stress. These results suggest that the exogenous melatonin application enhances the DPICT by modulating subcellular antioxidant systems and ABA levels in barley.     

经基因分析确诊的原发性范可尼综合征一例报告

摘要：原发性范可尼综合征是一类罕见的遗传病，由于HNF4A等基因缺陷导致近端肾小管功能障碍，重吸收受 阻引发营养物质丢失及电解质紊乱，从而以多饮、多尿、生长发育落后、佝偻病为主要表现。对于原发性范可尼综合 征的临床与遗传学研究，国内仅有数例病例报道，尚少见遗传学确诊病例报道。本文患者经临床、生化、影像学及 HNF4A基因分析，发现HNF4A基因存在c.187C>T（p.R63W）的杂合突变，未在患者父母中检出，经临床及遗传学确诊 为原发性范可尼综合征。给予患者左卡尼汀、辅酶Q10、纠酸、保肝、护肾、补充维生素D、改善线粒体功能等治疗并 进行随访，患者临床症状有所好转。     

Muscle-strengthening activities and risk of cardiovascular disease,type 2 diabetes,cancer and mortality: A review of prospective cohort studies

The benefits of aerobic moderate-to-vigorous physical activity (MVPA) on major non-communicable diseases (NCDs) are well established. However, much less is known whether muscle-strengthening activities (i.e., resistance/weight/strength training) confer similar benefits. Herein, we conducted a narrative literature review and summarized the existing evidence from large prospective cohort studies on muscle strengthening activities and risk of major chronic diseases and mortality in adults generally free of major NCDs at baseline. Current epidemiologic evidence suggests that engagement in muscle-strengthening activities over 1–2 sessions (or approximately 60–150 min) per week was associated with reduced risk of cardiovascular disease (seven studies; approximately 20%–25% reduction), type 2 diabetes (four studies; approximately 30% reduction), cancer mortality (four studies; approximately 15%–20% reduction) as well as all-cause mortality (six studies; approximately 20%–25% reduction). For diabetes, the risk appears to lower further with even higher levels of muscle-strengthening activities, but some studies for cardiovascular and all-cause mortality suggest a reversal whereby higher levels (≥2.5 h/week) have less benefit, or are even harmful, relative to lower levels of activity. The likely mechanisms contributing to a benefit include improvement in body composition, lipid profile, insulin resistance and inflammation. The evidence supports engaging in 1–2 sessions (up to 2.5 h) per week, preferably performed complementary to the recommended levels of aerobic MVPA. Although data are limited, caution is suggested for training exceeding 2.5 h per week. Further studies are required to better understand the influence of frequency, duration and intensity of muscle-strengthening activities on major NCDs and mortality in diverse populations.     

Effect of electroacupuncture on glial fibrillary acidic protein and nerve growth factor in the hippocampus of rats with hyperlipidemia and middle cerebral artery thrombus

Electroacupuncture (EA) has been shown to reduce blood lipid level and improve cerebral ischemia in rats with hyperlipemia complicated by cerebral ischemia. However, there are few studies on the results and mechanism of the effect of EA in reducing blood lipid level or promoting neural repair after stroke in hyperlipidemic subjects. In this study, EA was applied to a rat model of hyperlipidemia and middle cerebral artery thrombosis and the condition of neurons and astrocytes after hippocampal injury was assessed. Except for the normal group, rats in other groups were fed a high-fat diet throughout the whole experiment. Hyperlipidemia models were established in rats fed a high-fat diet for 6 weeks. Middle cerebral artery thrombus models were induced by pasting 50% FeCl₃ filter paper on the left middle cerebral artery for 20 minutes on day 50 as the model group. EA1 group rats received EA at bilateral ST40 (Fenglong) for 7 days before the thrombosis. Rats in the EA1 and EA2 groups received EA at GV20 (Baihui) and bilateral ST40 for 14 days after model establishment. Neuronal health was assessed by hematoxylin-eosin staining in the brain. Hyperlipidemia was assessed by biochemical methods that measured total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein in blood sera. Behavioral analysis was used to confirm the establishment of the model. Immunohistochemical methods were used to detect the expression of glial fibrillary acidic protein and nerve growth factor in the hippocampal CA1 region. The results demonstrated that, compared with the model group, blood lipid levels significantly decreased, glial fibrillary acidic protein immunoreactivity was significantly weakened and nerve growth factor immunoreactivity was significantly enhanced in the EA1 and EA2 groups. The repair effect was superior in the EA1 group than in the EA2 group. These findings confirm that EA can reduce blood lipid, inhibit glial fibrillary acidic protein expression and promote nerve growth factor expression in the hippocampal CA1 region after hyperlipidemia and middle cerebral artery thrombosis. All experimental procedures and protocols were approved by the Animal Use and Management Committee of Beijing University of Chinese Medicine, China (approval No. BUCM-3-2018022802-1002) on April 12, 2018.

Chinese Library Classification No. R459.9; R363; R364     

To compare the efficacy between fixation with tightrope and screw in the treatment of syndesmotic injuries: A meta-analysis

Background

To compare the efficacy between fixation with suture-button and screw in the treatment of syndesmotic injuries: a meta-analysis.

Genetic association of CHEK2, GSTP1, and ERCC1 with glioblastoma in the Han Chinese population

Glioblastoma (GBM), a deadly brain tumor, is the most malignant glioma. It mainly occurs in adults and occurs significantly more in males than in females. We genotyped 19 tag single nucleotide polymorphisms (tSNPs) from 13 genes in a case–control study of the Han Chinese population to identify genetic factors contributing to the risk of GBM. These tSNPs were genotyped by Sequenom MassARRAY RS1000. Statistical analysis was performed using χ ² test and SNPStats, a website software. Using χ ² test, we found that the distribution of two tSNPs (rs2267130 in checkpoint kinase 2 (CHEK2), p?=?0.040; rs1695 in GSTP1, p?=?0.023) allelic frequencies had significant difference between cases and controls. When we analyzed all of the tSNPs using the SNPStats software, we found that rs1695 in GSTP1 decreased the risk of GBM in log-additive model (OR?=?0.56, 95 % CI, 0.34–0.94, p?=?0.022). Besides, we found that there is an interaction between rs3212986 in excision repair cross-complementing group 1 (ERCC1) and gender under codominant and recessive models. The gene polymorphisms in CHEK2, GSTP1, and ERCC1 may be involved in GBM in the Han Chinese population. Since our sample size is small, further investigation needs to be performed.     

Gene Expression Omnibus资源库在肿瘤学研究中的应用

Gene Expression Ominibus （GEO）是供学者们分享基因表达谱芯片数据、高通量测序数据等的国际化的公共资源平台,其中涵盖了应用炎癌模型获得的大量相关实验数据,比如关于某些炎性因子的表达情况.这些数据为炎癌转化中的调控网络和分子机制的研究提供了帮助,也为肿瘤的防治提供了新思路.研究者针对新的预测基因进行研究时,起源于各种疾病模型或实验处理的GEO数据库为寻找其有关功能提供了有利条件和有力证据.