1.Unraveling the meta-hallmarks between senescent and tumor cells: A new perspective for senolytic drug discovery.
Wei LIU ; Bo FAN ; Te FANG ; Hongyao LI ; Jin ZHANG ; Bo LIU ; Zhiyu LIU
Acta Pharmaceutica Sinica B 2025;15(10):5071-5098
Aging and cancer share overlapping characteristics, referred to as meta-hallmarks, which elucidate the convergent, antagonistic, or contradictory relationships between aging and cancer. Likewise, as a key characteristic of aging, senescent cells share some meta-hallmarks with tumor cells. These hallmarks include apoptosis resistance, metabolic alterations, secretory phenotypes, epigenetic reprogramming, and immune surveillance, all of which play pivotal roles in both tumorigenesis and senescence. Moreover, senolytic drugs, which are a class of agents selectively designed to eliminate senescent cells, have emerged as promising therapeutic agents in oncology and aging-related diseases. Since the discovery of the first senolytic drug in 2015, a diverse array of such agents has been developed. Notably, most senolytic drugs are repurposed from existing anti-tumor therapies, leveraging their shared mechanisms with senescent cells and tumor cells. Thus, this review examines the similarities between senescent cells and tumor cells, providing a better understanding of the meta-hallmarks. Besides, we categorize existing senolytic drugs based upon meta-hallmarks and elucidate the potential molecular mechanisms underlying their effects. By integrating insights from cancer and senescence research, this work aims to inspire innovative strategies for senolytic drug discovery.
2.Effect of the multidisciplinary management model on the prognosis of patients with portal hypertension
Changxiang LAI ; Qiyuan TANG ; Zhiyu LI ; Yujin JIANG ; Xuan ZHOU ; Wenjie XIAN ; Ruikun CHEN ; Xiaojuan WU ; Qing HE ; Fang WANG
Journal of Clinical Hepatology 2025;41(10):2068-2074
ObjectiveTo investigate the effect of the multidisciplinary team (MDT) management model in improving the prognosis of patients with cirrhotic portal hypertension. MethodsA total of 86 patients with cirrhotic portal hypertension who were admitted to Shenzhen Third People’s Hospital from May 2022 to July 2024 were enrolled, and according to whether the MDT treatment regimen was implemented, they were divided into execution group with 51 patients and non-execution group with 35 patients. Baseline clinical data were collected, and the patients were observed in terms of gastrointestinal bleeding, hepatic encephalopathy, liver cancer, and death from admission to the end of follow-up (January 2025). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves for the cumulative incidence rates of endpoint events (gastrointestinal bleeding, hepatic encephalopathy, liver cancer, and death), and the Log-rank test was used for comparison between groups. The Cox proportional-hazards regression model analysis was used to investigate the effect of MDT management on the prognosis of patients. ResultsThere were significant differences between the execution group and the non-execution group in diameter of the portal vein (t=1.216, P=0.017) and ascites (χ2=4.515, P=0.034) at baseline. The patients were followed up for 14.6±6.2 months, and the survival curve analysis showed that there was a significant difference in the cumulative incidence rate of gastrointestinal bleeding between the two groups (χ2=4.573, P=0.024), while there were no significant differences in the incidence rates of other outcome events between the two groups (all P>0.05). The Cox regression analysis showed that the execution group had a reduced risk of gastrointestinal bleeding (hazard ratio=0.262, 95% confidence interval: 0.110 — 0.630, P=0.003). ConclusionImplementation of the MDT treatment regimen can significantly reduce the short-term risk of gastrointestinal bleeding in patients with cirrhotic portal hypertension, while its long-term benefits require further follow-up verification.
3.Research on the application of PBL case library in integrated teaching of circulation system
Fang QIN ; Huang ZHOU ; Jun'an CHEN ; Lili ZOU ; Xiexin TAO ; Qingsong XIONG ; Zulong XIE ; Xinting ZHU ; Yunlin CHEN ; Zhiyu LING
Chinese Journal of Medical Education Research 2024;23(11):1519-1522
To evaluate the advantages of using PBL case library in teaching circulatory system diseases to clinical medicine undergraduate students, a PBL case library was established and applied in teaching practice in the reform of circulatory system teaching. The PBL case library achieved the characteristics of combining theories with cases, morphology with functions, and basic knowledge with clinical knowledge. The PBL case library also realized the informatization, query, and update of cases. Preliminary application showed that the median practical score of students in the case library group was 94.00 points, which was significantly higher than the 92.00 points in the control group ( P=0.005). The average lesson preparation time for teachers in the case library group was (5.00±1.00) hours, which was significantly shorter than the (6.89±0.42) hours in the control group ( P<0.001). The difficulty score for lesson preparation among teachers in the case library group was significantly lower than that of the control group [(1.89±1.05) vs. (3.22±0.44), P<0.001]. However, there were no significant difference in theoretical scores and student satisfaction with teachers and courses. These results suggest that the construction of case library can improve practical teaching effectiveness and enhance the efficiency of lesson preparation for teachers.
4.Establishment of a noninvasive predictive model for antiviral therapy in patients with chronic hepatitis B virus infection and an age of≤30 years
Changxiang LAI ; Qingrong TANG ; Xiulian ZHANG ; Qiyuan TANG ; Zhiyu LI ; Xuan ZHOU ; Wenjie XIAN ; Ruikun CHEN ; Xiaojuan WU ; Fang WANG
Journal of Clinical Hepatology 2024;40(7):1328-1333
Objective To predict whether antiviral therapy is required in patients with chronic hepatitis B virus(HBV)infection and an age of≤30 years by establishing a noninvasive model,and to investigate the diagnostic value of this model.Methods A retrospective analysis was performed for the clinical data of 175 patients with chronic HBV infection who were admitted to Shenzhen Third People's Hospital from January 2017 to January 2023 and met the inclusion criteria,and according to the results of liver biopsy,they were divided into treatment group with 41 patients(with indications for antiviral therapy)and observation group with 134 patients(without indications for antiviral therapy).The two groups were analyzed in terms of the indicators including clinical data,imaging examinations,and serum biochemical parameters.The univariate and multivariate Logistic regression analyses were used to investigate the parameters affecting the indication for antiviral therapy,and different models for predicting the need for antiviral therapy were constructed based on related parameters.The receiver operating characteristic(ROC)curve was used to compare the diagnostic value of different models.The independent-samples t test was used for comparison of normally distributed continuous variables between groups,and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous variables between groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups.Results There were significant differences between the treatment group and the observation group in alanine aminotransferase,ferritin,total cholesterol(CHOL),triglyceride,platelet count,liver stiffness measured by sound touch elastography(STE),and procollagen Ⅲ N-terminal propeptide(PIIIP)(all P<0.05).The multivariate Logistic regression analysis showed that CHOL(odds ratio[OR]=0.4,95%confidence interval[CI]:0.2—1.0),STE(OR=1.5,95%CI:1.0—2.1),and PIIIP(OR=1.1,95%CI:1.0—1.1)were independent predictive factors for the indications for antiviral therapy.Model 1(STE+PIIIP+CHOL),model 2(STE+PIIIP),model 3(STE+CHOL),model 4(PIIIP+CHOL)had an area under the ROC curve of 0.908,0.848,0.725,and 0.725,respectively,while STE,PIIIP,and CHOL used alone had an AUC of 0.836,0.725,and 0.634,respectively,suggesting that model 1 had the largest AUC,with a specificity of 77.34%and a sensitivity of 96.36%,and had a significant difference compared with STE,PIIIP,CHOL,and the models 2,3,and 4(Z=0.21,3.08,3.06,3.23,0.89,and 0.88,all P<0.05).Conclusion The noninvasive model established based on CHOL,STE,and PIIIP has a good value in predicting the need for antiviral therapy in patients with chronic HBV infection and an age of≤30 years.
5.Incidence of venous thromboembolism in esophageal cancer: a real-world study of 8 458 cases
Kunyi DU ; Xin NIE ; Kexun LI ; Changding LI ; Kun LIU ; Zhiyu LI ; Kunzhi LI ; Simiao LU ; Kunhan NI ; Wenwu HE ; Chenghao WANG ; Jialong LI ; Haojun LI ; Qiang ZHOU ; Kangning WANG ; Guangyuan LIU ; Wenguang XIAO ; Qiang FANG ; Qiuling SHI ; Yongtao HAN ; Lin PENG ; Xuefeng LENG
Chinese Journal of Digestive Surgery 2024;23(1):109-113
Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.
6.Quality and reporting standards appraisal of guidelines and consensuses on ketogenic diet therapy in children with refractory epilepsy
Junhan YANG ; Jiaxin FANG ; Jingjing LI ; Xiao LI ; Liqun GUO ; Zhiyu LONG ; Wenqing CHEN ; Dahua ZHANG
Chinese Journal of Modern Nursing 2023;29(21):2839-2846
Objective:To evaluate the quality and reporting standards of the ketogenic diet guidelines and consensuses in children with refractory epilepsy at home and abroad.Methods:A systematic search was conducted using the English and Chinese keywords for screening relevant guidelines and expert consensus on the Guidelines International Network, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, National Institute for Health and Clinical Excellence, the Joanna Briggs Institute (JBI) Center for Evidence-Based Health Care in Australia, DynaMed Evidence-Based Medicine Database, American Academy of Neurology, American Epilepsy Society, International League Against Epilepsy, Child Neurology Society, European Paediatric Neurology Society, International Ketogenic Diet Research Group, Cochrane Library, PubMed, CNKI, Wanfang Database, VIP, China Biology Medicine disc, etc. The search period was from establishment of databases to August 13, 2021. The quality of the guidelines was evaluated using the The Appraisal of Guidelines for Research and EvaluationⅡ, and the Reporting Items for Practice Guidelines in healthcare was used to evaluate the reporting standards of guidelines. The JBI Center for Evidence-based Health Care Quality Evaluation tool was used to evaluate the quality of expert consensuses, and the National Institutes of Health Reporting Standards was used to evaluate the reporting standards of expert consensuses.Results:A total of 1 864 literatures were searched initially. According to the inclusion and exclusion criteria and reading the literature content, 13 literatures were selected, and after manual search, 1 literature was supplemented. Finally, a total of 14 literatures were obtained, including 7 guidelines and 7 expert consensuses. The quality evaluation results showed that 2 guidelines were grade A, 2 guidelines were grade B and 3 guidelines were grade C. 5 expert consensuses were rated "Yes" in the six items of quality evaluation. The results of the evaluation of reporting norms showed that the seven expert consensus reports were of poor quality; the higher the methodological quality rating of the guidelines, the better their reporting quality.Conclusions:The overall quality of the 14 guidelines and expert consensuses included is high, and attention should be paid to research quality in terms of application and participants. The reporting standards need to be further improved, and in the future, researchers can pay more attention to the reporting standards in the process of formulating guidelines and expert consensus, achieving a more rigorous research process and better applying evidence to clinical practice.
7.Construction of Patient Version of Guideline for Ketogenic Diet Therapy in Children with Refractory Epilepsy
Jiaxin FANG ; Zhiyu LONG ; Dan YANG ; Xiaoyan ZHANG ; Xuejing LI ; Dahua ZHANG
Chinese Journal of Modern Nursing 2023;29(24):3301-3307
Objective:To construct the Patient Version of Guideline for Ketogenic Diet Therapy in Children with Refractory Epilepsy. Methods:This guideline was based on the theoretical framework of A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) and patient-oriented knowledge tools, forming the research roadmap. The Patient Version of Guideline for Ketogenic Diet Therapy in Children with Refractory Epilepsy was constructed by clarifying research questions, evidence integration, guideline formation and other normative steps. Results:A total of 17 research questions on ketogenic diet therapy in children with refractory epilepsy were formed. A total of 11 papers were included, including 4 guidelines and 7 consensuses. The final patient version of guideline included 4 themes, involving assessment, pre-implementation preparation, implementation and monitoring, follow-up, evaluation and termination, and 29 recommended items.Conclusions:The patient version of guideline constructed in this study is based on a scientific construction framework and method, and fully considers the needs of patients, which can provide a reference for the management of ketogenic diet therapy in children with refractory epilepsy.
8.Aripiprazole in the treatment of acute episode of schizophrenia: a real-world study in China.
Qian LI ; Yun'ai SU ; Xuemei LIAO ; Maosheng FANG ; Jianliang GAO ; Jia XU ; Mingjun DUAN ; Haiying YU ; Yang YANG ; Zhiyu CHEN ; Jintong LIU ; Shaoxiao YAN ; Peifen YAO ; Shuying LI ; Changhong WANG ; Bin WU ; Congpei ZHANG ; Tianmei SI
Chinese Medical Journal 2023;136(9):1126-1128
9.Early Diagnosis of Bipolar Disorder Coming Soon: Application of an Oxidative Stress Injury Biomarker (BIOS) Model.
Zhiang NIU ; Xiaohui WU ; Yuncheng ZHU ; Lu YANG ; Yifan SHI ; Yun WANG ; Hong QIU ; Wenjie GU ; Yina WU ; Xiangyun LONG ; Zheng LU ; Shaohua HU ; Zhijian YAO ; Haichen YANG ; Tiebang LIU ; Yong XIA ; Zhiyu CHEN ; Jun CHEN ; Yiru FANG
Neuroscience Bulletin 2022;38(9):979-991
Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism*
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Bipolar Disorder/metabolism*
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Depressive Disorder, Major/diagnosis*
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Early Diagnosis
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Humans
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Oxidative Stress
10.Factors related to false negative results of interferon-γ release test in patients with confirmed pulmonary tuberculosis
Ling YE ; Jianhua LAN ; Min FANG ; Shun WANG ; Zhiyu WU ; Shugen WU ; Chunxian PENG ; Weili LU ; Tao LU
Chinese Journal of Clinical Infectious Diseases 2022;15(6):454-458
Objective:To analyze the influencing factors related to false-negative results of interferon-γ release assay (IGRA) QFT-GIT in patients with confirmed pulmonary tuberculosis.Methods:Clinical data of 389 patients with bacteriologically confirmed pulmonary tuberculosis who underwent QFT-GIT in Quzhou Hospital Affiliated to Wenzhou Medical University between January 1 and December 31 2020 were retrospectively analyzed. Univariate and multivariate logistic regression were used to analyze the influencing factors related to the false-negative results of QFT-GIT.Results:Among 389 confirmed patients, 347 cases had positive QFT-GIT results and 42 cases had negative results. Univariate analysis showed that the false-negative results of QFT-GIT were associated with low BMI, reduced CD4 + T lymphocyte count, decreased lymphocyte count, increased C-reactive protein, negative sputum smear, anemia, diabetes mellitus, malignant tumor and sepsis ( P<0.05 or P<0.01). Multivariate conditional logistic regression analysis showed that BMI <18.5 kg/m 2( OR=1.585, 95% CI 1.076-2.336), complicated with diabetes( OR=5.157, 95% CI 2.340-11.365), malignant tumors ( OR=5.596, 95% CI 2.048-15.295)and sepsis ( OR=4.141, 95% CI 1.042-16.459) were independent risk factors for the false-negative results of QFT-GIT ( P<0.05 or P<0.01). Conclusion:When the pulmonary tuberculosis patients are extreme emaciation, complicated with diabetes, malignant tumor or sepsis, the QFT-GIT results will be false negative.

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