Genome-Wide Association Analysis of Protein-Coding Variants in IgA Nephropathy.

SIGNIFICANCE STATEMENT: Genome-wide association studies have identified nearly 20 IgA nephropathy susceptibility loci. However, most nonsynonymous coding variants, particularly ones that occur rarely or at a low frequency, have not been well investigated. The authors performed a chip-based association study of IgA nephropathy in 8529 patients with the disorder and 23,224 controls. They identified a rare variant in the gene encoding vascular endothelial growth factor A (VEGFA) that was significantly associated with a two-fold increased risk of IgA nephropathy, which was further confirmed by sequencing analysis. They also identified a novel common variant in PKD1L3 that was significantly associated with lower haptoglobin protein levels. This study, which was well-powered to detect low-frequency variants with moderate to large effect sizes, helps expand our understanding of the genetic basis of IgA nephropathy susceptibility. BACKGROUND: Genome-wide association studies have identified nearly 20 susceptibility loci for IgA nephropathy. However, most nonsynonymous coding variants, particularly those occurring rarely or at a low frequency, have not been well investigated. METHODS: We performed a three-stage exome chip-based association study of coding variants in 8529 patients with IgA nephropathy and 23,224 controls, all of Han Chinese ancestry. Sequencing analysis was conducted to investigate rare coding variants that were not covered by the exome chip. We used molecular dynamic simulation to characterize the effects of mutations of VEGFA on the protein's structure and function. We also explored the relationship between the identified variants and the risk of disease progression. RESULTS: We discovered a novel rare nonsynonymous risk variant in VEGFA (odds ratio, 1.97; 95% confidence interval [95% CI], 1.61 to 2.41; P = 3.61×10 -11 ). Further sequencing of VEGFA revealed twice as many carriers of other rare variants in 2148 cases compared with 2732 controls. We also identified a common nonsynonymous risk variant in PKD1L3 (odds ratio, 1.16; 95% CI, 1.11 to 1.21; P = 1.43×10 -11 ), which was associated with lower haptoglobin protein levels. The rare VEGFA mutation could cause a conformational change and increase the binding affinity of VEGFA to its receptors. Furthermore, this variant was associated with the increased risk of kidney disease progression in IgA nephropathy (hazard ratio, 2.99; 95% CI, 1.09 to 8.21; P = 0.03). CONCLUSIONS: Our study identified two novel risk variants for IgA nephropathy in VEGFA and PKD1L3 and helps expand our understanding of the genetic basis of IgA nephropathy susceptibility.

Modeling methods for busulfan-induced oligospermia and asthenozoospermia in mice: a systematic review and meta-analysis.

OBJECTIVE: Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time. METHODS: We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis. RESULTS: Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 106/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle. CONCLUSION: The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.

Corrigendum: Functional variant rs12614 in CFB confers a low risk of IgA nephropathy by attenuating complement alternative pathway activation in Han Chinese.

[This corrects the article DOI: 10.3389/fimmu.2022.973169.].

Amisulpride augmentation therapy improves cognitive performance and psychopathology in clozapine-resistant treatment-refractory schizophrenia: a 12-week randomized, double-blind, placebo-controlled trial.

BACKGROUND: Although clozapine is an effective option for treatment-resistant schizophrenia (TRS), there are still 1/3 to 1/2 of TRS patients who do not respond to clozapine. The main purpose of this randomized, double-blind, placebo-controlled trial was to explore the amisulpride augmentation efficacy on the psychopathological symptoms and cognitive function of clozapine-resistant treatment-refractory schizophrenia (CTRS) patients. METHODS: A total of 80 patients were recruited and randomly assigned to receive initial clozapine plus amisulpride (amisulpride group) or clozapine plus placebo (placebo group). Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Clinical Global Impression (CGI) scale scores, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Treatment Emergent Symptom Scale (TESS), laboratory measurements, and electrocardiograms (ECG) were performed at baseline, at week 6, and week 12. RESULTS: Compared with the placebo group, amisulpride group had a lower PANSS total score, positive subscore, and general psychopathology subscore at week 6 and week 12 (PBonferroni < 0.01). Furthermore, compared with the placebo group, the amisulpride group showed an improved RBANS language score at week 12 (PBonferroni < 0.001). Amisulpride group had a higher treatment response rate (P = 0.04), lower scores of CGI severity and CGI efficacy at week 6 and week 12 than placebo group (PBonferroni < 0.05). There were no differences between the groups in body mass index (BMI), corrected QT (QTc) intervals, and laboratory measurements. This study demonstrates that amisulpride augmentation therapy can safely improve the psychiatric symptoms and cognitive performance of CTRS patients. CONCLUSION: This study indicates that amisulpride augmentation therapy has important clinical significance for treating CTRS to improve clinical symptoms and cognitive function with tolerability and safety. Trial registration Clinicaltrials.gov identifier- NCT03652974. Registered August 31, 2018, https://clinicaltrials.gov/ct2/show/NCT03652974.

Functional variant rs12614 in CFB confers a low risk of IgA nephropathy by attenuating complement alternative pathway activation in Han Chinese.

Activation of the alternative pathway (AP) of complement is thought to play an important role in Immunoglobin A nephropathy (IgAN). Our previous study showed that rs4151657 within the complement factor B (CFB) gene increased the risk of IgAN. The protein encoded by the CFB gene is an initial factor that promotes AP activation. The aim of this study was to investigate whether other variants of CFB confer susceptibility to IgAN and elucidate their potential roles in AP activation. A total of 1,350 patients with IgAN and 1,420 healthy controls were enrolled and five tag single-nucleotide polymorphisms were selected for genotyping. The levels of key AP components, such as CFB, complement factor H and complement split product C3a, were measured by enzyme-linked immunosorbent assay. Molecular docking and molecular dynamic simulation were carried out to characterize the mutation of residues in the protein structure and the dynamic properties of wide type and mutation models of CFB protein. The allele-specific effect on CFB expression and its binding affinity to C3b were investigated through cell transfection and surface plasmon resonance analysis, respectively. We found that rs12614 significantly reduced the risk of IgAN (OR = 0.69, 95% CI = 0.52-0.91, P = 0.009), and the rs12614-T (R32W mutation) was correlated with lower CFB levels, higher serum C3 level, and less mesangial C3 deposition in patients with IgAN. The structural model showed that the R32W mutation reduced the structural stability of CFB protein. Furthermore, in vitro study revealed that rs12614-T decreased the expression of CFB and reduced its binding affinity to C3b by four-fold compared with rs12614-C. In conclusion, the rs12614-T in CFB was associated with low risk of IgAN probably by attenuating AP activation.

The screening value of RT-LAMP and RT-PCR in the diagnosis of COVID-19: systematic review and meta-analysis.

The purpose of this systematic review is to evaluate the test accuracy of reverse-transcription loop-mediated isothermal amplification (RT-LAMP) and reverse transcription-PCR (RT-PCR) for the diagnosis of coronavirus disease 2019 (COVID-19). We comprehensively searched PUBMED, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until September 1, 2021. We included clinical studies assessing the sensitivity and specificity of RT-PCR and RT-LAMP using respiratory samples. Thirty-three studies were included with 9360 suspected cases of SARS-CoV-2 infection. The RT-PCR or other comprehensive diagnostic method was defined as the reference method. The results showed that the overall pooled sensitivity of RT-PCR and RT-LAMP was 0.96 (95 % CI, 0.93-0.98) and 0.92 (95 % CI, 0.85-0.96), respectively. RT-PCR and RT-LAMP had a 0.06 (95 % CI, 0.04-0.08) and 0.12 (95 % CI, 0.06-0.16) false-negative rates (FNR), respectively. Moreover, subgroup analysis showed mixed sampling and multiple target gene diagnosis methods had better diagnostic value than single-site sampling and a single target gene. The sensitivity and FNR were also significantly affected by the reference method. Comparing RT-LAMP with established suboptimal RT-PCR may exaggerate the performance of RT-LAMP. RT-PCR and RT-LAMP showed high values in the diagnosis of COVID-19, but there was still a FNR of about 6%-12%.

[Types and prognosis of human papillomavirus infection in the male urethra and skin lesions].

OBJECTIVE: To determine the types and investigate the distribution and prognosis of human papillomavirus (HPV) infection in different parts of the urethra and skin lesions in men. METHODS: Using real-time fluorescence quantitative (RT-qPCR), we determined and analyzed the genotypes of HPV in the urethra and skin lesions of 620 male patients. RESULTS: The results of HPV examination were comparable in the urethra and skin lesions of 53.39% of the patients (331/620) and different in 46.61% (289/620). HPV positive was detected in 36.61% (227/620) in the urethra and 44.84% (278/620) in skin lesions. Various HPV subtypes were identified in both the urethra and skin lesions, mostly of the low-risk type. High-risk types in the urethra included types 16, 52, 18 and 56, and those in the skin lesions included types 16, 51, 52 and 58 types. CONCLUSION: Analysis of HPV infection in different parts and its prognosis helps to predict the risk of morbidity. Attention should be paid to the early detection of high-risk HPV infection in males so as to give positive and effective intervention and take targeted preventive measures for the high-risk population.

High-level uric acid in asymptomatic hyperuricemia could be an isolated risk factor of cardio-cerebrovascular diseases: A prospective cohort study.

BACKGROUND AND AIMS: Whether the asymptomatic hyperuricemia (AH) raise the cardiovascular disease risk with or without hyperuricemia-related comorbidities still remains contentious. Our study was aimed to quantitatively access the incidence risk of coronary heart disease (CHD) and stroke associated with AH. METHODS AND RESULTS: In this prospective cohort study, multivariate-adjusted Cox regression models were applied to evaluate the risk of cardiovascular disease (CVD). Baseline serum uric acid beyond normouricemia (357 mmol/L) was quarterly stratified based on the distribution of healthy populations without CVD onset. 1062 CVD first-attack cases were collected among the 29,974 study population (age range: 18-91, mean age: 47.2 ± 13.9 years-old) with a mean follow-up duration of 5.78 ± 0.83 years. The AH showed overall non-association with the CVD incident. However, significantly increased adjusted hazard ratio (HR) of CVD with 95% confidence interval (CI) were observed when the fourth quartile compared with normouricemia stratum in the total cohort population (CHD: 1.42, 1.21-1.68; stroke: 1.27, 1.06-1.41), male (CHD: 1.26, 1.12-1.55), female (CHD: 1.34, 1.04-2.02; stroke: 2.06, 1.13-3.77) and aged over 50 years-old population. Meanwhile, the age-standardized incidence rate of CVD in the fourth quartile was 2-3 times higher than the normouricemia population. After excluded 14,464 baseline population with diabetes, dyslipidemia, and hypertension, consistent results were also observed in the AH population in absence of comorbidities (CHD: 1.51, 1.22-2.25; stroke: 1.68, 1.13-2.39). CONCLUSION: Asymptomatic hyperuricemia patients exposed to a higher level of uric acid (>=428 mmol/L) could significantly increase the incidence risk of CHD and stroke, with or without hyperuricemia-related comorbidities.

A new mouse model of type 2 diabetes mellitus established through combination of high-fat diet, streptozotocin and glucocorticoid.

AIM: A stable induced type 2 diabetes model (T2DM) still needs to be explored for basic and clinical research, due to nonuniform model methods and unstable consequences. Our aims were to explore and establish an optimized induced T2DM model in mice that exhibits insulin resistance and ß-cell damage. MATERIALS AND METHODS: C57BL/6 mice were treated with a high-fat diet (HFD), streptozotocin (STZ) and dexamethasone (DEX) at different doses and in combination. The general growth status, blood glucose and fasting insulin were detected, and the success rate and insulin sensitivity indices were calculated. KEY FINDING: Low-dose STZ injection multiple times was more secure in the process of T2DM model production. Combined intervention was more efficient in reducing insulin sensitivity and improving the success rate of T2DM model construction. SIGNIFICANCE: Combined with a high-fat diet, glucocorticoids and streptozotocin, a new mouse model of T2DM with insulin resistance and ß-cell damage could be established. The optimized experimental method can serve as a stable model for further studies on the mechanisms and therapy of T2DM.

Dataset of testicular germ cell tumors (TGCT) risk associated with serum polychlorinated biphenyl (PCB) by age at diagnosis and histologic types.

In a population-based case control study of testicular germ cell tumors (TGCT), we reported a strong positive association between serum levels of Wolff's Group 1 (potentially estrogenic) polychlorinated biphenyl (PCBs) and risk of TGCT, and the observed associations were similar for both seminoma and non-seminoma. While the observed specific associations between TGCT and Wolff's Group 1 PCBs cannot be easily explained by bias or confounding, a question can still be asked, that is, could the relationship between PCBs and TGCT differ by age at diagnosis? PCBs tend to bioaccumulate, with more heavily chlorinated PCB congeners tending to have longer half-lives. Half-lives of PCB congeners were reported ranging from 4.6 years for PCB-28 to 41.0 years for PCB-156. The half-life for the heavy PCB congeners (17.8 years) was found to be approximately twice that for the light PCBs (9.6 years) in early studies. Therefore, the same PCB concentration measured in a 20-year-old vs. a 55-year-old is unlikely to represent the same lifetime PCB exposure or type of PCB exposure. In this analysis, we stratified the data by median age of diagnosis of TGCT and further stratified by histologic type of TGCT (seminoma vs non-seminoma) to explore if the risk of TGCT associated with PCB exposures differs by age.

Serum polychlorinated biphenyl (PCB) levels and risk of testicular germ cell tumors: A population-based case-control study in Connecticut and Massachusetts.

The incidence rate of testicular germ cell tumors (TGCT) has continuously increased in Western countries over the last several decades. Some epidemiologic studies have reported that the endocrine disrupting polychlorinated biphenyls (PCBs) in serum may be associated with TGCT risk, but the evidence is inconsistent. Our goal was to investigate whether serum levels of PCBs are associated with the increase of TGCT risk. We conducted a population-based case-control study of 308 TGCT cases and 323 controls, all residents of Connecticut and Massachusetts. Serum levels of 56 PCBs congeners were measured using gas chromatography and unconditional logistic regression model was used to evaluate the risk of TGCT associated with total PCBs exposure, groups of PCBs categorized by Wolff's functional groups, and individual PCB congeners. The results showed that there was no association between total serum levels of PCBs and risk of TGCT overall (quartile 4 (Q4) vs. quartile 1 (Q1) odds ratio (OR) and 95% confidence interval (C.I.) = 1.0 (0.6-1.9), ρ trend = 0.9). However, strong positive association was observed between total serum levels of Wolff's Group 1 (potentially estrogenic) PCBs and risk of overall TGCT (Q4 vs. Q1 OR = 2.5, 95% CI = 1.3-4.7, ρ trend <0.05) as well as seminoma and non-seminoma subtypes. Wolff's Group 1 PCB congeners that showed an increased risk of TGCT included: 25, 44, 49, 52, 70, 101, 174, and 201/177. Considering the continuing increase of TGCT, these associations should be replicated in different populations with larger sample size.

Health-related quality of life of patients with colorectal neoplasms in China: A multicenter cross-sectional survey.

BACKGROUND AND AIM: This study aimed to clarify health-related quality of life (HRQoL) of patients with colorectal precancer and colorectal cancer (CRC) in China and to better understand related utility scores. METHODS: A hospital-based cross-sectional survey was conducted in precancer and CRC patients from 2012 to 2014, covering 12 provinces in China. HRQoL was assessed with EuroQol 5-Dimensions 3-Levels. Utility scores were derived using Chinese value set. A multivariate regression model was established to explore potential predictors of utility scores. RESULTS: A total of 376 precancer (mean age 58.7 years, 61.2% men) and 2470 CRC patients (mean age 58.6 years, 57.6% men) were included. In five dimensions, there was a certain percentage of problem reported among precancer (range: 12.0% to 36.7%) and CRC (range: 32.4% to 50.3%) patients, with pain/discomfort being the most serious dimension. Utility scores of precancer and CRC patients were 0.870 (95% confidence interval [CI], 0.855-0.886) and 0.751 (95% CI, 0.742-0.759), both of which were lower than those of general Chinese population (0.960 [95% CI, 0.960-0.960]). Utilities for patients at stage I to stage IV were 0.742 (95% CI, 0.715-0.769), 0.722 (95% CI, 0.705-0.740), 0.756 (95% CI, 0.741-0.772), and 0.745 (95% CI, 0.742-0.767), respectively. Multivariate analysis showed that therapeutic regimen, time point of the interview, education, occupation, annual household income, and geographic region were associated with utilities of CRC patients. CONCLUSION: Health-related quality of life of both precancer and CRC patients in China declined considerably. Utility scores differed by sociodemographic and clinical characteristics, and findings of these utilities may facilitate implementation of further cost-utility evaluations.

Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.

BACKGROUND: Eighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk. METHODS: Genome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny. RESULTS: Identification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119). CONCLUSIONS: A meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs.  These variants may explain susceptibility differences between Chinese and European populations.

[Analysis of volatile organic compounds (VOCs) fingerprint of raw and honey-fried licorice based on headspace-gas-chromatography ion-mobility spectrometry (HS-GC-IMS)].

Licorice is one of the most commonly used traditional Chinese medicine. In clinic, raw licorice and honey-fried licorice are used in medicines, with the main effects in clearing away heat and detoxifying, moistening lungs and removing phlegm. Honey-fried licorice has effects in nourishing the spleen and stomach and replenishing Qi and pulse. Because traditional Chinese medicine exerts the effects through multiple components and multiple targets, the index components used in the quality evaluation of licorice are often difficult to reflect their real quality. In addition, most of studies for the quality standards have shown that honey-fried licorice are the same as licorice, with a lack of quality evaluation standards that can demonstrate their processing characteristics. The quality of medicine is directly related to its clinical efficacy, so it is necessary to establish a more effective quality control method. Licorice has a beany smell, which is one of the main quality identification characteristics. In this study, by taking advantage of the odor characteristics, a headspace-gas chromatography-ion migration mass spectrometry technology was used to establish a quality evaluation method. A total of 76 volatile components were identified. Through the dynamic principal component analysis, 7 kinds of volatile substances in raw licorice and 13 kinds of volatile substances in honey-fried licorice were statistically obtained, and could be taken as index components for the quality evaluation of raw and honey-fried licorice, respectively. This study could help realize the combination and unification of modern detection and traditional quality evaluation methods, and make a more realistic evaluation for the quality of licorice.

Effects of metformin in obesity treatment in different populations: a meta-analysis.

OBJECTIVE: Some studies have shown that metformin can reduce body weight. However, metformin has not been officially approved as a medicine for weight loss because its effect on different populations remains inconsistent. This meta-analysis aimed to summarize the weight loss effect of metformin quantitatively. METHOD: The randomized controlled and high-quality case-control trials of metformin monotherapy in obesity treatment were eligible. Baseline body mass index (BMI) was chosen as a self-control to compare the changes in BMI of different populations before and after treatment. All changes were calculated as differences between the final and initial BMI values (with negative values indicating a decrease). Results were presented as weighted mean difference (WMD) with a 95% confidence interval (CI 95%). Subgroup analysis was performed based on baseline BMI, age, daily dose, and duration of medication. RESULTS: A total of 21 trials (n = 1004) were included, and the meta-analysis of metformin treatment in different populations showed that metformin has a modest reduction in the BMI of included participants (WMD -0.98; 95% CI, -1.25 to -0.72), and the reduction of BMI was most significant in the simple obesity population (WMD -1.31; 95% CI, -2.07 to -0.54). The subgroup analysis showed that metformin treatment significantly reduced BMI in obesity patients with a BMI >35kg/m2 (WMD -1.12; 95% CI, -1.84 to -0.39) compared with before treatment. BMI in the high dose group decreased by 1.01 units (WMD-1.01; 95% CI, -1.29 to -0.73) and BMI did not continue to decrease significantly after treatment of more than 6 months. CONCLUSION: Patients treated with metformin experienced about a one-unit reduction in BMI at the end of treatment. But whether this decreased value produced enough weight loss (5% of baseline body weight) to qualify as a "weight loss drug" as current guidelines require, requires larger specific randomized control trials.

[Study on internal and external quality control methods of Platycladi Cacumen Carbonisata based on QAMS and color recognition].

In order to effectively solve the over-processing problem of Platycladi Cacumen Carbonisata, which was commonly used as a hemostatic drug in clinical application, we used the quantitative analysis method of multi-components by single marker(QAMS) in this study, with quercetin as internal reference to simultaneously determine the content of six flavonoids which can be used to control the internal quality of Platycladi Cacumen Carbonisata. Based on the comparison of QAMS and external standard method(ESM) results, the limit standards of contents were established as follows: isoquercitroside ≥0.002 0%, quercitroside ≥0.050%, quercetin ≥0.030%, kaempferol and amentoflavone both ≥0.010%, hinokiflavone ≥0.050%. Based on the color detection of Platycladi Cacumen and Platycladi Cacumen Carbonisata with different processing degrees, the law of influence of different processing degrees on the color of Platycladi Cacumen Carbonisata was found. A new external quality standard of Platycladi Cacumen Carbonisata was established by fitting curve of color recognition for the external quality control, based on which the standard ranges of ΔL~*, Δb~* and ΔE were-50.00--44.00, 6.00-11.00 and 45.00-50.00 respectively. Effective combination of established internal and external quality control standards by this study can be used to evaluate the processing degree and quality of Platycladi Cacumen Carbonisata more comprehensively and objectively, which can guarantee its clinical efficacy. At the same time, this study also provides reference and basis for further improving the quality control standard of Platycladi Cacumen Carbonisata.

Effects of hepatitis B virus infection, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase on prediabetes and diabetes mellitus: A cohort study.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to confirm whether hepatitis B virus (HBV) infection and the levels of liver enzymes would increase the risk of prediabetes and diabetes mellitus (DM) in China. MATERIALS AND METHODS: A total of 10,741 individuals was enrolled in this prospective cohort study. Cox regression analysis was used to calculate the Hazard ratios (HRs) to evaluate the relationships between HBV infection and the risk of DM and prediabetes. Decision trees and dose response analysis were used to explore the effects of liver enzymes levels on DM and prediabetes. RESULTS: In baseline population, HBV infection ratio was 5.31%. In non-adjustment model, the HR of DM in HBV infection group was 1.312 (95% CI, 0.529-3.254). In model adjusted for gender, age and liver cirrhosis, the HR of DM in HBV infection group were 1.188 (95% CI, 0.478-2.951). In model adjusted for gender, age, liver cirrhosis, smoking, drinking, the HR of DM was 1.178 (95% CI, 0.473-2.934). In model further adjusted for education, family income and occupation, the HR of DM was 1.230 (95% CI, 0.493-3.067). With the increases of levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Gamma-glutamyl transferase (GGT), the risk of prediabetes was gradually increasing (Pnon-linearity<0.05). There were dose-response relationships between ALT, GGT and the risk of DM (Pnon-linearity<0.05). CONCLUSIONS: HBV infection was not associated with the risk of prediabetes and DM. The levels of liver enzymes increased the risk of prediabetes and DM.

Total cholesterol to high-density lipoprotein cholesterol ratio is a significant predictor of nonalcoholic fatty liver: Jinchang cohort study.

BACKGROUND: Some studies found out that TC/HDL-C ratio is a predictor of Cardiovascular disease (CVD) and Nonalcoholic fatty liver (NAFLD) is related to CVD. And some researches have already studied that Apolipoprotein B to Apolipoprotein A1 ratio (ApoB/ApoA1) and Triglyceride to High-density lipoprotein cholesterol ratio (TG/HDL-C) were both related with CVD and NAFLD, but few studied the association between TC/HDL-C ratio and NAFLD. So, we suspected the ratio was also related to NAFLD. The research aims to study the predictive value of TC/HDL-C to NAFLD and to help the early detection of NAFLD. METHODS: Based on the Jinchang Cohort, the study contained 32,121 participants. We assessed the incidence of NAFLD by the quartiles of TC, HDL-C and TC/HDL-C. Then, the does-response relationship between these indicators and the risk of NAFLD was obtained. Finally, the receiver operator characteristic curve (ROC) was applied to decide the predictive value of TC/HDL-C. RESULTS: Among the study participants, the cumulative incidence of NAFLD was 6.30% and the rate of dyslipidemia was 40.37%. The biochemical indicators of NAFLD had a difference with general population. The incidence of NAFLD raised with the quartiles of TC, TG and LDL-C raising, while decreased with the HDL-C' quartiles raising. After controlling confounding factors, TC and TC/HD-C had a positive relationship with NAFLD, while HDL-C had the opposite. Finally, the ROC analysis showed the area under the curve (AUC) of TC/HDL-C (0.645) was greater than TC (0.554), HDL-C (0.627) and Apolipoprotein B to Apolipoprotein A1 (ApoB/ApoA1) (0.613). CONCLUSIONS: The TC/HDL-C ratio has significant predictive value to NAFLD.

The Relationship between Nkx2.1 and DNA Oxidative Damage Repair in Nickel Smelting Workers: Jinchang Cohort Study.

Background: Occupational nickel exposure can cause DNA oxidative damage and influence DNA repair. However, the underlying mechanism of nickel-induced high-risk of lung cancer has not been fully understood. Our study aims to evaluate whether the nickel-induced oxidative damage and DNA repair were correlated with the alterations in Smad2 phosphorylation status and Nkx2.1 expression levels, which has been considered as the lung cancer initiation gene. Methods: 140 nickel smelters and 140 age-matched administrative officers were randomly stratified by service length from Jinchang Cohort. Canonical regression, χ² test, Spearman correlation etc. were used to evaluate the association among service length, MDA, 8-OHdG, hOGG1, PARP, pSmad2, and Nkx2.1. Results: The concentrations of MDA, PARP, pSmad2, and Nkx2.1 significantly increased. Nkx2.1 (rs = 0.312, p < 0.001) and Smad2 phosphorylation levels (rs = 0.232, p = 0.006) were positively correlated with the employment length in nickel smelters, which was not observed in the administrative officer group. Also, elevation of Nkx2.1 expression was positively correlated with service length, 8-OHdG, PARP, hOGG1 and pSmad2 levels in nickel smelters. Conclusions: Occupational nickel exposure could increase the expression of Nkx2.1 and pSmad2, which correlated with the nickel-induced oxidative damage and DNA repair change.

Liver Enzymes, Fatty Liver and Type 2 Diabetes Mellitus in a Jinchang Cohort: A Prospective Study in Adults.

OBJECTIVES: It is unclear whether liver enzymes or the interactions of various liver enzymes is a predictor of type 2 diabetes mellitus (T2DM), which is independent of fatty liver. METHODS: A total of 48,001 subjects participated in baseline examinations. Among the subjects, 33,355 were followed for an average of 2.2 years. Cox proportional hazard models were used to examine the adjusted associations of AST, GGT and ALT with T2DM. RESULTS: The cumulative incidence of T2DM was 8.05% to 9.02% for fatty liver and 2.25% to 4.10% for non-fatty liver, both showing statistically significant differences. Compared with the normal liver enzyme levels in the group with fatty liver, the adjusted incident hazard ratios in T2DM were: ALT 1.23 (95% CI 1.10 to 1.50); AST 1.30 (95% CI 1.07-1.59); and GGT 1.34 (95% CI 1.08 to 1.65). In addition, compared with the normal liver enzyme levels in the group with non-fatty liver, the adjusted incident hazard ratios in type 2 diabetes were: ALT 1.27 (95% CI 1.02 to 1.59); AST 1.33 (95% CI 1.02 to 1.59); and GGT 1.53 (95% CI 1.19 to 1.98). There are significant interactions of T2DM hazard ratios between GGT and ALT and between GGT and AST in addition to ALT and AST. CONCLUSIONS: Our results suggest that the incidence of T2DM in the group with fatty liver is significantly higher than that in the normal population, and the rise of serum AST, GGT and ALT levels are risk factors independent of fatty liver for the development of T2DM after adjusting for confounding factors.