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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.  相似文献   
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ABSTRACT

Purpose

Work-related eye injuries have been reported with a variety of epidemiologic and clinical characteristics. We aimed to identify epidemiologic characteristics of work-related eye injuries and risk factors associated with severe injury in a large metropolitan city.  相似文献   
5.
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.  相似文献   
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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.  相似文献   
8.

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.

Methods

We analyzed consecutive patients who underwent access surgery between 2013 and 2016. Primary success (PS) and primary patency (PP) data were analyzed between the older and younger groups before and after propensity score matching of the patients' characteristics and access composition. PS was defined as the achievement of access function that was amenable to two sessions of successful cannulation without early occlusion or maturation failure requiring revision. PP was defined as the time with uninterrupted patency without intervention.

Results

A total of 594 consecutive accesses were created among 563 patients, of whom 119 were allocated into each group after propensity score matching. In the whole cohort, 193 accesses (32.5%) were performed in older patients. AVFs were performed in 130 (67.4%) older patients and 293 (73.1%) younger patients. Regarding AVFs, the PS rate (83.6% in the older group vs 94.3% in the younger group; P = .001) and the overall PP at 6 and 12 months (73.1% and 57.1%, respectively, in the older group vs 86.7% and 77.7%, respectively, in the younger group; P = .009) were lower in the older group than in the younger group. However, no differences were found in the PS and PP rates for arteriovenous grafts between groups. Regarding the AVF location, the PS rate for forearm AVFs was significantly lower in the older group than in the younger group (76% vs 93%; P < .001); however, the PS rate of the upper arm was not different between the groups (94% vs 97%; P = .425). In the patients with PS, the PP rate of AVFs was similar between the two groups. In the older group with forearm AVFs, the median diameter of the radial artery was larger in the patients with PS than in the patients without PS (2.20 mm with PS vs 2.00 mm without PS; P = .008). The propensity score matching results demonstrated similar trends for the whole cohort, with lower PS (P = .042) and PP rates (P = .023) for AVF in the older group.

Conclusions

The outcomes after AVF were poorer in the older group than in the younger group, which was primarily due to unsatisfactory outcomes in patients with forearm AVFs. Thus, stricter criteria, especially regarding the radial artery diameter, should be applied for forearm AVFs in older patients, and additional research is necessary to delineate the risk factors for primary failure.  相似文献   
9.
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.  相似文献   
10.

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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