MTR-G is a high-risk allele for lower-extremity arteriosclerotic occlusion.

OBJECTIVE: This study investigated the relationship between the MTRA2576G polymorphism of the key enzyme in homocysteine metabolism and deep vein thrombosis (DVT), chronic venous insufficiency (CVI) and arteriosclerotic occlusion (ASO) of the lower extremities. METHODS: Genomic DNA was extracted from the peripheral blood of patients with lower-extremity vascular diseases, including 125 cases of DVT, 125 cases of CVI and 125 cases of ASO. DNA samples extracted from 197 healthy individuals were used as control samples. PCR-RFLP was used to investigate the polymorphisms of MTR in these subjects. RESULTS: The frequency of the G allele in MTR was 6.8%, 6.1% and 12.8% for the DVT group, CVI group and ASO group, respectively (p = 0.003). The frequency of the GG allele was 13.6%, 12.2% and 22.4% for the DVT group, CVI group and ASO group, respectively (p = 0.014). Only the allele frequency of GG in the ASO group was higher than that in the control group, and the disease risk was also 1.3 times higher than that in the control group (OR = 1.299, 95% CI = 1.025 ∼ 2.575). CONCLUSION: Patients with the G allele in MTR have a high risk for ASO, and the GG allele is a risk gene for ASO.

[Pharmacogenomic Research in Direct Oral Anticoagulants].

Oral anticoagulants play an important role in the prevention and treatment of thromboembolic diseases.Warfarin,a traditional oral anticoagulant,is limited in clinical use due to its limitations such as narrow therapeutic window and requirements on frequent monitoring and dose adjustment.Direct oral anticoagulants(DOACs)such as dabigatran,rivaroxaban,apixaban,and edoxaban are increasingly used to prevent and treat venous thrombosis or thrombus formation.However,recent studies have documented inter-individual variability in plasma drug levels of DOACs.This article summarizes the recent advances in the pharmacogenomics of DOACs.

A study on the information-motivation-behavioural skills model among Chinese adults with peritoneal dialysis.

AIM AND OBJECTIVE: To examine whether the information-motivation-behavioural skills model could predict self-care behaviour among Chinese peritoneal dialysis patients. BACKGROUND: Peritoneal dialysis is a treatment performed by patients or their caregivers in their own home. It is important to implement theory-based projects to increase the self-care of patients with peritoneal dialysis. The information-motivation-behavioural model has been verified in diverse populations as a comprehensive, effective model to guide the design, implementation and evaluation of self-care programmes. DESIGN: A cross-sectional, observational study. METHODS: A total of 201 adults with peritoneal dialysis were recruited at a 3A grade hospital in China. Participant data were collected on demographics, self-care information (knowledge), social support (social motivation), self-care attitude (personal motivation), self-efficacy (behaviour skills) and self-care behaviour. We also collected data on whether the recruited patients had peritoneal dialysis-associated peritonitis from electronic medical records. Measured variable path analysis was performed using mplus 7.4 to identify the information-motivation-behavioural model. RESULTS: Self-efficacy, information and social motivation predict peritoneal dialysis self-care behaviour directly. Information and personal support affect self-care behaviour through self-efficacy, whereas peritoneal dialysis self-care behaviour has a direct effect on the prevention of peritoneal dialysis-associated peritonitis. CONCLUSIONS: The information-motivation-behavioural model is an appropriate and applicable model to explain and predict the self-care behaviour of Chinese peritoneal dialysis patients. Poor self-care behaviour among peritoneal dialysis patients results in peritoneal dialysis-associated peritonitis. RELEVANCE TO CLINICAL PRACTICE: The findings suggest that self-care education programmes for peritoneal dialysis patients should include strategies based on the information-motivation-behavioural model to enhance knowledge, motivation and behaviour skills to change or maintain self-care behaviour.

Reduced production of ethyl carbamate for wine fermentation by deleting CAR1 in Saccharomyces cerevisiae.

Ethyl carbamate (EC), a pluripotent carcinogen, is mainly formed by a spontaneous chemical reaction of ethanol with urea in wine. The arginine, one of the major amino acids in grape musts, is metabolized by arginase (encoded by CAR1) to ornithine and urea. To reduce the production of urea and EC, an arginase-deficient recombinant strain YZ22 (Δcarl/Δcarl) was constructed from a diploid wine yeast, WY1, by successive deletion of two CAR1 alleles to block the pathway of urea production. The RT-qPCR results indicated that the YZ22 almost did not express CAR1 gene and the specific arginase activity of strain YZ22 was 12.64 times lower than that of parent strain WY1. The fermentation results showed that the content of urea and EC in wine decreased by 77.89 and 73.78 %, respectively. Furthermore, EC was forming in a much lower speed with the lower urea during wine storage. Moreover, the two CAR1 allele deletion strain YZ22 was substantially equivalent to parental strain in terms of growth and fermentation characteristics. Our research also suggested that EC in wine originates mainly from urea that is produced by the arginine.

COVID-19 pandemic impact on ocular trauma in a tertiary hospital.

AIM: To analyze the impact of the coronavirus disease-2019 (COVID-19) pandemic on the presentation and characteristics of patients hospitalized for ocular trauma in a tertiary hospital in China between 2019 and 2020. METHODS: A retrospective case study was designed to collect information on all cases of ocular trauma in a tertiary hospital from 2019 to 2020 and compare differences in inpatients' data (age, sex, admission vision acuity, type of diagnosis, hospital stays, mechanism of injury and location of injury). RESULTS: The total number of patients admitted to the Ophthalmology Department was 883 (mean 73.58±11.25 patients per month) in 2019 and 714 (59.50±17.92 patients per month) in 2020. The injury number of in work was also the most within the four types of location in this two year (42.36% in 2019, 43.84% in 2020). The mean hospital stays were 12.66d in 2019 and 10.81d in 2020. The highest incidence of ocular trauma was the middle-aged (41-65y) groups in 2019 and 2020. The most common cause of ocular trauma was sharp object in 2019 (47.34%) and 2020 (47.58%). The mechanical ocular trauma reaches 98.98% in 2019 and 99.72% in 2020. CONCLUSION: The number of patients with ocular trauma decreased in 2020, but middle-aged (41-65y) are still high incident groups. Mechanical ocular trauma remains the leading cause of hospitalization for ocular trauma patients and the proportion of patients injured at home increases. It is necessary to arouse social attention and the public's awareness of eye trauma protection should be strengthened during the pandemic.

Preparation of superhydrophobic cross-linked syndiotactic 1,2-polybutadiene membranes by electrospinning.

In this study, syndiotactic 1,2-polybutadiene (s-PB)/azobisisobutyronitrile (AIBN) membranes were prepared via electrospinning. The obtained membranes were intensively investigated by contact angle analyzer, differential scanning calorimetry (DSC) and environmental scanning electron microscope (ESEM). With increasing the concentration of spinning solution, the obtained membranes were changed from hydrophobic to surperhydrophobic and the contact angle (CA) as high as 157 degrees at higher s-PB concentration. In addition, the s-PB/AIBN membrane cross-linked completely through heat treatment and superhydrophobic property of s-PB/AIBN membrane has not changed. The diameter of cross-linked fiber-based membrane was much thinner than that of the uncross-linked fibers.

Various configuration types of the foveal avascular zone with related factors in normal Chinese adults with or without myopia assessed by swept-source OCT angiography.

AIM: To describe the morphological characteristics of foveal avascular zone (FAZ) in normal Chinese adults with or without myopia by swept-source optical coherence tomography angiography (SS-OCTA) and analyze the possible associated factors. METHODS: Normal Chinese adults with or without myopia aged between 18 and 60y were recruited into the study. One eye in each individual was randomly selected for scanning using SS-OCTA. FAZ parameters, central retinal thickness (CRT) and central choroidal thickness (CCT) were then analyzed. Correlations between systemic and ocular variables and FAZ parameters were subsequently evaluated. The subgroup analysis based on refractive error was also carried out. RESULTS: In total, 127 eyes out of 127 normal subjects were finally included in the study (mean age 29.5±8.22y, 61 males and 66 females). The pattern of FAZ was variable: round configuration in 28 eyes (22%), quadrilateral configuration in 23 eyes (18%), pentagonal configuration in 20 eyes (16%), oval configuration in 15 eyes (12%), triangular configuration in 6 eyes (5%) and irregular configuration in 35 eyes (28%). The mean area of FAZ was 0.37±0.12 mm2. Females had a larger FAZ (0.41±0.11 mm2 vs 0.32±0.11 mm2) compared with that of males (P<0.01). All myopic individuals showed smaller FAZ area and perimeter compared with that of normal individuals (P<0.01). There was no obvious correlation between age and FAZ. In the univariate regression analysis, both axial length (AL) and refractive error were significantly related to FAZ parameters. However, only CRT showed negative correlation with FAZ in the multivariate regression analysis. CONCLUSION: The pattern of FAZ configuration in normal Chinese adults with or without myopia is highly variable. Establishing quantitative parameters of FAZ would not only provide details of macular pathophysiology but could possibly contribute as a biomarker in disease staging.

Circular RNA ZNF609 drives tumor progression by regulating the miR-138-5p/SIRT7 axis in melanoma.

Melanoma serves as a prevailing and lethal skin malignancy with high mortality and a growing number of patients globally. Circular RNAs (circRNAs), as a type of emerging cellular regulator, are involved in the modulation of melanoma. Nevertheless, the function of circZNF609 in melanoma development remains obscure. In this study, we were interested in the effect and the underlying mechanism of circZNF609 on DNA damage during melanoma progression. The circZNF609 depletion significantly suppressed melanoma cell invasion, migration, and proliferation, and stimulated apoptosis. Meanwhile, comet assays showed that the tail length and γH2AX levels were elevated by circZNF609 depletion. Mechanically, circZNF609 sponged miR-138-5p and miR-138-5p targeted SIRT7 in the melanoma cells. The SIRT7 overexpression and miR-138-5p inhibitor could reverse circZNF609 depletion-mediated DNA damage and malignant progression in melanoma cells. Functionally, CircZNF609 promoted cell growth of melanoma in the nude mice. Consequently, we conclude that circZNF609 suppresses DNA damage and potentially enhances melanoma progression at the experimental condition by modulating the miR-138-5p/SIRT7 axis. Our finding provides new insights into the mechanism by which circZNF609 modulates the development of melanoma. CircZNF609 and miR-138-5p may be utilized as therapeutic targets for melanoma.

[Recent advances in uveitis studies in China].

Uveitis has become an intensive study area and great achievements have been obtained during recent years. Uveitis study team in China has become one of the most productive uveitis study groups in the world. Ophthalmologists in China have addressed the clinical patterns and characteristics of uveitis in China. Studies by Chinese ophthalmologists, for the first time, revealed that IL-23/IL-17 played an important role in the pathogenesis of uveitis. Decreased frequency and function of CD4+CD25high T cells were shown to be actively involved in the development of Vogt-Koyanagi-Harada syndrome. A number of immune-related genes were found to be associated with the susceptibility to or resistance against Behcet's disease or Vogt-Koyanagi-Harada syndrome. Various molecules, such as Tim-3 and IDO protein, and Treg cells including CD4+CD25+T, CD4+PD-1+T, CD8+Foxp3+T and CD8+CD94+T were found to be involved in the development of anterior chamber associated immune deviation, an important mechanism against intraocular inflammation. These studies have greatly contributed to the understanding as well as the treatment of this disease.

The synthesis of MP-CDCA conjugates and dissolution kinetics of model cholesterol gallstones.

The comb-like copolymers of polycarboxylic acid were synthesized and then reacted with chenodeoxycholic acid (CDCA) to obtain a series of conjugates, MPn-CDCA, where n is the number of the groups of oxyethylene in each graft chain. This was confirmed by infrared spectroscopy and thin-layer chromatography. We investigated the effects of dissolving model cholesterol gallstones with the MPn-CDCA conjugates in phosphate-buffered saline at pH 7.4. The dissolution rates of CDCA, MP40-CDCA, MP30-CDCA, MP20-CDCA and MP10-CDCA were 5.33, 5.717, 17.59, 6.868 and 9.615x10(-7)kgm(-2)s(-1), micellar solubilities were 0.2431, 3.095, 12.972, 5.248 and 5.790kgm(-3) and total resistances were 5.33, 5.717, 17.59, 6.868 and 9.615x10(-7)kgm(-2)s(-1), respectively. These studies suggested that the interfacial resistance was the dominant rate-determining factor in dissolving model cholesterol gallstones. Model cholesterol gallstones could be more effectively dissolved by increasing the steric interactive potential energy of side chains and ensuring that the hydrophilic-lipophilic properties of MP-CDCA are within an appropriate range. The micellar dissolution rates of model cholesterol gallstones by MP20-CDCA were significantly faster than by the other conjugates.

The impact of fixed-dose combination versus free-equivalent combination therapies on adherence for hypertension: a meta-analysis.

Nonadherence to antihypertensive medication is considered as a reason of inadequate control of blood pressure. This meta-analysis aimed to systemically evaluate the impact of fixed-dose combination (FDC) therapy on hypertensive medication adherence compared with free-equivalent combination therapies. Articles were retrieved from MEDLINE and Embase databases using a combination of terms "fixed-dose combinations" and "adherence or compliance or persistence" and "hypertension or antihypertensive" from January 2000 to June 2017 without any language restriction. A meta-analysis was performed to parallel compare the impact of FDC vs free-equivalent combination on medicine adherence or persistence. Studies were independently reviewed by two investigators. Data from eligible studies were extracted and a meta-analysis was performed using R version 3.1.0 software. A total of nine studies scored as six of nine to eight of nine for Newcastle-Ottawa rating with 62 481 patients with hypertension were finally included for analysis. Results showed that the mean difference of medication adherence for FDC vs free-equivalent combination therapies was 14.92% (95% confidence interval, 7.38%-22.46%). Patients in FDC group were more likely to persist with their antihypertensive treatment, with a risk ratio of 1.84 (95% confidence interval, 1.00-3.39). This meta-analysis confirmed that FDC therapy, compared with free-equivalent combinations, was associated with better medication adherence or persistence for patients with hypertension. It can be reasonable for physicians, pharmacists, and policy makers to facilitate the use of FDCs for patients who need to take two or more antihypertensive drugs.

A nucleic acid biosensor for the detection of a short sequence related to the hepatitis B virus using bis(benzimidazole)cadmium(II) dinitrate as an electrochemical indicator.

A novel hybridization indicator, bis(benzimidazole)cadmium(II) dinitrate (Cd(bzim)(2)(NO(3))(2)), was utilized to develop an electrochemical DNA biosensor for the detection of a short DNA sequence related to the hepatitis B virus (HBV). The sensor relies on the immobilization and hybridization of the 21-mer single-stranded oligonucleotide from the HBV long repeat at the glassy carbon electrode (GCE). The hybridization between the probe and its complementary sequence as the target was studied by enhancement of the peak of the Cd(bzim)(2)(2+) indicator using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Numerous factors affecting the probe immobilization, target hybridization, and indicator binding reactions were optimized to maximize the sensitivity and speed of the assay time. With this approach, a sequence of the HBV could be quantified over the range from 1.49x10(-7)M to 1.06x10(-6)M, with a linear correlation of r=0.9973 and a detection limit of 8.4x10(-8)M. The Cd(bzim)(2)(2+) signal observed from the probe sequence before and after hybridization with a four-base mismatch containing sequence was lower than that observed after hybridization with a complementary sequence, showing good selectivity. These results demonstrate that the Cd(bzim)(2)(2+) indicator provides great promise for the rapid and specific measurement of the target DNA.

Shanghai Score: A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection.

BACKGROUND: For Chinese patients with hepatocellular carcinoma (HCC), surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation. METHODS: A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, γ-glutamyltransferase, α-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell's concordance index (C-index) was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis. RESULTS: Shanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients), and in the three independent validation cohorts, the CI s for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α). The identified subset of patients at low risk could be ideal candidates for curative surgery, and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery. Finally, a web server with individualized outcome prediction and treatment recommendation was constructed. CONCLUSIONS: Based on the largest cohort up to date, we established Shanghai Score - an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery. The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.

Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2 diabetes mellitus model.

AIM: To examine the expression of high mobility group box-1 (HMGB-1) and intercellular adhesion molecule-1 (ICAM-1) in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier (BRB) and blood-brain barrier (BBB) in a rat model of type 2 diabetes. METHODS: The type-2 diabetes mellitus (DM) model was established with a high-fat and high-glucose diet combined with streptozotocin (STZ). Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection (P<0.01). The serum levels of fasting insulin, Insulin resistance homeostatic model assessment (IRHOMA), total cholesterol (TC), total triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) in the DM rats significantly higher than those in the controls (all P<0.01). HMGB-1 (0.96±0.03, P<0.01) and ICAM-1 (0.76±0.12, P<0.05) levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1 (0.83±0.13, P<0.01) and ICAM-1 (1.15±0.08, P<0.01) levels in the hippocampal tissues in the DM rats were also significantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls (P<0.01). However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM rats. CONCLUSION: BRB permeability increases significantly in rats with type-2 DM, which may be associated with the up-regulated retinal expression of HMGB-1 and ICAM-1.

Clinical patterns and characteristics of uveitis in a secondary hospital in southern China.

AIM: To investigate the characteristics of uveitis in a secondary hospital in southern China. METHODS: We reviewed all records of patients with uveitis at Hengli Hospital from January 2008 to December 2011. Demographic data, past history, ophthalmic examinations and other laboratory tests were analyzed. RESULTS: One hundred and ninety-nine uveitis patients were enrolled in this study, including 134 (67.3%) males and 65 females (32.7%) with an average age of 41.0±15.1y. The anatomical distribution included 103 (51.8%) cases of anterior uveitis, followed by panuveitis (65, 32.7%), posterior uveitis (29, 14.6%) and intermediate uveitis (2, 1.0%). Of the 98 (49.2%) non-idiopathic cases, there were 10.1% Behcet's disease, 9.5% Vogt-Koyanagi-Harada (VKH) syndrome, 7.5%infectious uveitis, 7.5% traumatic uveitis and 3.5% postoperative uveitis. CONCLUSION: Idiopathic anterior and posterior uveitis, Behcet's disease, VKH syndrome, infectious uveitis and traumatic uveitis are the most common uveitis entities in a secondary hospital in southern China. Additional measures should be taken to prevent infectious and traumatic uveitis.

Neurochip based on light-addressable potentiometric sensor with wavelet transform de-noising.

Neurochip based on light-addressable potentiometric sensor (LAPS), whose sensing elements are excitable cells, can monitor electrophysiological properties of cultured neuron networks with cellular signals well analyzed. Here we report a kind of neurochip with rat pheochromocytoma (PC12) cells hybrid with LAPS and a method of de-noising signals based on wavelet transform. Cells were cultured on LAPS for several days to form networks, and we then used LAPS system to detect the extracellular potentials with signals de-noised according to decomposition in the time-frequency space. The signal was decomposed into various scales, and coefficients were processed based on the properties of each layer. At last, signal was reconstructed based on the new coefficients. The results show that after de-noising, baseline drift is removed and signal-to-noise ratio is increased. It suggests that the neurochip of PC12 cells coupled to LAPS is stable and suitable for long-term and non-invasive measurement of cell electrophysiological properties with wavelet transform, taking advantage of its time-frequency localization analysis to reduce noise.