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.

ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Ehlers-Danlos syndromes(EDS)are a group of rare hereditary connective tissue disorders characterized by joint hypermobility,skin hyperextensibility,and tissue fragility.Short stature is defined as a height that is two standard deviations or more below the average height for individuals of the same age,sex,and race.The etiopathogenesis of short stature is complicated.Early detection and appropriate intervention are essential in disease treatment.However,short stature is not common among all EDS subtypes.It is frequently observed in patients with rare subtypes,such as spondylodysplastic EDS,dermatosparaxis EDS,and musculo-contractural EDS.Besides,height may be affected by other factors including spinal curvature and malnutrition.Deep phenotyping and multidisciplinary team approaches are recommended for the diagnosis and management.Short stature in patients with EDS has not been sufficiently acknowledged in China.There is currently a lack of high-level evidence for the treatment of EDS-related short stature.Therefore,this review aims to present recent progress of diagnosis and management of short stature in patients with EDS.Further studies focusing on short stature in rare subtypes are necessary to advance precision medicine and enhance patient care.

Objective:To assess the value of serum alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ)and glypican-3(GPC-3)in the diagnosis of hepatocellular carcinoma(HCC).Methods:Studies of AFP,PIVKA-Ⅱ,GPC-3 or in combination for the diagnosis of HCC since 2002 were searched in PubMed,Web of Science and Embase databases.The literature was screened according to the inclusion and exclusion criteria,the quality of the included articles was evaluated by QUADAS checklist,and relevant data were extracted by Meta DiSc,Review Manager 5.4 and Stata 15.1.The diagnostic values of AFP,PIVKA-Ⅱ and GPC-3 alone or in combination for HCC were assessed with receiver operating characteristic(ROC)curve.Results:A total of 32 articles were included in the study.Meta-analysis showed that when a single marker was used to diagnose HCC,the area under the ROC curve(AUC)of PIVKA-Ⅱ was the highest(0.88,95%CI:0.85-0.91),followed by GPC-3 and AFP.The AUC of combination of serum markers was higher than that of a single marker,and the AUC of PIVKA-Ⅱ combined with GPC-3 was the highest(0.90,95%CI:0.87-0.92).When a single marker was used for diagnosis,the sensitivity of PIVKA-Ⅱ and GPC-3 were relatively high(0.75 and 0.76),while the specificity of PIVKA-Ⅱ(0.88)and AFP(0.87)were higher than that of GPC-3(0.81).The sensitivity of the combination of serum markers was higher than that of a single marker,while the specificity was not significantly improved.When a single marker is used to diagnose HCC,the diagnostic odds ratio(DOR)of PIVKA-Ⅱ was the highest(22,95%CI:13-36),followed by GPC-3 and AFP.The DOR of the combination of two markers in the diagnosis of HCC was higher than that of a single marker,and the DOR of AFP combined with GPC-3 was the highest(25,95%CI:9-67).The DOR of the combination of the three markers was significantly reduced to 10(95%CI:7-45).Conclusions:When a single marker is used,PIVKA-Ⅱhas a higher diagnostic value for HCC.The combination of two markers can significantly improve the diagnostic sensitivity,and AFP combined with PIVKA-Ⅱ is recommended for the diagnosis of HCC.The combination of all three markers failed to further improve the diagnostic value.

OBJECTIVE To estimate the cost-utility of sacituzumab govitecan （SG） versus single-agent chemotherapy in the treatment of hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） advanced metastatic breast cancer. METHODS From the perspective of the Chinese medical system， a three-state partitioned survival model was constructed to examine the cost-utility of SG versus single-agent chemotherapy based on TROPiCS-02 trial. The cycle length was set to 1 month， and the time horizon was 10 years. The annual discount was 5%. The model output included total costs and quality adjusted life month （QALM）， and incremental cost-effectiveness ratio （ICER） was calculated for cost-utility analysis， by setting willingness-to-pay （WTP） threshold at 3 times gross domestic product （GDP） per capita of China in 2023 （22 340 yuan/QALM）. Univariate sensitivity analyses， probability sensitivity analyses， and scenario analyses were performed to evaluate the robustness of the results and calculate the price threshold when SG had economic advantages. RESULTS SG group gained incremental 4.25 QALM and 561 570 yuan compared with single-agent chemotherapy， which resulted in an ICER of 132 102/QALM that was higher than WTP. The results of the univariate sensitivity analysis showed that the monthly average cost of SG had the greatest impact on the results； the results of probability sensitivity analysis showed that the probability of SG scheme being cost-effective at the WTP threshold was 0. The results of scenario analysis showed that the conclusions of this study were robust under different time horizons （5， 10， 15 years）. The price threshold for SG being cost-effective was 1 344 yuan per 180 mg. CONCLUSIONS Based on the perspective of Chinese medical system， SG appears to be not cost-effective compared with single-agent chemotherapy for HR+/ HER2－ advanced metastatic breast cancer at the price of 8 400 yuan per 180 mg. A substantial price cut should be taken to be cost- effective.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

Objective To compare the effect of three-dimensional visual (3DV) model, three-dimensional printing (3DP) model and computer-aided design (CAD) modified 3DP model in video-assisted thoracoscopic surgery (VATS) sublobular resection. Methods The clinical data of patients who underwent VATS sublobular resection in the Affiliated Hospital of Hebei University from November 2021 to August 2022 were retrospectively analyzed. The patients were divided into 3 groups including a 3DV group, a 3DP group and a CAD-3DP group according to the tools used. The perioperative indexes and subjective evaluation of operators, patients and their families were compared. Results A total of 22 patients were included. There were 5 males and 17 females aged 32-77 (56.95±12.50) years. There were 9 patients in the 3DV group, 6 patients in the 3DP group, and 7 patients in the CAD-3DP group. There was no statistical difference in the operation time, intraoperative blood loss, drainage volume, hospital stay time or postoperative complications among the groups (P>0.05). Based on the subjective evaluations of 4 surgeons, the CAD-3DP group was better than the 3DV group in the preoperative planning efficiency (P=0.025), intuitiveness (P=0.045) and doctor-patient communication difficulty (P=0.034); the CAD-3DP group was also better than the 3DP group in the overall satisfaction (P=0.023), preoperative planning difficulty (P=0.046) and efficiency (P=0.014). Based on the subjective evaluations of patients and their families, the CAD-3DP group was better than the 3DP group in helping understand the vessel around the tumor (P=0.016), surgical procedure (P=0.020), procedure selection (P=0.029), and overall satisfaction (P=0.048); the CAD-3DP group was better than the 3DV group in helping understand the tumor size (P=0.038). Conclusion CAD-modified 3DP model has certain advantages in pre-planning, intraoperative navigation and doctor-patient communication in the VATS sublobectomy.

OBJECTIVE To comprehensively evaluate the three oral Janus kinase inhibitors （JAKi） such as upadacitinib， abrocitinib and baricitinib in the treatment of atopic dermatitis. METHODS The six dimensions of safety， efficacy， economy， appropriateness， accessibility and innovativeness were used for evaluation. Meta-analysis was conducted to evaluate the safety and efficacy of three oral JAKi； pharmacoeconomic studies were searched， and the treatment costs were calculated to evaluate the economy of each JAKi. Appropriateness was described based on literature review and drug labels. Accessibility of three oral JAKi was assessed by using a questionnaire survey. The innovation of JAKi was elucidated from the perspective of its mechanism of action. RESULTS In terms of safety， the incidence of upper respiratory tract infection （OR＝1.47， 95%CI of 1.04-2.08， P＝0.03） and nasopharyngitis （OR＝1.44， 95%CI of 1.06-1.95， P＝0.02） in the upadacitinib 30 mg group was significantly higher than that in the placebo group； the incidence of nasopharyngitis in baricitinib 4 mg group was significantly higher than that in the placebo group （OR＝2.24， 95%CI of 1.39-3.61， P＝0.000 8） and baricitinib 2 mg group （OR＝0.48， 95%CI of 0.31-0.74，P＝0.001）. In terms of efficacy， regardless of the dosage， all three JAKi groups were superior to the placebo group， and the high-dose groups of upadacitinib and abrocitinib were superior to the low-dose groups （P＜0.000 1）. In terms of economy， the annual treatment cost of baricitinib was the lowest （13 870.0 yuan）， but it has not been approved for atopic dermatitis indication in China； next was upadacitinib （27 192.5 yuan）. In terms of appropriateness， the overall appropriateness of the three JAKis was good， but none of them was suitable for patients with severe liver injury. In terms of accessibility， baricitinib had the highest availability rate （59.4%）， but the affordability of upadacitinib was relatively good under China’s medical insurance system. In terms of innovation， among the three types of JAKi， upadacitinib and abrocitinib had better innovation. CONCLUSIONS Three oral JAKi treatments for atopic dermatitis have controllable safety and good efficacy. Considering the issue of medical insurance reimbursement， it is recommended that Chinese patients use upadacitinib.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide (Forner et al., 2018; He et al., 2023). Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle (SM) mass that may be age-related or the result of malnutrition in cancer patients (Cruz-Jentoft and Sayer, 2019). Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival (Voron et al., 2015; van Vugt et al., 2016). Previous studies have used various criteria to define sarcopenia, including muscle area and density. However, the lack of standardized diagnostic methods for sarcopenia limits their clinical use. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) renewed a consensus on the definition of sarcopenia: low muscle strength, loss of muscle quantity, and poor physical performance (Cruz-Jentoft et al., 2019). Radiological imaging-based measurement of muscle quantity or mass is most commonly used to evaluate the degree of sarcopenia. The gold standard is to measure the SM and/or psoas muscle (PM) area using abdominal computed tomography (CT) at the third lumbar vertebra (L3), as it is linearly correlated to whole-body SM mass (van Vugt et al., 2016). According to a "North American Expert Opinion Statement on Sarcopenia," SM index (SMI) is the preferred measure of sarcopenia (Carey et al., 2019). The variability between morphometric muscle indexes revealed that they have different clinical relevance and are generally not applicable to broader populations (Esser et al., 2019).
Humans ; Aged ; Sarcopenia/diagnostic imaging* ; Carcinoma, Hepatocellular/diagnostic imaging* ; Muscle, Skeletal/diagnostic imaging* ; Deep Learning ; Prognosis ; Radiomics ; Liver Neoplasms/diagnostic imaging* ; Retrospective Studies