Temporal variation in production performance, biochemical and oxidative stress markers, and gut microbiota in Pekin ducks during the late growth stage.

In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28-42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

Metabolomics and HS-SPME-GC-MS-based analysis of quality succession patterns and flavor characteristics changes during the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine.

This work set out to investigate how the physicochemical markers, volatiles, and metabolomic characteristics of mixed fermented the fermentation of Lycium barbarum and Polygonatum cyrtonema compound wine (LPCW) from S. cerevisine RW and D. hansenii AS2.45 changed over the course of fermentation. HS-SPME-GC-MS combined with non-targeted metabolomics was used to follow up and monitor the fermentation process of LPCW. In total, 43 volatile chemical substances, mostly alcohols, esters, acids, carbonyl compounds, etc., were discovered in LPCW. After 30 days of fermentation, phenylethyl alcohol had increased to 3045.83 g/mL, giving off a rose-like fresh scent. The biosynthesis of valine, leucine, and isoleucine as well as the metabolism of alanine, aspartic acid, and glutamic acid were the major routes that led to the identification of 1385 non-volatile components in total. This study offers a theoretical foundation for industrial development and advances our knowledge of the fundamental mechanism underlying flavor generation during LPCW fermentation.

Phylogenetic analysis reveals multiple origins of Chinese gamecocks.

Cockfighting is popular worldwide, dating back to 2,800 BC. Primarily, 5 modern Chinese gamecock breeds exist, located in the northeast (Luxi and Henan), west (Turpan), south (Xishuangbanna), and southeast (Zhangzhou) of China. However, whether Chinese gamecocks were derived from a single origin or multiple origins remains controversial. Therefore, this study used next-generation resequencing data to elucidate the origin of Chinese gamecocks by constructing genome-wide and SRY-box transcription factor 5 (SOX5) gene phylogenetic trees. Data from 161 chickens from 27 breeds, including 9 gamecock breeds, were included. Before constructing the SOX5 gene tree, we validated that the pea-comb phenotype mutation in all gamecock breeds was attributed to copy number variation in intron 1 of the SOX5 gene, as previously reported. The specific region was chr1: 65,838,000 to 65,846,000. The phylogenetic tree results suggested that Zhangzhou and Xishuangbanna gamecocks have a monophyletic origin, while Luxi, Henan, and Turpan gamecocks have a common ancestor. Our study provides genome-wide evidence that Chinese gamecocks have multiple origins and advances the understanding of the genetic mechanisms of the pea-comb characteristic.

Prevalence and risk factors for colonisation and infection with carbapenem-resistant Enterobacterales in intensive care units: A prospective multicentre study.

OBJECTIVES: This study aimed to investigate the prevalence and risk factors for carbapenem-resistant Enterobacterales colonisation/infection at admission and acquisition among patients admitted to the intensive care unit. RESEARCH METHODOLOGY/DESIGN: A prospective and multicentre study. SETTING: This study was conducted in 24 intensive care units in Anhui, China. MAIN OUTCOME MEASURES: Demographic and clinical data were collected, and rectal carbapenem-resistant Enterobacterales colonisation was detected by active screening. Multivariate logistic regression models were used to analyse factors associated with colonisation/infection with carbapenem-resistant Enterobacterales at admission and acquisition during the intensive care unit stay. RESULTS: There were 1133 intensive care unit patients included in this study. In total, 5.9% of patients with carbapenem-resistant Enterobacterales colonisation/infection at admission, and of which 56.7% were colonisations. Besides, 8.5% of patients acquired carbapenem-resistant Enterobacterales colonisation/infection during the intensive care stay, and of which 67.6% were colonisations. At admission, transfer from another hospital, admission to an intensive care unit within one year, colonisation/infection/epidemiological link with carbapenem-resistant Enterobacterales within one year, and exposure to any antibiotics within three months were risk factors for colonisation/infection with carbapenem-resistant Enterobacterales. During the intensive care stay, renal disease, an epidemiological link with carbapenem-resistant Enterobacterales, exposure to carbapenems and beta-lactams/beta-lactamase inhibitors, and intensive care stay of three weeks or longer were associated with acquisition. CONCLUSION: The prevalence of colonisation/infection with carbapenem-resistant Enterobacterales in intensive care units is of great concern and should be monitored systematically. Particularly for the 8.5% prevalence of carbapenem-resistant Enterobacterales acquisition during the intensive care stay needs enhanced infection prevention and control measures in these setting. Surveillance of colonisation/infection with carbapenem-resistant Enterobacterales at admission and during the patient's stay represents an early identification tool to prevent further transmission of carbapenem-resistant Enterobacterales. IMPLICATIONS FOR CLINICAL PRACTICE: Carbapenem-resistant Enterobacterales colonization screening at admission and during the patient's stay is an important tool to control carbapenem-resistant Enterobacterales spread in intensive care units.

Exploring the effects of the fermentation method on the quality of Lycium barbarum and Polygonatum cyrtonema compound wine based on LC-MS metabolomics.

This study aimed to examine the effect of fermentation methods on the quality of Lycium barbarum and Polygonatum cyrtonema compound wine (LPW) by combining non-targeted metabolomic approaches with chemometrics and path profiling to determine the chemical and metabolic properties of LPW. The results demonstrated that SRA had higher leaching rates of total phenols and flavonoids, reaching 4.20 ± 0.10 v/v ethanol concentration. According to LC-MS non-targeting genomics, the metabolic profiles of LPW prepared by different mixtures of fermentation methods (Saccharomyces cerevisiae RW; Debaryomyces hansenii AS2.45) of yeast differed significantly. Amino acids, phenylpropanoids, flavonols, etc., were identified as the differential metabolites between different comparison groups. The pathways of tyrosine metabolism, biosynthesis of phenylpropanoids, and metabolism of 2-oxocarboxylic acids enriched 17 distinct metabolites. SRA stimulated the production of tyrosine and imparted a distinctive saucy aroma to the wine samples, providing a novel research concept for the microbial fermentation-based production of tyrosine.

Extensive intra- and inter-genetic admixture of Chinese gamecock and other indigenous chicken breeds revealed by genomic data.

Genomic admixture is a widespread phenomenon among domestic animal breeds, including chickens. However, reports on admixture within Chinese gamecocks or other indigenous chickens are limited. This study focuses on the population genetic structure and admixture of 5 Chinese gamecock breeds and the admixture with 9 other indigenous Chinese chicken breeds. Our results showed that Turpan and Henan gamecocks were grouped into one cluster, whereas Luxi, Zhangzhou, and Xishuangbanna gamecocks were grouped into the other cluster. Gene flow occurred between Xishuangbanna and Turpan and Turpan and Luxi gamecocks. Simultaneously, gene flow was observed between gamecocks and indigenous chickens, such as Xishuangbanna and Wenchang. Ancestral component analysis indicated that modern domestic chickens in southern China played an important role in the history of the domestication of modern Chinese gamecock. Our study will be helpful in better understanding the domestication and evolution of Chinese gamecock.

Systematic Selection Signature Analysis of Chinese Gamecocks Based on Genomic and Transcriptomic Data.

Selection pressures driven by natural causes or human interference are key factors causing genome variants and signatures of selection in specific regions of the genome. Gamecocks were bred for cockfighting, presenting pea-combs, larger body sizes, stronger limbs, and higher levels of aggression than other chickens. In this study, we aimed to explore the genomic differences between Chinese gamecocks and commercial, indigenous, foreign, and cultivated breeds by detecting the regions or sites under natural or artificial selection using genome-wide association studies (GWAS), genome-wide selective sweeps based on the genetic differentiation index (FST), and transcriptome analyses. Ten genes were identified using GWAS and FST: gga-mir-6608-1, SOX5, DGKB, ISPD, IGF2BP1, AGMO, MEOX2, GIP, DLG5, and KCNMA1. The ten candidate genes were mainly associated with muscle and skeletal development, glucose metabolism, and the pea-comb phenotype. Enrichment analysis results showed that the differentially expressed genes between the Luxi (LX) gamecock and Rhode Island Red (RIR) chicken were mainly related to muscle development and neuroactive-related pathways. This study will help to understand the genetic basis and evolution of Chinese gamecocks and support the further use of gamecocks as an excellent breeding material from a genetic perspective.

Metatranscriptomic insights into the microbial electrosynthesis of acetate by Fe2+/Ni2+ addition.

As important components of enzymes and coenzymes involved in energy transfer and Wood-Ljungdahl (WL) pathways, Fe2+ and Ni2+ supplementation may promote the acetate synthesis through CO2 reduction by the microbial electrosynthesis (MES). However, the effect of Fe2+ and Ni2+ addition on acetate production in MES and corresponding microbial mechanisms have not been fully studied. Therefore, this study investigated the effect of Fe2+ and Ni2+ addition on acetate production in MES, and explored the underlying microbial mechanism from the metatranscriptomic perspective. Both Fe2+ and Ni2+ addition enhanced acetate production of the MES, which was 76.9% and 110.9% higher than that of control, respectively. Little effect on phylum level and small changes in genus-level microbial composition was caused by Fe2+ and Ni2+ addition. Gene expression of 'Energy metabolism', especially in 'Carbon fixation pathways in prokaryotes' was up-regulated by Fe2+ and Ni2+ addition. Hydrogenase was found as an important energy transfer mediator for CO2 reduction and acetate synthesis. Fe2+ addition and Ni2+ addition respectively enhanced the expression of methyl branch and carboxyl branch of the WL pathway, and thus promoted acetate production. The study provided a metatranscriptomic insight into the effect of Fe2+ and Ni2+ on acetate production by CO2 reduction in MES.

Effect of fermentation methods on the quality and in vitro antioxidant properties of Lycium barbarum and Polygonatum cyrtonema compound wine.

Lycium barbarum and Polygonatum cyrtonema are known for their medicinal, edible, and ornamental properties. The sensory indices of the novel high-quality L. barbarum and P. cyrtonema compound wine (LPCW) fermented by Saccharomyces cerevisiae RW and Debaryomyces hansenii AS2.45 under different inoculation methods were analyzed. The alcohol content of the LPCW ranged from 3.88 to 4.75 % under three mixed inoculations. The total saponin and total polysaccharide contents in LPCW inoculated with D. hansenii first and S. cerevisiae after 24 h were 4.39 mg/mL and 0.21 mg/mL, respectively. Ethyl butyrate, citronellol, and 3-(methylthio) propanol were unique metabolites of D. hansenii. 4-Methoxybenzoic acid was the core product of brewing of by S. cerevisiae. Except for wine inoculated with S. cerevisiae only, the acceptability scores of all the LPCW samples were higher than 7.3. Our data provided the foundation for the development and application of medicinal and food homologous substances in food fermentation.

Genetic polymorphism of clopidogrel metabolism related gene CYP2C19 gene in Chinese from Foshan area of Guangdong Province.

BACKGROUND: The CYP2C19 gene is highly polymorphic, and CYP2C19 is involved in the broad interindividual variability of the clinical efficacy of certain clinical medications, such as clopidogrel. However, data on the CYP2C19 genotype in the Chinese population of the Foshan area of Guangdong Province are scarce. The purpose of this study was to determine CYP2C19 genetic polymorphisms in patients in the Foshan area and to compare the CYP2C19 genotype frequencies in different populations to determine the allele distribution pattern to identify the most appropriate prescription. METHODS: The CYP2C19 gene was detected in 1231 patients on a gene chip platform, and the genotype frequencies of CYP2C19 in Foshan populations from different populations were compared. RESULTS: The frequencies of CYP2C19*1, *2 and *3 in the Foshan population were 63.89%, 30.46% and 5.65%, respectively. For the three metabolic types, the frequency associated with the rapid metabolism type (*1/*1) was 41.51 [95% confidence interval (CI) 40.11 to 42.91%]; that for the intermediate metabolism type (*1/*2, *1/*3) was 44.76% (95% CI 43.34 to 46.18) and that for the slow metabolism type (*2/*2, *2/*3, *3/*3) was 13.73% (95% CI 12.75 to 14.71%). In the Foshan population, the frequencies of the CYP2C19 *2 and *3 alleles were similar to those previously reported for Chinese and other Asian populations. CONCLUSION: Our study is a report on the genetic basis of CYP2C19 polymorphism in the Foshan population. Our results will potentially contribute to the improvement of pharmacotherapy effectiveness by providing personalized medicine for the Foshan population.

Unraveling the Phase Stability and Physical Property of Modulated Martensite in Ni2Mn1.5In0.5 Alloys by First-Principles Calculations.

Large magnetic field-induced strains can be achieved in modulated martensite for Ni-Mn-In alloys; however, the metastability of the modulated martensite imposes serious constraints on the ability of these alloys to serve as promising sensor and actuator materials. The phase stability, magnetic properties, and electronic structure of the modulated martensite in the Ni2Mn1.5In0.5 alloy are systematically investigated. Results show that the 6M and 5M martensites are metastable and will eventually transform to the NM martensite with the lowest total energy in the Ni2Mn1.5In0.5 alloy. The physical properties of the incommensurate 7M modulated martensite (7M-IC) and nanotwinned 7M martensite (7M-(52¯)2) are also calculated. The austenite (A) and 7M-(52¯)2 phases are ferromagnetic (FM), whereas the 5M, 6M, and NM martensites are ferrimagnetic (FIM), and the FM coexists with the FIM state in the 7M-IC martensite. The calculated electronic structure demonstrates that the splitting of Jahn-Teller effect and the strong Ni-Mn bonding interaction lead to the enhancement of structural stability.

Interaction between Gelatin and Mulberry Leaf Polysaccharides in Miscible System: Physicochemical Characteristics and Rheological Behavior.

In this study, the miscible system was formed by mixing gelatin (G) with mulberry leaf polysaccharides (MLPs) continuously extracted with a hot buffer (HBSS), a chelating agent (CHSS), a dilute alkali (DASS), and a concentrated alkali (CASS), and the zeta potential, turbidity, particle size, distribution, and rheological properties of the miscible systems were evaluated. Under acidic conditions, the miscible systems of four polysaccharides and gelatin were in a clear state; under alkaline conditions, G-HBSS and G-CHSS were clarified, and G-DASS and G-CASS changed from clarification to turbidity. The zeta potential changed from positive to negative with the increase in pH. When the pH was at 7, it increased with the increase in polysaccharide concentration but was still negative. The four miscible systems all showed polydispersity. The particle sizes of G-HBSS and G-CHSS decreased with the increase in pH, while the particle sizes of G-DASS and G-CASS were increased. The four miscible systems showed "shear thinning" behavior, and the addition of gelatin reduced the apparent viscosity of the four polysaccharide solutions. G-CHSS was highly stable, and G-CASS was more suitable as a stabilizer in the freezing process.

Effect of drug combination on tacrolimus target dose in renal transplant patients with different CYP3A5 genotypes.

Various factors, including genetic polymorphisms, drug-drug interactions, and patient characteristics influence the blood concentrations of tacrolimus in renal transplant patients. In the present study, we established a population pharmacokinetic model to explore the effect of combined use of Wuzhi capsules/echinocandins and the patients' biochemical parameters such as haematocrit on blood concentrations and target doses of tacrolimus in renal transplant patients with different CYP3A5 genotypes. The aim of the study was to propose an individualised tacrolimus administration regimen for early renal transplant recipients.In this retrospective cohort study, we included 240 renal transplant recipients within 21 days of surgery (174 males and 66 females, mean age 39.4 years), who received tacrolimus alone (n = 54), in combination with Wuzhi capsules (99) or caspofungin (57) or micafungin (30). We collected demographic characteristics, clinical indicators, CYP3A5 genotypes, and 1950 steady-state concentrations of tacrolimus and included them in population pharmacokinetic model. An additional 110 renal transplant recipients and 625 steady-state concentrations of tacrolimus were included for external validation of the model. The population pharmacokinetic model was established and Monte Carlo was used to simulate probabilities for achieving the target concentration for individual tacrolimus administration.A two-compartment model of first-order absorption and elimination was developed to describe the population pharmacokinetics of tacrolimus. CYP3A5 genotypes and co-administration of Wuzhi capsules, as well as time after renal transplantation and haematocrit, were important factors affecting the clearance of tacrolimus. We found no obvious change in trend in the scatter plot of tacrolimus clearance rate vs. haematocrit. The Monte Carlo simulation indicated the following recommended doses of tacrolimus alone: 0.14 mg⋅kg-1⋅d-1 for genotype CYP3A5*1*1, 0.12 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.10 mg⋅kg-1⋅d-1 for CYP3A5*3*3. For patients receiving the combination with Wuzhi capsules, the recommended doses of tacrolimus were 0.10 mg⋅kg-1⋅d-1 for CYP3A5*1*1, 0.08 mg⋅kg-1⋅d-1 for CYP3A5*1*3, and 0.06 mg⋅kg-1⋅d-1 for CYP3A5*3*3 genotypes. Caspofungin or micafungin had no effect on the clearance of tacrolimus in renal transplant recipients.The population pharmacokinetics of tacrolimus in renal transplant patients was evaluated and the individual administration regimen of tacrolimus was simulated. For early kidney transplant recipients receiving tacrolimus treatment, not only body weight, but also CYP3A5 genotypes and drugs used in combination should be considered when determining the target dose of tacrolimus.

GOLPH3/CKAP4 promotes metastasis and tumorigenicity by enhancing the secretion of exosomal WNT3A in non-small-cell lung cancer.

Cancer metastasis is the main cause of mortality associated with non-small-cell lung cancer (NSCLC), accounting for up to 70% of deaths among patients. The mechanisms underlying distal metastasis remain largely unknown. Golgi phosphoprotein 3 (GOLPH3) correlates negatively with overall survival in multiple tumors. In this study, we evaluated the function of GOLPH3 in NSCLC distal metastasis. GOLPH3 was expressed at high levels in samples from patients with NSCLC and was positively associated with clinicopathologic characteristics including clinical stage (P < 0.001), T (P = 0.001), N (P = 0.007), and M (P = 0.001) classification. Functionally, Transwell and wound-healing assays suggested that GOLPH3 overexpression enhances NSCLC cell migration and invasion abilities. Tumor-sphere formation and flow cytometry assays demonstrated that GOLPH3 overexpression enhances a stem cell-like phenotype of NSCLC cells. Metastasis models established by tail vein and intracardiac injection confirmed the pro-metastatic function of GOLPH3 in vivo. A subcutaneous tumor formation model confirmed that GOLPH3 overexpression increased the tumorigenicity of NSCLC cells. Mechanistically, gene set enrichment analysis revealed a positive association of GOLPH3 mRNA expression with WNT-activated gene signatures. Luciferase-reporter and nuclear extract assays showed that GOLPH3 overexpression enhances metastasis and tumorigenicity through activation of the WNT/ß-catenin pathway. Immunoprecipitation-mass spectrometry and gene ontology analysis demonstrated that GOLPH3 interacts with cytoskeleton-associated protein 4 (CKAP4) in exosome-mediated distal metastasis. We found that GOLPH3 decreased the amount of plasma membrane-localized CKAP4 and increased the amount of exosome-localized CKAP4 to promote the formation of CKAP4-containing exosomes. Furthermore, we demonstrated that CKAP4 binds exosomal WNT3A to enhance its secretion. Therefore, the GOLPH3/CKAP4 axis plays a crucial role in promoting exosomal-WNT3A secretion to enhance and maintain the stem-like phenotype and metastasis in NSCLC, thus indicating the therapeutic potential of GOLPH3 in patients with NSCLC metastasis.

Identification of candidate genomic regions for chicken egg number traits based on genome-wide association study.

BACKGROUND: Since the domestication of chicken, various breeds have been developed for food production, entertainment, and so on. Compared to indigenous chicken breeds which generally do not show elite production performance, commercial breeds or lines are selected intensely for meat or egg production. In the present study, in order to understand the molecular mechanisms underlying the dramatic differences of egg number between commercial egg-type chickens and indigenous chickens, we performed a genome-wide association study (GWAS) in a mixed linear model. RESULTS: We obtained 148 single nucleotide polymorphisms (SNPs) associated with egg number traits (57 significantly, 91 suggestively). Among them, 4 SNPs overlapped with previously reported quantitative trait loci (QTL), including 2 for egg production and 2 for reproductive traits. Furthermore, we identified 32 candidate genes based on the function of the screened genes. These genes were found to be mainly involved in regulating hormones, playing a role in the formation, growth, and development of follicles, and in the development of the reproductive system. Some genes such as NELL2 (neural EGFL like 2), KITLG (KIT ligand), GHRHR (Growth hormone releasing hormone receptor), NCOA1 (Nuclear receptor coactivator 1), ITPR1 (inositol 1, 4, 5-trisphosphate receptor type 1), GAMT (guanidinoacetate N-methyltransferase), and CAMK4 (calcium/calmodulin-dependent protein kinase IV) deserve our attention and further study since they have been reported to be closely related to egg production, egg number and reproductive traits. In addition, the most significant genomic region obtained in this study was located at 48.61-48.84 Mb on GGA5. In this region, we have repeatedly identified four genes, in which YY1 (YY1 transcription factor) and WDR25 (WD repeat domain 25) have been shown to be related to oocytes and reproductive tissues, respectively, which implies that this region may be a candidate region underlying egg number traits. CONCLUSION: Our study utilized the genomic information from various chicken breeds or populations differed in the average annual egg number to understand the molecular genetic mechanisms involved in egg number traits. We identified a series of SNPs, candidate genes, or genomic regions that associated with egg number, which could help us in developing the egg production trait in chickens.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients.

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients. Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD. Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 µmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 µmol/L) (P=0.491). Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.

The Genetic Architecture of the Chickens Dropping Moisture by Genetic Parameter Estimation and Genome-Wide Association.

Dropping moisture (DM) refers to the water content of feces. High DM in chickens could be disadvantageous to pathogen control and fecal treatment in chicken farms. DM can be affected by environment, nutrition, disease, and genetics. In the present study, significant individual differences were presented in the DM of Rhode Island Red (RIR) chicken population, indicating that genetics could contribute to DM in the chickens. Subsequently, we estimated the genetic parameters of DM and conducted a genome-wide association study (GWAS) to find the potential genomic regions related to DM. The results showed that the heritability of DM ranged from 0.25 to 0.32. Furthermore, 11 significant loci on chromosome 7 were found to be associated with DM levels by the GWAS. The SNP rs15833816 within the COL6A3 gene was the most significant SNP related to DM. Hens carrying the G allele including GA and GG produced higher DM (P < 0.01) levels than those carrying the other genotype AA. Our results showed that DM is a medium-inheritable trait and that COL6A3 could be a potential candidate gene that regulates DM level in chickens.

Challenge of parents caring for children or adolescents with early-stage schizophrenia in China: A qualitative study.

PURPOSE: To explore the challenges of parents caring for early-stage schizophrenia (ESS) children/adolescents in China. DESIGN AND METHODS: Thirteen parents of ESS subjects completed semi-structured interviews. Thematic analysis was used to analyze data. FINDINGS: Seven themes emerged from the data: psychological shock and emotional burden; lack of disease knowledge and care skill; poor treatment compliance of the patient; difficulty getting along with the patient; conflict within the family or in the workplace; financial burden; and need sufficient social support. Each challenge was produced and influenced under the Chinese special social context. PRACTICE IMPLICATIONS: Professional support was needed to help patients with schizophrenia to cope with their situation promptly. Education initiatives should focus on mental health to prevent discrimination from society and enable people to recognize the early symptoms of schizophrenia in children. Telemedicine should be explored for application in the treatment of mental illness. Also, a broader nationwide healthcare policy would be needed to help to reduce the individual and societal financial burdens associated with schizophrenia.

Does Routine Anti-Osteoporosis Medication Lower the Risk of Fractures in Male Subjects? An Updated Systematic Review With Meta-Analysis of Clinical Trials.

Background: Several epidemiological articles have reported the correlations between anti-osteoporosis medication and the risks of fractures in male and female subjects, but the specific efficacy of anti-osteoporosis medication for male subjects remains largely unexplored. Objective: The aim of this study was to evaluate the correlation between anti-osteoporosis medication and the risk of fracture in relation to low bone mass [including outcomes of osteoporosis, fracture, and bone mineral density (BMD) loss] in male subjects analyzed in studies within the updated literature. Methods: Randomized controlled trials (RCTs) that analyzed the effectiveness of a treating prescription for male subjects with osteoporosis (or low BMD) and that focused on the outcomes of fracture were included. Relevant studies from Embase, Web of Science, PubMed, and Chinese database of CNKI were retrieved from inception to January 30th, 2019. Two staff members carried out the eligibility assessment and data extraction. The discrepancies were settled by consultation with another researcher. We calculated the pooled relative risks (RRs) based on 95% confidence intervals (CIs). Results: Twenty-seven documents (28 studies) with 5,678 subjects were identified. For the category of bisphosphonates, significant results were observed in pooled analyses for decreased risk of the vertebral fracture domain (RR, 0.44 [95% CI, 0.31-0.62]), nonvertebral fracture domain (RR, 0.63 [95% CI, 0.46-0.87]), and clinical fracture domain (RR, 0.59 [95% CI, 0.48-0.72]) compared with those of controls. Participants with bisphosphonates had a 56% (95% CI = 38-69%) lower risk of vertebral fractures, 37% (95% CI = 13-54%) lower risk of nonvertebral fractures, and 41% (95% CI = 28-52%) lower risk of clinical fractures. Furthermore, meta-analyses also demonstrated a decreased risk of the vertebral fracture domain via treatment with risedronate (RR, 0.45 [95% CI, 0.28-0.72]) and alendronate (RR, 0.41 [95% CI, 0.23-0.74]), but not with calcitriol, calcitonin, denosumab, ibandronate, monofluorophosphate, strontium ranelate, teriparatide, or zoledronic acid, compared with that of controls. Conclusions: This systematic review confirms that bisphosphonates were connected with a decreased risk of vertebral fractures, nonvertebral fractures, and clinical fractures for male subjects with osteoporosis. Future research is needed to further elucidate the role of nonbisphosphonates in treating fractures of osteoporosis subjects.

Pharmacogenetics of statins treatment: Efficacy and safety.

WHAT IS KNOWN AND OBJECTIVE: Statins are widely used worldwide in the prevention and treatment of coronary atherosclerotic heart disease and ischaemic stroke. However, in clinical application, statins have shown great individual differences in terms of the efficacy and safety, some of which are related to genetic factors. The purpose of this article was to summarize the recent advances about the correlation between gene polymorphisms and the efficacy/safety of statins. METHODS: We searched the databases including PharmGKB and PubMed (published before June 2019) using the keywords such as 'statin', 'gene polymorphism' and 'SNP' and obtained more than 100 articles. In this review, we described the clinical studies of genetic variants associated with both the efficacy and adverse reactions of statins. We also clarified the importance of taking pharmacogenetic variation into account to improve the clinical application of statins. RESULTS AND DISCUSSION: The available data were collected and analysed to present the polymorphisms of candidate genes encoding the most promising proteins including SLCO1B1 (encoding uptake transporters); ABCB1, ABCC2, ABCG2 (encoding effluent transporter); APOE, APOA5 (encoding apolipoprotein); genes encoding cytochrome P450 enzyme system; KIF6, HMGCR, LDLR, LPA, PCSK9, COQ2, CETP, etc These genes were proved to be related to the pharmacodynamics and pharmacokinetics of statins, thus affecting the efficacy and safety. WHAT IS NEW AND CONCLUSION: In this paper, the correlation between gene polymorphisms and the efficacy/safety of statins was summarized. The authors reached a consensus that the variants of the genes encoding uptake and effluent transporters have the most effect on the efficacy/safety of statins. It pointed out that it is desirable to do genetic testing of these transporter genes to reduce the incidence of myopathy or to achieve better outcomes before patients use statins, especially in the regions with high frequency of risk allele.