1.Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.
Zhipeng WANG ; Jie WANG ; Dengxiong LI ; Ruicheng WU ; Jianlin HUANG ; Luxia YE ; Zhouting TUO ; Qingxin YU ; Fanglin SHAO ; Dilinaer WUSIMAN ; William C CHO ; Siang Boon KOH ; Wei XIONG ; Dechao FENG
Journal of Pharmaceutical Analysis 2025;15(9):101232-101232
Prostate cancer is the most prevalent malignant tumor among men, ranking first in incidence and second in mortality globally. Novel hormone therapies (NHT) targeting the androgen receptor (AR) pathway have become the standard of care for metastatic prostate cancer. This review offers a comprehensive overview of NHT, including abiraterone, enzalutamide, apalutamide, darolutamide, and rezvilutamide, which have demonstrated efficacy in delaying disease progression and improving patient survival and quality of life. Nevertheless, resistance to NHT remains a critical challenge. The mechanisms underlying resistance are complex, involving AR gene amplification, mutations, splice variants, increased intratumoral androgens, and AR-independent pathways such as the glucocorticoid receptor, neuroendocrine differentiation, DNA repair defects, autophagy, immune evasion, and activation of alternative signaling pathways. This review discusses these resistance mechanisms and examines strategies to counteract them, including sequential treatment with novel AR-targeted drugs, chemotherapy, poly ADP-ribose polymerase inhibitors, radionuclide therapy, bipolar androgen therapy, and approaches targeting specific resistance pathways. Future research should prioritize elucidating the molecular basis of NHT resistance, optimizing existing therapeutic strategies, and developing more effective combination regimens. Additionally, advanced sequencing technologies and resistance research models should be leveraged to identify novel therapeutic targets and improve drug delivery efficiencies. These advancements hold the potential to overcome NHT resistance and significantly enhance the management and prognosis of patients with advanced prostate cancer.
2.Construction of evidence graph for modifiable risk factors for diabetic retinopathy
Shuyuan SHI ; Qingxin ZHOU ; Hongyu SUN ; Siyan ZHAN ; Feng SUN ; Shuyan ZHANG
Chinese Journal of Epidemiology 2024;45(12):1736-1744
Objective:Diabetic retinopathy (DR) has been reported as the leading cause of blindness among diabetic adults, which is closely related to poor quality of life and increased burden of disability. This study aimed to aggregate the optimally available evidence on modifiable risks of DR.Methods:Until June 2023, PubMed, Cochrane Library, CNKI, and Wanfang databases were used to retrieve Meta-analysis about various risk factors for DR, and Meta-analysis were analyzed and summarized. R 4.3.2 software was used for each Meta-analytic association to calculate the effect size, 95% CI, heterogeneity, small-study effects, excess significance bias, and 95% prediction intervals. The credibility of significant evidence was graded. Results:We captured 23 eligible papers (72 associations) covering a wide range of medication use, concomitant diseases, daily intervention, biomarkers, lifestyle, and physical measurement index. Among them, higher HbA1c variability ( RR=1.45, 95% CI: 1.26-1.66) and urine microalbumin positive ( OR=2.44, 95% CI: 1.99-2.97) were convincing (grade Ⅰ) evidence, and insulin use ( RR=3.48, 95% CI: 2.14-5.67) was highly suggestive (grade Ⅱ) evidence. Moreover, hypertension ( OR=2.03, 95% CI: 1.06-3.97), poor glycemic control ( OR=4.35, 95% CI: 1.47-12.85), positive macroalbuminuria ( OR=8.42, 95% CI: 3.52-20.15), long sleep duration ( OR=2.05, 95% CI: 1.37-3.05), vitamin D deficiency ( OR=2.02, 95% CI: 1.17-3.50), periodontitis ( OR=4.51, 95% CI: 1.76-11.55) were the main risk factors for DR. Intensive blood pressure intervention ( RR=0.78, 95% CI: 0.65-0.94), dietary control ( OR=0.64, 95% CI: 0.47-0.89) and moderate intensity physical activity ( RR=0.76, 95% CI: 0.59-0.97) yielded significant protective associations with DR. Conclusions:Intensive blood pressure glycemic control, and a healthy lifestyle pattern could reduce the risk of DR. This study provides the evidence to identify high-risk populations and recommends rational treatment options and healthy living interventions.
3.Association between serum uric acid and airflow obstruction based on the health-checkup population
Qingxin ZHOU ; Qingqing YANG ; Shuyuan SHI ; Pei LI ; Feng SUN
Journal of Peking University(Health Sciences) 2024;56(4):693-699
Objective:To investigate the association between serum uric acid,pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects.Methods:All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender.The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction.Results:A total of 35 465 people were included in the study,in-cluding 16 411 men and 19 054 women.Among them,the serum uric acid concentration of men was higher than that of women,and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction.There was a negative correlation between serum uric acid level and the forced expiratory volume in one second(FEV1)and the force vital capacity(FVC)in women(P<0.05),but in men the correlation didn't exist(P>0.05).After adjusting for age,education,smoking status,drinking status,work strength,body mass index,history of cough,his-tory of hypertension,history of diabetes,history of dyslipidemia,white blood cells and blood albumin,the airflow obstruction in women was more likely to exist with the serum uric acid elevated(OR=1.12,95%CI:1.02-1.22,P<0.05).The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia(OR=1.36,95%CI:1.06-1.75,P<0.05).There was no correlation between serum uric acid concentration and airflow obstruction in men(OR=1.04,95%CI:0.96-1.13,P>0.05),also the hyperuricemia and airflow obstruction(OR=1.12,95%CI:0.89-1.39,P>0.05).Conclusion:There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women,and there is an association between elevated serum uric acid and airflow obstruction in women,but not in men.Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.
4.Construction and practice of an intelligent prevention and treatment system for venous thromboembolism in grassroots hospitals
Zhenxing HU ; Yang HE ; Yihua WANG ; Feng ZOU ; Kai YE ; Qin ZHANG ; Ting LEI ; Junmei ZHANG ; Surong HU ; Qingxin HU ; Xue LIAO
Journal of Clinical Medicine in Practice 2024;28(22):26-29
Objective To explore the construction and practice of an intelligent prevention and treatment system for venous thromboembolism (VTE) in grassroots hospitals. Methods Based on relevant guidelines and expert consensuses on VTE prevention and treatment, domestic and foreign literature was reviewed. A research and development team composed of clinical experts in VTE prevention and treatment, medical and nursing quality management experts, and information engineers conducted investigations and research in surrounding grassroots hospitals. Through evidence-based research and surveys, the team identified relevant business needs, user needs, and functional requirements of grassroots hospitals, and finally formulated a detailed design plan. The main program of system was written in Java. The interface obtained data from the hospital's data platform through Webservice and view interfaces. To prevent issues of repeated data extraction when multiple applications perform time tasks to assess the same patient during later server usage and expansion, the XXL-JOB distributed task scheduling platform was adopted to handle VTE assessments by medical staff. Results After the clinical application of the intelligent VTE prevention and treatment system, the bleeding risk assessment rate increased from 26.20% at the initial system launch in January 2023 to 83.04% by the end of 2023. In January 2023, the implementation rates of mechanical prevention, pharmacological prevention, and combined prevention for medium-to-high-risk VTE patients were 21.39%, 16.39%, and 5.26%, respectively, which increased to 51.75%, 25.50%, and 25.65% in December 2023. Conclusion The VTE prevention and treatment software system developed by grassroots hospitals can improve development efficiency, enhance the clinical practicality of the system, reduce the workload of medical staff, promote standardization and normalization in VTE prevention and treatment, strengthen closed-loop management of medical quality for VTE as a single disease, and effectively improve the prevention and treatment capabilities and levels of VTE within hospitals.
5.Analysis of the effects of different personalized cutting modes of SPT-Trans PRK on visual quality and cor-neal higher order aberrations after myopic astigmatism surgery
Yu FENG ; Xin LI ; Zhenjia ZHANG ; Xinping JIA ; Qingxin ZHAO
The Journal of Practical Medicine 2024;40(23):3337-3342
Objective To investigate and analyze the impact of three personalized surgical design schemes for SPT trans PRK on postoperative visual quality and higher-order aberrations in individuals with myopic astigma-tism,aiming to provide a foundation for more rational selection of personalized design schemes.Methods The 96 cases(96 eyes)with myopic astigmatism were divided into three groups based on three personalized design schemes and a conventional mode.Specifically,24 eyes were assigned to the personalized group 1,which focused on coma elimination;another 24 eyes belonged to personalized group 2,where the aim was to minimize spherical aberration elimination;and the remaining 24 eyes were further categorized into personalized group 3 based on a model that aimed at minimizing spherical aberration.Additionally,there were also 24 eyes in the control group treated using the conventional mode.The study compared and analyzed various parameters including best corrected visual acuity,spherical aberration,coma,total higher-order aberration of the anterior corneal surface,as well as differences in corneal ablation thickness between personalized and conventional schemes within the surgical design software.Results(1)The postoperative visual acuity of the personalized group was significantly superior to that of the control group(P<0.05);(2)Among the personalized groups,Group 2 exhibited a reduced amount of cor-neal tissue ablation compared to other groups(P<0.01);(3)Group 2 demonstrated lower values than the other groups after surgery(P<0.05).(4)Coma:The control group showed a significantly higher level of coma com-pared to preoperative measurements(P<0.01).No significant differences were observed between Groups 1,2,and 3 after surgery(P>0.05).(5)Total higher-order aberrations:All groups experienced a significant increase in total higher-order aberrations following surgery(P<0.01).Group 2 exhibited lower values than the other groups postoperatively(P<0.05).Conclusion For myopic astigmatism,SPT trans PRK incorporates the personalized surgical scheme with a focus on minimizing spherical aberration elimination mode,resulting in enhanced optimiza-tion of postoperative high-order aberration and improved visual quality,while preserving corneal tissue.
6.Analysis of the effects of different personalized cutting modes of SPT-Trans PRK on visual quality and cor-neal higher order aberrations after myopic astigmatism surgery
Yu FENG ; Xin LI ; Zhenjia ZHANG ; Xinping JIA ; Qingxin ZHAO
The Journal of Practical Medicine 2024;40(23):3337-3342
Objective To investigate and analyze the impact of three personalized surgical design schemes for SPT trans PRK on postoperative visual quality and higher-order aberrations in individuals with myopic astigma-tism,aiming to provide a foundation for more rational selection of personalized design schemes.Methods The 96 cases(96 eyes)with myopic astigmatism were divided into three groups based on three personalized design schemes and a conventional mode.Specifically,24 eyes were assigned to the personalized group 1,which focused on coma elimination;another 24 eyes belonged to personalized group 2,where the aim was to minimize spherical aberration elimination;and the remaining 24 eyes were further categorized into personalized group 3 based on a model that aimed at minimizing spherical aberration.Additionally,there were also 24 eyes in the control group treated using the conventional mode.The study compared and analyzed various parameters including best corrected visual acuity,spherical aberration,coma,total higher-order aberration of the anterior corneal surface,as well as differences in corneal ablation thickness between personalized and conventional schemes within the surgical design software.Results(1)The postoperative visual acuity of the personalized group was significantly superior to that of the control group(P<0.05);(2)Among the personalized groups,Group 2 exhibited a reduced amount of cor-neal tissue ablation compared to other groups(P<0.01);(3)Group 2 demonstrated lower values than the other groups after surgery(P<0.05).(4)Coma:The control group showed a significantly higher level of coma com-pared to preoperative measurements(P<0.01).No significant differences were observed between Groups 1,2,and 3 after surgery(P>0.05).(5)Total higher-order aberrations:All groups experienced a significant increase in total higher-order aberrations following surgery(P<0.01).Group 2 exhibited lower values than the other groups postoperatively(P<0.05).Conclusion For myopic astigmatism,SPT trans PRK incorporates the personalized surgical scheme with a focus on minimizing spherical aberration elimination mode,resulting in enhanced optimiza-tion of postoperative high-order aberration and improved visual quality,while preserving corneal tissue.
7.A pyrene-based ratiometric fluorescent probe with a large Stokes shift for selective detection of hydrogen peroxide in living cells
Qingxin CHEN ; Ke CHENG ; Wanhe WANG ; Liu YANG ; Yusheng XIE ; Ling FENG ; Jie ZHANG ; Huatang ZHANG ; Hongyan SUN
Journal of Pharmaceutical Analysis 2020;10(5):490-497
Hydrogen peroxide (H2O2) plays a significant role in regulating a variety of biological processes. Dys-regulation of H2O2 can lead to various diseases. Although numerous fluorescent imaging probes for H2O2 have been reported, the development of H2O2 ratiometric fluorescent probe with large Stokes shift re-mains rather limited. Such probes have shown distinct advantages, such as minimized interference from environment and improved signal-to noise ratio. In this work, we reported a new pyrene-based com-pound Py-VPB as H2O2 fluorescent probe in vitro. The probe demonstrated ratiometric detection behavior, large Stokes shift and large emission shift. In addition, the probe showed high sensitivity and selectivity towards H2O2 in vitro. Based on these excellent properties, we successfully applied Py-VPB to the visualization of exogenous and endogenous H2O2 in living cells. Cell imaging study also showed that our probe was localized in the mitochondria. We envision that the probe can provide a useful tool for unmasking the biological roles of mitochondrial H2O2 in living systems.
8.Construction of key question list in the evidence-based guidelines for colorectal cancer screening in China
Le GAO ; Shuqing YU ; Qingxin ZHOU ; Junling MA ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2020;41(2):267-272
Objective To establish the key question list for the development of evidencebased guideline in China according to the content and limitation of current evidence-based guidelines around the world.Methods First,we introduced the evidence-based guidelines in detail which met the criteria based on World Health Organization guideline development handbook and then formulated the draft list of key questions for the development of evidence-based guidelines.At last,the Delphi method was used to determine the list of key questions in developing evidence-based guidelines of colorectal cancer screening.Results Totally,34 questionnaires were collected,with experts from clinical and epidemiological fields.The average experts' authority coefficient was 0.81,indicating a high degree of authority.The concentration of opinions on all items in the questionnaire was relatively high,with the full score ratio greater than 75% and the coefficient of variation less than 0.3.The list of key questions on evidence-based guidelines for colorectal cancer screening has been divided into six parts:epidemiological problems,risk classification,screening age,screening tools,implementation and selection of steering group members,which covers the issues that need to be considered in the development of evidence-based colorectal cancer screening guidelines in China.Conclusion The key question list for evidence-based guideline development in our study can be applied to the development of evidence-based guidelines for colorectal cancer screening in the future,as well as the development of evidence-based guidelines for other cancer screening in China.
9.Current global development of screening guidelines for hepatocellular carcinoma: a systematic review
Jichun YANG ; Shuqing YU ; Le GAO ; Qingxin ZHOU ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2020;41(7):1126-1137
Objective:The objective of the study was systematically summarized the current status of the hepatocellular carcinoma (HCC) screening guidelines, and evaluated the HCC screening guidelines according to the authoritative framework of cancer screening guidelines of authoritative institutions, which provided important value for the formulation of HCC screening evidence-based guidelines.Methods:Literature search was conducted in multiple databases from their inception dates to January 3, 2019. In addition, we sought relevant websites further was searched to identify potentially eligible studies. Two reviewers independently screened literature and extracted data. Qualitative description of the basic information, recommendations of HCC screening, source of evidence and update progress of the HCC screening guidelines was conducted.Results:At present, there were no independent HCC screening guidelines worldwide. There were only 17 clinical practice HCC guidelines briefly provided the recommendation of HCC screening. Current HCC screening guidelines only recommended screening for high-risk groups of HCC. All guidelines have identified patients with chronic hepatitis B, hepatitis C and cirrhosis as high-risk groups for HCC. Most of guidelines recommended screening intervals was 6 months. The latest guidelines in Europe and the United States recommended ultrasound for screening HCC. The combination of ultrasound and AFP was recommended in the Asian guidelines. Currently, HCC screening guidelines mainly recommended screening strategies based on factors such as risk of HCC, accuracy of screening modality, screening cost, etc.. The key factors such as screening efficacy and safety have not yet been considered comprehensively. Conclusions:There were no independent HCC screening guidelines worldwide. Only some clinical practice HCC guidelines briefly mentioned HCC screening. Currently, the guidelines only recommend screening for high-risk groups of HCC, with a screening interval of 6 months. There are differences in screening modalities recommended by European, American and Asian guidelines for screening HCC. It is suggested that the relevant institutions should formulate the evidence-based HCC screening guidelines by referring to the theoretical framework of other authoritative other cancer screening guidelines.
10.Introduction to COSMOS-E: Guidance on conducting systematic reviews and Meta-analyses on etiology of observational studies
Weiwei WANG ; Zhirong YANG ; Qingxin ZHOU ; Shuyuan SHI ; Ge ZHANG ; Siyan ZHAN ; Feng SUN
Chinese Journal of Epidemiology 2020;41(12):2149-2159
This paper introduces the conducting systematic reviews and Meta-analyses of observational studies of etiology (COSMOS-E) and illustrates the critical issues of COSMOS-E with a published systematic review. This document provides researchers with guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis.


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