DNA Methylation of KLRC1 and KLRC3 in Autoimmune Thyroiditis:Perspective of Different Water Iodine Exposure

Objective This study aimed to identify differentially methylated genes(DMGs) associated with natural killer cells in patients with autoimmune thyroiditis(AIT), focusing on the influence of varying water iodine exposure levels.Methods Participants were divided into categories based on median water iodine(MWI)concentrations: iodine-fortified areas(IFA, MWI < 10 μg/L), iodine-adequate areas(IAA, 40 ≤ MWI ≤ 100μg/L), and iodine-excessive areas(IEA, MWI > 300 μg/L). A total of 176 matched AIT cases and controls were recruited and divided into 89, 40, and 47 pairs for IFA, IAA, and IEA, respectively. DMGs were identified using 850K Bead Chip analysis for 10/10 paired samples. Validation of DNA methylation and m RNA expression levels of the DMGs was conducted using Methyl Target^(TM) and QRT-PCR for 176/176paired samples.Results KLRC1, KLRC3, and SH2D1B were identified as significant DMGs. Validation revealed that KLRC1 was hypomethylated and highly expressed, whereas KLRC3 was hypermethylated and highly expressed in individuals with AIT. Furthermore, KLRC1 was hypomethylated and highly expressed in both IFA and IEA.Conclusion The DNA methylation status of KLRC1 and KLRC3 may play crucial roles in AIT pathogenesis. Additionally, DNA methylation of KLRC1 seems to be influenced by different iodine concentrations in water.

The Effect of Macronutrient Restrictions on Gut Microbiome and Biochemical Parameters of Wistar Albino Rats

Macronutrients serve as a source of energy for both gut microbiota and its host. An increase or decrease in macronutrients can either increase or decrease the composition of gut microbiota, leading to gut dysbiosis which has been implicated in many diseases state including non-communicable diseases. To achieve this, seven diets were formulated by restricting 60% of each macronutrient. These diets were fed on 42 albino rats (Wistar), divided into 7 groups of 6 rats each. Group 1 was fed on a normal laboratory chow diet (ND), group 2 received a fat-restricted diet (FRD), group 3 received a protein-restricted diet, (PFD), group 4 received a carbohydrate-restricted diet (CRD), group 5 received a protein and fat-restricted diet (PFRD), group 6 re-ceived a carbohydrate and fat-restricted diet (CFRD) and group 7 received a carbohydrate and protein-restricted diet (CPRD). Feed and water intake were given ad libitum and daily weight and food intake were recorded. The experiment went on for 4 weeks after which animals were sacrificed and intestinal content and blood were collected for analysis (gut microbial composition, glucose, insulin levels, serum lipid, and enzyme). Compared to the control group results showed a decrease in Bacteroides (40.50 - 14.00 CFU), HDL (68.20 - 40.40 mg/dl), and AST (66.62 - 64.74 U/L) in FRD. An increase in AST (66.6 - 69.43 U/L), Bifidobacterial (59.50 - 92.00 CFU) and decreased Bacteroides (40.5 - 19.5 CFU) for PRD was also recorded. CRD reduced Lactobacillus (73 - 33.5 CFU), total bacterial count (129 - 48 CFU), HDL (68.2 - 30.8 mg/dl), and cholesterol (121.44 - 88.65 mg/dl) whereas intestinal composition of E. coli (30.5 - 51.5 CFU) increased. PFRD increased Lactobacillus (73.00 - 102.5 CFU), Bifidobacterial (59.5 - 100 CFU), HDL (68.2 - 74.7 mg/dl), and Triglyceride (111.67 - 146.67 mg/dl) concentration. Meanwhile, a reduction in Bifidobacterial (59.5 - 41.5 CFU), and an increasing of AST (66.62 - 70.30 U/l) were recorded for CFRD. However, Bacteroides (40.5 69.5 CFU), LDL (30.95 - 41.98 mg/dl) increased and Bifidobacterial (59.5 - 38.00 CFU) and HDL (68.2 - 53.5 mg/dl) decreased for CPRD. This work, therefore, concludes that macronutrient restriction causes significant changes in serum marker and enzyme profile, and gut microbial composition which can cause gut dysbiosis and later on could expose the host to inflammatory diseases in the long run.

One-sided empirical Bayes test for location parameter in Gamma distribution

In this paper, we devote to constructing the one-sided empirical Bayes(EB) test for the location parameter in the Gamma distribution by nonparametric method. Under some mild conditions, we prove that the EB test is asymptotically optimal with the rate of the order O(n^(-δs/(2s+1))), where 1/2 ≤ δ < 1 and s > 1 is a given natural number. An example is also given to illustrate that the conditions of the main theorems are easily satisfied.

Analysis of inpatient payments of breast cancer patients with different medical insurance coverages in China(mainland) in 2011–2015

Objective： An understanding of the levels and trends of medical cost is made for breast cancer patients with different medical insurance coverages in China（mainland）, in an attempt to offer a clue to further control the costs.Methods： The inpatient payments of 9,716,180 breast cancer patients spent in medical institutions of different types and grades during 2011–2015 were collected from the inpatient medical record home page（IMRHP） dataset.The data were then processed with SAS（Version 9.3; SAS Institute, Cary, NC, USA）. Indicators like means,increase（decrease） percentages were used to descriptively analyze the average hospitalization expense of each time（AHEET） and its trends of breast cancer patients with different medical insurance coverages treated in medical institutions of different types and grades.Results：In 2011–2015,the AHEET borne by breast cancer patients in China had been constantly increasing.Specifically,the self-pay inpatients had the largest increase,inpatients covered by Urban Employee Basic Medical Insurance（UEBMI）and Urban Resident Basic Medical Insurance（URBMI）were the next,and those covered by New Rural Cooperative Medical System（NRCMS）had the least increase.Breast cancer inpatient treated in public hospitals had quite greater increase and higher expenditure level than those in private hospitals.The AHEET borne by the inpatients in Grade 3 hospitals had greater increase and higher cost than those in Grade 2 hospitals.Conclusions：The inpatient payments of breast cancer patients will be wisely controlled by reducing the number of self-pay inpatients,taking advantage of restriction mechanism of the medical insurances,and promoting healthy competition between private hospitals and public hospitals.The economic burden imposed on the society by breast cancer can be relieved through further control of inpatient payments of UEBMI-and URBMI-covered breast cancer patients and of Grade 3 hospitals.

How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells?

A body of evidence suggests that ethanol can lead to damage of neuronal cells. However, the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cell viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle of the SK-N-SH neuroblastoma cells. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cells. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cell death. Ethanol also increased p53 phosphorylation, followed by an increase in p21 tumor suppressor protein and a decrease in phospho-Rb （retinoblastoma） protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol mediates apoptosis of SK-N-SH neuroblastoma cells by activating p53-related cell cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cell death pathway.

Effects of wet-cupping on blood pressure in hypertensive patients:a randomized controlled trial

BACKGROUND： Although cupping remains a popular treatment modality worldwide, its efficacy for most diseases, including hypertension, has not been scientifically evaluated. OBJECTIVE： We aimed to determine the efficacy of wet-cupping for high blood pressure, and the incidence of the procedure＇s side effects in the intervention group. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This is a randomized controlled trial conducted in the General Practice Department at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, between May 2013 and February 2014. There were two groups （40 participants each）： intervention group undergoing wet-cupping （hijama） in addition to conventional hypertension treatment, and a control group undergoing only conventional hypertension treatment. Three wet-cupping sessions were performed every other day. MAIN OUTCOME MEASURE： The mean systolic and diastolic blood pressures were measured using a validated automatic sphygmomanometer. The follow-up period was 8 weeks. RESULTS： Wet-cupping provided an immediate reduction of systolic blood pressure. After 4 weeks of follow-up, the mean systolic blood pressure in the intervention group was 8.4 mmHg less than in the control group （P = 0.046）. After 8 weeks, there were no significant differences in blood pressures between the intervention and control groups. In this study, wet-cupping did not result in any serious side effects. CONCLUSION： Wet-cupping therapy is effective for reducing systolic blood pressure in hypertensive patients for up to 4 weeks, without serious side effects. Wet-cupping should be considered as a complementary hypertension treatment, and further studies are needed.

Spatio-temporal co-occurrence of hotspots of tuberculosis, poverty and air pollution in Lima, Peru

Growing evidence suggests pollution and other environmental factors have a role in the development of tuberculosis(TB),however,such studies have never been conducted in Peru.Considering the association between air pollution and specific geographic areas,our objective was to determine the spatial distribution and clustering of TB incident cases in Lima and their co-occurrence with clusters of fine particulate matter(PM2.5)and poverty.We found co-occurrences of clusters of elevated concentrations of air pollutants such as PM2.5,high poverty indexes,and high TB incidence in Lima.These findings suggest an interplay of socio-economic and environmental in driving TB incidence.