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Background/Objectives: Whether an increased genetic risk of steatotic liver disease (SLD) can be offset by maintaining a healthy weight remains unknown. We aimed to clarify the associations among the body mass index (BMI) and its change patterns with SLD and assess whether genetic susceptibility can modify these associations in Chinese people. Methods: A total of 10,091 and 6124 participants from the Health Omics Preventive Examination (HOPE) Program were enrolled in cross-sectional and follow-up analyses, respectively. BMI change patterns were defined according to the BMI at baseline and the last follow-up visit. Genetic risk was estimated using the polygenic risk score (PRS) derived from variants in PNPLA3 , TM6SF2 , MBOAT7 , and GCKR . Data were analyzed using logistic regression models and Cox proportional-hazards models. Results: The analyses of the BMI and genetic risk simultaneously showed a dose-response association with the risk of SLD ( p -trend < 0.001). Significant interactions between BMI and PRS were found for alanine aminotransferase (ALT) elevation ( p = 0.007) and aspartate aminotransferase (AST) elevation ( p < 0.001). Weight loss led to a 71%, 60%, and 67% lower risk of SLD, ALT elevation, and AST elevation, compared with stable overweight/obesity. A significant interaction between the genetic risk and BMI change patterns in ALT elevation was observed ( p = 0.008). The absolute risk reductions associated with weight loss were greater for participants at a high genetic risk (26.60, 12.29, and 9.31 per 100 person years for SLD, ALT elevation, and AST elevation, respectively). Conclusions: Maintaining a healthy weight reduces the liver injury risk among all individuals, and the risk reduction is greater among the subset with a high genetic risk of SLD.

Background: In recent years, neonatal hearing screening (NHS) has gained rapid traction in both developed and developing nations. However, the efficacy of these efforts depends on comprehensive standardization across all screening facets. This study aimed to assess the status and quality of NHS by investigating the knowledge, attitudes, beliefs, and practices of hearing screening practitioners regarding NHS., Methods: A cross-sectional survey was conducted, and an online questionnaire based on the knowledge-attitude/belief ( A / B )-practice model was distributed to all NHS practitioners in Luzhou, western China. Valid questionnaires were examined and uniformly graded., Results: A total of 63 valid questionnaires were collected. The practitioners were mainly female (96.83%), with nursing backgrounds (63.49%), and undergraduate degrees (66.67%). Most had ≤5 years of experience (74.60%) and had junior/intermediate titles (93.65%). The NHS within the Luzhou area started in 2006 with provincial institutions, expanding to 42 institutions by 2022. Statistically significant correlations were observed between the A / B score and the conducting years of each NHS institution ( p  < .05) as well as between the Knowledge (K) and Practice (P) scores ( p  < .01). No significant correlation was found between the K score, P score, A / B score, and working years of practitioners ( p  > .05), or in the total score of NHS institutions at different levels or in different counties by one-way ANOVA ( p  > .05)., Conclusions: It has been 17 years since the first medical institution in Luzhou launched NHS, and the overall performance of practitioners from different institutions has been consistent in terms of their knowledge, attitudes, or level of practice. However, there is room for further improvement in both the professional development of individuals and aspects related to work, such as health education and long-term follow-up.

Introduction: It is difficult to detect acute low-tone sensorineural hearing loss (ALHL) because of only low-frequency hearing loss and atypical early symptoms. The etiology of ALHL is still elusive, and psychosomatic factors influence deafness and tinnitus. Therefore, this study aimed to clarify the correlation between psychosomatic factors and the incidence of ALHL to facilitate the prevention of ALHL., Methods: Patients with stuffy ears and tinnitus who were admitted to the Outpatient Clinic of the Affiliated Hospital of Southwestern Medical University (Luzhou, China) from July 2020 to May 2023 were identified in this retrospective study. The general data, hearing screening form, the Life Event Scale, and the Pittsburgh Sleep Quality Index scale were employed to assess patients' hearing levels and stimuli of psychosomatic symptoms. Finally, the correlation among the stimuli of life events, sleep quality, and ALHL was statistically analyzed., Results: A total of 97 ALHL patients and 97 healthy participants were enrolled in the case group and control group, respectively. The two groups had no significant differences in general information (all p  > 0.05). The amount of negative life event stimuli was significantly larger in ALHL patients than in the normal population ( p  = 0.000). Patients with ALHL had significantly poorer sleep quality than the healthy population ( p  = 0.000). There was a positive correlation between sleep quality and ALHL severity (250 Hz: r  = 0.336, p  = 0.001; 500 Hz: r  = 0.299, p  = 0.003), and a positive correlation between the stimuli of life events and sleep quality ( r  = 0.535, p  = 0.000)., Discussion: Sleep quality was found to be closely associated with the degree of hearing loss in ALHL patients, and there was also a strong correlation between sleep quality and the stimuli of life events. Therefore, psychosomatic factors may play an important role in the occurrence of ALHL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Huang, Jiang, Lan, Huang, Liu and Lai.)

Background: Recent genome-wide association studies (GWASs) in liver diseases have generated some polygenic risk scores (PRSs), but their predictive effectiveness on hepatocellular carcinoma (HCC) risk assessment remains unclear., Methods: Here, we constructed a novel combined polygenic risk score and evaluated its increment to the well-established risk model. We used 15 HCC-associated genetic loci from two PRSs and FinnGen GWAS data to calculate a PRS-combined score and to fit the related PRS model in the UK Biobank cohort (N = 436,162). The PRS-combined score was further assessed for risk stratification for HCC integrating with the recommended clinical risk scores., Results: The PRS-combined model achieved a better AUC (0.657) than that of PRS-HFC (0.637) and PRS-cirrhosis (0.645). The top 20% of the PRS-combined distribution had a 3.25 increased risk of HCC vs. the middle decile (45-55%). At the population level, the addition of PRS-combined to the CLivD score significantly increased the C-statistic (from 0.716 to 0.746) and provided a remarkable improvement in reclassification (NRI = 0.088) at the 10-year risk threshold of 0.2%. In clinic, additional assessment of PRS-combined would reclassify 34,647 intermediate-risk participants as high genetic risk, corresponding to an increase of 63.92% (62/97) of the HCC events classified at high risk using the Fibrosis-4 alone., Conclusions: The PRS may enhance HCC risk prediction effectiveness in the general population and refine risk stratification of the conventional clinical indicator., (© 2024. Japanese Society of Gastroenterology.)

Background and Aims: Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA are structural somatic variants that indicate clonal hematopoiesis. This study aimed to investigate whether mCAs contribute to the risk of cirrhosis and modify the effect of a polygenic risk score (PRS) on cirrhosis risk prediction., Methods: mCA call sets of individuals with European ancestry were obtained from the UK Biobank. The PRS was constructed based on 12 susceptible single-nucleotide polymorphisms for cirrhosis. Cox proportional hazard models were applied to evaluate the associations between mCAs and cirrhosis risk., Results: Among 448,645 individuals with a median follow-up of 12.5 years, we identified 2,681 cases of cirrhosis, 1,775 cases of compensated cirrhosis, and 1,706 cases of decompensated cirrhosis. Compared to non-carriers, individuals with copy-neutral loss of heterozygosity mCAs had a significantly increased risk of cirrhosis (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.81). This risk was higher in patients with expanded cell fractions of mCAs (cell fractions ≥10% vs. cell fractions <10%), especially for the risk of decompensated cirrhosis (HR 2.03 [95% CI 1.09-3.78] vs. 1.14 [0.80-1.64]). In comparison to non-carriers of mCAs with low genetic risk, individuals with expanded copy-neutral loss of heterozygosity and high genetic risk showed the highest cirrhosis risk (HR 5.39 [95% CI 2.41-12.07])., Conclusions: The presence of mCAs is associated with increased susceptibility to cirrhosis risk and could be combined with PRS for personalized cirrhosis risk stratification., Competing Interests: The authors have no conflict of interests related to this publication., (© 2024 Authors.)

Epidemiological data is scarce regarding the association between exposure to mixtures of per- and polyfluoroalkyl substances (PFASs) and liver injury in the general populace. The current research used data from the National Health and Nutrition Examination Survey (2009-2018). The PFAS exposure levels were defined by the serum concentrations of PFASs with > 70% detection in samples, namely perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDeA), and perfluorooctane sulfonic acid (PFOS). Liver injury was assessed from two aspects: first, the degree of liver inflammation was determined based on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyltransferase (GGT), and total bilirubin (TBIL) levels; second, the degree of liver fibrosis was determined based on fibrosis-4 (FIB-4) index. We assessed the associations between individual or total PFAS exposure and these outcomes using multivariable linear regression models and logistic regression models, restricted cubic splines, and weighted quantile sum regression. Among the samples of 7484 American adults, the median concentration of PFOS was the highest, followed by PFOA and PFHxS. Using multivariable linear regression, a positive correlation was observed between all PFASs and liver enzymes such as ALT, AST, and TBIL. Additionally, the weighted quantile sum model indicated an overall positive association between the five PFASs and liver injury indicators. For liver function biomarkers and liver fibrosis, PFNA and PFOS were the most heavily weighting chemicals, respectively. Our findings provide new epidemiological evidence indicating a potential association between PFAS exposure and adverse effects on liver injury biomarkers, highlighting the potentially harmful effects of PFAS exposure on liver health.

Background & Aims: Physical activity, sedentary behaviour, and genetic variants have been associated with the nonalcoholic fatty liver disease (NAFLD). However, whether and how the degree of healthy activity patterns may modify the impact of genetic susceptibility on NAFLD remains unknown., Methods: Behaviour activity factors were determined according to total physical activity (TPA) and sedentary time. The polygenic risk score (PRS) was calculated by variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Cox regression was used to analyse the associations of genetic and behaviour activity factors with incident NAFLD in the UK Biobank (N = 338 087)., Results: During a median follow-up of 12.4 years, 3201 incident NAFLD cases were ascertained. Analyses of TPA and sedentary time simultaneously showed a dose-response association with the risk of NAFLD (p trend  < .001). The association of behaviour activity patterns with NAFLD varied by genetic variants. Of the subjects with high genetic risk, we observed a null protective effect of moderate or high TPA on NAFLD risk, while sitting less than three hours a day significantly decreased the risk of NAFLD (p = 3.50 × 10 -4 ). The high genetic risk of NAFLD can also be offset by the combination of moderate physical activity and shorter sedentary time. Moreover, the high genetic risk group has the greatest reduction of 10-year absolute risk (6.95 per 1000 person-years) if reaching both healthy activities., Conclusions: Moderate-to-high physical activity and favourable sedentary behaviour may be lifestyle modifications in preventing NAFLD, which could offset the harmful effect of predisposing genetic factors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Cognitive impairment is prevalent among individuals, especially women, with methamphetamine dependence. Although aerobic exercise has been shown to affect cognitive function in humans and animals, few related studies have focused on subjects with methamphetamine dependence., Purpose: The aim of this study was to assess the detoxification-related effects of aerobic exercise on cognitive function in women with methamphetamine dependence., Methods: A randomized controlled trial was used with 98 women with methamphetamine dependence undergoing a detoxification program at a mental hospital. The women were distributed using a computer-generated grouping random method into either the study or control group. The investigator conducting the baseline questionnaire, the neuropsychologist assessing the cognitive function, and the data analyst were blinded to group assignment. In addition to hospital routine care, the study group received an aerobic exercise intervention for 3 months. The control group only received hospital routine care. Attention and working memory were measured using the Trail Making Test and Digit Span Test, verbal memory was measured using Logical Memory (LM) and Memory for Persons Data (MPD), and executive function was measured using the Color-Word Stroop Test., Results: Forty-nine participants were randomized into each group, and the valid data of 43 participants in the study group and 46 in the control group were analyzed. The study group showed significantly more improvement over time in terms of Digit Span Test, Trail Making Test, LM-delayed, MPD-5 minutes delayed, MPD-30 minutes delayed, and Color-Word Stroop Test than the control group (p < .05). LM-immediate and MPD-immediate scores showed that the effects of time and the interaction between time and group were significant but that the main effect of group was not., Conclusions/implications for Practice: Women undergoing detoxification for methamphetamine dependence may practice aerobic exercise to improve attention, working memory, executive function, and parts of verbal memory. Aerobic exercise may be incorporated into detoxification treatment programs to facilitate the recovery of cognitive functions in women., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc.)