Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Objective:To analyze the changes in the incidence trend of liver cancer in Taizhou of Jiangsu Province, from 2012 to 2020 and provide reference for tumor prevention and control and management.Methods:Liver cancer incidence data from 2012 to 2020 were extracted from the Taizhou Center for Disease Control and Prevention's tumor registry system. Demographic data were used to calculate the crude incidence rate, age-standardized incidence rate (ASIR), Chinese age-standardized incidence rate (CASIR; based on China's 2010 standard population), and world age-standardized incidence rate (WASIR; based on Segi's world standard population). The Joinpoint regression model was applied to identify inflection points in liver cancer incidence trends during 2012-2020, and annual percentage change (APC) with average annual percentage change (AAPC) were calculated.Results:In 2020, the crude incidence ratio (CIR) of liver cancer in Taizhou was 34.6 per 100 000, with CASIR and WASIR at 19.6 per 100 000 and 14.9 per 100 000, respectively. From 2012 to 2020, the male-to-female ratio of new liver cancer cases was 2.94∶1 (10 455 males vs. 3 559 females), with male incidence consistently higher than female. Overall liver cancer incidence in Taizhou initially increased and then decreased after 2017 (2012-2017: APC=6.4%, P=0.014; 2017-2020: APC=-9.5%, P=0.035), peaking at a CASIR of 26.2 per 100 000 in 2017. The trend in male incidence mirrored the overall pattern, rising before 2017 and declining thereafter (2012-2017: APC=6.2%, P=0.005; 2017-2020: APC=-9.0%, P=0.016). Female incidence remained relatively stable (2012-2016: APC=11.0%, P=0.054; 2016-2020: APC=-6.5%, P=0.130). Conclusions:Liver cancer incidence in Taizhou increased before 2017 and declined thereafter, with 2017 as the turning point. Amid population aging, liver cancer remains a persistent public health challenge requiring sustained attention.

Objective The causal relationship between endometriosis(EMs)and 15 trace elements including copper,calcium,carotene,folic acid,iron,magnesium,potassium,selenium,vitamin A,vitamin B12,vitamin B6,vitamin C,vitamin D,vitamin E and zinc was analyzed by double sample Mendelian randomization(MR).Methods Multiple trace elements were used as exposure factors,and the incidence risk of EMs was used as the outcome factor for two-sample MR analysis.The data were sourced from the publicly available integrative epidemiology unit open Genome-Wide Association Studies database and Finnish Genome Research Project database.Five Mendelian randomization analysis methods were employed to investigate the causal relationship between EMs and trace elements.Additionally,sensitivity analysis was carried out to evaluate the influence of heterogeneity and horizontal pleiotropy on the results of the MR analysis.Results The impact of trace elements on various types of EMs varies.The results of the inverse variance weighted(IVW)method indicated that trace element calcium(OR=1.465,95％CI:1.094-1.962)and vitamin B6(OR=1.580,95％CI:1.146-2.178)might be risk factors for ovarian EMs.Vitamin B6(OR=0.203,95％CI:0.044-0.939)may be a protective factor for tubal EMs.The above research results were not affected by heterogeneity and horizontal pleiotropy(P＞0.05).This study did not find a causal relationship between other trace elements and EMs.Conclusion The trace elements calcium and vitamin B6 predicted by genetics may play a regulatory role in the development of EMs.

Objective To investigate the relationship between different interleukins (ILs) and gynecological tumors, including cervical cancer, endometrial cancer, and uterine leiomyoma using two-sample Mendelian randomization (MR) analysis. Methods IL and gynecological tumor data were obtained from European populations by using the IEU OpenGWAS open database. Two-sample MR analysis was applied, different interleukins were used as exposure factors, significant SNP in GWAS data were selected as instrumental variables, and the instrumental variables were independent of each other. The risk of three kinds of gynecological tumors was analyzed separately to explore the causal relationship between ILs predicted by genes and outcome indicators. The TwoSampleMR package in R language (4.3.1) software was used for statistical analysis. MR analysis was performed using inverse variance weighted, MR Egger regression, weighted median, simple mode, and weighted mode methods. Results IL-18 receptor 1 (P=0.039) and IL-24 (P=0.025) were negatively correlated with the risk of cervical cancer. IL-4 (P=0.040), IL-21 (P=0.026), and IL-37 (P=0.027) were positively correlated with the risk of endometrial cancer. IL-15 receptor subunit alpha (P=0.005) was negatively correlated with the risk of endometrial cancer. IL-17A (P=0.005) and IL-37 (P=0.018) were negatively correlated with the risk of uterine leiomyoma. IL-21 (P=0.035) was positively correlated with the risk of uterine leiomyoma. Conclusion Genetically predicted IL-4, IL-15Rα, IL-17A, IL-18R1, IL-21, IL-24, and IL-37 are causally associated with the risk of three gynecological tumors. Further exploration of the molecular mechanism of ILs in gynecological tumors may provide potential therapeutic targets for the treatment of gynecological tumors.

Objective:To investigate the clinical significance of prenatal screening and genetic analysis in the diagnosis of fetal aberrant right subclavian artery(ARSA).Methods:The ultrasonographic features of ARSA fetu-ses detected by prenatal ultrasound at the University of Hong Kong-Shenzhen Hospital from October 2017 to March 2022 were retrospectively analyzed.The fetuses were divided into isolated ARSA group and complicated ARSA group.Their genetic analysis results and pregnancy outcome were analyzed.Results:Among 30,260 preg-nant women,185 fetuses were diagnosed with ARSA by prenatal ultrasound screening,with an incidence of 0.6％;5 fetuses(2.6％)were diagnosed by ultrasound in the first trimester,and the remaining were diagnosed by fetal grade Ⅲ structural ultrasound examination at 20～24 weeks' gestation.Among them,158 fetuses(85.4％)had isolated ARSA,and 27(14.6％)had complicated ARSA.Among fetuses with ARSA and other structural abnormal-ities,cardiovascular system accounted for the highest proportion(44.4％),followed by nervous system(22.2％)and urinary system(22.2％).Through genetic analysis,8.3％(4/48)fetuses with isolated ARSA and 40.0％(4/10)fetuses with complicated ARSA were found to have chromosomal numerical or structural abnormalities,with statis-tically significant difference between the two groups(P=0.024).Genetic analysis was completed in 48 isolated ARSA,and the positive rate of pathogenic copy number variants(CNV)was 4.2％(2/48),which was not signifi-cantly different from the pathogenic CNV incidence rate of 0.4％(1/239)in elderly pregnant cases during the same period(P=0.074).The Down syndrome positive likelihood ratio(LR+)for isolated ARSA was 2.5 and the Down syndrome LR+for complicated ARSA was 49.6.Conclusions:Complicated ARSA is often associated with cardiovascular abnormalities and is more likely to develop Down syndrome than isolated ARSA.Although the inci-dence of pCNV in isolated ARSA is slightly higher than the natural incidence,the correlation between pCNV and i-solated ARSA has not been clearly determined by the current sample size.

Objective The causal relationship between endometriosis(EMs)and 15 trace elements including copper,calcium,carotene,folic acid,iron,magnesium,potassium,selenium,vitamin A,vitamin B12,vitamin B6,vitamin C,vitamin D,vitamin E and zinc was analyzed by double sample Mendelian randomization(MR).Methods Multiple trace elements were used as exposure factors,and the incidence risk of EMs was used as the outcome factor for two-sample MR analysis.The data were sourced from the publicly available integrative epidemiology unit open Genome-Wide Association Studies database and Finnish Genome Research Project database.Five Mendelian randomization analysis methods were employed to investigate the causal relationship between EMs and trace elements.Additionally,sensitivity analysis was carried out to evaluate the influence of heterogeneity and horizontal pleiotropy on the results of the MR analysis.Results The impact of trace elements on various types of EMs varies.The results of the inverse variance weighted(IVW)method indicated that trace element calcium(OR=1.465,95％CI:1.094-1.962)and vitamin B6(OR=1.580,95％CI:1.146-2.178)might be risk factors for ovarian EMs.Vitamin B6(OR=0.203,95％CI:0.044-0.939)may be a protective factor for tubal EMs.The above research results were not affected by heterogeneity and horizontal pleiotropy(P＞0.05).This study did not find a causal relationship between other trace elements and EMs.Conclusion The trace elements calcium and vitamin B6 predicted by genetics may play a regulatory role in the development of EMs.

Objective:To analyze the changes in the incidence trend of liver cancer in Taizhou of Jiangsu Province, from 2012 to 2020 and provide reference for tumor prevention and control and management.Methods:Liver cancer incidence data from 2012 to 2020 were extracted from the Taizhou Center for Disease Control and Prevention's tumor registry system. Demographic data were used to calculate the crude incidence rate, age-standardized incidence rate (ASIR), Chinese age-standardized incidence rate (CASIR; based on China's 2010 standard population), and world age-standardized incidence rate (WASIR; based on Segi's world standard population). The Joinpoint regression model was applied to identify inflection points in liver cancer incidence trends during 2012-2020, and annual percentage change (APC) with average annual percentage change (AAPC) were calculated.Results:In 2020, the crude incidence ratio (CIR) of liver cancer in Taizhou was 34.6 per 100 000, with CASIR and WASIR at 19.6 per 100 000 and 14.9 per 100 000, respectively. From 2012 to 2020, the male-to-female ratio of new liver cancer cases was 2.94∶1 (10 455 males vs. 3 559 females), with male incidence consistently higher than female. Overall liver cancer incidence in Taizhou initially increased and then decreased after 2017 (2012-2017: APC=6.4%, P=0.014; 2017-2020: APC=-9.5%, P=0.035), peaking at a CASIR of 26.2 per 100 000 in 2017. The trend in male incidence mirrored the overall pattern, rising before 2017 and declining thereafter (2012-2017: APC=6.2%, P=0.005; 2017-2020: APC=-9.0%, P=0.016). Female incidence remained relatively stable (2012-2016: APC=11.0%, P=0.054; 2016-2020: APC=-6.5%, P=0.130). Conclusions:Liver cancer incidence in Taizhou increased before 2017 and declined thereafter, with 2017 as the turning point. Amid population aging, liver cancer remains a persistent public health challenge requiring sustained attention.

Objective:To investigate the clinical significance of prenatal screening and genetic analysis in the diagnosis of fetal aberrant right subclavian artery(ARSA).Methods:The ultrasonographic features of ARSA fetu-ses detected by prenatal ultrasound at the University of Hong Kong-Shenzhen Hospital from October 2017 to March 2022 were retrospectively analyzed.The fetuses were divided into isolated ARSA group and complicated ARSA group.Their genetic analysis results and pregnancy outcome were analyzed.Results:Among 30,260 preg-nant women,185 fetuses were diagnosed with ARSA by prenatal ultrasound screening,with an incidence of 0.6％;5 fetuses(2.6％)were diagnosed by ultrasound in the first trimester,and the remaining were diagnosed by fetal grade Ⅲ structural ultrasound examination at 20～24 weeks' gestation.Among them,158 fetuses(85.4％)had isolated ARSA,and 27(14.6％)had complicated ARSA.Among fetuses with ARSA and other structural abnormal-ities,cardiovascular system accounted for the highest proportion(44.4％),followed by nervous system(22.2％)and urinary system(22.2％).Through genetic analysis,8.3％(4/48)fetuses with isolated ARSA and 40.0％(4/10)fetuses with complicated ARSA were found to have chromosomal numerical or structural abnormalities,with statis-tically significant difference between the two groups(P=0.024).Genetic analysis was completed in 48 isolated ARSA,and the positive rate of pathogenic copy number variants(CNV)was 4.2％(2/48),which was not signifi-cantly different from the pathogenic CNV incidence rate of 0.4％(1/239)in elderly pregnant cases during the same period(P=0.074).The Down syndrome positive likelihood ratio(LR+)for isolated ARSA was 2.5 and the Down syndrome LR+for complicated ARSA was 49.6.Conclusions:Complicated ARSA is often associated with cardiovascular abnormalities and is more likely to develop Down syndrome than isolated ARSA.Although the inci-dence of pCNV in isolated ARSA is slightly higher than the natural incidence,the correlation between pCNV and i-solated ARSA has not been clearly determined by the current sample size.

AIM:This study investigates the protective effect of the selective peroxisome proliferator-activated receptor δ(PPARδ)agonist seladelpar on podocytes in a mouse model of diabetic kidney disease(DKD).METHODS:A DKD mouse model was established using streptozotocin and a high-fat diet.Mice were randomly assigned to three groups:control,DKD with vehicle treatment,and DKD with seladelpar treatment at dosages of 1,5 and 10 mg/kg(6 to 7 mice per group).After four weeks of treatment,mice were euthanized,and various parameters were measured,including urinary albumin,creatinine,blood urea nitrogen,serum triglycerides,and cholesterol using respective kits.Renal tissues were processed for histological examination through HE and PAS staining to assess glomerular pathology.The RNA from glomerular tissues was analyzed via RT-qPCR for podocyte marker(Nphs1,Nphs2,Wt1 and Synpo)expression,and the protein expression was evaluated using Western blot for PPARδ.Immunofluorescence staining of frozen renal cortical sec-tions was conducted to quantify WT1-positive cells and desmin protein levels.Transmission electron microscopy was used to observe glomerular ultrastructural changes.RESULTS:(1)PPARδ protein levels in the glomerular tissue of DKD mice were significantly lower than in controls.(2)Mice treated with 10 mg/kg of seladelpar showed reduced blood glu-cose,triglycerides,and cholesterol levels compared to the diabetic nephropathy group.(3)Both 5 mg/kg and 10 mg/kg se-ladelpar treatment groups exhibited decreased urine albumin/creatinine ratios,along with improvements in glomerular hy-pertrophy and mesangial matrix deposition.Increased mRNA expression levels of Nphs1,Nphs2,Wt1,and Synpo were also observed,alongside an increase in WT1-positive cells and a decrease in desmin expression.Additionally,there was a reduction in podocyte foot process fusion and glomerular basement membrane thickness.(4)RNA sequencing indicated that 5 mg/kg seladelpar treatment modulated PPAR signaling pathway and influenced various metabolic pathways,includ-ing bile acid metabolism,carbon metabolism,glutathione metabolism,glycerophospholipid metabolism,and fatty acid metabolism.CONCLUSION:Seladelpar,a PPARδ agonist,mitigates podocyte injury and reduces proteinuria in DKD mice.Notably,the protective effects of seladelpar are partially independent of its hypolipidemic properties.

BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease characterized by joint pain,swelling,and dysfunction.Acupuncture,as a traditional medical treatment,has proved its effectiveness and safety in many diseases.However,the efficacy of acupuncture in the treatment of rheumatoid arthritis remains controversial.Therefore,the purpose of this study is to evaluate and explore the effect of Tiaodu Tongmai acupuncture in the treatment of preclinical rheumatoid arthritis of different ages through the generalized estimating equation,and to provide a basis for the application of acupuncture in rheumatoid arthritis. OBJECTIVE:To investigate the effect of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis(pre-RA)patients at different ages based on generalized estimating equation. METHODS:A total of 123 patients with preclinical rheumatoid arthritis treated from January to September 2023 were selected as the study objects and divided into study group(n=64)and control group(n=59)according to different treatment methods.The study group was given Tiaodu Tongmai acupuncture treatment,and the control group was given acetaminophen tablets.The baseline balance was adjusted by propensity score matching method.The clinical efficacy and cytokine levels before and after treatment between the two groups were compared.The generalized estimating equation model was established to evaluate the efficacy of Tiaodu Tongmai acupuncture therapy on preclinical rheumatoid arthritis patients at different ages. RESULTS AND CONCLUSION:(1)After 0 days of treatment,there were significant differences in joint pain and C-reactive protein expression between study and control groups(P＜0.05).After 4 weeks of treatment,there were significant differences in visual analogue scale scores,joint pain,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).After 8 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).After 12 weeks of treatment,there were significant differences in visual analogue scale scores,C-reactive protein and erythrocyte sedimentation rate between the two groups(P＜0.05).(2)The total effective rate of the study group was 93.75%,while that of the control group was 79.17%.The clinical efficacy of the study group was significantly better than that of the control group(P＜0.05).(3)There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the study group before and after treatment(P＜0.05).The levels of interleukin-6,interferon-γ,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,metallomatrix proteinase 9,and anti-cyclic citrulline antibody in the control group after treatment were significantly different from those before treatment(P＜0.05).There were significant differences in interleukin-6,interferon-γ,macrophage migration inhibitory factor,rheumatoid factor IgA,rheumatoid factor IgM,metallomatrix proteinase 3,and anti-cyclic citrulline antibody between the two groups after treatment(P＜0.05).(4)After 12 weeks of treatment,the comprehensive efficacy of patients of all ages in the study group was better than that of the control group(P＜0.05).After 8 weeks of treatment,the comprehensive efficacy of patients aged 23-35,36-50,and 51-60 years old in the study group was better than that of the control group(P＜0.05),and the comprehensive efficacy of patients aged 18-22 years old was comparable between the two groups.After 4 weeks of treatment,the comprehensive efficacy of patients aged 36-50 and 51-60 years old in the study group was better than that of the control group(P＜0.05),and the comprehensive efficacy was comparable between the two groups of patients aged 18-22 and 23-35 years.Overall,Tiaodu Tongmai acupuncture therapy has advantages in treating preclinical rheumatoid arthritis patients aged 36-50 and 51-60 years.