Epithelial polarization in the 3D matrix requires MST3 signaling to regulate ZO-1 position.

Apical-basal cell polarity must be tightly controlled for epithelial cyst and tubule formation, and these are important functional units in various epithelial organs. Polarization is achieved through the coordination of several molecules that divide cells into an apical domain and a basolateral domain, which are separated from tight and adherens junctions. Cdc42 regulates cytoskeletal organization and the tight junction protein ZO-1 at the apical margin of epithelial cell junctions. MST kinases control organ size through the regulation of cell proliferation and cell polarity. For example, MST1 relays the Rap1 signal to induce cell polarity and adhesion of lymphocytes. Our previous study showed that MST3 was involved in E-cadherin regulation and migration in MCF7 cells. In vivo, MST3 knockout mice exhibited higher ENaC expression at the apical site of renal tubules, resulting in hypertension. However, it was not clear whether MST3 was involved in cell polarity. Here, control MDCK cells, HA-MST3 and HA-MST3 kinase-dead (HA-MST3-KD) overexpressing MDCK cells were cultured in collagen or Matrigel. We found that the cysts of HA-MST3 cells were fewer and smaller than those of control MDCK cells; ZO-1 was delayed to the apical site of cysts and in cell-cell contact in the Ca2+ switch assay. However, HA-MST3-KD cells exhibited multilumen cysts. Intensive F-actin stress fibers were observed in HA-MST3 cells with higher Cdc42 activity; in contrast, HA-MST3-KD cells had lower Cdc42 activity and weaker F-actin staining. In this study, we identified a new MST3 function in the establishment of cell polarity through Cdc42 regulation.

Estimating the incidence rate ratio of common cold among patients with non-apnea sleep disorders: a retrospective cohort study.

The purpose was to explore the potential effects of nonapnea sleep disorders (NSDs) and hypnotic use on the incidence of common cold. This study adapted population-based retrospective cohort study designed. We used the data from the Taiwan National Health Insurance Research Database between 1998 and 2011. In total, 59,476 patients with NSDs were included in the study cohort, and the reference cohort comprised 59,476 propensity score-matched patients. We conducted a Poisson regression analysis to assess the incidence of common cold. The overall incidence of common cold was significantly higher than that in the reference cohort. Compared with the patients of the reference cohort without hypnotic use, those of the NSDs cohort with benzodiazepines and zolpidem use had higher incidence of common cold. In conclusion, study cohort had a higher incidence of developing common cold, and particularly pronounced in NSDs with hypnotic use.

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. METHODS: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. RESULTS: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38). CONCLUSIONS: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

Leptin Is Associated with Poor Clinical Outcomes and Promotes Clear Cell Renal Cell Carcinoma Progression.

Emerging evidence has shown the oncogenic roles of leptin in modulating cancer progression in addition to its original roles. Analyses of transcriptomic data and patients' clinical information have revealed leptin's prognostic significance in renal cell carcinoma (RCC). However, its biological effects on RCC progression have not yet been explored. Clinical and transcriptomic data of a RCC cohort of 603 patients were retrieved from The Cancer Genome Atlas (TCGA) and analyzed to reveal the correlation of leptin with clinical outcomes and the hierarchical clustering of gene signatures based on leptin levels. In addition, cox univariate and multivariate regression analyses, cell migration upon leptin treatment, identification of putative leptin-regulated canonical pathways via ingenuity pathway analysis (IPA), and the investigation of induction of Wnt5a, ROR2, and Jun N-terminal Kinases (JNK) phosphorylation activation were performed. We first observed a correlation of high leptin levels and poor outcomes in RCC patients. Knowledge-based analysis by IPA indicated the induction of cancer cell migration by leptin, which was manifested via direct leptin treatment in the RCC cell lines. In RCC patients with high leptin levels, the planar cell polarity (PCP)/JNK signaling pathway was shown to be activated, and genes in the axis, including CTHRC1, FZD2, FZD10, ROR2, WNT2, WNT4, WNT10B, WNT5A, WNT5B, and WNT7B, were upregulated. All of these genes were associated with unfavorable clinical outcomes. WNT5A and ROR2 are pivotal upstream regulators of PCP/JNK signaling, and their correlations with leptin expression levels were displayed by a Pearson correlation analysis. The inhibition of signal transduction by SP600125 reversed leptin-mediated cell migration properties in RCC cell lines. The results indicate the prognostic impact of leptin on RCC patients and uncover its ability to promote cell migration via PCP/JNK signaling.

Positive association of Parkinson's disease with ankylosing spondylitis: a nationwide population-based study.

BACKGROUND: Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson's disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. METHODS: A population-based matched cohort study was performed using data from the 2000-2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. RESULTS: This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p < .001). Particularly, AS cohort to non-AS cohort relative risk of PD significantly increased for the patients aged below 49 and above 65 years (aHR 4.70, p < .001; aHR 1.69, p < .001, respectively) and the patients with and without comorbidities (aHR 1.61, p < .001; aHR 2.71, p < .001, respectively). Furthermore, NSAID use was associated with lower risk of PD (aHR 0.69, p < .05). However, the risk of PD was higher (aHR 2.40, p < .01) in patients with AS receiving immunosuppressants than in those not receiving (aHR 1.70, p < .001). CONCLUSIONS: Patients with AS had an increased risk of PD which might be related to underlying chronic inflammation. Further research is required to elucidate the underlying mechanism.

Effects of endogenous inflammation signals elicited by nerve growth factor, interferon-γ, and interleukin-4 on peripheral nerve regeneration.

BACKGROUND: Large gap healing is a difficult issue in the recovery of peripheral nerve injury. The present study provides in vivo trials of silicone rubber chambers filled with collagen containing IFN-γ or IL-4 to bridge a 15 mm sciatic nerve defect in rats. Fillings of NGF and normal saline were used as the positive and negative controls. Neuronal electrophysiology, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide and histology of the regenerated nerves were evaluated. RESULTS: At the end of 6 weeks, animals from the groups of NGF and IL-4 had dramatic higher rates of successful regeneration (100 and 80%) across the wide gap as compared to the groups of IFN-γ and saline controls (30 and 40%). In addition, the NGF group had significantly higher NCV and shorter latency compared to IFN-γ group (P < 0.05). The IL-4 group recruited significantly more macrophages in the nerves as compared to the saline controls and the NGF-treated animals (P < 0.05). CONCLUSIONS: The current study demonstrated that NGF and IL-4 show potential growth-promoting capability for peripheral nerve regeneration. These fillings in the bridging conduits may modulate local inflammatory conditions affecting recovery of the nerves.

Risk of aortic dissection, congestive heart failure, pneumonia and acute respiratory distress syndrome in patients with clinical vertebral fracture: a nationwide population-based cohort study in Taiwan.

OBJECTIVE: Studies on the association between clinical vertebral fractures (CVFs) and the subsequent risk of cardiopulmonary diseases, including aortic dissection (AD), congestive heart failure (CHF), pneumonia and acute respiratory distress syndrome (ARDS) are scarce. Therefore, we used the National Health Insurance Research Database to investigate whether patients with CVF have a heightened risk of subsequent AD, CHF, pneumonia and ARDS. DESIGN: The National Health Insurance Research Database was used to investigate whether patients with CVFs have an increased risk of subsequent AD, CHF, pneumonia and ARDS. PARTICIPANTS: This cohort study comprised patients aged ≥18 years with a diagnosis of CVF and were hospitalised at any point during 2000-2010 (n=1 08 935). Each CVF patient was frequency-matched to a no-CVF hospitalised patients based on age, sex, index year and comorbidities (n=1 08 935). The Cox proportional hazard regressions model was used to estimate the adjusted effect of CVF on AD, CHF, pneumonia and ARDS risk. RESULTS: The overall incidence of AD, CHF, pneumonia and ARDS was higher in the CVF group than in the no-CVF group (4.85 vs 3.99, 119.1 vs 89.6, 283.3 vs 183.5 and 9.18 vs 4.18/10 000 person-years, respectively). After adjustment for age, sex, comorbidities and Charlson comorbidity index score, patients with CVF had a 1.23-fold higher risk of AD (95% CI=1.03-1.45), 1.35-fold higher risk of CHF (95% CI=1.30-1.40), 1.57-fold higher risk of pneumonia (95% CI=1.54-1.61) and 2.21-fold higher risk of ARDS (95% CI=1.91-2.57) than did those without CVF. Patients with cervical CVF and SCI were more likely to develop pneumonia and ARDS. CONCLUSIONS: Our study demonstrates that CVFs are associated with an increased risk of subsequent cardiopulmonary diseases. Future investigations are encouraged to delineate the mechanisms underlying this association.

Increased risk of chronic fatigue syndrome following psoriasis: a nationwide population-based cohort study.

BACKGROUND: The onset of chronic fatigue syndrome (CFS) has been shown to be associated with several immunological conditions such as infections or atopy. The aim of this study was to clarify the risk of chronic fatigue syndrome following the diagnosis of psoriasis, an immune-related dermatological disease, by analyzing the National Health Insurance Research Database of Taiwan. METHOD: 2616 patients aged 20 years or older with newly diagnosed psoriasis during 2004-2008 and 10,464 participants without psoriasis were identified. Both groups were followed up until the diagnoses of CFS were made at the end of 2011. RESULTS: The relationship between psoriasis and the subsequent risk of CFS was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 2.27 and 3.58 per 1000 person-years among the non-psoriasis and psoriasis populations, respectively (adjusted hazard ratio [HR] = 1.48, with 95% confidence interval [CI] 1.07-2.06). In the stratified analysis, the psoriasis group were consistently associated with a higher risk of CFS in male sex (HR = 2.05, 95% CI 1.31-3.20) and age group of ≥ 60 years old (HR = 2.32, 95% CI 1.33-4.06). In addition, we discovered that the significantly increased risk of CFS among psoriasis patients is attenuated after they receive phototherapy and/or immunomodulatory drugs. CONCLUSIONS: The data from this population-based retrospective cohort study revealed that psoriasis is associated with an elevated risk of subsequent CFS, which is differentiated by sex and age.

Risk of Parkinson disease in Sjögren syndrome administered ineffective immunosuppressant therapies: A nationwide population-based study.

To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database.In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort.We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93).We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.

Ghrelin Upregulates Oncogenic Aurora A to Promote Renal Cell Carcinoma Invasion.

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin's role in cancer progression. We previously characterized ghrelin's prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin's activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis.

Association between intensive periodontal treatment and spontaneous intracerebral hemorrhage-a nationwide, population-based cohort study.

Periodontal disease is a chronic inflammation of periodontium and has a high prevalence. Periodontal disease has been discovered to be a possible risk factor for cerebrovascular diseases. The available evidence are not enough to set up a causal relationship between periodontal disease and cerebrovascular diseases. Patients with spontaneous intracerebral hemorrhage have high mortality rates. The present study investigated whether intensive periodontal treatment is a protective factor of spontaneous intracerebral hemorrhage and can reduce the risk of spontaneous intracerebral hemorrhage.In total, 64,960 patients with a history of periodontal disease were picked out from the National Health Insurance Research Databases as a case-cohort from January 01, 2000 to December 31, 2010. They were divided on the basis of whether periodontal disease patients received intensive surgical treatment (treatment cohort) or not (control cohort). The periodontal disease patients in treatment and control cohorts were selected by propensity score matching at a ratio of 1:1. Incidences of spontaneous intracerebral hemorrhage in both cohorts were analyzed and compared.The total hazard of spontaneous intracerebral hemorrhage was significantly decreased in the treatment cohorts compared with the control cohorts (adjusted hazard ratio = 0.60, 95% confidence interval = 0.45-0.79).Compared with the control cohort, intensive periodontal treatment may reduce the overall incidence of spontaneous intracerebral hemorrhage, particularly in elderly patients, males, and those who received more than 2 intensive treatments.

Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study.

BACKGROUND: Similarities in the symptoms of chronic fatigue syndrome (CFS) and inflammatory bowel disease (IBD) have been observed as follows: severe disease activity in IBD correlates with severe fatigue, major psychiatric signs, the common use of medication, and bacterial translocation. One of several hypotheses for explaining the mechanisms underlying CFS suggests a similarity to the impaired intestinal mucosa of IBD. "This study investigated the risk of incident CFS among patients with IBD". METHODS: We conducted a population-based retrospective cohort study by using Taiwan's National Health Insurance Research Database to evaluate the subsequent risk of CFS in patients with IBD, according to demographic characteristics and comorbidities. The exposure cohort comprised 2163 patients with new diagnoses of IBD. Each patient was randomly selected and frequency matching according to gender and age with four participants from the general population who had no history of CFS at the index date (control cohort). Cox proportional hazards regression analysis was conducted to estimate the relationship between IBD and the subsequent risk of CFS. RESULTS: The exposure cohort had a significantly higher overall risk of subsequent CFS than that of the control group [adjusted hazard ratio (Christophi in Inflamm Bowel Dis 18(12):2342-2356, 2012) = 2.25, 95%, confidence interval (Aaron and Buchwald in Ann Intern Med 134(9 Pt 2):868-881, 2001; Farraye et al. in Am J Gastroenterol 112:241, 2017) 1.70-2.99]. Further analysis indicated a significantly higher risk of CFS in patients who were male (HR = 3.23, 95% CI 2.12-4.91), were older than 35 years, and had IBD but without comorbidity status, e.g. Cancers, diabetes, obesity, depression, anxiety, sleep disorder, renal disease (HR = 2.50, 95% CI 1.63-3.84) after adjustment. CONCLUSION: The findings from this population-based retrospective cohort study suggest that IBD, especially Crohn's disease, is associated with an increased risk of subsequent CFS.

Dry eye syndrome and the subsequent risk of chronic fatigue syndrome-a prospective population-based study in Taiwan.

BACKGROUND AND AIM: The clinical association between dry eye syndrome (DES) and chronic fatigue syndrome (CFS) remain unclear with less evidences. We aimed to investigate the relationship between CFS and DES using a national insurance and prospective cohort study. METHODS: Data from the Longitudinal Health Insurance Database 2000 was applied to estimate the incidence of CFS among patients with DES, and their age- and sex-matched controls without DES over a long-term follow-up period. All participants were CFS free at baseline, before the interval (2005-2007), but were later diagnosed with CFS. DES patients and its relative matched controls were excluded prevalent CFS before the same interval. RESULTS: We identified 884 patients with DES and 3,536 matched controls in baseline and estimated the hazard ratios for incident CFS in the follow-up period. Patients with DES had a 2.08-fold considerably increasing risk of developing CFS, compared to non-DES group. An elevated risk of developing CFS remained (1.61-fold risk) even after adjusting for age, sex, and comorbidities. There was a presence of increasing risk in DES-related CFS when CFS-related comorbidities existing (adjusted hazard ratio, 1.98, 95% confidence interval, 1.19-3.29; p < 0.01). The subsequent risk for CFS between DES and non-DES patients was significant increased with three or more annual medical visits, the adjusted risk for CFS was 4.88-fold risk (95% CI, 2.26-10.58, p < 0.001). CONCLUSION: We recommended that physicians should be aware of the increased risk of CFS among DES patients and adequately assess the health impacts among these patients.

Does nephrotic syndrome without chronic kidney disease increase the risk of Parkinson's disease and secondary parkinsonism? A nationwide population-based study in Taiwan.

OBJECTIVES: Previous research has shown that patients with nephrotic syndrome (NS) have a higher risk of cognitive impairment, dementia or neurodegenerative disorder. The present study aimed to examine a relationship, if any exists between NS and Parkinson's disease (PD), a neurodegenerative disorder and secondary parkinsonism (sPS). METHODS: A nationwide retrospective observational study conducted using data from the 2000-2010 Taiwan National Health Insurance Research Database. This study included 3663 patients with NS and 14 652 randomly selected, age-matched and sex-matched patients without NS. A Cox multivariable proportional hazards model was used to evaluate the risk of PD and sPS (PDsPS) in the NS cohort. RESULTS: This study identified a positive association between NS and the risk of PDsPS in both men and women and in all age groups (adjusted HR 1.51; 95% CI 1.37 to 1.66). Compared with patients without NS and comorbidities, those with NS with two or more comorbidities exhibited an 8.23-fold higher risk of PDsPS (95% CI 6.22 to 10.9) and patients with NS and one comorbidity exhibited a 2.93-fold higher risk of PDsPS (95% CI 2.37 to 3.63). CONCLUSIONS: Patients with NS have an increased risk of PDsPS. This increased risk may be related to brain vascular damage or blood-brain barrier impairment. Further research is necessary to explore the underlying relationship between NS and PDsPS.

Leptin signaling axis specifically associates with clinical prognosis and is multifunctional in regulating cancer progression.

Leptin is a peptide hormone that has been characterized as the ligand of leptin receptor (LEPR). The observation of leptin secretion and leptin receptor expression beyond the normal tissues suggests the potentially critical roles other than its physiological function. In addition to the original function in controlling appetite and energy expenditure, leptin-mediated signaling axis through leptin receptor is multifunctional which plays role in the regulation toward broad types of cancer. Emerging evidences has indicated leptin's function in promoting several processes which are relevant to cancer progression including cell proliferation, metastasis, angiogenesis and drug resistance. We relatively display leptin and leptin receptor expression levels in pan-cancer panel based on the transcriptome analysis via dataset The Cancer Genome Atlas (TCGA), and show the clinical association of the axis in predicting cancer prognosis. The results indicate the pathological impacts of this axis on many types of cancer. This review mainly focuses on leptin-mediated effects and its downstream signaling related to the progression of cancers, and displays the clinical significance of this axis including the impact on cancer patient survival.

Increased risk of Parkinson's disease following tension-type headache: a nationwide population-based cohort study.

PURPOSE: Previous studies have suggested associations between primary headache and neurodegenerative diseases; however, the relationship between tension-type headache (TTH), which is the most common type of primary headache, and Parkinson's disease (PD) remains controversial. Hence, in this nationwide, population-based, retrospective cohort study, we explored the temporal association between TTH and PD. METHODS: Using claims data in the National Health Insurance Research Database of Taiwan, we evaluated 12,309 subjects aged ≥20 years who were newly diagnosed with TTH from 2000 to 2005. The non-TTH group included 49,236 randomly selected sex- and age-matched patients without TTH. Subjects were followed up until the end of 2011, diagnosis of PD, or death. The incidence of PD was compared between the two groups. A Cox multivariable proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to estimate the risk of PD. RESULTS: The overall incidence of PD (per 1,000 person-years) in the TTH and non-TTH groups was 3.01 and 1.68, respectively. After adjustment for sex, age, and comorbidities, the association between TTH and PD remained statistically significant (adjusted HR = 1.37, 95% CI = 1.19-1.57). The TTH group had a higher risk of PD than the non-TTH group did, regardless of subjects' sex, age, and comorbidity status. CONCLUSIONS: These findings demonstrate that patients diagnosed with TTH exhibit an increased risk of PD. Additional studies should investigate the potential shared pathophysiological mechanisms of TTH and PD. Clinicians should be aware that TTH is a potential risk factor for PD.

Increased Calcitonin Gene-Related Peptide and Macrophages Are Involved in Astragalus membranaceus-Mediated Peripheral Nerve Regeneration in Rats.

Astragalus membranaceus (AM) is one of 50 fundamental herbs in traditional Chinese medicine. Previous studies have shown that AM extract can be a potential nerve growth-promoting factor, being beneficial for the growth of peripheral nerve axons. We further investigated the effects of AM extract on regeneration in a rat sciatic nerve transection model. Rats were divided into three groups ([Formula: see text]): normal saline (intraperitoneal) as the control, and 1.5[Formula: see text]g/kg or 3.0[Formula: see text]g/kg of AM extract (every other day for four weeks), respectively. We evaluated neuronal electrophysiology, neuronal connectivity, macrophage infiltration, expression levels and location of calcitonin gene-related peptide (CGRP), and expression levels of both nerve growth factors (NGFs) and immunoregulatory factors. In the high-dose AM group, neuronal electrophysiological function (measured by nerve conductive velocity and its latency) was significantly improved ([Formula: see text]). Expression levels of CGRP and macrophage density were also drastically enhanced ([Formula: see text]). Expression levels of fibroblast growth factor (FGF), NGF, platelet-derived growth factor (PDGF), transforming growth factor-[Formula: see text], interleukin-1 (IL-1), and interferon (IFN)-[Formula: see text] were reduced in the high-dose AM group ([Formula: see text]), while FGF, NGF, PDGF, IL-1, and IFN-[Formula: see text] were increased in the low-dose AM group ([Formula: see text]). These results suggest that AM can modulate local inflammatory conditions, enhance nerve regeneration, and potentially increase recovery of a severe peripheral nerve injury.

Association between the rs1800795G>C polymorphism in the promoter of interleukin-6 gene and bladder cancer.

Interleukin-6 (IL-6) is an inflammatory cytokines that plays a role in the development of cancer. Several studies have examined the relationship between the IL-6 -174G>C polymorphism and bladder cancer, but these results are inconclusive. Therefore, we conducted a meta-analysis to explore the association between IL-6 -174G>C polymorphism and bladder cancer risk. A comprehensive literature search was performed to identify eligible studies regarding the IL-6 -174G>C polymorphism and bladder cancer. Effect sizes under fixed- and random-effects models were calculated using odds ratios (ORs) with 95% confidence intervals (CIs). Finally, five case-control studies were included in the subsequent analyses. In the fixed-effect analysis, significantly higher bladder cancer risks of 1.20 (95% CI = 1.07-1.36) and 1.30 (95% CI = 1.08-1.56) were found for the dominant model (C/C+G/C vs. G/G) and recessive model (C/C vs. G/C+G/G), respectively. Especially for the Asian population, significantly greater bladder cancer risks of 1.63 (95% CI = 1.32-2.00) and 1.54 (95% CI = 1.07-2.21) were observed for the dominant model (C/C+G/C vs. G/G) and the recessive model (C/C vs. G/C+G/G), respectively. Non-significantly increased risks of bladder cancer were observed for the dominant and recessive models under the random-effects analysis. The major findings of this meta-analysis suggest that IL-6 -174G>C polymorphism is significantly associated with bladder cancer risk in the Asian population. Further studies with a larger sample size are needed to validate the effects of IL-6 polymorphisms on bladder cancer risk.

Increased risk of peripheral arterial disease in patients with alcohol intoxication: A population-based retrospective cohort study.

Previous studies have reported that light-to-moderate drinkers have a lower risk of peripheral arterial disease (PAD) than abstainers, and that heavy drinking increases the risk of PAD. However, reports of the effects of severe alcohol drinking on PAD are lacking within a population-based cohort. Alcohol intoxication is typically considered a medical emergency at clinics in Taiwan and is commonly attributed to excessive alcohol use. The present study aimed to investigate the association between alcohol intoxication and PAD risk. We conducted a retrospective, population-based, health insurance cohort study consisting of 56,544 adult patients with alcohol intoxication between January 1, 2000 and December 31, 2009, using claims data from the National Health Insurance Research Database (NHIRD) of Taiwan. This database included a control cohort of 226,176 residents without alcohol intoxication. The patients were age- and gender-matched. The incidence rate of PAD, after data regarding alcohol intoxication were obtained, was 12.8 per 10,000 person-years, and the adjusted hazard ratio (aHR) of PAD was 3.80 (95% confidence interval [CI] = 3.35-4.32, p < 0.05). The log-rank test showed that patients with alcohol intoxication had a considerably higher PAD cumulative incidence rate than those without alcohol intoxication. Alcohol intoxication was significantly associated with an increased risk of PAD in men (hazard ratio [HR] = 3.77, 95% CI = 3.30-4.31) and women (HR = 4.26, 95% CI = 2.60-6.97). The aHRs of PAD risk were 7.64 (95% CI = 4.39-13.3), 4.51 (95% CI = 3.83-5.29), and 2.16 (95% CI = 1.69-2.77) for patients with alcohol intoxication compared to participants of the control group aged <35 years, 35-64 years, and ≥65 years, respectively. The individuals with alcohol intoxication and without any comorbidities had a 3.77-fold increased risk of PAD in comparison to that of the control cohorts (HR = 3.77, 95% CI = 3.30-4.30). The aHR of PAD in patients with alcohol intoxication was 4.53 (95% CI = 2.51-8.16) in comparison to the control cohort, which consisted of patients with at least one existing comorbidity. Alcohol intoxication, along with the severe complications of excessive alcohol use, should be considered as major risk factors of PAD in the setting of a medical emergency. Further research needs to be performed to evaluate the quantitative effect of alcohol use on PAD.

Increased risk of pyogenic liver abscess in patients with alcohol intoxication: A population-based retrospective cohort study.

We designed a population-based retrospective cohort study to investigate the association between the event of alcohol intoxication and the risk of pyogenic liver abscess. The present study enrolled 245,076 patients with a history of alcohol intoxication from 2000 to 2010 and matched each of them with four comparison patients, with similar mean age and sex ratios. We determined the cumulative incidences and adjusted hazard ratios (aHRs) of liver abscess. A significant association was observed between alcohol intoxication and liver abscess. The incidence density rate of liver abscess was 3.47-fold greater in the alcohol intoxication (AI) cohort than in the non-AI cohort (12.2 vs. 3.43 per 10,000 person-years), with an adjusted HR (aHR) of 2.64 (95% CI = 2.26 to 3.08). This population-based study positively associated the event of alcohol intoxication with increased risk of liver abscess. Our findings warrant further large-scale and in-depth investigations in this area.