1.From Gene Expression to Transcriptome-wide Association Study: Development and Comparison of Methodology
Kun FANG ; Guozhuang LI ; Linting WANG ; Qing LI ; Kexin XU ; Lina ZHAO ; Zhihong WU ; Jianguo ZHANG ; Nan WU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):223-229
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.
2.Standardization Challenges in Outcome Evaluation Systems of Animal Experiments and Considerations for Core Outcome Set Construction Strategies
Qingyong ZHENG ; Yongjia ZHOU ; Tengfei LI ; Jianguo XU ; Chen TIAN ; Hui LIU ; Min TIAN ; Ziyu ZHOU ; Caihua XU ; Yating CUI ; Junfei WANG ; Jinhui TIAN
Laboratory Animal and Comparative Medicine 2026;46(1):138-148
Animal experimentation constitutes a critical link between basic research and clinical application, making its research quality and translational efficiency paramount. Although considerable progress has been made in standardizing operational procedures and ethical guidelines, the standardization of outcome evaluation systems has significantly lagged, creating a key bottleneck that constrains the quality of biomedical research and evidence synthesis. This deficiency is manifested by pronounced heterogeneity in outcome selection across similar studies, incomplete methodological reporting, and disparate criteria for result interpretation, which severely impairs the comparability of findings and the evidence integration. To cope with this challenge, this paper systematically introduces a mature methodological tool from clinical research–the core outcome set (COS)–and explores its construction strategies and application potential in the field of animal experimentation. Given the extensive diversity of animal experiments, a pragmatic strategy of "focusing on key areas, implementing phased pilots, and promoting gradual expansion" should be adopted. This approach prioritizes the development of domain-specific COS for disease areas characterized by high research volume, urgent translational needs, and well-established animal models. A multi-source integration pathway for COS development is detailed, comprising systematic literature searches, methodological appraisals, and expert consensus, with the feasibility of leveraging artificial intelligence (AI) to enhance efficiency also being examined. The development and promotion of such COS are not intended to restrict scientific exploration; rather, they aim to establish a new, tiered evaluation paradigm consisting of "core outcomes" (mandatory), "recommended outcomes" (encouraged), and "exploratory outcomes" (optional). This framework is expected not only to enhance research quality through standardization and to adhere to the "3R" principles but also to accelerate the accumulation of high-quality evidence. This, in turn, provides a solid foundation for higher-level evidence synthesis, ultimately facilitating the effective translation of basic research findings into clinical practice and providing an essential methodological framework for scientific advancement in relevant disciplines.
3.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
4.Trends in disease burden and years lived with disability of bladder cancer in China,1990—2023
Maochuan FAN ; Cangjian WANG ; Yuchun LI ; Xianglong MA ; Jianguo WEN ; Shunchao LI ; Linsen YANG
Journal of Modern Urology 2026;31(6):517-527
Objective Based on data from the Global Burden of Disease Study 2023 (GBD 2023), this study analyzes the trends in disease burden and years lived with disability (YLD) of bladder cancer in China from 1990 to 2023. Methods Epidemiological data on bladder cancer in China were obtained from the GBD 2023 database.The age-standardized prevalence rate (ASPR), YLD and population attributable fraction (PAF) of risk factors were calculated.Temporal trends were evaluated using the estimated annual percentage change (EAPC), and Joinpoint regression was applied to compute the annual percent change (APC) and average annual percent change (AAPC) for trend analysis. Results Between 1990 and 2023, the number of bladder cancer patients requiring rehabilitation services increased from 213 568 cases to 587 191 cases, representing a 175.0% increase.The YLD rose from 22 158 to 56 620, marking a 155.6% growth.The ASPR increased from 22.6/100 000 to 25.7/100 000 (EAPC=0.06), indicating a stable trend.The age-standardized YLD rate (ASYR) remained at 2.5/100 000 (EAPC=-0.32), indicating a downward trend.Notably, gender disparities in disease burden were evident, with male patients and YLD being 4.63 times and 4.25 times higher than their female counterparts, respectively.Risk factor analysis showed that smoking and high fasting plasma glucose were the main risk factors for bladder cancer.The ASYR attributable to high fasting plasma glucose showed an increasing trend in males (EAPC=0.13) but a decreasing trend in females (EAPC=-1.41). Conclusion The demand for rehabilitation and disease burden of bladder cancer in China have significantly increased, with particularly heavy burdens among males and the elderly population.It is urgent to formulate targeted interventions, strengthen tobacco control, occupational protection, and weight management, and establish an integrated rehabilitation service system to address the increasingly severe disease burden caused by bladder cancer.
5.Construction features and practical applications of an intelligent morning meeting management platform in the radiology department
Weiwei LIU ; Haichang XING ; Jianguo WANG
Chinese Journal of Radiological Health 2026;35(3):455-459
Objective To investigated how morning meetings are conducted in radiology departments across different levels of hospitals in Shandong Province. It also explored the role of an intelligent morning meeting platform in supporting digital management of radiology departments. Methods This study was conducted through the Shandong Provincial Regional Medical Center Alliance. A questionnaire survey was administered to 241 hospitals of different grades to assess their morning meeting practices. Based on the findings, an intelligent and process-oriented management model suitable for the regional context was summarized and developed, leading to the construction of an intelligent morning meeting management platform. A comparative analysis was then performed in our hospital's radiology department. Key management indicators were compared before and after using the platform. These indicators included: weekly frequency of morning meetings, number of meeting types, staff attendance rate, rate of electronic management of meeting materials, proportion of case discussions that met teaching requirements, and staff satisfaction. Results The intelligent morning meeting management platform integrates multiple functions. These functions included morning meeting management, case management, archiving of meeting materials, quality control management, electronic attendance tracking, and online meetings across multiple hospital campuses. After the platform was implemented in the radiology department, all key indicators improved significantly. Specifically, weekly meeting frequency, number of meeting types, attendance rate, rate of electronic management of meeting materials, proportion of case discussions meeting teaching requirements, and staff satisfaction were all significantly higher than before implementation (all P<0.05). Conclusion The application of the intelligent morning meeting management platform can digitize, standardize, and make traceable the morning meetings in radiology departments.It significantly improves the efficiency and quality of these meetings. It also effectively enhances the digital management level of radiology departments. This study aimed to investigate the current operation of morning meetings in radiology departments at different levels of hospitals in Shandong Province, and to explore the role of the intelligent morning meeting platform in the digital management of radiology departments.
6.Huoxue Wentong Prescription Ameliorates Post-myocardial Infarction Ventricular Remodeling in Rats via HIF-1α/TGF-β1/POSTN-mediated Regulation of EndMT
Xiaoning SUN ; Xiaoxiao ZHANG ; Cheng LI ; Qingqing WANG ; Jianguo LIN ; Mingyue WANG ; Ying YANG ; Kuiwu YAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(22):148-158
ObjectiveTo explore the potential mechanism by which Huoxue Wentong prescription (HXWT) ameliorates post-myocardial infarction (MI) ventricular remodeling by regulating endothelial-to-mesenchymal transition (EndMT) via the hypoxia-inducible factor-1α (HIF-1α)/transforming growth factor-β1 (TGF-β1)/periostin (POSTN) signaling pathway. MethodsEighty SPF-grade male Sprague-Dawley rats were randomly assigned to a sham-operated group (n=10) and a modeling group (n=70). The MI model was established by left anterior descending coronary artery ligation. Successfully modeled rats were further randomized into a model group, a sacubitril/valsartan (Entresto, 0.021 g·kg-1) group, and low, medium, and high-dose (4.15, 8.30, and 16.60 g·kg-1, respectively) HXWTF groups (n=10 per group). From postoperative day 2, rats received HXWTF or sacubitril/valsartan by gavage once daily for 4 weeks, and those in sham and model groups received an equal volume of normal saline. After intervention, general conditions were assessed. Echocardiography was performed to measure the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end diastolic diameter (LVEDD), and left ventricular end systolic diameter (LVESD). Hematoxylin and eosin (HE) staining was employed to evaluate myocardial histopathology, and Masson's trichrome staining to assess myocardial fibrosis. Serum levels of B-type natriuretic peptide (BNP), interleukin (IL)-6, IL-10, and matrix metalloproteinase-9 (MMP-9) were determined by enzyme-linked immunosorbent assay (ELISA). Collagen type Ⅰ (ColⅠ) expression was assessed by immunohistochemistry. Immunofluorescence double staining was adopted to detect the expression of platelet endothelial cell adhesion molecule-1 (CD31) and α-smooth muscle actin (α-SMA). Western blot was performed to quantify the expression of collagen type Ⅰ α2 (Col1A2), VE-cadherin, CD31, α-SMA, HIF-1α, TGF-β1, and POSTN. ResultsCompared with the sham group, the model group exhibited thinning and collapse of the left ventricular wall, decreased LVEF and LVFS and increased LVEDD and LVESD (P<0.01), disrupted myocardial fibers with marked inflammatory cell infiltration, increased collagen deposition, enhanced ColⅠ immunoreactivity, elevate serum BNP, IL-6, and MMP-9 levels, a reduced IL-10 level (P<0.01), downregulated expression of CD31 and VE-cadherin, and upregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN (P<0.05,P<0.01), accompanied by increased CD31/α-SMA co-localization. Compared with the model group, the sacubitril/valsartan group and all HXWTF groups showed improved ventricular wall structure, increased LVEF and LVFS, decreased LVEDD and LVESD, attenuated myocardial injury with reduced inflammatory infiltration and collagen deposition, declined serum BNP, IL-6, and MMP-9 levels, an elevated serum IL-10 level, upregulated expression of CD31 and VE-cadherin, downregulated expression of α-SMA, Col1A2, HIF-1α, TGF-β1, and POSTN, and reduced CD31/α-SMA co-localization (P<0.05,P<0.01). No significant differences were observed between the sacubitril/valsartan group and the medium- and high-dose HXWTF groups. ConclusionHXWTF may regulate the HIF-1α/TGF-β1/POSTN pathway to inhibit EndMT, thereby ameliorating post-MI ventricular remodeling.
7.A comparison of short-term efficacy and safety of small-caliber polyvinyl alcohol microsphere-based versus conventional TACE for unresectable hepatocellular carcinoma
Shaowei LI ; Jianguo LI ; Junchen WANG ; Shuxia WANG ; Guoqiang MA ; Yumin LI ; Li GUO ; Wei HU
China Pharmacy 2026;37(20):2732-2738
OBJECTIVE To compare the short-term efficacy and safety of small-caliber polyvinyl alcohol (PVA) microsphere-based transcatheter arterial chemoembolization (TACE) versus conventional iodized oil emulsion-based TACE in the treatment of unresectable hepatocellular carcinoma (HCC).METHODS Clinical data of 146 patients with unresectable HCC who underwent TACE at Gansu Provincial Second People’s Hospital (Affiliated Hospital of Northwest Minzu University) from June 1, 2024, to June 30, 2025, were retrospectively collected. According to the treatment strategy, the patients were divided into the control group (conventional iodized oil emulsion-based TACE, n =79) and the observation group (small-caliber PVA microsphere-based TACE, n =67). One-to-one propensity score matching (PSM) was performed, and the matched cohort (62 patients in each group) was used for the primary analysis. The objective response rate (ORR) and disease control rate (DCR) at 1 and 3 months post-treatment, serum levels of tumor markers (alpha-fetoprotein, alpha-fetoprotein lectin-binding fraction L3, and protein induced by vitamin K absence or antagonist-Ⅱ) before treatment and at 1 and 3 months post-treatment, the occurrence of adverse events, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Sensitivity and interaction analyses were also performed.RESULTS After PSM, the ORRs in the observation group at 1 and 3 months post-treatment were both 59.7%, and the DCRs were 91.9% and 93.5%, respectively, significantly higher than those in the control group (ORRs: 41.9% and 38.7%; DCRs: 77.4% and 75.8%; P <0.05). At 1 and 3 months post-treatment, the serum levels of tumor markers decreased significantly from baseline in both groups, with significantly lower levels in the observation group than in the control group ( P <0.05). No statistically significant differences were observed in the overall incidence of adverse events or the incidence of grade≥3 adverse events between the two groups ( P >0.05). The median PFS was 10.6 months in the control group and 14.3 months in the observation group, with no statistically significant difference [hazard ratio (HR) of 0.69, 95% confidence interval (CI) of 0.44-1.09, P =0.111]. During follow-up, 8 and 9 patients died in the control and observation groups, respectively, and the median OS was not reached in either group. The 12-month OS rates were 88.8% and 87.3%, respectively, with no statistically significant difference (HR of 0.88, 95%CI of 0.35-2.24, P =0.790). After adjustment for potential confounding factors in the original cohort, the ORR at 3 months post-treatment remained significantly higher in the observation group than in the control group (adjusted odds ratio of 2.67, 95%CI of 1.28-5.56, P =0.009). Additionally, the interaction between treatment modality and Barcelona Clinic Liver Cancer staging had no statistically significant impact on the ORR at 3 months post-treatment ( P =0.391).CONCLUSIONS For patients with unresectable HCC, compared with conventional iodized oil emulsion-based TACE, small-caliber PVA microsphere-based TACE demonstrates superior efficacy in terms of early radiological response and improvement in tumor markers, and the two regimens are comparable in terms of safety.
8.Performance evaluation of an acridinium ester-based chemiluminescence assay for heparin-binding protein and its application in the diagnosis of sepsis
Yuying WANG ; Sujuan YU ; Qi CHEN ; Bicui ZHAN ; Kang CHEN ; Guoqiang CHEN ; Longbin HONG ; Jianguo WU
Chinese Journal of Preventive Medicine 2025;59(9):1546-1551
This study aims to comprehensively evaluate the analytical performance and clinical application value of an acridinium ester-based chemiluminescence assay for detecting heparin-binding protein (HBP), providing more accurate laboratory evidence for the early diagnosis of infections and sepsis. The analytical performance of the HBP detection kit based on acridinium ester chemiluminescence was verified in Hangzhou Hospital of Traditional Chinese Medicine in January 2024 to June 2024, including limit of blank (LoB), accuracy, precision, linear range, anti-interference ability, and clinical diagnostic concordance. The potential of this assay in early diagnosis and treatment monitoring of sepsis was assessed. HBP levels were measured in 97 patients with sepsis and 160 healthy controls, and intergroup differences were analyzed using the Mann-Whitney U test. The results showed that the LoB of the HBP detection kit based on acridinium ester chemiluminescence was 0.10 RLU, and low-concentration sample testing showed good discrimination. In the accuracy evaluation, the regression equation between the test reagent and the comparator was y=1.015 2 x-2.850 8 (R2=0.995 1). For precision, the CV in intra-assay was ≤3.51%, and the CV in inter-assay was ≤4.18%. Within the linear range of 0.42-493.46 ng/ml, the regression equation was y=0.996 9 x+3.066 0 (R2=0.999 1). In interference experiments, the relative deviation was <3%. Clinically, the median HBP concentration in the sepsis group (median: 121.1 ng/ml) was significantly higher than in the control group (median: 6.3 ng/ml, P<0.000 1), with a diagnostic sensitivity of 98.97% and specificity of 96.25%. Age stratification had no effect on HBP levels ( U=448 ,P=0.780 0). In conclusion,the acridinium ester-based chemiluminescence assay requires only about 10 minutes to complete the detection and deliver results, demonstrating acceptable sensitivity, precision, and anti-interference capability. Its wide linear range and rapid detection meet emergency testing needs. Clinical validation confirms HBP′s extremely high sensitivity and specificity for sepsis diagnosis, supporting its role as a key marker for early diagnosis, treatment monitoring, and prognosis assessment.
9.Analysis of the relationship between stromal fibrosis degree and targeted therapy resistance and prognosis in EGFR mutant lung adenocarcinoma
Xiaoyue LI ; Na WANG ; Xianni LIU ; Tingli DAI ; Haiwen CHEN ; Jianguo XIN ; Wei WANG ; Menglan ZHANG
The Journal of Practical Medicine 2025;41(15):2381-2387
Objective To assess stromal fibrosis in epidermal growth factor receptor(EGFR)mutant lung adenocarcinoma and its association with resistance to targeted therapy and patient prognosis.Methods Medical records of 207 patients diagnosed with EGFR-mutant advanced lung adenocarcinoma who received treatment at a hospital between January 2021 and December 2022 were reviewed.A total of 86 patients were ultimately included based on their prognosis and survival duration.These patients were categorized into a resistance group(32 cases)and a non-resistance group(54 cases),depending on whether they developed resistance to targeted therapy within one year.Additionally,patients were classified into mild,moderate,and severe fibrosis groups according to the extent of fibrosis observed.Clinical and pathological characteristics,as well as fibrosis levels,were compared between the two groups.Factors influencing the development of resistance to targeted therapy in patients with EGFR-mutant lung adenocarcinoma were analyzed,and the survival outcomes of patients with varying degrees of fibrosis were evaluated during follow-up.Results In the resistance group,the prevalence of EGFR exon 20 insertion mutations,elevated CA125 levels,and the presence of moderate-to-severe fibrosis were significantly higher compared to the non-resistance group(P<0.05).Multivariate logistic regression analysis revealed that EGFR exon 20 inser-tion mutation(OR=3.691,95%CI:1.043~13.057),elevated CA125 levels(OR=4.104,95%CI:1.160~14.517),and moderate-to-severe fibrosis(OR=3.959,95%CI:1.410~11.115)were independent risk factors associated with resistance to targeted therapy among patients with EGFR-mutant lung adenocarcinoma(P<0.05).The Cox proportional hazards model demonstrated a C-index of 0.72(95%CI:0.65~0.79),with area under the curve(AUC)values for 1-year and 2-year survival predictions of 0.781 and 0.734,respectively.EGFR exon 20 insertion mutation(HR=3.691),moderate-to-severe fibrosis(HR=3.959),and elevated CA125 levels(HR=4.104)were identified as independent prognostic factors for overall survival in these patients following targeted therapy.The median progression-free survival(PFS)for patients with mild,moderate,and severe fibrosis was 10.5 months,7.2 months,and 3.9 months,respectively,while the median overall survival(OS)was 21.4 months,16.1 months,and 11.5 months,respectively.Statistically significant differences in both PFS and OS were observed across the three fibrosis severity groups.(P<0.05).Conclusion The extent of stromal fibrosis in EGFR-mutant lung adenocarcinoma influences resistance to targeted therapy,and the progression of fibrosis is correlated with an unfavorable prognosis.
10.A study on correlation between pro-inflammatory cytokine factor and memory in the patients with chronic insomnia disorder comorbid with depression
Fang WANG ; Jianguo GAO ; Zhezhe ZHANG ; Guihai CHEN
Chinese Journal of Nervous and Mental Diseases 2025;51(3):156-161
Objective To explore the changes in serum pro-inflammatory cytokine factor and their relationship with memory function in patients with chronic insomnia comorbid and depression(ICD).Methods A total of 40 ICD patients and 41 chronic insomnia disorder(CID)patients were recruited at the Clinic of Sleep Disorder,and concurrently 41 healthy individuals as controls(CON)were recruited during the same period.The Pittsburgh sleep quality index(PSQI)and 17-item Hamilton depression rating scale(HAMD-17)were used to assess the severity of insomnia and depression in the subjects,and the nine box maze was used to evaluate their memory function.Enzyme linked immunosorbent assay was used to detect the levels of serum tumor necrosis factor(TNF)-α,TNF-β,interleukin(IL)-1β,IL-6,and serum amyloid A(SAA),and the correlation between pro-inflammatory cytokine factor levels and cognitive function was analyzed.Results The HAMD and PSQI scores were significantly higher in ICD and CID groups than in CON[HAMD:19.0(14.0,22.0)vs.10.0(7.5,12.5)vs.2.0(1.0,4.0);PSQI:17(15,19)vs.15(13,16)vs.2(0,3);P<0.01]which was also higher in ICD group than in CID group(P<0.01).The number of errors in spatial reference memory(SRM)and spatial working memory(SWM)were higher in the ICD and CID groups than in CON[SRM:2.5(1.0,4.0),vs.1.0(0,3.0)vs.0(0,1.0);SWM:5.00(4.00,7.75)vs.4.00(2.00,5.00)vs.1.00(1.00,2.50);P<0.01].The number of errors were also higher in SRM and SWM in ICD group than in CID group(P<0.01).The serum levels of TNF-α,TNF-β,IL-1β,IL-6,and SAA were higher in ICD and CID groups than in CON(P<0.01),and the serum levels of TNF-β and IL-6 were also higher in ICD group than in the CID group(P<0.01).In the ICD group,the partial correlation analysis showed that TNF-α(r=0.394,P=0.021)and IL-1β(r=0.398,P=0.020)were positively correlated with the number of SRW errors,while TNF-β(r=0.381,P=0.026)and SAA(r=0.446,P=0.008)were positively correlated with the number of SWM errors.TNF-β were also positively correlated with the number of recognition memory errors(r=0.347,P=0.044).Conclusion ICD patients have memory impairment,which may relate to increased levels of pro-inflammatory cytokine factor in their serum.

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