Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

Radiographic Imaging for the Diagnosis and Treatment of Patients with Skeletal Class III Malocclusion.

Skeletal Class III malocclusion is one type of dentofacial deformity that significantly affects patients' facial aesthetics and oral health. The orthodontic treatment of skeletal Class III malocclusion presents challenges due to uncertainties surrounding mandibular growth patterns and treatment outcomes. In recent years, disease-specific radiographic features have garnered interest from researchers in various fields including orthodontics, for their exceptional performance in enhancing diagnostic precision and treatment effect predictability. The aim of this narrative review is to provide an overview of the valuable radiographic features in the diagnosis and management of skeletal Class III malocclusion. Based on the existing literature, a series of analyses on lateral cephalograms have been concluded to identify the significant variables related to facial type classification, growth prediction, and decision-making for tooth extractions and orthognathic surgery in patients with skeletal Class III malocclusion. Furthermore, we summarize the parameters regarding the inter-maxillary relationship, as well as different anatomical structures including the maxilla, mandible, craniofacial base, and soft tissues from conventional and machine learning statistical models. Several distinct radiographic features for Class III malocclusion have also been preliminarily observed using cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI).

Prediagnostic plasma metabolite concentrations and liver cancer risk: a population-based study of Chinese men.

BACKGROUND: Previous metabolic profiling of liver cancer has mostly used untargeted metabolomic approaches and was unable to quantitate the absolute concentrations of metabolites. In this study, we examined the association between the concentrations of 186 targeted metabolites and liver cancer risk using prediagnostic plasma samples collected up to 14 years prior to the clinical diagnosis of liver cancer. METHODS: We conducted a nested case-control study (n = 322 liver cancer cases, n = 322 matched controls) within the Shanghai Men's Health Study. Conditional logistic regression models adjusted for demographics, lifestyle factors, dietary habits, and related medical histories were used to estimate the odds ratios. Restricted cubic spline functions were used to characterise the dose-response relationships between metabolite concentrations and liver cancer risk. FINDINGS: After adjusting for potential confounders and correcting for multiple testing, 28 metabolites were associated with liver cancer risk. Significant non-linear relationships were observed for 22 metabolites. The primary bile acid biosynthesis and phenylalanine, tyrosine and tryptophan biosynthesis were found to be important pathways involved in the aetiology of liver cancer. A metabolic score consisting of 10 metabolites significantly improved the predictive ability of traditional epidemiological risk factors for liver cancer, with an optimism-corrected AUC increased from 0.84 (95% CI: 0.81-0.87) to 0.89 (95% CI: 0.86-0.91). INTERPRETATION: This study characterised the dose-response relationships between metabolites and liver cancer risk, providing insights into the complex metabolic perturbations prior to the clinical diagnosis of liver cancer. The metabolic score may serve as a candidate risk predictor for liver cancer. FUNDING: National Key Project of Research and Development Program of China [2021YFC2500404, 2021YFC2500405]; US National Institutes of Health [subcontract of UM1 CA173640].

Sex-specific impact of dietary patterns on liver cancer incidence: updated results from two population-based cohort studies in China.

PURPOSE: The associations between dietary patterns and liver cancer risk have received much attention, but evidence among the Chinese population is scarce. This study aims to update the results of two cohort studies and provide the sex-specific associations in the Chinese population. METHODS: This study was based on two cohorts from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). Diet information was collected by validated food frequency questionnaires. Dietary patterns were derived by factor analysis. Cox regression model was utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for associations between dietary patterns and liver cancer risk. RESULTS: During median follow-up years of 11.2 (male) and 17.1 (female) years, 427 males and 252 females were identified as incident primary liver cancer cases. In males, vegetable-based dietary pattern was inversely associated with liver cancer (HRQ4-Q1: 0.67, 95%CI 0.51-0.88, Ptrend < 0.001). Interaction analysis indicated that in males lower vegetable-based dietary pattern score and older age/medical history of chronic hepatitis combined increase the hazard of liver cancer more than the sum of them, with a 114% and 1061% higher risk, respectively. In females, the fruit-based dietary pattern was associated with a reduced risk of liver cancer (HRQ4-Q1: 0.63, 95%CI 0.42-0.95, Ptrend = 0.03). In both males and females, null associations were observed between the meat-based dietary pattern and the risk of liver cancer. CONCLUSION: A vegetable-based dietary pattern in males and a fruit-based dietary pattern in females tended to have a protective role on liver cancer risk. This study provided updated information that might be applied to guide public health action for the primary prevention of liver cancer.

A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese men.

Dietary factors have been extensively investigated as possible risk factors for liver cancer, but the evidence is inconclusive. Our study systematically assessed the association between 142 foods and nutrients and liver cancer risk in a Chinese population using a diet-wide association study. Based on data from 59,844 men in the Shanghai Men's Health Study (SMHS), we assessed the diet intake by dietary questionnaires. Cox regression was used to quantify the association between each food and nutrient and liver cancer risk. A false discovery rate (FDR) of 0.05 was used to select the foods and nutrients for validation. In the cohort, 431 liver cancer cases were identified during 712,373 person-years of follow-up. Retinol (HR per 1 SD increment = 1.09, 95% CI: 1.03-1.14) was associated with a higher risk of liver cancer, whereas onions (HR per 1 SD increment = 0.67, 95% CI: 0.54-0.84) and manganese (HR per 1 SD increment = 0.85, 95% CI: 0.78-0.94) were inversely associated with liver cancer risk. In the replication analysis, estimates for these foods and nutrients were similar in magnitude and direction. Our findings confirm that retinol, onions and manganese were associated with liver cancer risk, which provides reliable evidence between diet and liver cancer development.

3DSN-Net: A 3-D Scale-Aware convNet With Nonlocal Context Guidance for Kidney and Tumor Segmentation From CT Volumes.

Automatic kidney and tumor segmentation from CT volumes is a critical prerequisite/tool for diagnosis and surgical treatment (such as partial nephrectomy). However, it remains a particularly challenging issue as kidneys and tumors often exhibit large-scale variations, irregular shapes, and blurring boundaries. We propose a novel 3-D network to comprehensively tackle these problems; we call it 3DSN-Net. Compared with existing solutions, it has two compelling characteristics. First, with a new scale-aware feature extraction (SAFE) module, the proposed 3DSN-Net is capable of adaptively selecting appropriate receptive fields according to the sizes of targets instead of indiscriminately enlarging them, which is particularly essential for improving the segmentation accuracy of the tumor with large scale variation. Second, we propose a novel yet efficient nonlocal context guidance (NCG) mechanism to capture global dependencies to tackle irregular shapes and blurring boundaries of kidneys and tumors. Instead of directly harnessing a 3-D NCG mechanism, which makes the number of parameters exponentially increase and hence the network difficult to be trained under limited training data, we develop a 2.5D NCG mechanism based on projections of feature cubes, which achieves a tradeoff between segmentation accuracy and network complexity. We extensively evaluate the proposed 3DSN-Net on the famous KiTS dataset with many challenging kidney and tumor cases. Experimental results demonstrate our solution consistently outperforms state-of-the-art 3-D networks after being equipped with scale aware and NCG mechanisms, particularly for tumor segmentation.

Predictive model for persistent hypertension after surgical intervention of primary aldosteronism.

Primary aldosteronism (PA) is one of the most common causes of secondary hypertension and is potentially curable. However, a large number of patients still undergo persistent hypertension (PHT) after unilateral adrenal surgery. This research retrospectively studied the factors associated with this clinical difficulty and established a prediction model for the postoperative PHT; Methods: 353 patients from 2014 to 2021 with PA undergoing unilateral adrenal surgery were enrolled in this study. Clinical and biochemical characteristics were reviewed and the associating factors were examined using univariate and multivariate analysis. A nomogram-based prediction model was established correspondingly; results: 46.2% (163/190) of patients had post-surgical PHT. Multivariate analysis suggested that BMI ≥ 25, diabetes, duration of hypertension, male gender, and ARR were independent predictors of PHT after surgery. The prediction model based on the nomogram showed good discrimination ability (the C index of the training group and the validation group were 0.783 and 0.769, respectively), and the calibration curves and the Hosmer-Lemeshow test were good as well. Clinical usefulness was quantified using the decision curve analysis; This nomogram is an integration of the clinical and biochemical data of patients before surgery, and is a reliable tool with high accuracy for predicting the postoperative PHT in patients with PA.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range = 1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

Mutational characteristics of Chinese Han and ethnic minorities in southwestern China: a propensity score matched analysis.

Background: In China, there has never been a comprehensive analysis of lung cancer-associated genetic mutations focused on ethnic minorities in the southwestern region. Our study aimed to provide valuable information on lung cancer-associated genetic alterations for cancer diagnosis and treatment, especially in ethnic minorities. Methods: Retrospective data acquisition was conducted spanning 3 years (2016.01-2019.06) among all patients who were diagnosed with lung cancer at the Third Affiliated Hospital of Kunming Medical University Hospital. A total of 5,167 patients including 373 ethnic minorities were included in this study. Propensity score matching (PSM) was used to eliminate the bias between Han and other ethnic minorities, including gender, age, smoking history, metastasis status, clinical stage, histological type, sample type, region, and Xuanwei origin. All tests were two-tailed, and significance was defined as P less than 0.05. Results: In terms of the prevalence of EGFR, EGFR L858R, EGFR T790M, ROS1, RET, MET, BRAF, and ERBB2 mutations, there was no significant difference among ethnic groups in Yunnan Province (P>0.05). A higher proportion of EGFR 19 deletion was observed in Hui patients with lung cancer compared with patients of other ethnicities in Yunnan (P=0.048). The prevalence of KRAS mutations was higher in Hani (17.65%, 3/17) and Han patients (11.44%, 80/699) than that in other Yunnan ethnicities (6.04%, 9/149; P=0.07). In Hui patients, ALK fusion was correlated with a history of non-smoking and male gender. In Bai patients, BRAF mutation was also correlated with a history of non-smoking. In all ethnic groups, EGFR mutation was more frequent in women. Conclusions: This study is the first in-depth large case-control study on genetic mutation profiles among multi-ethnic patients in southwestern China, especially focused on ethnic minorities in this area. Our study may facilitate the understanding of the etiology of this malignant disease and consequently help to reduce the incidence of lung cancer in Yunnan ethnic minority areas.

Characteristics of Environmentally Persistent Free Radicals in PM2.5 and the Influence of Air Pollutants in Shihezi, Northwestern China.

Environmentally persistent free radicals (EPFRs) are a kind of hazardous substance that exist stably in the atmosphere for a long time. EPFRs combined with fine particulate matter (PM2.5) can enter the human respiratory tract through respiration, causing oxidative stress and DNA damage, and they are also closely related to lung cancer. In this study, the inhalation risk for EPFRs in PM2.5 and factors influencing this risk were assessed using the equivalent number of cigarette tar EPFRs. The daily inhalation exposure for EPFRs in PM2.5 was estimated to be equivalent to 0.66-8.40 cigarette tar EPFRs per day. The concentration level and species characteristics were investigated using electron paramagnetic resonance spectroscopy. The concentration of EPFRs in the study ranged from 1.353-4.653 × 1013 spins/g, and the types of EPFRs were mainly oxygen- or carbon-centered semiquinone-type radicals. Our study showed that there is a strong correlation between the concentrations of EPFRs and conventional pollutants, except for sulfur dioxide. The major factors influencing EPFR concentration in the atmosphere were temperature and wind speed; the higher the temperature and wind speed, the lower the concentration of EPFRs. The findings of this study provide an important basis for further research on the formation mechanism and health effects of EPFRs.

Incidence, Mortality Features and Lifetime Risk Estimation of Digestive Tract Cancers in an Urban District of Shanghai, China.

Digestive tract cancers are the common cause of cancer deaths in both China and worldwide. This study aimed to describe the burden, recent trends and lifetime risks in the incidence and mortality of digestive tract cancers in an urban district of Shanghai, China. Our study extracted data on stomach, colon, rectum and liver cancers diagnosed in Changning District between 2010 and 2019 from the Shanghai Cancer Registry. We calculated age-standardized incidence and mortality rates, the risks of developing and dying from cancer, and the estimated annual percent changes. Between 2010 and 2019, 8619 new cases and 5775 deaths were registered with digestive tract cancers in the district. The age-standardized incidence rates (ASIRs) of liver cancer decreased steadily, whereas the ASIRs of stomach, colon and rectum cancers remained stable from 2010 to 2019. The age-standardized mortality rates (ASMRs) of stomach and liver cancers showed significant declining changes from 2010 to 2019 in both sexes, but that of colon and rectum cancers remained stable during the entire period. The risks of developing and dying from digestive tract cancers were substantially higher in men than women. The burden of digestive tract cancer and its disparities between sex and age group remain major public health challenges in urban Shanghai. To reduce the burden of digestive tract cancers, the government and researchers should develop and promote a healthy diet, organize a screening, and reduce the prevalence of smoking, alcohol drinking, and hepatitis B virus and hepatitis C virus infections.

Tooth Loss after Jaw Curettage Surgery: Associated Factors and Potential Benefit of Splint Application.

BACKGROUND: This retrospective study is aimed at (I) assessment of tooth loss and related parameters after jaw curettage of benign lesions and (II) assessment of the outcome of jaw curettage supported by splint insertion after at least six months of follow-up. Material and Methods. For (I), patients who had jaw curettage surgery in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University (Guangzhou, China) from July 2015 to June 2019 were included. For part (II), consecutive patients who came to the department from July to December 2019 that were additionally treated with dental splinting were involved in this study. Based on the patient records, age, gender, initial tooth mobility, follow-up outcome, and potential tooth loss (intra- or postoperatively) were recorded. Based on available radiographs, alveolar crest bone loss and root surface area supported by bone (RSA) were determined. RESULTS: (I) 128 patients with 305 teeth were included, of which 40 teeth were lost (success rate 86.9%), without statistical difference in gender, age, or tooth type (P > 0.05). Tooth mobility, RSA, and the presence of alveolar crest bone defects were associated to tooth loss (P < 0.001). (II) 17 patients with a medium follow-up period of 11 months (range 9 to 13 months) were enrolled. All lesion-involving teeth supported by splint treatment at risks of loss were preserved, showing an effective tooth retention rate in 17/17 cases (74/74 teeth, success rate: 100%). CONCLUSIONS: Tooth mobility and bone loss (lesion-related and/or periodontal) are potential risk predictors for tooth loss in the first year after jaw curettage surgery. Dental splints could be recommendable for teeth involved by jaw benign lesions with little bone support.

Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults.

BACKGROUND: People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared with their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared with uninfected people remain understudied. SETTING: The study site was Brigham and Women's Hospital, Harvard Medical School, Boston, MA. METHODS: We evaluated skeletal muscle tissue for levels of total nicotinamide adenine dinucleotide (NAD), NAD+, and nicotinamide adenine dinucleotide (NADH) in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus and/or cytomegalovirus and compared them with uninfected control participants. RESULTS: Of the 54 persons with muscle biopsy data, the mean age was 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection and was exacerbated by hepatitis C virus and cytomegalovirus coinfection, with lowest levels of total NAD, NAD+, and NADH among persons who were coinfected with all 3 viruses (P = 0.015, P = 0.014, and P = 0.076, respectively). Levels of total NAD, NAD+, and NADH in skeletal muscle were inversely associated with inflammation (P = 0.014, P = 0.013, and P = 0.055, respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P < 0.001 and sCD163: P < 0.001) and immune activation (CD38 and human leukocyte antigen-DR expression on CD8 T cells: P < 0.001). In addition, coinfection was associated with increased physiologic frailty based on the Veteran Aging Cohort Study 1.0 index assessment (P = 0.001). CONCLUSIONS: Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.

Dose-response relationship between fat distribution and liver cancer incidence: A prospective cohort study in Chinese men.

BACKGROUND: Based on a prospective cohort study in middle-aged Chinese men, the current study characterized the dose-response relationships between fat distribution measurements and the incidence of primary liver cancer. METHODS: Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression models for the association between waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI) with liver cancer incidence. Dose-response curves were characterized using a restricted cubic spline function. RESULTS: After a mean follow-up time of 11.9 (SD = 2.4) years, 440 liver cancer cases were identified from 60,625 participants. WC, WHtR, ABSI, and BRI were found to be associated with an increased risk of liver cancer at a given level of body mass index (BMI), with multivariable-adjusted HRs of 1.19 (95% CI: 1.01-1.41), 1.26 (95% CI: 1.02-1.50), 1.12 (95% CI: 1.05-1.23) and 1.28 (95% CI: 1.08-1.53) for per SD increment, respectively. Dose-response curves suggested that the risk increased rapidly above the median levels of WC, WHtR, and BRI. For ABSI, the risk decreased from the minimum level to about the 35th percentile and increased slowly thereafter. CONCLUSIONS: The current study suggested an association between abdominal obesity in middle age and increased risk of primary liver cancer at a given level of BMI. WHtR and BRI were better predictors of liver cancer risk compared with WC and ABSI.

Joint impact of BMI, physical activity and diet on type 2 diabetes: Findings from two population-based cohorts in China.

AIMS: Limited epidemiological data on the combined impact of several lifestyle factors on type 2 diabetes (T2D) incidence was reported in Chinese population. This study aimed to examine how combinations of BMI, physical activity and diet relate to T2D incidence and estimate corresponding population attributable risk in the general population. METHODS: A total of 56,691 male and 70,849 female participants aged 40-74 years old in two population-based cohorts from the Shanghai Men's and Women's Health Studies were used for analysis. The Cox regression model was used to estimate the association between lifestyle factors collected at baseline and T2D incidence. Multivariable-adjusted population attributable risks were calculated for specific combinations of lifestyle factors. RESULTS: There were 3315 male and 5925 female incident T2D, with corresponding density incidence rates of 6.39 and 6.04 per 1000 person-years. If the healthiest group of healthy lifestyle index (HLI) was used as a reference, the hazard ratios (95% confidence intervals) of T2D increased monotonically in men [2.04 (1.75, 2.38); 2.94 (2.53, 3.42); 4.31 (3.66, 5.07)] and women [1.85 (1.64, 2.08); 2.79 (2.49, 3.13); 4.14 (3.66, 4.67)]. One point increase of HLI was related to 35% and 35% lower risk in men and women. About 52.7% and 58.4% cases in men and women could have been avoided if participants had been adherent to a healthy lifestyle of maintaining healthy body weight, eating a healthy diet and keeping physically active. CONCLUSIONS: An increased number of healthy lifestyle factors were associated with a decreased risk of T2D in the Chinese population. Future interventions targeted at combined healthy lifestyle factors are needed to reduce the burden of T2D.

Global pattern and trends of colorectal cancer survival: a systematic review of population-based registration data.

This review will describe the global patterns and trends of colorectal cancer survival, using data from the population-based studies or cancer registration. We performed a systematic search of China National Knowledge Infrastructure (CNKI), Wanfang Data, PubMed, Web of Science, EMBASE, and SEER and collected all population-based survival studies of colorectal cancer (up to June 2020). Estimates of observed and relative survival rates of colorectal cancer by sex, period, and country were extracted from original studies to describe the temporal patterns and trends from the late 1990s to the early 21st century. Globally, 5-year observed survival rates were higher in Seoul, Republic of Korea (1993-1997; 56.8% and 54.3% for colon and rectum cancers, respectively), Zhejiang province (2005-2010; 52.9% for colon cancer), Tianjin (1991-1999; 52.5% for colon cancer), Shanghai (2002-2006; 50.0% for rectum cancer) of China, and in Japan (1993-1996, 59.6% for colorectal cancer). Five-year relative survival rates of colorectal cancer in the Republic of Korea (2010-2014), Queensland, Australia (2005-2012), and the USA (2005-2009) ranked at relatively higher positions compared to other countries. In general, colorectal cancer survival rates are improving over time worldwide. Sex disparities in survival rates were also observed in the colon, rectum, and colorectal cancers in most countries or regions. The poorest age-specific 5-year relative survival rate was observed in patients > 75 years of age. In conclusion, over the past 3 decades, colorectal cancer survival has gradually improved. Geographic variations, sex differences, and age gradients were also observed globally in colorectal cancer survival. Further studies are therefore warranted to investigate the prognostic factors of colorectal cancer.

Dietary fat intake and liver cancer risk: A prospective cohort study in Chinese women.

OBJECTIVE: This study aimed to determine whether dietary fat intake increased liver cancer risk in Chinese women from a prospective population-based cohort. METHODS: A total of 72,704 Chinese women were followed up from the time of baseline recruitment (1996-2000) to the end of 2016. Dietary fat intake was calculated using a validated food frequency questionnaire. The Cox regression model was used to assess the hazard ratio (HR) and 95% confidence intervals (CI) for dietary fat intake and liver cancer risk. RESULTS: We identified 252 incident liver cancer cases out of 1,267,845 person-years during the overall follow-up time. Null associations, neither in quartiles nor per standard deviation (SD) increment, were detected between liver cancer risk and dietary total fat, fat subtypes and subtype ratios, and food sources. The HR (95% CI) of the 1-SD increment was 1.03 (0.90-1.17) for total fat, 1.06 (0.93-1.20) for saturated fat, 1.06 (0.93-1.21) for monounsaturated fat, and 1.00 (0.89-1.13) for polyunsaturated fat. Similar null associations were observed in stratification analyses according to body mass index and menopausal status. CONCLUSIONS: In our prospective cohort study, no significant association was observed in Chinese women between dietary fat and liver cancer risk, and in stratification and sensitivity analyses.

A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial.

BACKGROUND: Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer. METHODS: In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers. RESULTS: Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73). CONCLUSIONS: Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.

Dose-Response Association between Adiposity and Liver Cancer Incidence: A Prospective Cohort Study among Non-Smoking and Non-Alcohol-Drinking Chinese Women.

BACKGROUND: Based on a population with very low prevalence of smoking and alcohol drinking, we examined the associations between overall obesity and fat distribution in middle age, obesity in early adulthood, and adult weight gain with the risk of liver cancer incidence. METHODS: The associations between body mass index (BMI) at study enrollment and at age 20, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), adult weight gain, and annual average weight gain with the risk of liver cancer were estimated using Cox regression models. Multivariable-adjusted HRs and 95% confidence intervals (CIs) were calculated. RESULTS: After a mean follow-up time of 17.5 years, 241 liver cancer cases were identified from 69,296 participants. The HRs for per 5-kg/m2 increment of BMI, per 10-cm increment of WC and HC, and per 0.1-unit increment of WHtR in middle age were 1.29 (95% CI, 1.07-1.57), 1.23 (95% CI, 1.05-1.43), 1.30 (95% CI, 1.10-1.55), and 1.37 (95% CI, 1.07-1.75), respectively. The HRs for per 5-kg increment of absolute adult weight gain and per 0.5-kg/year increment of annual average weight gain were 1.15 (95% CI, 1.06-1.25) and 1.44 (95% CI, 1.08-1.92). CONCLUSIONS: Overall and abdominal obesity in middle age and weight gain through adulthood were positively associated with liver cancer risk among non-smoking and non-alcohol-drinking women. IMPACT: Based on a cohort of non-smoking and non-alcohol-drinking women, the current study confirmed the association between obesity in middle age and increased liver cancer risk and suggested weight gain through adulthood as a risk factor for liver cancer.

Silencing of Vangl2 attenuates the inflammation promoted by Wnt5a via MAPK and NF-κB pathway in chondrocytes.

BACKGROUND: The Wnt planar cell polarity (PCP) pathway is implicated in osteoarthritis (OA) both in animals and in humans. Van Gogh-like 2 (Vangl2) is a key PCP protein that is required for the orientation and alignment of chondrocytes in the growth plate. However, its functional roles in OA still remain undefined. Here, we explored the effects of Vangl2 on OA chondrocyte in vitro and further elucidated the molecular mechanism of silencing Vangl2 in Wnt5a-overexpressing OA chondrocytes. METHODS: Chondrocytes were treated with IL-1ß (10 ng/mL) to simulate the inflammatory microenvironment of OA. The expression levels of Vangl2, Wnt5a, MMPs, and related proinflammatory cytokines were measured by RT-qPCR. Small interfering RNA (siRNA) of Vangl2 and the plasmid targeting Wnt5a were constructed and transfected into ATDC5 cells. Then, the functional roles of silencing Vangl2 in the OA chondrocytes were investigated by Western blotting, RT-qPCR, and immunocytochemistry (ICC). Transfected OA chondrocytes were subjected to Western blotting to analyze the relationship between Vangl2 and related signaling pathways. RESULTS: IL-1ß induced the production of Vangl2, Wnt5a, and MMPs in a time-dependent manner and the significantly increased expression of Vangl2. Vangl2 silencing effectively suppressed the expression of MMP3, MMP9, MMP13, and IL-6 at both gene and protein levels and upregulated the expression of type II collagen and aggrecan. Moreover, knockdown of Vangl2 inhibited the phosphorylation of MAPK signaling molecules (P38, ERK, and JNK) and P65 in Wnt5a-overexpressing OA chondrocytes. CONCLUSIONS: For the first time, we demonstrate that Vangl2 is involved in the OA process. Vangl2 silencing can notably alleviate OA progression in vitro by inhibiting the expression of MMPs and increasing the formation of the cartilage matrix and can inhibit the proinflammatory effects of Wnt5a via MAPK and NF-κB pathway. This study provides new insight into the mechanism of cartilage inflammation.