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 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 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.

Objective To explore the clinical value of shear wave elastic imaging(SWE)for renal cortical elasticity in patients with hypertension.Methods According to the diagnostic criteria of 2020 International Society of Hypertension(ISH)Global Hypertension Practice Guidelines,44 patients with simple hypertension admitted to the Department of Cardiology of our hospital were selected and 46 healthy controls were selected for the same period.The general data and and renal function indicators of blood biochemical were recorded.All subjects were examined by two-dimensional ultrasound and SWE elasticity to obtain the conventional ultrasound parameters and the Young's modulus(YM)value of the right.The above parameters between the two groups were compared.The influence factors were analyzed by multiple linear regression among the YM value of the right renal cortex,the general data,conventional ultrasound indicators and renal function indicators in the simple hypertension group.Results The course,systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the simple hypertension group was higher than those in the control group,and the difference was statistically significant(P＜0.05).The YM value of the right renal cortex in the simple hypertension group was higher than that in the control group,and the difference was statistically significant(P＜0.05).The correlation analysis showed that the YM value of the right renal cortex was positively correlated with the duration of hypertension(P＜0.05),but not with age,blood pressure,right renal volume,right renal cortex thickness,right renal artery trunk peak systolic flow velocity(PSV),right renal artery trunk resistance index(RI),blood urea nitrogen,blood creatinine,or uric acid(P＞0.05).Further simple linear regression analysis showed that the duration of hypertension was an independent factor affecting the YM value of the right renal cortex.Conclusion SWE may be used to find the variation in elasticity of renal cortex in patients with simple hypertension.

Objective To investigate the clinical application of 3D printed bolus with specific density in breast cancer radiotherapy,and to evaluate its effects on dose distribution and positioning.Methods Forty post-mastectomy patients undergoing intensity-modulated radiotherapy were randomly enrolled for 3D printed bolus(n=20)and conventional bolus(n=20),and all patients were fixed in the supine position using styrofoam.Conventional positioning was performed based on in-room lasers and body markers,with daily Catalyst HD optical surface monitoring combined with weekly CBCT verification.The absolute dose,patients'skin surface dose,surgical incision,planned field,target area doses(VCTV50Gy,VPTV50Gy)and organs-at-risk doses in patients with different boluses were recorded,and the conformity index and homogeneity index were calculated,and the setup errors using CBCT and Catalyst HD were also analyzed.Results The difference in absolute dose between different boluses was trivial,but the skin surface dose with 3D printed bolus was significantly higher than with conventional bolus[(54.83±0.44)Gyvs(54.43±0.51)Gy,P<0.05].Patients with 3D printed boluses had a higher conformity index than with conventional boluses(0.69±0.04 vs 0.65±0.02).For different boluses,there was no significant difference in VCTV50 Gy,while the VPTV50 Gy and organs-at-risk doses were lower in those with 3D printed bolus than conventional boluses(P<0.05),with heart Vmean of 9.68%±3.24%vs11.43%±3.60%.In patients with 3D printed boluses,both planned field arrangement and surgical incision affected the target doses,and the doses of the target area without an internal breast wrap was greater than those with internal breast wrap(P<0.05).When the field was not wrapped around the internal breast,the surgical incisions only affected VPTV50 Gy,and the VPTV50 Gy was greater with the transverse fusiform incision than with the oblique vertical incision(P<0.05),which were 95.58%±0.51%vs95.44%±0.71%.The optical monitoring accuracies with different boluses differed only in the left-right direction(P<0.05),with(0.08±0.57)cm and(-0.15±0.46)cm for 3D printed and conventional boluses.Conclusion Compared with conventional bolus,3D printed bolus can improve dose distribution and optical monitoring accuracy.The surgical incision and planned field arrangement under 3D-printed bolus would exert effects on target doses.