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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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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.  相似文献   
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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.  相似文献   
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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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Zygomatic implant treatment is widely applied for severe maxillary atrophy to help rehabilitate the maxillary dentition. This retrospective study was performed to evaluate the actual radiographic bone–implant contact (rBIC) lengths of zygomatic implants. The records of 28 patients who underwent zygomatic implant surgery and subsequent follow-up examinations between August 2013 and September 2018 in the Department of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital were reviewed. The surgeries were performed by a single surgeon using the same treatment protocol. All patients had a computed tomography scan at 1 year after the surgery. Using three-dimensional imaging software, an investigator measured the rBIC lengths of 66 implants and documented their clinical status. The implant survival rate was 100%. The mean rBIC length was significantly longer in male patients than in female patients (20.80 ± 5.88 mm versus 17.79 ± 6.34 mm; P = 0.028). The mean rBIC length of double zygomatic implants was significantly longer when compared to that of single implants (21.11 ± 6.23 mm versus 17.75 ± 5.85 mm; P = 0.027). This article is novel in reporting the exact rBIC lengths of zygomatic implants in a clinical setting. The results showed that zygomatic implants are a viable treatment modality for full-mouth rehabilitation.  相似文献   
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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   
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