BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

Objective:To investigate the accuracy and clinical utility of a newly designed acetabular bone defect classification system based on the ischial-gluteal pillar in assessing the severity of acetabular bone defects and guiding hip revision surgery.Methods:A retrospective analysis was conducted on 474 patients who underwent hip revision surgery for prosthetic loosening after total hip arthroplasty at our institution from January 2010 to December 2020, including 296 males and 178 females with a mean age of 70.4±8.9 years (range: 52-86 years). The accuracy of our classification system in guiding surgical procedures was evaluated by comparing preoperative defect classifications with intraoperative findings. Clinical outcomes were evaluated using preoperative and final follow-up Harris hip scores (HHS) and Oxford hip scores (OHS), as well as the incidence of complications.Results:Preoperative classifications included 143 Type I, 192 Type II (Type IIa: 86 cases, Type IIb: 59 cases, Type IIc: 47 cases), 93 Type III (Type IIIa: 54 cases, Type IIIb: 27 cases, Type IIIc: 12 cases), and 46 Type IV cases (Type IVa: 32 cases, Type IVb: 9 cases, Type IVc: 5 cases). Compared with intraoperative findings, classification accuracy was 99.3% for Type I (1 errors), 98.4% for Type II (3 errors), 97.8% for Type III (2 errors), and 97.8% for Type IV (1 misclassified as Type III). The mean follow-up was 5.8±4.4 years (range: 2-12 years). At final follow-up, mean HHS improved from 36.65±10.27 to 91.36±7.53, and mean OHS increased from 11.35±4.36 to 44.6±5.27 with significant difference ( P<0.001). Complications included one Type IV periprosthetic infection, one Type II hip dislocation, one Type I and two Type IV re-revisions (due to femoral loosening or graft resorption), one Type II and one Type III death unrelated to surgery, and one Type I postoperative thigh hematoma. No neurovascular injuries occurred. Conclusions:This novel 3D acetabular bone defect classification system, based on ischial-gluteal pillar integrity, provides accurate preoperative assessment and effectively guides surgical planning. Its application demonstrates favorable mid-term outcomes in hip revision surgery.

Endometriosis(EMs)is a common estrogen-depend-ent clinical disease with the pathological characteristics of malig-nant tumors,which has great impact on women's physical and mental health.In recent years,experimental exploration has re-vealed that ectopic foci are in a hypoxic environment outside the uterine cavity,and mitochondria,as the"functional factories"of the cells,play an important role in the process of planting and in-vasion,and the mitochondrial quality control system,which in-cludes mitochondrial oxidative stress,kinetics,autophagy,bio-genesis and calcium homeostasis,is a key mechanism for the e-quilibrium of the mitochondrial function.The mitochondrial quality control system,including mitochondrial oxidative stress kinetics,autophagy,biogenesis and calcium homeostasis,is a key mechanism for mitochondrial functional balance.Therefore,to clarify the role of the mitochondrial quality control system in the development of EMs with the help of rational and rigorous experi-mental and clinical studies can not only help to clarify the patho-genesis of the disease,but also explore the key targets in the prevention and treatment of the disease.Therefore,this article summarizes the research progress of mitochondrial quality control system in endometriosis,with a view to providing reference and theoretical basis for the etiology,pathogenesis and prevention strategies of EMs.

Objective: To compare the transcriptomic profiles between three distinct metabolic dysfunction⁃associat⁃mal murine model that more closely resembles human MASH progression . Methods: Forty 8 ⁃week⁃old male C57BL/6J mice were randomly assigned to either a control group fed normal chow diet ( NCD) or one of three MASH model groups receiving high⁃fat high⁃cholesterol diet (HFHCD) , choline⁃deficient high⁃fat diet (CDHFD) ,from three randomly selected mice per group were collected for mRNA sequencing ( mRNA⁃seq) analysis . Mean⁃bases . Overlap of functional profiles was analyzed by gene set enrichment analysis (GSEA) profiles to compare the mouse transcriptome with that of human patients at different stages of the disease . Additionally , Pearson ′s correla⁃tion analysis was used to explore the correlation between gene expression of murine models and human MASH . Results: Seven commonly up⁃regulated genes (Col1a1 , Smoc2 , Col6a1 , Gpx3 , Col16a1 , Spp1 and Crtap) were de⁃ways involving steatosis , hepatocellular injury and fibrosis were detected in the three MASH models at the pathway level . HFHCD and MCD might share more common traits . In comparing gene expression and pathway profiles be⁃tween different murine models and patients with different stages of MASH , all three murine MASH models showed a closer resemblance to the human progressive stages of MASH . Notably , the transcriptomic features of the CDHFD model were more consistent with those of human MASH . Conclusion There are certain similarities and differences among the transcriptional profiles of the three MASH models . The MASH models are more similar to the advanced stage of MASH in human patients . Compared to the other two models , the CDHFD model ′ s transcriptome profile more closely resembles human MASH .

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Objective This study aims to provide theoretical support for the formulation of thyroid nodule prevention and treatment strategies in Northwest China and to investigate the characteristics of thyroid nodules and their association with metabolic indicators in this population.Methods A cross-sectional survey was conducted by retrospectively enrolling healthy individuals who underwent routine health examinations at our hospital between January 1 and December 31,2023.A total of 38 919 participants were included.The detection rate of thyroid nodules was stratified by age and sex.Univariate and multivariate binary logistic regression analyses were performed to identify risk factors for thyroid nodules.Results Among the 38 919 participants,20 395 were men(52.4%)and 18 524 were women(47.6%).The overall detection rate of thyroid nodules was 47.1%(18 317/38 919),including 40.1%(8 187/20 395)in men and 54.7%(10 130/18 524)in women.Across all age groups,women had a significantly higher detection rate than men(P<0.001).The detection rate increased with age in both sexes(χ2trend=1392.867,P<0.001 in men;χ2trend=1521.215,P<0.001 in women).Significant differences were observed between participants with and without thyroid nodules in age,body mass index(BMI),fasting blood glucose(FBG),glycated hemoglobin(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triiodothyronine(T3),thyroid-stimulating hormone(TSH),and anti-thyroglobulin antibodies(TGAB),anti-thyroid microsomal antibodies,the proportion of hypertension and central obesity(all P<0.05).Multivariate binary logistic regression analysis identified female sex(OR=2.158),older age(OR=1.040),central obesity(OR=1.144),elevated FBG(OR=1.039),hypertension(OR=1.095),elevated TGAB(OR=1.008),and elevated T3(OR=1.154)as independent risk factors for thyroid nodules(all P<0.05).Conclusion Women in Northwest China are at higher risk of developing thyroid nodules.Screening and health management should be prioritized for older individuals,those with central obesity,elevated FBG,hypertension,elevated TGAB,and elevated T3 levels.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

Objective:To investigate the accuracy and clinical utility of a newly designed acetabular bone defect classification system based on the ischial-gluteal pillar in assessing the severity of acetabular bone defects and guiding hip revision surgery.Methods:A retrospective analysis was conducted on 474 patients who underwent hip revision surgery for prosthetic loosening after total hip arthroplasty at our institution from January 2010 to December 2020, including 296 males and 178 females with a mean age of 70.4±8.9 years (range: 52-86 years). The accuracy of our classification system in guiding surgical procedures was evaluated by comparing preoperative defect classifications with intraoperative findings. Clinical outcomes were evaluated using preoperative and final follow-up Harris hip scores (HHS) and Oxford hip scores (OHS), as well as the incidence of complications.Results:Preoperative classifications included 143 Type I, 192 Type II (Type IIa: 86 cases, Type IIb: 59 cases, Type IIc: 47 cases), 93 Type III (Type IIIa: 54 cases, Type IIIb: 27 cases, Type IIIc: 12 cases), and 46 Type IV cases (Type IVa: 32 cases, Type IVb: 9 cases, Type IVc: 5 cases). Compared with intraoperative findings, classification accuracy was 99.3% for Type I (1 errors), 98.4% for Type II (3 errors), 97.8% for Type III (2 errors), and 97.8% for Type IV (1 misclassified as Type III). The mean follow-up was 5.8±4.4 years (range: 2-12 years). At final follow-up, mean HHS improved from 36.65±10.27 to 91.36±7.53, and mean OHS increased from 11.35±4.36 to 44.6±5.27 with significant difference ( P<0.001). Complications included one Type IV periprosthetic infection, one Type II hip dislocation, one Type I and two Type IV re-revisions (due to femoral loosening or graft resorption), one Type II and one Type III death unrelated to surgery, and one Type I postoperative thigh hematoma. No neurovascular injuries occurred. Conclusions:This novel 3D acetabular bone defect classification system, based on ischial-gluteal pillar integrity, provides accurate preoperative assessment and effectively guides surgical planning. Its application demonstrates favorable mid-term outcomes in hip revision surgery.