The effects of cucurbitacin E on GADD45ß-trigger G2/M arrest and JNK-independent pathway in brain cancer cells.

Cucurbitacin E (CuE), an active compound of the cucurbitacin family, possesses a variety of pharmacological functions and chemotherapy potential. Cucurbitacin E exhibits inhibitory effects in several types of cancer; however, its anticancer effects on brain cancer remain obscure and require further interpretation. In this study, efforts were initiated to inspect whether CuE can contribute to anti-proliferation in human brain malignant glioma GBM 8401 cells and glioblastoma-astrocytoma U-87-MG cells. An MTT assay measured CuE's inhibitory effect on the growth of glioblastomas (GBMs). A flow cytometry approach was used for the assessment of DNA content and cell cycle analysis. DNA damage 45ß (GADD45ß) gene expression and CDC2/cyclin-B1 disassociation were investigated by quantitative real-time PCR and Western blot analysis. Based on our results, CuE showed growth-inhibiting effects on GBM 8401 and U-87-MG cells. Moreover, GADD45ß caused the accumulation of CuE-treated G2/M-phase cells. The disassociation of the CDC2/cyclin-B1 complex demonstrated the known effects of CuE against GBM 8401 and U-87-MG cancer cells. Additionally, CuE may also exert antitumour activities in established brain cancer cells. In conclusion, CuE inhibited cell proliferation and induced mitosis delay in cancer cells, suggesting its potential applicability as an antitumour agent.

Individual and neighborhood socioeconomic status in the prediction of liver transplantation among patients with liver disease: A population-based cohort study in Taiwan.

Given the fact that >80% of liver transplantations (LTs) were living donor liver transplantation (LDLT) in Taiwan, we conducted this study to assess whether patients with lower socioeconomic status are subject to a lower chance of receiving hepatic transplantation.This was a cohort study including 197,082 liver disease patients admitted in 1997 to 2013, who were at higher risk of LT. Personal monthly income and median family income of living areas were used to indicate individual and neighborhood socioeconomic status, respectively. Cox proportional hazard model that considered death as a competing risk event was used to estimate subdistribution hazard ratio (sHR) of LT in association with socioeconomic status.Totally 2204 patients received LT during follow-up, representing a cumulative incidence of 1.12% and an incidence rate of 20.54 per 10 person-years. After adjusting for potential confounders, including age, sex, co-morbidity, location/urbanization level of residential areas, we found that patients with < median monthly income experienced significantly lower incidence of LT (aHR = 0.802, 95% confidence interval (CI) = 0.717-0.898), but those with >- median monthly income had significantly elevated incidence of LT (aHR = 1.679, 95% CI = 1.482-1.903), as compared to those who were not actively employed. Additionally, compared to areas with the lowest quartile of median family income, the highest quartile of median family income was also associated with significantly higher incidence rate of LT (aHR = 1.248, 95% CI = 1.055-1.478).Higher individual and neighborhood socioeconomic status were significantly associated with higher incidence of LT among patients with higher risk of LT.

Effect of arthrocentesis plus platelet-rich plasma and platelet-rich plasma alone in the treatment of temporomandibular joint osteoarthritis: A retrospective matched cohort study (A STROBE-compliant article).

Although the research on using platelet-rich plasma (PRP) for temporomandibular joint osteoarthritis (TMJ-OA) has advanced, no unified standards exist for determining the joint use of arthrocentesis and the injection dose and frequency of PRP. This study aimed to compare the efficacy of 2 TMJ-OA treatment approaches, arthrocentesis plus platelet-rich plasma (A+PRP) and PRP alone, and attempted to provide another potential treatment option with a single injection of 2 mL of high-concentration and high-purity PRP.This retrospective matched cohort study enrolled 208 patients who were treated for temporomandibular disorders (TMDs) in the Department of Oral and Maxillofacial Surgery of Tainan Sin-Lau Hospital between August of 2013 and January of 2016, from which 90 patients were selected for the final analysis. The predictor variables were treatment outcome indicators, including joint crepitus sounds, TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, temporomandibular joint (TMJ) arthralgia, pain when chewing most foods, and maximum assisted opening (MAO). The data were analyzed using χ tests, t tests, and multiple regression analyses.Among the 90 patients, 30 were assigned into the A+PRP group, and 60 were included in the PRP group. A matching method was used to ensure no statistically significant differences in the categorical and continuous variables between the 2 groups. After treatment, both the A+PRP and PRP groups showed improvements in TMJ-OA. The 2 treatment groups did not show statistically significant differences in the symptom improvement rates of joint crepitus sounds, reparative remodeling, and TMJ arthralgia. However, compared with PRP alone, the A+PRP treatment demonstrated superior performance in improving TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, and pain when chewing most foods.Both A+PRP and PRP treatments can effectively improve multiple symptoms of TMJ-OA. Based on the results from this study, we recommend a single injection with 2 mL of high-concentration and high-purity PRP for TMJ-OA treatment. For patients with TMJ-OA accompanied by other clinical symptoms, including TMD-associated headache, jaw range of motion <6 mm, myofascial pain with referral, and pain when chewing most foods, a treatment approach using arthrocentesis prior to a PRP injection can achieve a higher efficacy.

Demographic and Urbanization Disparities of Liver Transplantation in Taiwan.

Limited access to or receipt of liver transplantation (LT) may jeopardize survival of patients with end-stage liver diseases. Taiwan launched its National Health Insurance (NHI) program in 1995, which essentially removes financial barriers to health care. This study aims to investigate where there are still demographic and urbanization disparities of LT after 15 years of NHI program implementation. Data analyzed in this study were retrieved from Taiwan's NHI inpatient claims. A total of 3020 people aged ≥18 years received LT between 2000 and 2013. We calculated crude and adjusted prevalence rate of LT according to secular year, age, sex, and urbanization. The multiple Poisson regression model was further employed to assess the independent effects of demographics and urbanization on prevalence of LT. The biennial number of people receiving LT substantially increased from 56 in 2000-2001 to 880 in 2012-2013, representing a prevalence rate of 1.63 and 18.58 per 106, respectively. Such increasing secular trend was independent of sex. The prevalence was consistently higher in men than in women. The prevalence also increased with age in people <65 years, but dropped sharply in the elderly (≥65 years) people. We noted a significant disparity of LT in areas with different levels of urbanization. Compared to urban areas, satellite (prevalence rate ratio (PRR), 0.63, 95% confidence interval (CI), 0.57-0.69) and rural (PRR, 0.76, 95% CI, 0.69-0.83) areas were both associated with a significantly lower prevalence of LT. There are still significant demographic and urbanization disparities in LT after 15 years of NHI program implementation. Given the predominance of living donor liver transplantation in Taiwan, further studies should be conducted to investigate factors associated with having a potential living donor for LT.

Clinical efficacy of a centric relation occlusal splint and intra-articular liquid phase concentrated growth factor injection for the treatment of temporomandibular disorders.

The agony that accompanies the incidence and symptoms of temporomandibular disorders (TMDs) is an important concern in the oral and maxillofacial region. The objective of this study was to explore the clinical findings after centric relation occlusal splint (CROS) treatment and intra-articular injection treatment with liquid phase concentrated growth factors (LPCGFs) in patients with disc displacement without reduction (DDWOR).The group under investigation of this retrospective cohort study included patients with DDWOR who received treatment from April 2014 until March 2016. The predictor variable was the therapeutic method. The outcome variables included joint crepitus sound, visual analog scale (VAS) of temporomandibular joint (TMJ) arthralgia, TMD-associated headache, myofascial pain with referral, deviation of the mandible during opening (DoM), and maximal interincisal opening (MIO). At the stage of CROS treatment, evaluation of all variables adopted the individual as the unit; at the stage after LPCGF injection, the evaluation of joint sound adopted the joint as the unit, whereas the other variables adopted the individual as the unit.Among the 29 patients, 6 (20.68%) were males and 23 (79.31%) were females. Distribution by age ranged from 15 to 84 years (mean age 39.55 ±â€Š15.49 years). After CROS treatment, except for the joint crepitus sound, which failed to achieve significant improvement (P > 0.05), other symptoms, such as DOM, TMD-associated headache, myofascial pain with referral, TMJ arthralgia, and MIO, all achieved statistically significant improvements (P < 0.05). After 2 mL of LPCGF was injected once after CROS treatment, 26 joint crepitus sound symptoms were relieved (P < 0.001) after an average of 48.5 ±â€Š64.1 days.CROS alone can alleviate TMD clinical symptoms, except for the joint crepitus sound. Approximately 72.2% of joint crepitus sounds could be improved within 48 days, on average, once 2 mL of LPCGF was injected. Comparisons were still required in the future, with the effects of other therapeutic methods.

Anti-Platelet Factor 4/Heparin Antibody Plays a Significant Role in Progression of Arterial Stiffness among Hemodialysis Patients.

BACKGROUND: Arterial stiffness is a determinant of cardiovascular disease in end stage renal disease. Hemodialysis patients may develop anti-platelet factor 4/heparin antibody (PF4-H Ab) because of heparin treatment in dialysis. We tested whether PF4-H Ab was associated with progression of arterial stiffness in a 3-year follow-up. METHODS: We enrolled 74 hemodialysis patients and studied their clinical, biochemical and arterial stiffness measurement with brachial-ankle pulse wave velocity (baPWV) over 3 years. Baseline and changes in baPWV after 3 years (ΔbaPWV) were collected and compared with related clinical and biochemical parameters. PF4-H Ab was evaluated by the enzyme-linked immunosorbent assay and titer ≥ 0.4 was defined to have PF4-H Ab. RESULTS: We found a positive PF4-H Ab status in 25 of 74 patients. Mean baPWV was 16.1 ± 3.8 (m/s) at baseline and 17.6 ± 4.0 (m/s) after 3 years. Mean ΔbaPWV was 3.4 ± 2.2 (m/s) in the PF4-H Ab positive group, and 0.6 ± 1.2 (m/s) in the PF4-H Ab negative group. Baseline baPWV was only significantly associated with age (ß = 0.49, p < 0.01). ΔbaPWV was significantly different between the PF4-H Ab positive and negative groups (p < 0.01). In multivariate regression analysis, only PF4-H Ab was positively associated with ΔbaPWV (ß = 0.71, p < 0.01). CONCLUSIONS: Our study concluded that PF4-H Ab was associated with progression of arterial stiffness in hemodialysis patients.

Ursolic acid suppresses leptin-induced cell proliferation in rat vascular smooth muscle cells.

Accumulating lines of evidence indicate that high leptin levels are associated with adverse cardiovascular health in obese individuals. Proatherogenic effects of leptin include endothelial cell activation and vascular smooth muscle cell proliferation and migration. Ursolic acid (UA) has been reported to exhibit multiple biological effects including antioxidant and anti-inflammatory properties. In this study, we investigated the effect of UA on leptin-induced biological responses in rat vascular smooth muscle cells (VSMCs). A-10 VSMCs were treated with leptin in the presence or absence of UA. Intracellular reactive oxygen species (ROS) was probed by 2',7'-dichlorofluorescein diacetate. The expression of extracellular signal-regulated kinase (ERK)1/2, phospho-(ERK)1/2, nuclear factor-kappa B (NF-κB) p65 and p50, and matrix metalloproteinase-2 (MMP2) was determined by Western blotting. Immunocytochemistry and confocal laser scanning microscopy were also used for the detection of NF-κB. The secretion of MMP2 was detected by gelatin zymography. UA exhibited antioxidant activities in vitro. In rat VSMCs, UA effectively inhibited cell growth and the activity of MMP2 induced by leptin. These suppressive effects appeared by decreasing the activation of (ERK)1/2, the nuclear expression and translocation of NF-κB, and the production of ROS. UA appeared to inhibit leptin-induced atherosclerosis, which may prevent the development of obesity-induced cardiovascular diseases.

A population-based cohort study suggests an increased risk of multiple sclerosis incidence in patients with type 2 diabetes mellitus.

BACKGROUND: To prospectively investigate the incidence and relative risks of multiple sclerosis (MS) in patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: Patients with T2DM (n = 614,623) and age- and sex-matched controls (n = 614,021) were followed from 2000 to 2008 to identify cases of newly diagnosed MS (ICD-9-CM: 340). The person-year approach with Poisson assumption was used to evaluate the incidence density. We estimated the covariate-adjusted hazard ratio (HR) of MS incidence in relation to T2DM diabetes using a multiple Cox proportional hazard regression model. RESULTS: Over 9 years of follow-up, 175 T2DM patients were newly diagnosed with MS, and 114 matched controls had the same first-ever diagnosis, representing a covariate-adjusted HR of 1.44 (95% confidence interval [CI], 1.08-1.94). The sex-specific adjusted HR for both men and women with T2DM was also elevated at 1.34 (95% CI, 0.81-2.23) and 1.51 (95% CI, 1.05-2.19), respectively. Women aged ≤50 years had the greatest risk of MS (HR 2.16; 95% CI, 1.02-4.59). CONCLUSION: This study demonstrated a moderate but significant association of T2DM with MS incidence, and the association was not confounded by socio-demographic characteristics or certain MS-related co-morbidities.

The Use of Solid-Phase Concentrated Growth Factors for Surgical Defects in the Treatment of Dysplastic Lesions of the Oral Mucosa.

PURPOSE: Use of the skin graft and artificial dermis to reconstruct a defect after the excision of dysplastic lesions of the oral mucosa has been practiced for years. The purpose of this case series was to introduce a novel resolution-that is, an operating procedure using solid-phase concentrated growth factors (SPCGFs) to reconstruct oral mucosa defects-and observe the postoperative results and evaluate its clinical effects. MATERIALS AND METHODS: In this consecutive serial case study of patients with oral dysplastic lesions who underwent operations from April 2015 through July 2015, the primary endpoint of the study was to observe the clinical wound-healing profile at 1 week, 3 weeks, 3 months, and 6 months postoperatively. The secondary endpoint was to observe maximal interincisal opening (MIO) and wound pain preoperatively and at 1 and 3 days, 1 and 3 weeks, and 3 and 6 months postoperatively. The minimum follow-up was 8 months, and the longest was 1 year. RESULTS: All sites had healed with complete epithelialization after 3 weeks postoperatively. All patients had a wound-healing score no higher than 3 at 3 weeks postoperatively. The preoperative MIO was 52 ± 4.64 mm and the 6-month postoperative MIO was 49.2 ± 3.03 mm. No patient reported further pain from 3 weeks postoperatively. No recurrence of the lesion was found at or after the 6-month follow-up period. CONCLUSION: The results of this study show that the use of SPCGFs to reconstruct oral mucosa defects is feasible and practical. The efficacy of SPCGFs needs to be verified by additional studies with higher-level evidence bases in the future.

Serum ferritin is an independent factor in coronary artery stenosis among hemodialysis patients.

Hemodialysis patients frequently receive intravenous iron for the treatment of anemia. Iron status has been found to be correlated with coronary artery disease. In the post hoc study reported here, we evaluate the association between iron status and coronary arterial stenosis (CAS) in a 3-year follow-up period. We enrolled 76 patients and collected iron status, and clinical/biochemical data over 3 years. In this study, coronary arterial stenosis was considered significant when the narrowing of the coronary artery exceeded 50 % of the luminal diameter on coronary angiography. The mean age was 61 years old. The female/male ratio was 48/28, and the group included 16 diabetic patients and 23 smokers. Twenty-two of 76 patients had CAS. Mean intravenous iron dosage was 2167.11 ± 1738.38 in a 3-year period. On the univariate regression analysis, 3-year-averaged serum ferritin was positively associated with CAS (r = 0.288, P = 0.012). The 3-year-averaged intravenous iron dosage, DM, age, smoking, and other biochemical parameters showed no association with CAS. When these factors were added to the multivariate-adjusted models, 3-year-averaged serum ferritin remained a determinant of CAS event (ß = 0.290, P = 0.029). The odds ratio for CAS was 6.93 (95 % CI 2.41-19.94; P = 0.001) for patients with 3-year-averaged serum ferritin ≥600 ng/mL. In summary, serum ferritin was an independent risk factor for CAS among this group of hemodialysis patients, especially when serum ferritin was ≥600 ng/mL.

Prevalence of cardiovascular health and its relationship with job strain: a cross-sectional study in Taiwanese medical employees.

OBJECTIVES: To explore the prevalence and associated factors of cardiovascular health as defined by the AHA among different job categories in health settings. METHODS: This is a cross-sectional and hospital-based survey. A total of 1329 medical professionals with a mean age of 38 years in a regional hospital in Taiwan were recruited. Information for seven combined indicators including blood pressure, fasting sugar, blood cholesterol, body mass index, time of physical activity, dietary pattern and smoking status was obtained from the employees' health profiles and questionnaires. Degree of job strain was evaluated by the Chinese version of the Job Content Questionnaire, which was derived from Karasek's demand-control model. Three types of cardiovascular health were identified as poor, intermediate and ideal. RESULTS: Prevalence of cardiovascular health in this study's population was ideal in 0.2% of the sample, intermediate in 20.6% and poor in 79.2%. There was a significantly higher percentage of poor health in workers with high strain (85.1%), and in the professions of nurse (85.3%) and physician assistant (83.1%). In the multivariate analysis, the only significant factor correlated with job strain was physical inactivity. After being adjusted, workers with high strain exhibit a higher prevalence of physical inactivity compared to those with low strain (OR 1.9, 95% CI 1.38 to -2.81). CONCLUSIONS: Physical inactivity is the only significant factor correlated with job strain and is associated with a work situation characterised by high strain and the professions of nurse and physician assistant. Strategies for workplace health promotion should focus on employee health literacy and motivation to exercise regularly.

Reducing Trismus After Surgery and Radiotherapy in Oral Cancer Patients: Results of Alternative Operation Versus Traditional Operation.

PURPOSE: In patients with oral cancer, trismus (maximum interincisal opening [MIO] <35 mm) can develop as a result of surgery and radiotherapy. The aim of this study was to provide an alternative operation to both eradicate oral cancer and prevent postsurgical trismus. MATERIALS AND METHODS: In our retrospective cohort study of oral cancer patients who underwent operations during 2010 to 2014, the predictor variable was the type of operation (alternative operation or traditional operation) and the outcome variable was MIO. All of the cases were allocated by 2 periods: the traditional operations were performed from 2010 to 2011, and the alternative operations were performed from 2011 to 2014. All patients received marginal mandibulectomy, anterolateral thigh free flap, and adjuvant radiotherapy or concurrent chemoradiotherapy. In addition to traditional marginal mandibulectomy, the alternative operation included ipsilateral coronoidectomy and myotomy of the temporalis muscle insertion, masseter muscle, and medial pterygoid muscle. MIO was measured at 10 time points. The adjusted variables included demographic data, diagnostic parameters, treatment, and response. RESULTS: Of the 36 male patients with oral cancer, 16 were placed in the alternative operation group (AOG; mean age, 53.5 ± 11.9 years) and 20 were placed in the traditional operation group (TOG; mean age, 50.7 ± 7.1 years). Regarding the outcome indicator of patient MIO, the preoperative MIO in the AOG was on average 7.5 mm shorter than that in the TOG (P < .01), but it was consistently superior to the MIO in the TOG after the operation. Multivariate analysis of variance showed that patients in the AOG were more likely to have postoperative non-trismus. CONCLUSIONS: The alternative operation exhibited superior postoperative MIO values and similar postoperative complication rates. For the prevention of trismus, it is practical to perform the combined operation simultaneously, cutting all ipsilateral jaw closing muscles and the coronoid process and eradicating the tumor.

Hepatic angiosarcoma presenting as hepatic rupture in a patient with long-term ingestion of arsenic.

Hepatic angiosarcoma (HAS) is a rare primary mesenchymal malignancy of liver with close association to arsenic intoxication. Although the southwest coastal area of Taiwan is well known for its prevalence of arsenic intoxication from drinking well water, few cases of HAS associated with arsenic ingestion have been reported. We report a case of HAS complicated by spontaneous hepatic rupture in a 68-year-old female farmer who presented with acute onset of abdominal pain and shock. The arsenic level in her drinking water had been found to be 0.12 ppm at her childhood home and 0.005 ppm at her residence from age 21 to 68 years. The total ingested arsenic was estimated to be 1.9 g, and the latent period was about 25 years with a weighted mean exposure of 0.12 mg/day. We also reviewed data collected by the National Cancer Registry Program from 1981 to 1999 and identified 25 additional reported cases. The median age of these patients was 55 years, and the male-to-female ratio was 1.9 (17:9). Whereas no case was found during this period in the blackfoot disease (BFD) endemic area, a hyperendemic area of arsenic intoxication in Taiwan, this case demonstrates the existence of cases of HAS associated with exposure to high levels of arsenic near the BFD area in Taiwan.