Subclinical albuminuria is linked to gray matter atrophy in type 2 diabetes mellitus

Objective

Microalbuminuria (MA), a marker of renal microvascular disease, is associated with brain atrophy and neurovascular changes in older adults with type 2 diabetes mellitus (DM). We evaluated the relationship between urine albumin-to-creatinine ratio (UACR) and regional brain volumes to determine whether subclinical albuminuria may indicate early structural brain changes in type 2 DM.

Materials/Methods

We studied UACR and brain volumes in 85 type 2 DM patients (64.8 ± 8.3 years) and 40 age-matched controls using 3D magnetization prepared rapid acquisition with gradient echo (MP-RAGE) MRI (magnetic resonance imaging) at 3 Tesla. The relationship between UACR and brain volumes was analyzed using the least square models.

Results

In DM patients, UACR ≥ 5 mg/g, UACR ≥ 10 mg/g and clinically significant MA (UACR ≥ 17 mg/g [males] and 25 mg/g [females]) were associated with lower gray matter (GM) volume in the frontal lobe (r²_adj = 0.2–0.4, P = 0.01–0.05) and UACR ≥ 5 mg/g was also related to global GM atrophy (r²_adj = 0.1, P = 0.04), independent of DM duration, glucose levels, HbA_1c and hypertension. For UACR ≥ 5 mg/g, a lower global GM volume was related to worse executive function (P = 0.04) in the DM group. No associations were found for UACR (< 5 mg/g) and controls.

Conclusions

Subclinical albuminuria (UACR ≥ 5 mg/g) is associated with lower GM volume that has clinical impact on cognitive function in older diabetic patients, and these relationships are independent of DM control and hypertension. Therefore, UACR levels may serve as an additional marker of DM-related brain structural changes.     

Chebulagic acid,a COX–LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line

Ethnopharmacological relevance

Terminalia chebula has an esteemed origin in Indian mythology; its fruits are used to treat many diseases such as digestive, diabetes, colic pain, chronic cough, sore throat, asthma, etc.

Aim of the study

The water or ethanolic extracts of the fruits were reported to have anti-oxidant, anti-inflammatory, anti-cancer and radio-protector properties. The present study is to isolate and identify the compounds that inhibit COX and 5-LOX, the key enzymes involved in inflammation and carcinogenesis.

Materials and methods

The ethanolic extract of the fruits was fractionated by RP-HPLC and fractions were tested for enzyme inhibition activity against COX and 5-LOX. One of the fractionated compounds showed potent dual inhibition against COX and 5-LOX. It was identified as chebulagic acid by LC–MS, NMR and IR analyses. The chebulagic acid was also tested for anti-proliferative activity.

Results

Chebulagic acid showed potent COX–LOX dual inhibition activity with IC₅₀ values of 15 ± 0.288, 0.92 ± 0.011 and 2.1 ± 0.057 μM for COX-1, COX-2 and 5-LOX respectively. It also showed anti-proliferative activity against HCT-15, COLO-205, MDA-MB-231, DU-145 and K562 cell lines. Further mechanistic studies on COLO-205 cells revealed induction of apoptosis by chebulagic acid.

Conclusions

Chebulagic acid, a COX-2 and 5-LOX dual inhibitor isolated from the fruits of Terminalia chebula, induces apoptosis in COLO-205 cells.     

辛伐他汀对慢性心力衰竭患者心功能和运动耐量的影响

目的 观察辛伐他汀（舒降之）对慢性心衰患者心功能和运动耐量的影响，并分析其产生作用的可能机理。方法 本实验为随机、开放、对照临床研究，共选取39例因缺血性心肌病和扩张性心肌病而导致心衰的慢性心衰患者（NYHA Ⅱ、Ⅲ级），并将患者随机分为2组：对照组（n=20，应用常规药物）和用药组（n=19，应用常规药物＋辛伐他汀20mg qn）。用药观察期为3个月。全部入选患者在用药前和用药3月时行超声心动图（用LVEF、EDD、ESD、SV等指标）评价心脏收缩功能，行六分钟步行试验评价患者运动耐量。结果 入选时2组资料有可比性。用药12周后，对照组和辛伐他汀组患者比较，辛伐他汀组的六分钟步行距离、FS值、SV值和EF值与对照组相比增高。2组患者血生化检查、血压、心率在组间和组内比较，差异均无统计学意义。本研究未遇严重不良事件者。结论 在常规心衰治疗的基础上加用辛伐他汀可以改善慢性心衰患者的心脏收缩功能，提高慢性心衰患者的运动能力，具有较好的耐受性。     

Buyang Huanwu Decoction can improve recovery of neurological function,reduce infarction volume,stimulate neural proliferation and modulate VEGF and Flk1 expressions in transient focal cerebral ischaemic rat brains

Buyang Huanwu Decoction is a classic formula for treating stroke-induced disability in traditional Chinese medicine (TCM). To explore its pharmacological basis, we investigated the effects of the whole formula and its herbal components on the neurological behavior performance and infarction volume in focal cerebral ischaemia rats. The neurological deficit scores and infarction volume were measured at days 3, 7 and 14 after 30 min of occlusion of middle cerebral artery. The results showed that Buyang Huanwu Decoction and its herbal components significantly improved the neurological behavior performances and reduced the infarction volume in the ischaemic brains. To elucidate the potential therapeutic mechanisms, we investigated the proliferation of progenitors by detecting the immunohistochemical staining of thymidine analog 5-bromo-2′-deoxyuridine (BrdU) and found that the formula stimulated the proliferation of the progenitors at hippocampus and subventricular zone (SVZ) in the ischaemic brains. As vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase (Flk1) are important neurotrophic, neuroprotective and neuroproliferative factors, we studied the expressions of VEGF and Flk1 in the hippocampus, SVZ and cortex in the ischaemic brains and found that the formula led to increase the numbers of VEGF-positive and Flk1-positive cells in the SVZ and cortex in the ischaemic brains. The results indicate that the therapeutic effects of Buyang Huanwu Decoction for recovery of neurological deficits are associated with the stimulation of the proliferation of progenitors and the enhancement of the expressions of VEGF and Flk in ischaemic brains.     

基于“热敏灸”英译的质性研究探讨中医名词术语英译规范化实证分析

目的:文章以"热敏灸"英译为例,探讨中医名词术语英译规范化实施方法与路径。方法:通过数据库检索,以"热敏灸"英译为切入点,收集整理其不同的英译版本,采用Nvivo12软件对这一术语进行量化研究与质性分析。结果:根据中医术语规范研究中的基本原则,得出"heat-sensitive moxibustion"或"thermosensitive moxibustion"是"热敏灸"较为理想的翻译。结论:结合质性分析与量化研究,采用Nvivo12软件对术语英译进行实证分析,有助于中医术语翻译规范化与标准化,有助于中医名词术语的国际传播。     

阿托伐他汀联合米力农治疗慢性心力衰竭的临床研究

目的探讨阿托伐他汀钙联合米力农注射液治疗慢性心力衰竭的临床疗效。方法选取2018年12月—2019年12月于河南省人民医院进行治疗的慢性心力衰竭患者93例,随机分为对照组(46例)和治疗组(47例)。对照组iv米力农注射液,首次采用50μg/kg负荷剂量静脉推注10 min,随后以0.25～0.50μg/(kg·min)静脉匀速泵入,连续使用72 h;治疗组患者则在对照组基础上口服阿托伐他汀钙片,10 mg/次,2次/d。两组均连续治疗1周。观察两组的临床疗效,比较两组治疗前后临床症状评分、6 min步行距离、心功能指标及血清去甲肾上腺素、细胞间黏附分子-1(ICAM-1)、超敏C反应蛋白(hs-CRP)、醛固酮(ALD)、脑自然肽氨基端前体蛋白(NT-proBNP)、心肌肌钙蛋白I(cTnI)水平。结果治疗后,对照组临床总有效率78.26%明显低于治疗组93.62%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者临床症状评分显著降低,但6 min步行距离显著升高(P0.05);且治疗后治疗组临床症状评分和6 min步行距离相较于对照组改善更为显著(P0.05)。治疗后,两组患者心功能指标左心室射血分数(LVEE)、左心室收缩末内径(LVESD)、左心室收缩末期容积(LVESV)均较治疗前明显改善(P0.05);且治疗后治疗组心功能相关指标相较于对照组改善更为显著(P0.05)。治疗后,两组患者血清去甲肾上腺素、ICAM-1、hs-CRP、ALD、NT-proBNP、cTnI水平均较治疗前明显降低(P0.05);且治疗后治疗组这些相关血清生化指标显著低于对照组(P0.05)。结论阿托伐他汀钙联合米力农注射液治疗慢性心力衰竭疗效确切,能显著改善患者临床症状及心功能指标,可改善患者相关血清生化指标,具有一定的临床推广应用价值。     

Optimal birth weight percentile cut‐offs in defining small‐ or large‐for‐gestational‐age

Aims: It remains questionable what birth weight for gestational age percentile cut‐offs should be used in defining clinically important poor or excessive foetal growth. We aimed to evaluate the optimal birth weight percentile cut‐offs for defining small‐ or large‐for‐gestational‐age (SGA or LGA). Methods: In a birth cohort‐based analysis of 17 979 120 non‐malformation singleton live births, U.S. 1995–2001, we assessed the optimal birth weight percentile cut‐offs for defining SGA and LGA. The 25th–75th percentile group served as the reference. Primary outcomes are the risk ratios (RR) of neonatal death and low 5‐min Apgar score (<4) comparing SGA or LGA versus the reference group. More than 2‐fold risk elevations were considered clinically significant. Results: The 15th birth weight cut‐off already identified SGA infants at more than 2‐fold risk of neonatal death at pre‐term, term or post‐term, except for extremely pre‐term births <28 weeks (continuous risk reductions over increasing birth weight percentiles). LGA was associated with a reduced risk of low 5‐min Apgar score at pre‐term, but an elevated risk at term and post‐term. The 97th cut‐off identified LGA infants at 2‐fold risk of low 5‐min Apgar at term. Conclusion: The commonly used 10th and 90th birth weight percentile cut‐offs for defining SGA and LGA respectively seem largely arbitrary. The 15th and 97th percentiles may be the optimal cut‐offs to define SGA and LGA respectively.     

Notch1 signaling,hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress in adult ischemic rats

Accumulating evidence indicates that the Notch signaling pathway fulfills important roles in ischemia-stimulated neurogenesis, which may be regarded as an etiological factor in post-stroke depression. Here we explored Notch₁ signaling, hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress (CUMS) in adult ischemic rats. Animals were treated with permanent middle cerebral artery occlusion followed by an 18 day CUMS procedure. Proliferating cells in the hippocampus and their cell fate were investigated on days 19 and 28 after ischemic surgery. Additionally, expression of the Notch₁ intracellular domain (NICD) and its downstream targets Hes1 and Hes5 was examined. A sucrose preference test and forced swim test were used to assess behavioral responses. CUMS produced depressive-like behaviors and decreased the number of proliferating cells on day 19 (both p < 0.001), accompanied by a decreased expression of both Hes1 and Hes5 in the hippocampus of ischemic animals (p < 0.001). On day 28, CUMS resulted in a decreased number of neurogenically-differentiating cells in the subgranular zone (p < 0.001) while permitting differentiation into astrocytes in the hilus (p < 0.05). Hes1 and Hes5 protein expression levels were increased. The expression of the NICD was significantly decreased at both time-points. CUMS led to expression changes in the Notch₁ signaling cascade in ischemic rats, most of which concerned hippocampal neurogenesis. This suggests that variation in Notch₁ activity and subsequent expression of its downstream targets, including Hes1 and Hes5, may, at least in part, contribute to modulation of ischemia-related hippocampal neurogenesis by CUMS.