Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Improved Diagnostic Sensitivity of Bowel Disease of Prematurity on Contrast-Enhanced Ultrasound

Bowel diseases of prematurity, including necrotizing enterocolitis, are dreaded ailments of neonates. Early diagnosis is difficult, with clinical and radiographic findings often inconclusive. We present a novel use of contrast-enhanced ultrasound in detection of pediatric bowel disease. Early identification of compromised blood flow or an at-risk bowel can be quantitatively detected and monitored. This ability has implications for guidance of emerging therapies, allowing targeting of inflammation. These findings represent an advancement in detection of bowel disease in neonates.     

Comparative outcomes of vascular access in patients older than 70 years with end-stage renal disease

Objective

The advantage of arteriovenous fistulas (AVFs) in older patients requiring dialysis is controversial. We reviewed our vascular access experience in patients ≥70 years of age (older group) compared with younger patients.

Dorsal suspension for Morton’s neuroma: A comparison with neurectomy

BackgroundThe purpose of this study was to investigate and compare the clinical outcomes of dorsal suspension with those of neurectomy for the treatment of Morton’s neuroma.MethodsWe conducted a retrospective study of dorsal suspension and neurectomy group. The dorsal suspension was performed by dorsal transposition of neuroma over the dorsal transverse ligament after neurolysis. The visual analog scale (VAS), the Foot and Ankle Ability Measure (FAAM), postoperative satisfaction, and complications were evaluated.ResultsBoth groups reported significant pain relief, and there were no significant differences between the groups with respect to postoperative pain. The postoperative FAAM outcomes showed no significant between-group differences. Satisfaction analysis showed ‘excellent’ and ‘good’ results in the dorsal suspension and neurectomy groups (95% and 77.7%, respectively). Complications of numbness and paresthesia reported in the dorsal suspension group (5% and 5%, respectively) were significantly fewer than those of neurectomy group (61.1% and 33.3%, respectively) (both, p < .05).ConclusionsWith its favorable results, dorsal suspension can be another operative option for the treatment of Morton’s neuroma.Level of Evidence: Level III, retrospective comparative case series.     

Is Atrial Fibrillation a Risk Factor for Gastroesophageal Reflux Disease Occurrence?

Recent studies have reported an association between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF). The objective of the present study was to evaluate whether AF is one of the risk factors for GERD occurrence.In this hospital-based, retrospective, case–control study, the patients were classified into 2 groups. The patients diagnosed with new AF were assigned to the AF group (n = 1612); those diagnosed without AF and GERD were assigned to the control group (n = 1612). The subjects in the control group were selected from outpatients of total healthcare center without a history of AF or GERD, and matched for age and gender. We evaluated the incidence of GERD and risk factors for GERD occurrence between the 2 groups.The number of patients experiencing occurrence of GERD during the follow-up period was significantly higher in the AF group than those in the control group, respectively (129 patients vs 98 subjects, P = 0.037). The incidence of GERD was significantly higher in the AF group than in the control group by Kaplan–Meier analysis with log-rank test (P = 0.008). The AF group''s adjusted hazard ratio of GERD occurrence against that of the control group was 1.37 (95% confidence interval [CI]: 1.16–1.57; P = 0.009) according to Cox''s proportional hazard model.The presence of AF appears to increase the incidence of GERD and may be considered a risk factor for the development of GERD. Further, large prospective and cohort studies will be required to better establish the correlation of GERD with AF.     

Air Pollution and the Risk of Cardiac Defects: A Population-Based Case-Control Study

Previous epidemiologic studies have assessed the role of the exposure to ambient air pollution in the development of cardiac birth defects, but they have provided somewhat inconsistent results. To assess the associations between exposure to ambient air pollutants and the risk of cardiac defects, a population-based case-control study was conducted using 1087 cases of cardiac defects and a random sample of 10,870 controls from 1,533,748 Taiwanese newborns in 2001 to 2007.Logistic regression was performed to calculate odds ratios for 10 ppb increases in O₃ and 10 μg/m³ increases in PM₁₀. In addition, we compared the risk of cardiac defects in 4 categories-high exposure (>75th percentile); medium exposure (75th to 50th percentile); low exposure (<50th–25th percentile); reference (<25th percentile) based on the distribution of each pollutant. The risks of ventricular septal defects (VSD), atrial septal defects (ASD), and patent ductus arteriosus (PDA) were associated with 10 ppb increases in O₃ exposure during the first 3 gestational months among term and preterm babies. In comparison between high PM₁₀ exposure and reference category, there were statistically significant elevations in the effect estimates of ASD for all and terms births. In addition, there was a negative or weak association between SO_2, NO₂, CO, and cardiac defects_.The study proved that exposure to outdoor air O₃ and PM₁₀ during the first trimester of gestation may increase the risk of VSD, ASD, and PDA.     

钝性肝脾肾损伤的CT平扫与增强扫描比较

目的:比较CT平扫与增强扫描对肝脾肾钝性损伤的诊断能力。方法:回顾性分析临床疑似钝性肝脾肾损伤,并经手术和临床观察证实的CT平扫和增强扫描的患者84例。结果:平扫确定的损伤:肝12例,脾25例,肾5例;平扫可疑损伤:肝22例,脾15例,肾5例。增强确定的损伤:肝32例,脾40例,肾12例(全肾梗塞1例,局限性梗塞3例);对比剂外溢(活动性出血)3例;无可疑损伤。平扫无异常而增强确定有损伤:肝10例,脾5例,肾2例。增强显示的损伤灶比平扫范围明显大、病灶多、界限清楚。结论:CT增强扫描显示肝脾肾损伤明显优于平扫,延时扫描有助于发现活动性出血,应常规增强扫描。     

Juvenile Xanthogranuloma with Ocular Involvement

Abstract:   Juvenile xanthogranuloma is a benign histiocytic skin disorder encountered primarily in infancy and childhood. Approximately 0.4% of cases exhibit ocular manifestations, which can result in glaucoma and blindness. We present a case of a 7-month-old male with unilateral glaucoma associated with Juvenile xanthogranuloma, and emphasize the importance of an ocular screening in patients with Juvenile xanthogranuloma, especially those with periocular lesions.     

5-羟色胺受体激动剂对脊髓损伤猫排尿功能的影响

目的探讨5-羟色胺(5-HT)受体激动剂对猫脊髓损伤后膀胱过度活动的影响。方法雌性猫18只,其中正常假手术组5只,脊髓损伤组13只。术后6~8周,氯醛糖麻醉下,在猫颈动脉及膀胱内置管,连接压力感受器,记录诱发膀胱收缩的膀胱容量阈值、膀胱容量、剩余尿量、排尿量和血压。静脉注入5-HT1A受体激动剂8-OH-DPAT(0.3~30μg/kg)或5-HT1B/1D受体激动剂GR-46611(0.03~300μg/kg),得到剂量-效应曲线后再给予5HT1A受体抑制剂WAY-100635(300μg/kg),比较给药前后各项指标变化。结果正常猫使用8-OH-DPAT后,膀胱容量阈值、膀胱容量、剩尿量均有增加趋势,但差异无统计学意义;8-OH-DPAT和GR-46611均能使脊髓损伤猫的膀胱容量阈值、膀胱容量、剩余尿量增加,且效应随着剂量增加而增加,差异有统计学意义。WAY-100635能抵消8-OH-DPAT的作用,但对GR-46611无影响。结论5-HT1A和5-HT1B/1D受体激动剂能改善慢性脊髓损伤后的膀胱过度活动,增加膀胱容量。