Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake.

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.

A 10-year experience in microsurgical reconstruction of the nose with a lower extremity flap.

BACKGROUND: Traditionally, radial forearm free flaps are utilized for nasal lining reconstruction when local flaps cannot provide adequate coverage. However, according to our clinical observation, the skin of the forearm flap is relatively thin and prone to collapse. We present a series of nasal reconstructions using free flaps harvested from the lower extremities to determine if the thick flap could provide more support and decrease the tendency of airway collapse. METHODS: From March 2011 to July 2021, we identified 15 patients who underwent total or subtotal nasal reconstruction with free flap from the lower extremities (10 anterolateral thigh flap, 4 medial sural artery perforator flap, and 1 profunda artery perforator flap). We included 15 patients who underwent free forearm flap reconstruction as controls. The Nasal Obstruction Symptoms Evaluation (NOSE) score was utilized to subjectively evaluate the degree of nasal obstruction symptoms. RESULTS: The lower extremity group had a lower NOSE score than the forearm group (25.4 vs. 40). It took more time (6.5 vs. 4.2 months) and more surgeries (4.6 vs. 2.6) from the first free flap reconstruction till forehead flap reconstruction in the lower extremity group than in the forearm group, although the total number of surgeries was comparable between the 2 groups (7.2 vs. 8.1). CONCLUSIONS: Utilizing free flaps from the lower extremities in total or subtotal reconstruction of the nasal lining may decrease the tendency of flap collapse and alleviate airway obstruction symptoms and may also allow reconstruction of surrounding defects simultaneously compared with using forearm flaps.

Impact of bisoprolol and amlodipine on cardiopulmonary responses and symptoms during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39-51%, and ß-blockers and amlodipine are commonly used drugs for these patients. OBJECTIVES: We aimed to study the impact of ß-blockers and amlodipine on cardiopulmonary responses during exercise. METHODS: A total 81 patients with COPD were included and the patients underwent spirometry, cardiopulmonary exercise tests, and symptoms questionnaires. RESULTS: There were 14 patients who took bisoprolol and 67 patients who did not. Patients with COPD taking ß-blockers had lower blood oxygen concentration (SpO2) and more leg fatigue at peak exercise but similar exercise capacity as compared with patients not taking bisoprolol. There were 18 patients treated with amlodipine and 63 patients without amlodipine. Patients taking amlodipine had higher body weight, lower blood pressure at rest, and lower respiratory rates during peak exercise than those not taking amlodipine. Other cardiopulmonary parameters, such as workload, oxygen consumption at peak exercise, tidal volume at rest or exercise, cardiac index at rest or exercise were not significantly different between patients with or without bisoprolol or amlodipine. Smoking status did not differ between patients with or without bisoprolol or amlodipine. CONCLUSIONS: COPD is often accompanied by hypertension, and ß-blockers and amlodipine are commonly used antihypertensive drugs for these patients. Patients with COPD taking bisoprolol had lower SpO2 and more leg fatigue during peak exercise. Patients taking amlodipine had lower respiratory rates during exercise than those not taking amlodipine. Exercise capacity, tidal volume, and cardiac index during exercise were similar between patients with and without bisoprolol or amlodipine.

Comparison of Pathological Outcome and Recurrence Rate between En Bloc Transurethral Resection of Bladder Tumor and Conventional Transurethral Resection: A Meta-Analysis.

Current treatment for non-muscle invasive bladder cancer (NMIBC) is the conventional transurethral resection of bladder tumor (CTURBT), but the en bloc transurethral resection of bladder tumor (ERBT) has been gaining more attraction in recent years considering better specimen integrity. Thus, we conducted this meta-analysis to compare the safety and efficacy of ERBT versus CTURBT. Trials were collected from an online database. The primary outcomes included identification of detrusor muscle in specimen, residual tumor, 3, 12, and 24-month recurrence rates and same-site recurrence rate. A total of 31 trials were included. The ERBT group had a higher rate of identification of detrusor muscle in specimens (p = 0.003) and lower residual tumor (p < 0.001). Other than that, lower rates of 3-month (p = 0.005) and 24-month recurrence rate (p < 0.001), same-site recurrence rate (p < 0.001) and complications were also observed. For perioperative outcomes, shorter hospitalization time (HT) (p < 0.001), and catheterization time (CT) (p < 0.001) were also revealed in the ERBT group. No significant difference was found in operative time (OT) (p = 0.93). The use of ERBT showed better pathological outcomes and fewer complications, so it could be considered a more effective treatment option for NMIBC.

Fructose milieu undermines the therapeutic effect of Tribulus terrestris extract on neuroblastoma cell line via maintaining mitochondrial function.

Fructose overconsumption promotes tumor progression. Neuroblastoma is a common extracranial tumor with about 50% 5-year survival rate in high-risk children. The anti-tumor effect of Tribulus terrestris might bring new hope to neuroblastoma therapy. However, whether fructose disturbs the therapeutic effect of T. terrestris is currently unknown. In this study, the mouse neuroblastoma cell line, Neuro 2a (N2a) cells, was used to investigate the therapeutic effects of T. terrestris extract at various dosages (0.01, 1, 100 ng/ml) in regular EMEM medium or extra added fructose (20 mM) for 24 h. 100 ng/ml T. terrestris treatment significantly reduced the cell viability, whereas the cell viabilities were enhanced at the dosages of 0.01 or 1 ng/ml T. terrestris in the fructose milieu instead. The inhibition effect of T. terrestris on N2a migration was blunted in the fructose milieu. Moreover, T. terrestris effectively suppressed mitochondrial functions, including oxygen consumption rates, the activities of electron transport enzymes, the expressions of mitochondrial respiratory enzymes, and mitochondrial membrane potential. These suppressions were reversed in the fructose group. In addition, the T. terrestris-suppressed mitofusin and the T. terrestris-enhance mitochondrial fission 1 protein were maintained at basal levels in the fructose milieu. Together, these results demonstrated that T. terrestris extract effectively suppressed the survival and migration of neuroblastoma via inhibiting mitochondrial oxidative phosphorylation and disturbing mitochondrial dynamics. Whereas, the fructose milieu blunted the therapeutic effect of T. terrestris, particularly, when the dosage is reduced.

Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis.

Non-small-cell lung cancer (NSCLC) causes significant mortality worldwide. Patients with chronic renal failure have an increased risk of developing lung cancer. NSCLC Patients with chronic renal failure undergoing hemodialysis (HD) often exhibit poor performance, and chemotherapy is generally contraindicated. Oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective treatment agents for NSCLC patients. However, the benefits and adverse effects of EGFR-TKIs in NSCLC undergoing HD are known. There are no clinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD. We reviewed all previous case reports about EGFR-TKIs in NSCLC patients undergoing HD. It is difficult to design studies about the effects of EGFR-TKIs in patients undergoing HD, and this review is quite important. EGFR-TKIs are well tolerated in patients undergoing HD. The main routes of elimination of EGFR-TKIs are metabolism via the liver, and renal elimination is minor. The recommended doses and pharmacokinetics of these EGFR-TKIs for patients undergoing HD are similar to those for patients with normal renal function. The plasma protein binding of EGFR-TKIs is very high, and it is not necessary to adjust the dose after HD. In conclusion, EGFR-TKIs are effective and well tolerated in patients undergoing HD.

Associations Between Physical Activity, Smoking Status, and Airflow Obstruction and Self-Reported COPD: A Population-Based Study.

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with an increased mortality rate in recent years, mainly caused by exposure to tobacco smoke. Regular physical activity is thought to diminish the risk of COPD exacerbation, while very few studies investigate the interaction between smoking and physical activity on COPD development. This study aims to investigate the association between smoking status, physical activity and prevalent COPD. Methods: This study analyzed data of adults 20 to 79 years old from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. Results: A total of 6404 participants aged 20-79 were included and divided into four groups by their physical activity levels and smoking status. Amongst, 2819 (43.7%) were physically active non-smokers, 957 (14.8%) were physically inactive non-smokers, 1952 (30.3%) were physically active smokers, and 717 (11.1%) were physically inactive smokers. Prevalence of airflow obstruction were 5.7%, 7.1%, 17.7% and 18.6%, respectively. After adjustment, physically active smokers (aOR=2.71, 95% CI=1.94-3.80) and physically inactive smokers (aOR=2.70, 95% CI=1.78-4.09) but not physically active non-smokers were more likely to have airflow obstruction than physically active non-smokers. These associations were similar among most subgroups by age, sex, or BMI. Among smokers, being physically inactive was not significantly associated with a greater chance for prevalent airflow obstruction than being physically active. Conclusion: Smokers, regardless of their physical activity level, are more likely to have airflow obstruction as compared with physically active non-smokers. Within smokers, being physically inactive poses no excess chance to be airflow obstructed. The findings indicate that physical activity level seem not altering the relationship between smoking and airflow obstruction.

Deep Learning-based Artificial Intelligence Improves Accuracy of Error-prone Lung Nodules.

Introduction: Early detection of lung cancer is one way to improve outcomes. Improving the detection of nodules on chest CT scans is important. Previous artificial intelligence (AI) modules show rapid advantages, which improves the performance of detecting lung nodules in some datasets. However, they have a high false-positive (FP) rate. Its effectiveness in clinical practice has not yet been fully proven. We aimed to use AI assistance in CT scans to decrease FP. Materials and methods: CT images of 60 patients were obtained. Five senior doctors who were blinded to these cases participated in this study for the detection of lung nodules. Two doctors performed manual detection and labeling of lung nodules without AI assistance. Another three doctors used AI assistance to detect and label lung nodules before manual interpretation. The AI program is based on a deep learning framework. Results: In total, 266 nodules were identified. For doctors without AI assistance, the FP was 0.617-0.650/scan and the sensitivity was 59.2-67.0%. For doctors with AI assistance, the FP was 0.067 to 0.2/scan and the sensitivity was 59.2-77.3% This AI-assisted program significantly reduced FP. The error-prone characteristics of lung nodules were central locations, ground-glass appearances, and small sizes. The AI-assisted program improved the detection of error-prone nodules. Conclusions: Detection of lung nodules is important for lung cancer treatment. When facing a large number of CT scans, error-prone nodules are a great challenge for doctors. The AI-assisted program improved the performance of detecting lung nodules, especially for error-prone nodules.

Association between secondhand smoke and peripheral arterial disease: a meta-analysis of cross-sectional studies.

PURPOSE: The association between secondhand smoke (SHS) and peripheral arterial disease (PAD) was inconsistent and the studies were relatively scarce, hence, we conducted a meta-analysis of the association between SHS and PAD. MATERIALS AND METHODS: We systematically searched three electronic databases (PubMed, EMBASE, and Web of Science), and calculated the pooled prevalence risk ratio (RR) and estimated standard error by random effect model from the meta-analysis. Furthermore, we performed a subgroup meta-analysis according to the location of SHS exposure. RESULTS: We initially identified 502 articles from the electronic database, and 6 articles, cross-sectional data from 4 cross-sectional studies and 2 prospective cohort studies, were included in the meta-analysis. Among these six articles, two studies showed a significant correlation between SHS exposure and PAD, whereas no study showed a negative correlation between SHS exposure and PAD. In the meta-analysis, pooled prevalence showed a significant association between SHS exposure and PAD (RR = 1.23; 95% confidence interval [CI] 1.08-1.41; z = 3.02, p = 0.003). In the subgroup analysis based on location of SHS exposure, the prevalence RR of PAD at home was 1.30 (95% CI 1.14-1.49, Z-3.99, p < 0.0001). The prevalence RR in the subgroup of SHS exposure at work was not significant (RR = 0.89; 95% CI 0.55-1.44; z = 0.48, p = 0.63). CONCLUSION: Exposure to SHS was significantly and positively associated with PAD. Moreover, we found a significant association between exposure to SHS and PAD at home, but the association was not significant at work.

High fructose induced osteogenic differentiation of human valve interstitial cells via activating PI3K/AKT/mitochondria signaling.

BACKGROUND: Aortic valve stenosis (AS) is a common, lethal cardiovascular disease. There is no cure except the valve replacement at last stage. Therefore, an understanding of the detail mechanism is imperative to prevent and intervene AS. Metabolic syndrome (MetS) is one of the major risk factors of AS whereas fructose overconsuming tops the list of MetS risk factors. However, whether the fructose under physiological level induces AS is currently unknown. METHODS: The human valve interstitial cells (hVICs), a crucial source to develop calcification, were co-incubated with fructose at 2 or 20 mM to mimic the serum fructose at fasting or post-fructose consumption, respectively, for 24 h. The cell proliferation was evaluated by WST-1 assays. The expressions of osteogenic and fibrotic proteins, PI3K/AKT signaling, insulin receptor substrate 1 and mitochondrial dynamic proteins were detected by Western blot analyses. The mitochondrial oxidative phosphorylation (OXPHOS) was examined by Seahorse analyzer. RESULTS: hVICs proliferation was significantly suppressed by 20 mM fructose. The expressions of alkaline phosphatase (ALP) and osteocalcin were enhanced concurrent with the upregulated PI3K p85, AKT, phospho(p)S473-AKT, and pS636-insulin receptor substrate 1 (p-IRS-1) by high fructose. Moreover, ATP production capacity and maximal respiratory capacity were enhanced in the high fructose groups. Synchronically, the expressions of mitochondrial fission 1 and optic atrophy type 1 were increased. CONCLUSIONS: These results suggested that high fructose stimulated the osteogenic differentiation of hVICs via the activation of PI3K/AKT/mitochondria signaling at the early stage. These results implied that high fructose at physiological level might have a direct, hazard effect on the progression of AS.

The BUILT study: a single-center 5-year experience of Lung Cancer screening in Taiwan.

Background: There are no uniform guidelines on low-dose computed tomography (LDCT) follow-up in lung cancer screening. Few studies have analyzed the incidental abnormalities and role of tumor markers in lung cancer screening. The purpose of this study was to investigate the diagnostic performance of LDCT, optimal follow-up duration, incidental findings, and role of tumor markers in diagnosing lung cancer. Methods: We retrospectively analyzed subjects who underwent their first LDCT in Taipei Tzu Chi Hospital between September 1, 2015, and August 31, 2016. All chest CT scans until August 31, 2020, were recorded. A non-calcified nodule with a diameter ≥2 mm on LDCT was defined as a positive result. We extracted the data, including possible risk factors of lung cancer and follow-up outcomes. Results: A total of 1502 subjects were recruited. Of the 38 subjects who underwent biopsy, 31 had confirmed lung cancer. Lung cancer in all patients was diagnosed within 4 years. Univariate logistic regression analysis revealed that a family history of lung cancer in first-degree relatives and abnormal serum carcinoembryonic antigen (CEA) levels were the significant risk factors for lung cancer. A cumulative lung cancer incidence of 54.7 patients per 1000 person-years was determined solely via radiological follow-up. In total, 271 (18%) subjects exhibited incidental findings on baseline LDCT. Conclusion: The overall lung cancer detection rate in this study was 2.1% in the 5-year study period. A family history of lung cancer and abnormal serum CEA levels are important risk factors for lung cancer. A minimum of 4-year follow-up is required to track suspicious nodules. A purely radiological follow-up detects a high incidence of lung cancer.

Meta-Analysis of the Association between Asbestos Exposure and Esophageal Cancer.

BACKGROUND: We conducted a meta-analysis to quantitatively assess the association between asbestos exposure and esophageal cancer. METHODS: We systematically collected articles from three electronic databases and calculated the pooled standardized mortality rate (SMR) from the meta-analysis. Subgroup analysis according to the type of asbestos exposure, follow-up years, sample size, industry classification, sex, and high-dose exposure was conducted. RESULTS: From 242 studies, 34 cohort studies were included in our meta-analysis. Pooled SMR was positively associated with asbestos exposure and esophageal cancer (pooled SMR = 1.28; 95% confidence interval (CI) 1.19-1.38, p < 0.00001). In the subgroup analysis, (1) chrysolite, (2) four groups with follow-up over ten years, (3) the textile industry and shipyard, (4) both male and female, and (5) eight studies on highest asbestos exposure, all the subgroups showed significantly increased pooled SMRs. CONCLUSION: Asbestos exposure was significantly and positively associated with esophageal cancer, especially chrysolite. Considering the long latency period, we suggest that patients should be followed up for cancer, including esophageal cancer, for over ten years.

Characterization Associated with the Frequent Severe Exacerbator Phenotype in COPD Patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease with exacerbations causing hospitalizations, morbidity, and mortality. COPD exacerbation causes a substantial health impact, and its subtypes might differ in prognosis and treatment response. METHODS: This study evaluated the factors of COPD exacerbations and explored the probabilities of frequent severe COPD exacerbations. Categorical and continuous variables between groups were compared. The hazard ratio (HR) and the probability of no hospital readmission were also estimated. RESULTS: A total of 617 COPD patients were enrolled and comprised the frequent exacerbator (N = 226) and the non-frequent exacerbator (N = 391) groups. The frequent exacerbator group significantly displayed a higher eosinophil count (EC; p=0.004), a higher percentage of the frequent severe acute exacerbation history before the index hospitalization (IH; p < 0.001), a lower FEV1 value (p=0.001), and a higher triple combination inhaler prior and following the IH (p < 0.001 and p=0.002) than the non-frequent exacerbator one. Increasing age (aOR of 1.02), higher EC (aOR of 1.09), and lower FEV1 value (aOR of 0.72) were significantly associated with an increased hospital readmission risk. The readmission rate and risk were higher in patients with a history of frequent severe acute exacerbation (aHR of 3.38) than those without severe acute exacerbation. Cases treated with the triple combination inhaler before the IH had a higher readmission rate and risk than non-users. CONCLUSION: Patients with EC ≥2%, FEV1 <50%, or frequent severe acute exacerbation history before the IH have a higher risk of being diagnosed with a frequent exacerbator phenotype. Besides, higher age, triple combination inhaler before the IH, and smoking might be independently correlated with the frequent readmission risk within 1-year post-exacerbation. A better comprehension of the COPD exacerbation mechanism may further identify the best course of preventative strategy and lead to novel interventions.

Nipple-sparing Mastectomy and Immediate Breast Reconstruction After Recurrence From Previous Breast Conservation Therapy.

PURPOSE: Breast conservation therapy (BCT) is widely accepted for breast cancer treatment. Nipple-sparing mastectomy has been newly developed to preserve the nipple-areolar complex and enhance aesthetic results. The purpose of this study was to evaluate the oncological safety and results of nipple-sparing mastectomy (NSM) after previous BCT. METHODS: Eighteen patients who received NSM and immediate breast reconstruction for local recurrence after BCT were identified. An additional 127 affected breasts with NSM and immediate breast reconstruction for primary breast cancer were selected as the control group. The patient disease status, reconstructive method, postoperative complications, and oncological outcome were investigated. RESULTS: No apparent significant differences between the 2 groups were found regarding patient demographic data, tumor stage, reconstructive method, surgical complication, or tumor recurrence rate (all P values >0.05), except preoperative radiotherapy was higher in secondary NSM group (0% vs 77.8%, P < 0.001). The further nipple and secondary deep inferior epigastric artery perforator flap reconstruction rate was higher in the secondary NSM group (11.1% vs 0.8%, P = 0.041 and 16.7% vs 2.4%, P = 0.026, respectively). CONCLUSIONS: Prior BCT did not contribute to higher surgical complications in patients who received NSM and immediate reconstruction as a salvage procedure after tumor local recurrence. The oncological safety, general surgical result, and postoperative patient-reported satisfaction remain safe and reliable despite prior ipsilateral surgery and radiation. Care should be taken for possible higher nipple necrosis in the secondary NSM patients.

Nrf2 activation attenuates the early suppression of mitochondrial respiration due to the α-synuclein overexpression.

BACKGROUND: α-synuclein (SNCA) accumulation in the substantia nigra is one of the characteristic pathologies of Parkinson's disease (PD). A53T missense mutations in the SNCA gene has been proved to enhance the expression of SNCA and accelerate the onset of PD. Mitochondrial dysfunction in SNCA aggregation has been under debate for decades but the causal relationship remains uncertain. At a later stage of PD, the cellular dysfunctions are complicated and multiple factors are tangled. Our aim here is to investigate the mitochondrial functional changes and clarify the main causal mechanism at earlier-stage of PD. METHODS: We used the mutant A53T SNCA-expressed neuro 2a (N2a) cells without detectable cell death to investigate: 1) whether SNCA overexpression impairs the mitochondrial respiration and biogenesis. 2) The role of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signal in SNCA-induced mitochondria dysfunction. RESULTS: Accompanying with the increment of SNCA, reactive oxygen species (ROS) accumulation was increased. The maximal respiratory capacity was suppressed. Meanwhile, mitochondrial complex 1 activity and the activity of nicotinamide adenine dinucleotide (NADH) cytochrome C reductase (NCCR) were decreased. Moreover, the mitochondrial DNA (mtDNA) copy number was decreased. On the other hand, the nuclear peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), Nrf2, and the cytosolic mitochondrial transcription factor A (TFAM) were increased at an early stage and declined thereafter. Above factors triggered by SNCA were reversed by tBHQ, a Nrf2 activator. CONCLUSION: These results suggested that at an early stage, SNCA-overexpressed increase mtROS accumulation, mitochondrial dysfunction and mtDNA decrement. Nrf2, PGC-1α and TFAM were upregulated to compromise mitochondrial dysfunction. tBHQ effectively reversed the SNCA-induced mitochondrial dysfunction.

Promoting chondrocyte cell clustering through tuning of a poly(ethylene glycol)-poly(peptide) thermosensitive hydrogel with distinctive microarchitecture.

Hydrogels are considered to be attractive cell-matrix for chondrocytes due to their similarity in properties to the natural cartilage. However, the formation of chondrocyte cell clusters in hydrogels has been mostly limited to naturally-derived or relatively fast degrading materials. In this study, a series of diblock copolymer poly(ethylene glycol)-poly(alanine) (mPEG-PA) was synthesized and investigated as injectable biomimic hydrogels for the culturing of chondrocytes. Depending on the poly(alanine) chain length, afforded hydrogels exhibited variable mechanical property and microarchitecture due to difference in secondary structure arrangement. After 21days of culture, cell clusters were observed in all hydrogels with longer PA chains and these hydrogels supported more homogenous and established clustering as well as significantly higher glycosaminoglycan and collagen deposition. Interestingly, scanning electron microscopy revealed a distinct micron range fibrillar-like microarchitecture that may be responsible for maintaining chondrocyte phenotype and matrix production. In addition, micrographs revealed the presence of collagen fibrils and an extensive extracellular matrix network. Therefore, it is reasonable to conclude that mPEG-PA hydrogels possess the desirable properties for chondrocyte cluster formation and serve as potential candidate in cartilage tissue engineering.

Reconstruction of Through-and-through Oromandibular Defect: Comparison of Four Different Techniques.

BACKGROUND: Through-and-through oromandibular defects originate from surgical intervention of tumors of the oral cavity involving external skin, soft tissue, bone, and oral lining. Reconstruction of such composite defects is primarily achieved by 4 methods using distinct flaps in Chang Gung Memorial Hospital, including a single anterolateral thigh (ALT) flap, a single fibula flap, an osteomyocutaneous peroneal artery-based combined flap, and a combination of a fibular flap and an ALT flap, also known as a double flap. METHODS: In this retrospective study, 41 patients with through-and-through oromandibular defects reconstructed in Chang Gung Memorial Hospital Linkou branch from July 2007 to June 2009 using either of the 4 flaps were evaluated. Patients were divided into 4 groups according to the choice of flap, and their surgical outcomes, immediate and late complications, and their general condition were studied. Group 1 included 12 patients reconstructed with a single ALT flap, whereas group 2 included 15 patients using fibular flaps. Group 3 included 8 patients with osteomyocutaneous peroneal artery-based combined flaps, and group 4 included 6 patients who underwent reconstruction with double flaps. RESULTS: Among all statistical results, we found that none of the differences regarding either patient demography or surgical outcomes between groups were statistically significant, except for squamous cell carcinoma staging. CONCLUSIONS: Although the results were insignificant, trends within the data could be seen that support previous notions regarding each reconstruction method. For future studies, we strongly recommend a larger sample size.

Effects of high fructose intake on the development of hypertension in the spontaneously hypertensive rats: the role of AT1R/gp91PHOX signaling in the rostral ventrolateral medulla.

Both genetic and dietary factors determine the development of hypertension. Whether dietary factor impacts the development of hereditary hypertension is unknown. Here, we evaluated the effect of daily high-fructose diet (HFD) on the development of hypertension in adolescent spontaneously hypertensive rats (SHR). Six-week-old SHR were randomly divided into two groups to receive HFD or normal diet (ND) for 3 weeks. The temporal profile of systolic blood pressure, alongside the sympathetic vasomotor activity, in the SHR-HFD showed significantly greater increases at 9-12 weeks of age compared with the age-matched SHR-ND group. Immunofluorescence was used to identify the distribution of reactive oxygen species (ROS), oxidants and antioxidants in rostral ventrolateral medulla (RVLM) where sympathetic premotor neurons reside. In RVLM of SHR-HFD, the levels of ROS accumulation and lipid peroxidation were elevated. The changes in protein expression were measured by Western blot. NADPH oxidase subunit gp91phox and angiotensin II type I receptor were up-regulated in RVLM neuron. On the other hand, the expression of extracellular superoxide dismutase was suppressed. Both molecular and hemodynamic changes in the SHR-HFD were rescued by oral pioglitazone treatment from weeks 7 to 9. Furthermore, central infusion with tempol, a ROS scavenger, effectively ameliorated ROS accumulation in RVLM and diminished the heightened pressor response and enhanced sympathetic activity in the SHR-HFD. Together, these results suggest that HFD intake at adolescent SHR may impact the development of hypertension via increasing oxidative stress in RVLM which could be effectively attenuated by pioglitazone treatment.

Brain metastasis features and association with tumor epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung.

AIM: Epidermal growth factor receptor (EGFR) mutations are frequent in pulmonary adenocarcinoma patients. The association between tumor EGFR mutation and characteristics of brain metastasis (BM) is still unclear. METHODS: We retrospectively reviewed pulmonary adenocarcinoma patients with and without BMs, and characteristics of BM to analyze the association between tumor EGFR mutation and characteristics of BM. RESULTS: Of 374 cases, 239 had EGFR mutations; 69 had BM at initial diagnosis, and 82 with BMs after treatment. All eligible patients received EGFR-tyrosine kinase inhibitors treatment. Older patients (≥70 years old) were less likely to have BMs than younger patients (25.8% vs 48%, P < 0.001). Patients with higher N stage had higher proportion of BMs (P = 0.006). Patients with exon 19 deletion were more likely to have BMs than those without EGFR mutation (48.1% vs 34.1%, P = 0.021). Patients with exon 19 deletion didn't have significantly higher chance of BMs at initial diagnosis but had higher chance to develop BM after treatment than those without EGFR mutation (35.6% vs 21.2%, P = 0.019). Patients with exon 19 deletion survived longer than those without EGFR mutation (1-year survival rate 95.8% vs 78.7%, P = 0.003). Thus, longer survival may lead to higher proportion of BM occurrence in patients with exon 19 deletion than those without EGFR mutation. CONCLUSIONS: In pulmonary adenocarcinoma, there is no significant difference in frequency of BMs at initial diagnosis between patients with EGFR mutation and wild type. However, after treatment, patients with EGFR mutations are significantly more likely to develop BM.