Over the past two decades, genome-wide association study(GWAS) has identified numerous genetic variants and loci associated with heritable diseases. With the gradual maturation and saturation of GWAS methodologies, transcriptome-wide association study(TWAS) offers a novel perspective by linkinggenetic phenotypes to gene expression levels. By integrating TWAS with other multi-omics analyses, researchers can gain a deeper understanding of heritable diseases. This article provides an overview of recent groundbreaking and representative TWAS methods and tools, analyzes their strengths and limitations, and discusses future trends in TWAS development.

Objective: To understand the current status and associated factors of sleep problems among preschool children in Hainan Province, so as to provide scientific evidence for improving sleep health in this population. Methods: From January 2021 to June 2022, a total of 4 105 preschool children aged 3-6 years from 62 kindergartens in Hainan Province were selected using stratified cluster random sampling method. Demographic information and lifestyle habits were collected through the Hainan Province Child Growth and Development Survey Questionnaire. The Children s Sleep Habits Questionnaire (CSHQ) was employed to assess sleep status. Unconditional binary Logistic regression model was applied to investigate the associated factors of sleep problems among preschool children. Results: The overall CSHQ score for children was 58.03±18.84, with 80.95% of preschool children exhibiting sleep related issues. The top three most prevalent sleep problem domains were bedtime resistance (72.42%), sleep anxiety ( 54.88 %), and parasomnias (38.86%). Logistic regression analysis revealed that higher family annual income ( OR=0.60, 95%CI = 0.45-0.79), higher maternal education level ( OR=0.53, 95%CI =0.32-0.89), regular or daily vitamin D supplementation ( OR=0.77, 95%CI =0.60-0.99), and fully self initiated eating behavior ( OR=0.71, 95%CI =0.59-0.85) were negatively related with children s sleep problems; in addition, screen exposure ( OR=1.27, 95%CI =1.06-1.51) and picky eating ( OR= 1.47 , 95%CI =1.21-1.78) were positively related to children s sleep problems (all P <0.05). Conclusion The high detection rate of sleep problems among preschool children in Hainan Province is multifactorially associated with family environment, dietary habits, and lifestyle behaviors.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis （GS/CACM 337-2023） was released by the China Association of Chinese Medicine on December 13^th， 2023. This expert consensus was developed by experts in methodology， pharmacy， and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine （CACM） and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine （pulmonary diseases） and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung， acute bronchitis， and acute attack of chronic bronchitis from the aspects of applicable populations， efficacy evaluation， usage， dosage， drug combination， and safety. It is expected to guide the rational drug use in medical and health institutions， give full play to the unique value of Qinbaohong Zhike oral liquid， and vigorously promote the inheritance and innovation of Chinese patent medicines.

Objective:To explore the moderating and mediating roles of psychological resilience in the relationship between job satisfaction and depressive symptoms among petrochemical workers.Methods:In April 2022, a cluster sampling method was used to conduct a questionnaire survey among 1087 in-service employees of a petrochemical enterprise in Henan Province. A total of 861 questionnaires were recovered, including 857 valid ones, with an effective rate of 99.54%. Data on job satisfaction, psychological resilience, and depressive symptoms were collected using the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), Job Satisfaction Questionnaire, and Patient Health Questionnaire-9 (PHQ-9). Spearman rank correlation analysis was applied to analyze the relationships among the scores of job satisfaction, psychological resilience, and depressive symptoms. Hierarchical linear regression analysis was used to test the moderating effect of psychological resilience, and the Bootstrap method was employed to verify the mediating effect of psychological resilience.Results:The scores of job satisfaction, psychological resilience, and depressive symptoms among petrochemical workers were 36.00 (31.00, 36.00) points, 36.00 (30.00, 41.00) points, and 7.00 (3.00, 9.00) points. The detection rate of depressive symptoms was 65.7% (563/857). Results of Spearman rank correlation analysis showed that job satisfaction of petrochemical workers was positively correlated with psychological resilience ( rs=0.270, P<0.01) and negatively correlated with depressive symptoms ( rs=-0.386, P<0.01), psychological resilience was negatively correlated with depressive symptoms ( rs=-0.515, P<0.01). Results of hierarchical linear regression analysis indicated that psychological resilience had no moderating effect on the relationship between job satisfaction and depressive symptoms of petrochemical workers ( b=0.001, P>0.05). Results of the mediating effect test showed that psychological resilience played a partial mediating effect in the relationship between job satisfaction and depressive symptoms ( P<0.01), with a mediating effect value of -0.071 (95% CI: -0.125, -0.045), accounting for 20.16% of the total effect. Conclusion:Psychological resilience exerts a partial mediating effect rather than a moderating effect in the relationship between job satisfaction and depressive symptoms among petrochemical workers.

Objective:To investigate the distribution and clinical significance of amniotic fluid karyotype results in 2 725 cases from southern Anhui.Methods:The karyotypes of amniotic fluid from 2 725 cases of second-trimester pregnant women treated in our hospital from Jan 2017 to Dec 2023 were collected.The annual abnormal detection rate and overall abnormal rate were analyzed.Meanwhile,the abnormal detection rate was compared among 8 groups of different clinical indication including adverse pregnancy history,advanced maternal age(≥35 years),high risk of Down syndrome screening,high risk of non-invasive prenatal testing(NIPT),nuchal translucency thickness(NT)≥2.5 mm,abnormal ultrasound findings,two or more concurrent positive indications,and others.The abnormal detection rate was calculated within high risk of Down syndrome screening and NIPT.Results:Significant differences in annual abnormal rates were observed from 2017 to 2023(χ2=19.705,P=0.003).Among 2 725 cases,233(8.55%)showed abnormal karyotypes.Among them,abnormal autosomal number was the most prevalent(4.41%,120/2 725),with inversion being the most common chromosome structural abnormality.Significant differences in abnormal rates were noted among the eight clinical indication groups(χ2=438.516,P＜0.01).No statistical difference was found in abnormal detection rates among the three high-risk subgroups of Down syndrome screening(χ2=0.323,P=0.851),while significant differences were observed within the high-risk subgroups of NIPT(χ2=100.901,P＜0.01).Polymorphisms were detected in 65 cases(2.38%).Conclusions:Chromosomal numerical and structural abnormalities have been detected in southern Anhui over the past seven years,with variations across subgroups.Karyotype analysis effectively detects second-trimester fetal chromosomal abnormalities,aiding in the prevention of birth defects and worthing clinical application.

Objective To enhance the efficiency and accuracy of post-marketing safety monitoring and evaluation of drugs in China by studying large language models-based patient medical record pharmacovigilance profiling techniques,providing scientific methods and technical support to ensure the safe use of drugs for patients.Methods This study constructs a pharmacovigilance profile that includes individual patient differences,medication details,and adverse reaction manifestations.It enhances a large language model with a knowledge graph in the field of pharmacovigilance and designs targeted prompts to guide the model to output pharmacovigilance profiles.Results Large language models demonstrate significant advantages in active monitoring,effectively processing and analyzing medical text data,and improving the monitoring and prediction capabilities of drug adverse reactions.Through the design of prompts,the model can more accurately depict patient pharmacovigilance profiles,providing decision support for medical professionals.Conclusions The study of large language model-based patient medical record pharmacovigilance profiling technology provides scientific evidence and technical support for the early detection and prevention of drug adverse reactions,helping to reduce medical costs,improve medical outcome prognoses,and opens new paths to ensure patient drug safety.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective To analyze the relationship between the visceral adiposity index(VAI)and nocturia in the US adult population.Methods A cross-sectional study was performed.Data from subjects aged≥20 years in the National Health and Nutrition Examination Survey(NHANES)database from 2007 to 2020 were collected,including waist circumference,triglyceride,body mass index(BMI),high-density lipoprotein,age,gender,race,poverty income ratio,education level,marital status,smoking,alcohol consumption,sleep disorders,depression,occupation,hypertension,diabetes,congestive heart failure,cancer,and nocturnal urination frequency.Weighted analysis,multivariate logistic regression,generalized additive model(GAM),and curve fitting were employed to evaluate the association between VAI and nocturia,adjusting for age,gender,race,poverty income ratio,education level,marital status,smoking,alcohol consumption,sleep disorders,depression,occupation,hypertension,diabetes,congestive heart failure,and cancer.Subgroup analyses were conducted based on age,gender,race,hypertension and diabetes to further evaluate the relationship between VAI and the risk of nocturia.Results A total of 29,196 American adults were included.All subjects were divided into 4 groups based on VAI quartiles:Q1 group(0.32≤VAI<1.01),Q2 group(1.01≤VAI<1.70),Q3 group(1.70≤VAI<2.95),and Q4 group(2.95≤VAI<13.59),with nocturia prevalence rates of 28.5%,31.4%,33.3%,and 34.9%,respectively.In subgroup analyses,the risk of nocturia significantly increased with higher VAI in the 20-40 age group,females and other Hispanics(OR=1.04,95%CI 1.01-1.08,P=0.006;OR=1.02,95%CI 1.00-1.04,P=0.035;OR=1.05,95%CI 1.01-1.09,P=0.026).GAM analysis results showed a nonlinear relationship between VAI and nocturia.Conclusion VAI is positively associated with the risk of nocturia,and may be an effective indicator for predicting the risk of nocturia occurrence.