Munkwinstead5044

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>Tp.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delAp.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.Serum osteocalcin (OCN) is closely related to metabolic risk factors, and the relationship between OCN and atherosclerosis has been investigated. However, it is still controversial. Herein, we explored the potential correlation between serum total OCN and lower extremity atherosclerotic disease (LEAD) in 326 hospitalized Chinese patients with type 2 diabetes mellitus (T2DM). PKM2 inhibitor solubility dmso Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound. Subjects with LEAD had significantly lower serum OCN levels compared with those without LEAD (14.54 [14.10-14.89] ng/mL versus 16.79 [15.86-18.04] ng/mL, p less then 0.001). Spearman's correlation analysis revealed that serum OCN levels were positively associated with high density lipoprotein cholesterol (HDL-C) and negatively associated with fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), hemoglobin A1c (HbA1c), waist-to-hip ratio (WHR) and F-IMT. Multiple logistic analysis revealed that OCN (OR 0.938, 95% confidence interval (CI 0.933-0.950, p = 0.003) and glomerular filtration rate (GFR) (OR 0.990, 95% CI 0.985-0.996, p = 0.003) were independently and inversely associated with LEAD, while age (OR 1.140, 95% CI 1.127-1.148, p less then 0.001), diabetes duration (OR 1.068, 95% CI 1.039-1.080, p less then 0.005) and uric acid (UA) (OR 1.005, 95% CI 1.002-1.007, p = 0.032) were independently and positively associated with LEAD. Additionally, multiple linear regression analysis revealed that serum OCN levels were negatively associated with F-IMT (standardized β = -0.180, p = 0.002). In Chinese patients with T2DM, serum OCN levels were independently and inversely correlated with LEAD.Diabetes mellitus (DM) is widely considered to be associated with the risk of diverse cancers; however, the association between DM and the risk of leukemia is still controversial. Thus, a detailed meta-analysis of cohort studies was conducted to elucidate this association. Eligible studies were screened through the electronic searches in PubMed, Web of Science, and Embase from their inception to August 11, 2020. Summary relative risks (RRs) and 95% confidence intervals (CIs) were computed through the random-effects model. Eighteen articles involving 10,516 leukemia cases among a total of 4,094,235 diabetic patients were included in this meta-analysis. Overall, twenty-five RRs were synthesized for type 2 diabetes mellitus (T2DM) and yielded a summary RR of 1.33 (95%CI, 1.21-1.47; p less then 0.001). For type 1 diabetes mellitus (T1DM), 7 RRs were combined, however, the pooled RR was insignificant (RR, 1.08; 95%CI, 0.87-1.34; p = 0.48). Interestingly, the summary RR for East Asia (RR, 1.83, 95%CI, 1.63-2.06) was significantly higher than that for Europe (RR, 1.11, 95%CI, 1.06-1.15), Western Asia (RR, 1.40, 95%CI, 1.25-1.54), North America (RR, 1.14, 95%CI, 1.08-1.20), and Australia (RR, 1.47, 95%CI, 1.25-1.71). Moreover, we found that patients with a shorter T2DM duration (1-5 years) had a higher risk of leukemia compared to those with a longer duration (5.1-10 years). Overall, this meta-analysis suggests there is a moderately increased risk of leukemia among T2DM patients, but not in T1DM patients. Further investigation is warranted.Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.Berberine (BBR), a kind of quaternary ammonium benzylisoquinoline alkaloids with multiple pharmacological activities, has been regarded as a promising lipid-lowering agent in the field of drug repurposing. Particularly, the chemical modification at the C-9 position of BBR can remarkably improve its lipid-lowering efficacy. In this study, thirteen novel BBR derivatives were rationally designed, synthesized, and evaluated by preliminary pharmacological tests. The results showed that most compounds exhibited more potent hypolipidemic activities when compared with BBR and simvastatin. Among these compounds, compound 2h-1 and 2h-2 exhibited better activity profiling in these four tests involving with inhibition of total cholesterol (TCHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) and the increase of high-density lipoprotein cholesterol (HDLC). Correspondingly, the BBR analogs with 9-O-cinnamic moiety probably exhibited potent lipid-lowering activity, and should be exploited as an important versatile template for the development of BBR-like lipid-lowering agents.Objectives　The main purpose of rehabilitation is to improve the activities of daily living (ADL). Although convalescent wards are required to provide intensive rehabilitation to patients to improve their ADL, they have not been verified sufficiently. With a focus on the rehabilitation time, this study investigated the association of the amount of rehabilitation with ADL using a complete enumeration survey of a hospital bed function report system.Methods　This retrospective cohort study focusing on convalescent wards nationwide was conducted using the panel data from hospital bed function reports between 2014 and 2017. We used a fixed effects regression analysis with the improvement rate of ADL as the outcome measure and the number of rehabilitation units as the exposure variable.Results　The study sample included 2,003 wards, which were identified as having convalescent care functions from the report in 2014; a total of 437 wards (317 hospitals) were analyzed. The mean annual improvement rates of ADL were 0.601, 0.613, and 0.627 points in 2014, 2015, and 2017, respectively. The mean annual numbers of rehabilitation units provided were 6.302, 6.477, and 6.642 units in 2014, 2015, and 2017, respectively. The panel data analysis showed that the improvement rate of ADL was associated with an increase in the number of rehabilitation units (coefficient for an increase of one unit 0.015, P=0.015).Conclusion　In the study of ward units using a national-level survey, a longer rehabilitation time was significantly associated with improvements in ADL.17β Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is the key enzyme in the biosynthesis of testosterone, which is an attractive therapeutic target for prostate cancer (PCa). H10, a novel curcumin analogue, was identified as a potential 17β-HSD3 inhibitor. The pharmacokinetic study of H10 in rats were performed by intraperitoneal (i.p.), intravenous (i.v.) and oral (p.o.) administration. In addition, the inhibitory effects of H10 against liver CYP3A4 were investigated in vitro using human liver microsomes (HLMs). The acute and chronic toxicological characteristics were characterized using single-dose and 30 d administration. All the mice were alive after i.p. H10 with dose of no more than 100 mg/kg which are nearly the maximum solubility in acute toxicity test. The pharmacokinetic characteristics of H10 fitted with linear dynamics model after single dose. Furthermore, H10 could bioaccumulate in testis, which was the target organ of 17β-HSD3 inhibitor. H10 distributed highest in spleen, and then in liver both after single and multiple i.p. administration. Moreover, H10 showed weak inhibition towards liver CYP3A4, and did not cause significant changes in aspartate transaminase (AST) and alanine transaminase (ALT) levels after treated with H10 for continuously 30 d. Taken together, these preclinical characteristics laid the foundation for further clinical studies of H10.Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis, the most common neoplastic disease of cattle worldwide and a serious problem for the cattle industry. Previous studies have shown the molecular prevalence of BLV and the coexistence of BLV genotype-1 and -4 in Egyptian dairy cattle; however, the molecular characteristics of BLV in Egyptian beef cattle are unknown. Therefore, we collected blood samples of 168 beef cattle from slaughterhouses in three governorates in Egypt. Based on BLV-CoCoMo-qPCR-2 targeting long terminal repeats and nested PCR targeting the env-gp51 gene, the BLV provirus infection rates were found to be 47/168 (28.0%) and 42/168 (25.0%), respectively. Phylogenetic analysis based on 501 bp of the BLV env-gp51 gene from 42 BLV isolates revealed that at least six distinctive strains (b, e, f, g, x, and z) were prevalent in cattle across the examined regions. Furthermore, phylogenetic analysis of the 420 bp sequence of the BLV env-gp51 region of the six strains against 11 known genotypes showed that the strains b, e, f, and g were clustered into genotype-1, and strains x and z were clustered into genotype-4.