A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.

In vivo study of a reserved atrial septal puncture area patent foramen ovale occluder.

PURPOSE: After patent foramen ovale interventional closure, puncture of the interatrial septum through the occluder is difficult but sometimes needed for further interventional treatment. This paper presents findings from an in vivo experimental study of a reserved atrial septal puncture area patent foramen ovale occluder. MATERIALS AND METHODS: A patent foramen ovale model was established in canines using trans-septal puncture of the fossa ovale and high-pressure balloon dilation. Then, patent foramen ovale closure was performed with a reserved atrial septal puncture area and all canines were raised for 3 months. Then, the occluder was crossed and left atrial angiography was performed on the septal area with the occluder. Finally, DSA angiography, echocardiography, and histology were used to evaluate the performance and feasibility of the reserved atrial septal puncture area. RESULTS: A patent foramen ovale model was successfully established in 10 canines using the atrial septal puncture method. The average diameter of the patent foramen ovale was 3.77 ±0.19 mm, and the patent foramen ovale was successfully closed in all canines using a reserved atrial septal puncture area. As assessed using transoesophageal echocardiography, the new occluder exhibited an ideal position and was occluded entirely without a residual shunt intraoperatively and postoperatively. A 100% success rate of atrial septum puncture was achieved across the new occluder. The occluders were completely endothelialised 3 months post-implantation. CONCLUSIONS: The reserved atrial septal puncture area was effective in patent foramen ovale closure and exhibited positive sealing performance and biological compatibility. Trans-septal puncture was feasible and effective after reserved atrial septal puncture area patent foramen ovale closure.

Experimental study of the bilateral asymmetric single-rivet occluder device for transcatheter patent foramen ovale closure with reserved interatrial septal puncture area.

Purpose: To evaluate a noval bilateral asymmetric single-rivet occluder with reserved interatrial septal puncture area for treating patent foramen ovale (PFO). Materials and methods: The study established a pig model of patent foramen ovale (PFO) by puncturing the oval fossa and then performing high-pressure balloon dilation. A specially designed bilateral asymmetric occluder for the reserved interatrial septal puncture area was then. used to close the PFO through catheter-based intervention. The pigs were kept for 3 months before undergoing a second catheter-based intervention, involving interatrial septal puncture using a newly developed occluder in the reserved interatrial septal puncture area. During 6 months, the experimental pigs underwent assessment using digital subtraction angiography (DSA), echocardiography, and histological evaluation. Results: A patent foramen ovale (PFO) model was successfully established in 6 pigs using the puncture atrial septum high-pressure balloon dilation method. The diameter of the unclosed PFO was measured (3.56 ± 0.25 mm). Using the newly developed occluder device, all 6 pigs with unclosed PFO underwent successful catheter-based closure surgeries, with intraoperative and postoperative transesophageal echocardiography showing excellent device positioning and complete closure without residual shunting. After 3 months of implantation, the catheter-based interatrial septal puncture was performed through the reserved interatrial septal puncture area, and all procedures were successful. Immediately following euthanasia, a histological examination revealed intact and undamaged occluder devices with visible puncture holes in the reserved interatrial septal puncture area. No fracture of the nitinol wire was observed, and the surface of the occluder device showed coverage of endothelial and connective tissues. Utilizing a bilateral asymmetric single-rivet occluder device implanted through the reserved interatrial septal puncture area has proven effective in closing PFO. After implantation, the occluder device allows subsequent interatrial septal puncture procedures through the reserved area. Conclusion: The novel occluder device demonstrated excellent closure performance, biocompatibility, and puncturability in the experiment. This indicates the feasibility of conducting further catheter-based interventions on the interatrial septum.

Gender and Age-Specific Differences in the Association of Thyroid Function and Hyperuricemia in Chinese: A Cross-Sectional Study.

Objective: We aimed to explore gender and age-specific influences on the association between thyroid function and hyperuricemia (HUA) in a large Chinese population. Methods: A total of 19,013 individuals (10,563 males and 8,450 females) were recruited. The association between HUA and thyroid function was analyzed by multivariate logistic regression, and the analyses were stratified by gender and age. Thyroid function subgroups were determined in 2 methods including thyroid status and thyroid-stimulating hormone (TSH) quartiles. Results: Overall prevalence of serum uric acid (SUA) and HUA was significantly higher in males, while TSH value and thyroid dysfunction were higher in females. Increasing trends of the TSH level in both genders as well as HUA prevalence in females were found positively along with aging. However, males showed a reduced trend in HUA risk negatively with aging. Our population showed that the risk of developing HUA in hyperthyroidism, normal euthyroidism, mild hypothyroidism, and overt hypothyroidism subgroups had adjusted ORs of 0.634, 1.229, 1.370, and 1.408, respectively, in males. Subjects in females showed a similar increased risk of HUA with ORs of 0.770, 1.198, 1.256, and 1.458, respectively. Similar tendency was observed in TSH quartiles; the above two models showed significantly higher risk of HUA in the high TSH group of males, but not of females. Aging was a significant risk factor for HUA, particularly in older females after adjusting for TSH. Conclusion: The risk of HUA was positively associated with an elevation in TSH levels in both genders irrespective of age, indicating the protective effects of low TSH on HUA. Males with high TSH value were more vulnerable to suffer significant risk of HUA.

The older, the less potential benefit for type 2 diabetes from weight control.

BACKGROUND: Although moderate weight loss improves outcomes of type 2 diabetes mellitus (T2DM) in young and middle-aged adults, there is a lack of high-quality evidence to support the strong relationship between obesity and T2DM in older people. This study aims to investigate whether the association of obesity with T2DM changes with aging. METHODS: In this cross-sectional study, we recruited 63,180 Chinses and US subjects from 3 datasets. Subjects were divided into young & middle-aged (≤59 years), young-old (60-75 years), and old-old (≥75 years). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for the association between obesity and T2DM, stratified by common confounders. A sliding-window based algorithm and restricted cubic splines were used to smoothly estimate the changes with aging. RESULTS: The OR (95% CI) for the associations between general obesity and T2DM were decreased from the young & middle-aged group (OR, 5.91; 95% CI, 5.33-6.56) to the young-old group (OR, 3.98; 95% CI, 3.56-4.45) and then to the old-old group (OR, 3.06; 95% CI, 2.57-3.66). The trend for this reduced association with aging persisted after stratification by obesity type, region, gender, recruiting time, hypertension, and hyperlipidemia in both Chinese and Americans. We also identified a weakened gender disparity for this association between the young & middle-aged subjects (P for disparity < 0.001) and the old-old group (P for disparity = ~ 0.36). CONCLUSIONS: The obesity-T2DM association is clearly reduced with aging, which indicates that the elderly may gain fewer potential benefits in weight lose than the younger patients. Considering this attenuated association, as well as the increased incidence of geriatric syndrome in the elderly, clinicians should comprehensively balance the benefits and side effects of weight loss in geriatric T2DM interventions.

Inhibition of endoplasmic reticulum stress prevents high-fat diet mediated atrial fibrosis and fibrillation.

Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High-fat diet (HFD)-induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD-induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4-phenylbutyric acid (4-PBA) group, and the HFD + 4-PBA group. At the age of 4 weeks, the HFD group and the HFD + 4-PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP-78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p-PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4-PBA group. In summary, HFD-induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF-associated obesity.

Identification of new genetic variants of HLA-DQB1 associated with human longevity and lipid homeostasis-a cross-sectional study in a Chinese population.

Healthy longevity has been an unremitting pursuit of human, but its genetic and the environment causes are still unclear. As longevity population is a good healthy aging model for understanding how the body begin aging and the process of aging, and plasma lipids metabolism and balance is a very important to life maintain and physiologic functional turnover. It is important to explore how the effect of genetic variants associated long-life individuals on lipids metabolism and balance. Therefore, we developed a comparative study based population which contains 2816 longevity and 2819 control. Through whole-exome sequencing and sanger sequencing genotypes, we identified four new single nucleotide polymorphisms of HLA-DQB1(major histocompatibility complex, class II, DQ beta 1), rs41542812 rs1049107 rs1049100 rs3891176(Prange=0.048-2.811×10-8 for allele frequencies), associated with longevity in Chinese Longevity Cohort. Further, by analysis of the longevity-variants linked to blood lipids, we identified HLA-DQB1 rs1049107, T-carriers (PHDL=0.006, OR: 11.277; PTG=9.095×10-7, OR: 0.025; PLDL/HDL=0.047, OR: 1.901) and HLA-DQB1 rs1049100, T-carriers (PTG=1.799×10-6, OR: 0.028) associated with lipid homeostasis in long lived individuals. Our finding showed that longevity and lipid homeostasis were associated with HLA-DQB1 and suggested that immune gene variants could act on both new function of maintaining the homeostasis and anti-aging in longevity.

Prevalence of metabolically obese but normal weight (MONW) and metabolically healthy but obese (MHO) in Chinese Beijing urban subjects.

The aim of this study was to assess the prevalence of metabolic syndrome (MetS) in non-obese adults (body mass index (BMI) < 25 kg/m2) and the prevalence of obese adults (body mass index (BMI) ≥ 25 kg/m2) without MetS in Chinese Beijing urban subjects. A cross-sectional study was conducted and the subjects who came to the hospital to receive a health examination were enrolled randomly. Regardless of age stratification, men have a higher prevalence of MetS than women. Among the urban Beijing population, prevalence of metabolically obese but normal weight (MONW) is lower than metabolically healthy but obese (MHO) regardless of gender. Except for the underweight group, participants exhibit significant differences between MetS and non-MetS subgroups in all tested variables in normal weight and overweight groups, whereas MONW and MHO participants exhibit significant differences in all variables except for creatinine (CR), aspartate aminotransferase (AST), uric acid (UAC) and high-density lipoprotein cholesterol (HDL-C). Women tend to have a higher MONW prevalence but lower MHO prevalence than men. Accordingly, MetS happens more frequently among those 40-59 yr. Besides, sex, age, WC, SBP, DBP, ALT, FG, UAC, TG, HDL-C and LDL-C are risk factors for MetS after multivariate adjustment. In conclusion, the prevalence of MONW is lower than MHO regardless of gender. Women tend to have a higher MONW prevalence but lower MHO prevalence than men.

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population.

In European populations, 7 single nucleotide polymorphisms (SNPs) on chromosome 17q, 3 SNPs on 17q12, and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study. In Japanese populations, the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment. However, whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown. Therefore, we conducted a case-control study in a northern Chinese population and tested 2 SNPs, rs4430796 and rs1859962, on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with sequencing. We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles, onset ages, Gleason scores, PSA levels, and pathologic stages. We found a significant difference in the G allele of SNP rs1859962 (P = 0.035, OR = 1.51, 95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls (P > 0.05). Neither of the SNPs was significantly associated with the onset age, Gleason score, PSA level, pathologic stage, or other clinical indicators of patients with prostate cancer (P > 0.05). Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.