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.     

Safety and Efficacy of the Moderate Sedation During Flexible Bronchoscopic Procedure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Moderate sedatives have been increasingly used to improve patient comfort during flexible bronchoscopy (FB). However, routine use of moderate sedation during FB is controversial because its efficacy and safety are not well established.This study aims to evaluate the efficacy and safety of moderate sedation during FB.A search was made of Medline, EMBASE, and the Cochrane Library to May 2014.Randomized controlled trials (RCTs) and quasi-RCTs were included.The main analysis was designed to examine the efficacy of moderate sedation during FB in sedation than no-sedation.The willingness to repeat FB was significantly more in sedation than no-sedation (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.11–4.73; P = 0.02; I² = 22.5). The duration of FB was shorter in sedation group than no-sedation group (standardized mean difference [SMD] −0.21; 95% CI −0.38 to −0.03; P = 0.02; I² = 78.3%). Event of hypoxia was not significantly different between sedation and no-sedation groups (OR 0.86; 95% CI 0.42–1.73; P = 0.67; I² = 0%). The SpO₂ during procedure was not different between sedation and no-sedation groups (SMD −0.14; 95% CI −0.37 to 0.08; P = 0.21; I² = 49.9%). However, in subgroup analysis without supplemental oxygen, the SpO₂ was significantly lower in sedation than no-sedation group (SMD −0.45; 95% CI −0.78 to −0.11; P = 0.01; I² = 0.0%).According to this meta-analysis, moderate sedation in FB would be useful in patients who will require repeated bronchoscopies as well as safe in respiratory depression. To our knowledge, although the various sedative drugs are already used in the real field, this analysis was the first attempt to quantify objective results. We anticipate more definite and studies designed to elucidate standardized outcomes for moderate sedation in FB.     

Troubled-Cell Indicator Based on Mean Value Property for Hybrid WENO Schemes

In this paper, we introduce a new type of troubled-cell indicator to improve hybrid weighted essentially non-oscillatory (WENO) schemes for solving the hyperbolic conservation laws. The hybrid WENO schemes selectively adopt the high-order linear upwind scheme or the WENO scheme to avoid the local characteristic decompositions and calculations of the nonlinear weights in smooth regions. Therefore, they can reduce computational cost while maintaining non-oscillatory properties in non-smooth regions. Reliable troubled-cell indicators are essential for efficient hybrid WENO methods. Most of troubled-cell indicators require proper parameters to detect discontinuities precisely, but it is very difficult to determine the parameters automatically. We develop a new troubled-cell indicator derived from the mean value theorem that does not require any variable parameters. Additionally, we investigate the characteristics of indicator variable; one of the conserved properties or the entropy is considered as indicator variable. Detailed numerical tests for 1D and 2D Euler equations are conducted to demonstrate the performance of the proposed indicator. The results with the proposed troubled-cell indicator are in good agreement with pure WENO schemes. Also the new indicator has advantages in the computational cost compared with the other indicators.     

Pseudocystic pilomatricoma: A new variant and review of the literature

A classic pilomatricoma, which usually presents with an asymptomatic, solitary, firm, subcutaneous nodule in the head, neck, or extremities of the paediatric population, is easily diagnosed based on its characteristic clinical and histopathological features. However, its variants often pose particular diagnostic challenges to clinicians due to their rarity and diverse clinicopathological features. We present a new pseudocystic variant, manifesting as solid lesions floating in a fluid‐filled sac.     

八段锦治疗神经根型颈椎病的系统评价与Meta分析

[目的] 系统评价八段锦治疗神经根型颈椎病的临床疗效。[方法] 计算机检索中国知网数据库（CNKI）、维普资讯中文科技期刊数据库（VIP）、万方数据库（Wan-fang）、中国生物医学文献数据库（SinoMed）、Web of science、Clinical Trials gov、Pubmed、EMBASE、CENTRAL、Cochrane Library，查找出八段锦治疗神经根型颈椎病的随机对照试验（RCT），检索时限均从建库至2019年7月1日。两名研究者按照纳入与排除标准独立进行文献筛选、资料提取和偏倚风险评估，应用RevMan 5.3软件对最后纳入的研究进行Meta分析。[结果] 最终纳入10个RCT，共843例患者。Meta分析结果显示：八段锦+常规治疗与常规治疗比较，其临床疗效的总有效率差异具有统计学意义[OR=4.19，95% CI（2.42，7.26），P<0.000 01]；八段锦+常规治疗与常规治疗+颈部“米”字操比较，其临床疗效的总有效率差异具有统计学意义[OR=3.41，95% CI（1.56，7.46），P=0.002]；八段锦+常规治疗与常规治疗比较，其疼痛视觉模拟评分法（VAS）评分差异具有统计学意义[MD=-1.90，95% CI（-1.97，-1.83），P<0.000 01]。[结论] 基于现有的研究，该系统评价显示，与常规治疗相比，八段锦+常规治疗在临床疗效总有效率、VAS评分方面有一定的治疗优势。与常规治疗+颈部“米”字操比较，八段锦+常规治疗在临床疗效的总有效率方面有一定的治疗优势。但由于纳入研究的质量不高，仍需要大样本、多中心、随机、双盲试验及试验参照CONSORT标准和STRICTA声明进行RCT研究。     

体外转染Cyclin A2基因对原代大鼠心肌细胞增殖的影响

目的探讨体外转染细胞周期素A2(Cyclin A2)基因对原代大鼠心肌细胞增殖的影响,为心脏再生提供细胞学依据。方法 SD乳鼠12只,分离、培养、鉴定原代乳鼠心肌细胞并分为3组,实验组:转染带有强化绿色荧光蛋白(GFP)和Cyclin A2基因的重组腺病毒(Ad-Cyclin A2-GFP);空病毒组:转染不含目的基因带有GFP的重组腺病毒(Ad-Null-GFP);阴性对照组:未做转染处理,仅加入等量的培养基。利用GFP示踪技术,评估原代心肌细胞转染效率;转染后的细胞继续体外培养3~5d,利用免疫荧光技术分别检测Cyclin A2、磷酸化组蛋白H3(H3P)、心肌肌钙蛋白-T(c Tn T)。结果 1.荧光GFP示踪表明原代心肌细胞的转染效率高达(97±0.74)%;2.免疫荧光标记显示,空病毒组和对照组结果相似;心肌细胞特异性标记蛋白c Tn T分布于细胞质,原代心肌细胞纯度高达(95±0.62)%;心肌细胞Cyclin A2主要在胞核内聚集,少数分布于细胞质。H3P为核蛋白在细胞核内分布。3.转染Cyclin A2后,实验组H3P阳性率明显高于空病毒组和对照组,差异具有统计学意义(P0.05);实验组可见大量多核细胞,以双核为主,伴少量3核细胞。结论腺病毒作为转染载体对原代心肌细胞有很好的侵染效率;Cyclin A2超表达促进原代心肌细胞形成双核。     

Symptomatic perineural cyst after spontaneous subarachnoid hemorrhage: A case report

Rationale:Tarlov or perineurial cysts are nerve root lesions often found in the sacral region. Most perineural cysts (PCs) remain asymptomatic throughout a patient''s life. While their pathogenesis is still unclear, trauma resulting in hemorrhaging into subarachnoid space has been put forward as a possible cause of these cysts. Recently, we worked with a patient experiencing symptomatic PCs after spontaneous subarachnoid hemorrhage.Patient concerns:A 45-year-old man had a coil embolization procedure performed after being diagnosed with a subarachnoid hemorrhage from a ruptured anterior communicating artery. His symptoms were relieved after the procedure, but 7 days later he reported worsening pain in the left perineal area. The pain was intermittent at its onset and exacerbated by sitting, walking, and coughing.Diagnoses:Two weeks after the embolization procedure, a lumbar spine MRI revealed 2 PCs at the S1 and S2 level affecting the left S2 root with high signal intensity in T2 and T1 images, suggestive of bleeding within the cyst.Interventions:We operated using a posterior approach. Cyst fenestration was done after S1 laminectomy. We aspirated approximately 1 cc of old blood.Outcomes:His pain was relieved immediately after cyst removal and no neurologic deterioration occurred during the postoperative period.Lessons:Subarachnoid hemorrhage can be the source of the development of pain from asymptomatic PCs, making them symptomatic. Surgical extirpation is 1 treatment option for these symptomatic PCs.     

Erythema induratum of Bazin in a 10‐year‐old boy

Erythema induratum of Bazin (EIB) is a form of tuberculid resulting from hypersensitivity to tuberculosis antigen. EIB occurs most commonly in middle‐aged women and is not typically seen in children. Here, we present a rare case of EIB, presenting as a chronic nodular panniculitis, in a 10‐year‐old Korean boy.