Transperitoneal vs retroperitoneal laparoscopic radical nephrectomy: a double-arm, parallel-group randomized clinical trial.

OBJECTIVE: To compare the outcomes of patients undergoing Retroperitoneal laparoscopic Radical nephrectomy (RLRN) and Transperitoneal laparoscopic Radical nephrectomy (TLRN). METHODS: A total of 120 patients with localized renal cell carcinoma were randomized into either RLRN or TLRN group. Mainly by comparing the patient perioperative related data, surgical specimen integrity, pathological results and tumor results. RESULTS: Each group comprised 60 patients. The two group were equivalent in terms of perioperative and pathological outcomes. The mean integrity score was significantly lower in the RLRN group than TLRN group. With a median follow-up of 36.4 months after the operation, Kaplan-Meier survival analysis showed no significant difference between RLRN and TLRN in overall survival (89.8% vs. 88.5%; P = 0.898), recurrence-free survival (77.9% vs. 87.7%; P = 0.180), and cancer-specific survival (91.4% vs. 98.3%; P = 0.153). In clinical T2 subgroup, the recurrence rate and recurrence-free survival in the RLRN group was significantly worse than that in the TLRN group (43.2% vs. 76.7%, P = 0.046). Univariate and multivariate COX regression analysis showed that RLRN (HR: 3.35; 95%CI: 1.12-10.03; P = 0.030), male (HR: 4.01; 95%CI: 1.07-14.99; P = 0.039) and tumor size (HR: 1.23; 95%CI: 1.01-1.51; P = 0.042) were independent risk factor for recurrence-free survival. CONCLUSIONS: Our study showed that although RLRN versus TLRN had roughly similar efficacy, TLRN outperformed RLRN in terms of surgical specimen integrity. TLRN was also significantly better than RLRN in controlling tumor recurrence for clinical T2 and above cases. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=24400 ), identifier: ChiCTR1800014431, date: 13/01/2018.

Association of hTERT Gene Polymorphism and Colorectal Cancer (CRC) Risk in the Chinese Han Population.

The catalytic subunit telomerase reverse transcriptase (hTERT) is a prerequisite for malignant transformation of human cells. Colorectal cancer (CRC) is a common malignant tumor. The genetic association of hTERT gene rs2853669 and rs2736098 polymorphisms with CRC was surveyed in the Chinese population. Two hundreds patients with CRC and 200 healthy controls were taken for blood sample collection. Sanger sequencing was applied for genotyping. Multiple logistic regression analysis was performed, and odds ratio (OR) together with confidence interval (CI) were calculated to obtain the corresponding association power. Among CRC cases (49.50%), hTERT gene rs2736098 GA genotype carriers were more prevalent compared with the control group (41.00%, P = 0.035), which increased the risk of CRC by 1.576 times (95% CI, 1.031-2.409). Distribution of the rs2736098 genotypes was significantly associated with TNM stage, tumor differentiation, tumor size and lymph node metastasis (P < 0.05). The frequencies of hTERT gene rs2853669 polymorphism were not significantly different between CRC patients and healthy controls. Logistic regression analysis indicated that both body mass index (BMI) and hTERT gene rs2736098 polymorphism remained significantly correlated with CRC susceptibility. The frequencies of hTERT gene rs2853669 polymorphism did not differ significantly between CRC patients and control group (P > 0.05). The hTERT gene rs2736098 polymorphism was correlated with CRC risk in the Chinese Han population, and the GA genotype was a risk element for the onset of CRC.

The association between the scarlet fever and meteorological factors, air pollutants and their interactions in children in northwest China.

Scarlet fever (SF) is an acute respiratory transmitted disease that primarily affects children. The influence of meteorological factors and air pollutants on SF in children has been proved, but the relevant evidence in Northwest China is still lacking. Based on the weekly reported cases of SF in children in Lanzhou, northwest China, from 2014 to 2018, we used geographical detectors, distributed lag nonlinear models (DLNM), and bivariate response models to explore the influence of meteorological factors and air pollutants with SF. It was found that ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), temperature, pressure, water vapor pressure and wind speed were significantly correlated with SF based on geographical detectors. With the median as reference, the influence of high temperature, low pressure and high pressure on SF has a risk effect (relative risk (RR) > 1), and under extreme conditions, the dangerous effect was still significant. High O3 had the strongest effect at a 6-week delay, with an RR of 5.43 (95%CI: 1.74,16.96). The risk effect of high SO2 was strongest in the week of exposure, and the maximum risk effect was 1.37 (95%CI: 1.08,1.73). The interactions showed synergistic effects between high temperatures and O3, high pressure and high SO2, high nitrogen dioxide (NO2) and high particulate matter with diameter of less than 10 µm (PM10), respectively. In conclusion, high temperature, pressure, high O3 and SO2 were the most important factors affecting the occurrence of SF in children, which will provide theoretical support for follow-up research and disease prevention policy formulation.

Adults in Northwest China experienced the largest outbreak of Japanese encephalitis in history 10 years after the Japanese encephalitis vaccine was included in the national immunization program: A retrospective epidemiological study.

Mainland China included Japanese encephalitis (JE) vaccine in the national immunization program in 2008 to control the JE epidemic. However, Gansu province in Western China experienced the largest JE outbreak since 1958 in 2018. We conducted a retrospective epidemiological study to explore the causes of this outbreak. We found that adults aged ≥20 years (especially those in rural areas) were the main JE cases in Gansu Province, with a significant increase in the JE incidence in older adults aged ≥60 years in 2017 and 2018. In addition, JE outbreaks in Gansu Province were mainly located in the southeastern region, while the temperature and precipitation in Gansu Province were gradually increasing in recent years, which made the JE epidemic areas in Gansu Province gradually spread to the western of Gansu Province. We also found that adults aged ≥20 years in Gansu Province had lower JE antibody positivity than children and infants, and the antibody positivity rate decreased with age. In the summer of 2017 and 2018, the density of mosquitoes (mainly the Culex tritaeniorhynchus) in Gansu Province was significantly higher than in other years, and the genotype of JEV was mainly Genotype-G1. Therefore, in the future JE control in Gansu Province, we need to strengthen JE vaccination for adults. Moreover, strengthening mosquito surveillance can provide early warning of JE outbreaks and the spread of epidemic areas in Gansu Province. At the same time, strengthening JE antibody surveillance is also necessary for JE control.

Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study.

BACKGROUND: The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown. METHODS: We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data. RESULTS: The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased. CONCLUSIONS: The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.

Immediate and long-term changes in infectious diseases in China at the "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" stages from 2020 to 2022: a multistage interrupted-time-series-analysis.

BACKGROUND: From January 2020 to December 2022, China implemented "First-level-response", "Normalized-control" and "Dynamic-COVID-zero" to block the COVID-19 epidemic; however, the immediate and long-term impact of three strategies on other infectious diseases and the difference in their impact is currently unknown. We aim to provide a more comprehensive understanding of the impact of non-pharmacological interventions (NPIs) on infectious diseases in China. METHODS: We collected data on the monthly case count of infectious diseases in China from January 2015 to July 2022. After considering long-term trends using the Cox-Stuart test, we performed the two ratio Z tests to preliminary analyze the impact of three strategies on infectious diseases. Next, we used a multistage interrupted-time-series analysis fitted by the Poisson regression to evaluate and compare the immediate and long-term impact of three strategies on infectious diseases in China. RESULTS: Compared to before COVID-19, the incidence of almost all infectious diseases decreased immediately at stages 1, 2, and 3; meanwhile, the slope in the incidence of many infectious diseases also decreased at the three stages. However, the slope in the incidence of all sexually transmitted diseases increased at stage 1, the slope in the incidence of all gastrointestinal infectious diseases increased at stage 2, and the slope in the incidence of some diseases such as pertussis, influenza, and brucellosis increased at stage 3. The immediate and long-term limiting effects of "Normalized-control" on respiratory-transmitted diseases were weaker than "First-level-response" and the long-term limiting effects of "Dynamic-COVID-zero" on pertussis, influenza, and hydatid disease were weaker than "Normalized-control". CONCLUSIONS: Three COVID-19 control strategies in China have immediate and long-term limiting effects on many infectious diseases, but there are differences in their limiting effects. Evidence from this study shows that pertussis, influenza, brucellosis, and hydatid disease began to recover at stage 3, and relaxation of NPIs may lead to the resurgence of respiratory-transmitted diseases and vector-borne diseases.

Ponatinib after failure of second-generation tyrosine kinase inhibitor in resistant chronic-phase chronic myeloid leukemia.

Ponatinib, the only third-generation pan-BCR::ABL1 inhibitor with activity against all known BCR::ABL1 mutations including T315I, has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to prior second-generation (2G) TKI treatment. We present efficacy and safety outcomes from the Ponatinib Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and CML Evaluation (PACE) and Optimizing Ponatinib Treatment in CP-CML (OPTIC) trials for this patient population. PACE (NCT01207440) evaluated ponatinib 45 mg/day in CML patients with resistance to prior TKI or T315I. In OPTIC (NCT02467270), patients with CP-CML and resistance to ≥2 prior TKIs or T315I receiving 45 or 30 mg/day reduced their doses to 15 mg/day upon achieving ≤1% BCR::ABL1IS or received 15 mg/day continuously. Efficacy and safety outcomes from patients with CP-CML treated with ≥1 2G TKI (PACE, n = 257) and OPTIC (n = 93), 45-mg starting dose cohort, were analyzed for BCR::ABL1IS response rates, overall survival (OS), progression-free survival (PFS), and safety. By 24 months, the percentages of patients with ≤1% BCR::ABL1IS response, PFS, and OS were 46%, 68%, and 85%, respectively, in PACE and 57%, 80%, and 91%, respectively, in OPTIC. Serious treatment-emergent adverse events and serious treatment-emergent arterial occlusive event rates were 63% and 18% in PACE and 34% and 4% in OPTIC. Ponatinib shows high response rates and robust survival outcomes in patients whose disease failed prior to 2G TKIs, including patients with T315I mutation. The response-based dosing in OPTIC led to improved safety and similar efficacy outcomes compared with PACE.

Cohort Profile Update: the China Metal-Exposed workers Cohort Study (Jinchang Cohort).

The Jinchang Cohort was an ongoing 20-year ambispective cohort with unique metal exposures to an occupational population. From January 2014 to December 2019, the Jinchang Cohort has completed three phases of follow-up. The baseline cohort was completed from June 2011 to December 2013, and a total of 48 001 people were included. Three phases of follow-ups included 46 713, 41 888, and 40 530 participants, respectively. The death data were collected from 2001 to 2020. The epidemiological, physical examination, physiological, and biochemical data of the cohort were collected at baseline and during follow-up. Biological specimens were collected on the baseline to establish a biological specimen bank. The concentrations of metals in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The new areas of research aim to study the all-cases mortality, the burden of diseases, heavy metals and diseases, and the course of the chain from disease to high-risk outcomes using a combination of macro and micro means, which provided a scientific basis to explore the pathogenesis of multi-etiology and multi-disease and to evaluate the effects of the intervention measures in the 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.

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.

DNase I-Responsive Calixpyridinium-Mediated DNA Aggregation.

In this work, cationic macrocyclic calixpyridinium was employed as a new strategy to condense DNA. Moreover, the degradation of DNA by DNase I could lead to the calixpyridinium-DNA supramolecular aggregates being dissipated. Therefore, the present system is potentially applicable as the targeted drug delivery model at DNase I-overexpressed sites.

Linear and nonlinear variable selection in competing risks data.

Subdistribution hazard model for competing risks data has been applied extensively in clinical researches. Variable selection methods of linear effects for competing risks data have been studied in the past decade. There is no existing work on selection of potential nonlinear effects for subdistribution hazard model. We propose a two-stage procedure to select the linear and nonlinear covariate(s) simultaneously and estimate the selected covariate effect(s). We use spectral decomposition approach to distinguish the linear and nonlinear parts of each covariate and adaptive LASSO to select each of the 2 components. Extensive numerical studies are conducted to demonstrate that the proposed procedure can achieve good selection accuracy in the first stage and small estimation biases in the second stage. The proposed method is applied to analyze a cardiovascular disease data set with competing death causes.

Socio-ecological factors and hand, foot and mouth disease in dry climate regions: a Bayesian spatial approach in Gansu, China.

The influence of socio-ecological factors on hand, foot and mouth disease (HFMD) were explored in this study using Bayesian spatial modeling and spatial patterns identified in dry regions of Gansu, China. Notified HFMD cases and socio-ecological data were obtained from the China Information System for Disease Control and Prevention, Gansu Yearbook and Gansu Meteorological Bureau. A Bayesian spatial conditional autoregressive model was used to quantify the effects of socio-ecological factors on the HFMD and explore spatial patterns, with the consideration of its socio-ecological effects. Our non-spatial model suggests temperature (relative risk (RR) 1.15, 95 % CI 1.01-1.31), GDP per capita (RR 1.19, 95 % CI 1.01-1.39) and population density (RR 1.98, 95 % CI 1.19-3.17) to have a significant effect on HFMD transmission. However, after controlling for spatial random effects, only temperature (RR 1.25, 95 % CI 1.04-1.53) showed significant association with HFMD. The spatial model demonstrates temperature to play a major role in the transmission of HFMD in dry regions. Estimated residual variation after taking into account the socio-ecological variables indicated that high incidences of HFMD were mainly clustered in the northwest of Gansu. And, spatial structure showed a unique distribution after taking account of socio-ecological effects.

Effects of Age, Sex, Body Weight, and Quantity of Alcohol Consumption on Occurrence and Severity of Alcoholic Hepatitis.

BACKGROUND & AIMS: Only a minority of heavy drinking individuals develop alcoholic hepatitis (AH), for unclear reasons. We analyzed data from the Translational Research and Evolving Alcoholic Hepatitis Treatment cohort, consisting of subjects who drink heavily with normal results from liver tests (controls) and patients with AH. We examined risk factors for the development of AH including body mass index (BMI), drinking pattern and quantity, and sex. METHODS: We compared data from 145 patients with AH and 124 controls based on BMI when they joined the cohort; groups were matched for sex and race. Drinking patterns were assessed using the timeline followback method, the Alcohol Use Disorders Identification Test, and the National Institute of Alcohol Abuse and Alcoholism 6-question survey. We performed univariable and multivariable analyses to assess the effects of these factors and their interaction in increasing the risk for AH. We also explored the association between PNPLA3 variants and AH. RESULTS: Cases with AH were older (47 vs 44 y; P = .03). For nearly all measures of quantity of alcohol consumed or frequency of binge drinking, controls drank more heavily than cases with AH. We did not find an association between BMI, sex, drinking patterns, and the presence of AH. Age and BMI were independent predictors for the severity of AH. When we analyzed cases and controls of European ancestry, the PNPLA3 single-nucleotide polymorphism rs738409 was associated with risk for AH (odds ratio, 1.89; P = .007). CONCLUSIONS: Compared with heavy drinkers without liver disease, subjects with AH consumed lower levels of alcohol and had less binge drinking, suggesting an increased sensitivity to the toxic effects of alcohol. The risk for AH may be associated with the PNPLA3 rs738409 polymorphism.

Effects of multiple firings on metal-ceramic bond strength of Co-Cr alloy fabricated by selective laser melting.

STATEMENT OF PROBLEM: Selective laser melting (SLM) is a new technique for fabricating dental restorations, but the metal-ceramic bond strength of the restorations after multiple firings must be considered because adequate bond strength is a clinical requirement for long-term performance. PURPOSE: The purpose of this study was to investigate the effects of repeated firing on the metal-ceramic bond strength of an SLM Co-Cr alloy. MATERIAL AND METHODS: Thirty-six SLM-fabricated (Group SLM) and conventional lost wax cast (Group Cast) Co-Cr metal bars were prepared. Eighteen bars from each group were molded into dimensions of 25×3×0.5 mm, following International Organization for Standardization (ISO) standard 9693:2012. In the center of each bar, a 1.1-mm thickness of porcelain was fused onto an 8×3-mm rectangular area. In each group, specimens were divided into 3 subgroups based on the number of firing cycles (3, 5, 7) for the veneering process. Metal-ceramic bond strength, fracture mode analysis, and area fraction of adherence porcelain (AFAP) of each subgroup was evaluated with a 3-point bend test and by measuring the Si content of specimens with scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). The results were statistically analyzed first with the Shapiro-Wilk test, where a P value of .364 was considered normally distributed, and then with the Student t test to determine significant differences (α=.05). RESULTS: Student t test results showed no statistical differences between the metal-ceramic bond strength of SLM and that of conventionally cast groups after firing 3, 5, and 7 times (P>.05). However, after SEM/EDS analyses, the SLM group showed significantly more porcelain adherence than that of the control group (P<.05) after 5 or 7 firings. CONCLUSIONS: The SLM group showed superior metal-ceramic bond strength that exceeded ISO 9691:1999 (E) requirements at all firing periods. Also, the bond showed better behavior in terms of AFAP than the conventional cast group, especially after 5 or 7 firings.

Etiological epidemiology of viral diarrhea on the basis of sentinel surveillance in children younger than 5 years in Gansu, northwest China, 2009-2013.

To explore the etiological spectrum of diarrhea and its epidemiological characteristics in diarrhea symptoms surveillance cases younger than 5 years from 2009 to 2013 in Gansu province, northwest China. Systematic diarrhea symptoms surveillance were conducted in 27 sentinel sites in Gansu province and outpatients with three or more loose, watery, or sticky pus stools per day were defined as surveillance cases. All stool specimens were tested for Rotavirus, Human calicivirus, Adenovirus, and Astrovirus. Totally, 1,119 cases (51.54%) were identified as any enteric virus. The average isolation rate of Rotavirus was 51.13%, Astrovirus was 10.84%, Adenovirus was 6.94%, and Human calicivirus was 6.60% (P < 0.01). Rotavirus was identified with the highest frequency among these enteric pathogens except in 2011, with a notable downward trend over time (P < 0.01). Rotavirus A was the most proportion in rotavirus, G3P[8] and G9P[8] were the most common combination. Rotavirus mixed Human calicivirus infections was the most common mixed infected patterns. Viral-positive rate was higher among children aged group of 0-12 and 13-24 months (P < 0.01, respectively). The isolation rates of four enteric viral pathogens showed a similar distinct seasonal variation with a higher rate in spring, autumn, and winter months. Rotavirus was the major epidemiological viral pathogen in diarrhea symptom surveillance cases in Gansu province, northwest China, during period 2009-2013. Seasonal and age-related variations were observed in enteric viral pathogen isolation rate. The comprehensive and continuous surveillance is needed to identify the prevalence of different enteric viral pathogens.

The Utility of Commonly Used Laboratory Tests to Screen for Excessive Alcohol Use in Clinical Practice.

BACKGROUND: This current study was undertaken to carefully assess the accuracy of routinely used laboratory tests in detecting excessive/recent alcohol use. We also determined the kinetics of these markers in subjects who underwent an intensive alcohol rehabilitation program. METHODS: The study cohort consisted of 210 nonexcessive drinkers, 272 excessive drinkers, and 76 with alcoholic cirrhosis. To determine the kinetics of these markers during alcohol abstinence, we followed 45 subjects with history of excessive alcohol use for 12 weeks during the intensive alcohol treatment program. RESULTS: Percentage of carbohydrate deficient transferrin (%CDT) provided the highest diagnostic performance (area under the curve [AUC] 0.77) followed by gamma-glutamyl transferase (GGT) (AUC 0.68) to detect excessive drinkers. The percentage of excessive drinkers with aspartate aminotransferase:alanine aminotransferase (AST:ALT) > 2 was only 2%, whereas 51% of subjects with alcoholic cirrhosis had AST:ALT > 2. In the multivariate analysis, the levels of GGT and %CDT were associated with the level of alcohol consumed during the past 30 days. The levels of GGT, mean corpuscular volume (MCV), and %CDT were significantly lower compared to those at baseline before alcohol rehabilitation, whereas the AST, ALT, and AST:ALT ratio were unchanged. The percent reduction was ~2.7% (for MCV), 19% (for GGT), and 43% (for %CDT) at the end of the 12-week follow-up compared to the baseline. CONCLUSIONS: %CDT are useful markers to screen for excessive alcohol use and for follow-up of abstinence. Most subjects with excessive alcohol use do not have a high AST:ALT ratio. Rather, the AST:ALT > 2 is suggestive of alcoholic cirrhosis. The performance of the %CDT to screen for heavy alcohol use is still not ideal. Further research to identify the noninvasive marker(s) (i.e., using proteomic or metabolomics approach) should be considered.

Preparation of 17ß-estradiol-imprinted material by surface-initiated atom transfer radical polymerization and its application.

A novel 17ß-estradiol molecularly imprinted polymer was grafted onto the surface of initiator-immobilized silica by surface-initiated atom transfer radical polymerization. The resulting molecularly imprinted polymer was characterized by elemental analysis and thermogravimetric analysis. The binding property of molecularly imprinted polymer for 17ß-estradiol was also studied with both static and dynamic methods. The results showed that the molecularly imprinted polymer possessed excellent recognition capacity for 17ß-estradiol (180.65 mg/g at 298 K), and also exhibited outstanding selectivity for 17ß-estradiol over the other competitive compounds (such as testosterone and progesterone). Then, the determination of trace 17ß-estradiol in beef samples was successfully developed by using molecularly imprinted polymer solid-phase extraction coupled with high-performance liquid chromatography. The limit of detection was 0.25 ng/mL, and the amount of 17ß-estradiol in beef samples was detected at 2.83 ng/g. This work proposed a sensitive, rapid, reliable, and convenient approach for the determination of trace 17ß-estradiol in complicated beef samples.

Prenatal exposure to fine particulate matter chemical constituents and the risk of stillbirth and the mediating role of pregnancy complications: A cohort study.

Evidence on the association of fine particulate matter (PM2.5) exposure with stillbirth is limited and inconsistent, which is largely attributed to differences in PM2.5 constituents. Studies have found that the hazards of certain PM2.5 constituents to the fetus are comparable to or even higher than total PM2.5 mass. However, few studies have linked PM2.5 constituents to stillbirth. Moreover, the mediating role of pregnancy complications in PM2.5-related stillbirth remains unclear. To our knowledge, this study was the first to explore the individual and mixed associations of PM2.5 and its constituents with stillbirth in China. After matching the concentrations of PM2.5 and its constituents (sulfate [SO42-], nitrate [NO3-], ammonium [NH4+], organic matter [OM], and black carbon [BC]) for participants according to their geographical location, there were 170,507 participants included in this study. We found that stillbirth was associated with exposure to PM2.5 and its constituents in the year before pregnancy and during the entire pregnancy, and the associations in trimester 1 were strongest. The risk of stillbirth increased sharply when PM2.5 and its constituents during pregnancy exceeded the median concentrations. Moreover, stillbirth was associated with exposure to the mixtures of SO42-, NO3-, NH4+, OM, and BC before and during pregnancy (trimesters 1 and 2). Meanwhile, two-pollutant models also suggested stillbirth was associated with PM2.5 and its constituents in the year before and during pregnancy. The associations of PM2.5 and its constituents with stillbirth were stronger in mothers with advanced age and without cesarean delivery history. Additionally, hypertensive disorders in pregnancy, gestational diabetes, and placental abruption mediated the association of PM2.5 with stillbirth. Therefore, enhanced protection against PM2.5 for pregnant women before and during pregnancy and targeted interventions for pregnancy complications and anthropogenic sources of PM2.5 constituents are important to reduce stillbirth risk.

Vilaprisan for the treatment of symptomatic endometriosis: results from a terminated phase 2b randomized controlled trial.

Objective: To evaluate the efficacy and safety of 2 doses of vilaprisan vs. placebo in participants with symptomatic endometriosis. Design: Multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 2b trial (NCT03573336). The initially planned sample size was 315 patients. Recruitment was paused to assess long-term toxicity findings in rodents; although the findings were assessed as likely to be of limited clinical relevance in humans, the study was closed by the sponsor. During the pause, enrolled patients completed 3 or 6 months of treatment per their assigned regimen. Setting: University hospitals, a regional hospital, and a private clinic. Patients: Premenopausal adults with confirmed endometriosis and moderate-to-severe pelvic pain (≥4/10 on a numerical rating scale) were enrolled. Inclusion required protocol adherence, including ≥24 diary entries, and an average pain score of ≥3.5. Intervention: Participants were randomly assigned 1:1:1 to receive vilaprisan (2 mg), vilaprisan (4 mg), or placebo. Main Outcome Measures: The primary outcome was a change in the 7-day mean "worst pain" (per the endometriosis symptom diary item 1) from baseline to month 3. All analyses were descriptive only. Results: Eight participants were randomly assigned to treatment before the study pause: 6 received vilaprisan (4 mg, n = 4 and 2 mg, n = 2), and 2 received placebo. The 6 vilaprisan recipients experienced an improvement in endometriosis-associated pelvic pain, whereas the 2 placebo recipients experienced no change or increased pain; all 8 participants had decreased use of pain medication. Bleeding intensity decreased from baseline in the vilaprisan group. Conclusion: The study findings suggest that vilaprisan may improve outcomes in patients with endometriosis. Further studies in larger populations would be needed to accurately assess treatment effects. Clinical Trial Registration Number: NCT03573336.