1.Progress on the application of system dynamics model in the field of health management.
Qiwei WU ; Huijie ZHOU ; Binyu ZHAO ; Jing SHAO
Journal of Zhejiang University. Medical sciences 2025;54(5):676-684
Health management is highly complex due to interactions across multiple levels and factors. System dynamics model (SDM) offers a holistic perspective and a dynamic analytical framework for understanding such complex systems. It has been applied across various domains of health management, including psychological interventions, chronic disease management, rehabilitation, optimization of medical services, and health policy development. By identifying key factors and pathways influencing health behaviors, determining critical targets for interventions, conducting cost-benefit analyses and process optimization, and simulating the long-term effects of health policies, SDM provides quantitative support for decision-making from individual-level interventions to macro-level policies. This article reviews the application of SDM in these four major areas within health management, discusses its advantages and limitations, and serves as a reference for researchers and practitioners aiming to utilize SDM in future studies. The goal is to advance health management toward greater personalization and precision, thereby offering stronger support for health interventions and policy development.
Humans
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Health Policy
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Models, Theoretical
2.PARP1 promotes the progression of hepatocellular carcinoma by regulating expression of POU2F2
Ziqiang WEN ; Junliang LAN ; Bo ZHOU ; Qiwei XU
China Oncology 2024;34(9):848-856
Background and purpose:Hepatocellular carcinoma(HCC)is a major disease seriously threatening human health.Poly(ADP-ribose)polymerase-1(PARP1)is an enzyme that catalyzes poly ADP-ribosylation.Given the role of PARP1 in DNA damage repair,it is generally considered as an oncogene.However,the expression of PARP1 and its mechanism in HCC are not yet clear.This study aimed to investigate the role of PARP1 in the occurrence and development of HCC and its potential mechanisms.Methods:First,we analyzed the expression pattern of PARP1 in The Cancer Genome Atlas(TCGA)and Clinical Proteomic Tumor Analysis Consortium(CPTAC)HCC database,and identified the expression trend of PARP1 in our HCC cohort using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Then,the enzyme activity of PARP1 was inhibited by PJ34,an inhibitor of PARP1 and the expression of PARP1 in HCC cell lines was downregulated with small RNA interference technology.Based on these models,the following experiments were conducted:First,the effect of PARP1 on cell viability was assessed by cell counting kit-8(CCK-8)assay and flow cytometry;Second,the expression levels of stemness-related genes in HCC cells were identified using RTFQ-PCR;Third,the effect of inhibition of PARP1 on migration and invasion of HCC cells was detected by migration and invasion assay(transwell assay).Finally,bioinformatic analysis was performed to identify new target genes and the pathways regulated by PARP1 in HCC progression.Rescue experiments were performed to determine whether PARP1 target genes were involved in the malignant phenotypes of HCC cells.Results:The expression of PARP1 was significantly up-regulated in HCC tissues in both TCGA and CPTAC database.RTFQ-PCR and Western blot assays showed that PARP1 was obviously up-regulated in HCC tissues compared to paracancerous tissues.Survival analysis showed that PARP1 expression was significantly negatively correlated with the prognosis of patients.The results of CCK-8,flow cytometry,RTFQ-PCR and transwell assay indicated that inhibition of PARP1 attenuated proliferation and activity of HCC cells,as well as weakened their stemness,migration and invasion.Bioinformatics analysis suggested that PARP1-regulated genes were enriched in the nuclear factor-κB(NF-κB)and necroptosis pathways,with POU class homeobox 2(POU2F2)potentially being a target gene of PARP1.Correlation analysis,along with RTFQ-PCR and Western blot detection,confirmed that the expression of POU2F2 was regulated by PARP1,while not affected by PJ34,indicating the effect of nonenzymatic function of PARP1 on POU2F2.CCK-8,flow cytometry and RTFQ-PCR results showed that the reintroduction of POU2F2 enhanced proliferative capacity,increased activity,and promoted stemness of HCC cell lines with PARP1 knockdown.Conclusion:By positively regulating the expression of POU2F2,PARP1 promotes malignant phenotypes of HCC cells,providing new insights for clinical treatment and drug development for HCC.
3.Predictive value of serum TGF-β1 and VEGF levels in patients with non-small cell lung cancer after single-port thoracoscopic radical resection
Kun WANG ; Zhongxin ZHOU ; Qiwei ZANG
Journal of International Oncology 2024;51(4):198-203
Objective:To analyze the predictive value of serum transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in patients with non-small cell lung cancer (NSCLC) after single-port thoracoscopic radical resection.Methods:A total of 50 patients with NSCLC who underwent single-port thoracoscopic radical resection in Affiliated Hospital of Xuzhou Medical University from May 2018 to May 2020 were selected as the observation objects. Serum TGF-β1, VEGF levels and Karnofsky functional status (KPS) scores before and after surgery were compared, and the total incidence of complications was calculated. All subjects were followed up for 3 years, and serum levels of TGF-β1, VEGF and KPS scores were compared between relapsed group and non-relapsed group, survival group and death group. Pearson correlation analysis was used to explore the correlation between TGF-β1, VEGF and KPS scores. The receiver operator characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive value of serum TGF-β1 and VEGF alone and combined detection in patients with NSCLC after single-port thoracoscopic radical resection.Results:The serum levels of TGF-β1 and VEGF were (7.16±1.94) μg/L and (42.26±5.04) ng/L in 50 patients with NSCLC one month after single-port thoracoscopic radical resection, which were lower than those before surgery [ (13.62±3.52) μg/L and (136.52±20.66) ng/L, t=11.37, P<0.001; t=31.34, P<0.001]. The KPS score one month after surgery was 66.57±8.11, which was higher than that before surgery (53.62±5.62, t=9.28, P<0.001). Postoperative wound healing was delayed in 1 of the 50 patients, pulmonary infection in 1 patient, and no pulmonary embolism and other complications occurred. The total incidence of complications was 4.00%. The serum levels of TGF-β1 and VEGF in patients in the relapsed group ( n=6) were (12.95±4.26) μg/L and (72.46±6.05) ng/L respectively, which were higher than those in the non-relapsed group ( n=44) [ (6.37±1.25) μg/L and (38.14±5.37) ng/L; t=8.34, P<0.001; t=29.99, P<0.001]. The KPS score in the relapsed group was 52.16±8.16, which was lower than that in the non-relapsed group (67.55±12.67, t=2.88, P=0.006). Serum levels of TGF-β1 and VEGF in the death group ( n=5) were (13.99±6.82) μg/L and (75.95±9.05) ng/L, which were higher than those in the survival group ( n=45) [ (6.41±3.06) μg/L and (38.52±8.37) ng/L; t=4.56, P<0.001; t=21.47, P<0.001]. The KPS score in the death group was 1.25±0.34, which was lower than that in the survival group (65.11±12.94, t=10.93, P<0.001). Pearson correlation analysis showed that serum levels of TGF-β1 ( r=-0.45, P<0.001) and VEGF ( r=-0.48, P<0.001) were negatively correlated with KPS scores. ROC curve analysis showed that when the optimal cut-off value of TGF-β1 was 8.14 μg/L, the AUC for predicting recurrence after single-port thoracoscopic radical resection was 0.516 (95% CI: 0.446-0.676), the sensitivity was 71.85%, and the specificity was 80.69%. When the optimal cut-off value of VEGF was 142 ng/L, the AUC was 0.659 (95% CI: 0.534-0.761), the sensitivity was 76.04%, and the specificity was 82.52%. The AUC of the combined detection was 0.828 (95% CI: 0.786-0.951), the sensitivity was 91.86%, and the specificity was 87.52%. The AUC of combined detection was higher than that of serum TGF-β1 ( Z=2.63, P=0.007), VEGF ( Z=2.32, P=0.013) single detection. Conclusion:The serum levels of TGF-β1 and VEGF are significantly decreased in NSCLC patients after one month of single-port thoracoscopic radical resection, and the combined detection of the two has predictive value for recurrence after single-port thoracoscopic radical resection.
4.Effects of hypoxia-inducible factors on tumor mesenchymal cells: a review
ZHAO Qiwei ; ZHOU Xinyue ; LIU Xiayang ; LI Zhuang ; GUO Xiaohong
Journal of Preventive Medicine 2024;36(1):34-38
Hypoxia is the most common tumor microenvironment caused by rapid proliferation of tumor cells, and hypoxia-inducible factor (HIF) is the main transcription factor for tumor cells to adapt to hypoxia. Current research has found that HIF can interact with a variety of mesenchymal cells such as fibroblasts, endothelial cells and immune cells in the tumor microenvironment, leading to the transcription and expression of target genes in response to hypoxia, which ultimately promotes tumor angiogenesis, and induces physiological changes such as migration, invasion, and immune escape of tumor cells. However, the signaling pathways involved in the HIF regulatory mechanism are complex, and the mechanism of HIF in the tumor microenvironment need to be further investigated, also most HIF inhibitors are still in the preclinical research stage. This paper reviews the research progress on the effects of HIF on tumor mesenchymal stromal cells to provide a theoretical basis for the diagnosis, prevention and treatment of tumors targeting HIF.
5.Tumor deposit is an independent prognostic factor in patients with gastric cancer after radical gastrectomy
Liquan ZHOU ; Yushi ZHOU ; Qiwei XIE ; Yingjiang YE ; Bin LIANG
Chinese Journal of General Surgery 2024;39(10):790-796
Objective:To investigate the effect of tumor deposit(TD) on the prognosis of patients with gastric cancer after radical surgery.Methods:A retrospective analysis was performed on gastric cancer patients who underwent radical surgery at the Department of Gastrointestinal Surgery, Peking University People's Hospital from Jan 2021 to Dec 2023. The relationship between the status of tumor deposit and clinicopathological features, as well as the impact on the overall postoperative survival of gastric cancer patients were evaluated.Results:Pathological examination revealed that among 212 patients with gastric cancer, 12 patients (5.1%) had tumor deposits (TD). The occurrence of TD was found to be associated with preoperative T stage, N stage, and extramural vascular invasion (EMVI) (all P<0.05). During the follow-up period, 31 patients experienced recurrence, metastasis, or death. The COX multivariate analysis indicated that N stage ( P=0.07), preoperative serum CEA level ( P<0.001), EMVI ( P=0.001), and TD ( P=0.011) were independent risk factors affecting the overall postoperative survival . Among patients who received neoadjuvant therapy and on pT4 stage, pN+ status, and EMVI status before surgery, the presence of TD was closely correlated with overall survival. Patients with TD had a worse prognosis and shorter overall survival( P<0.05). Conclusion:Tumor deposit is an important risk factor affecting the prognosis of patients after radical gastrectomy and may be a predictive biomarker of early peritoneal metastasis.
6.Clinical factors of positive surgical margin after robot-assisted laparoscopic radical prostatectomy in patients with high-risk prostate cancer
Weijun FU ; Yong SONG ; Jian ZHAO ; Jinpeng SHAO ; Ziyan AN ; Qiwei ZHOU ; Shengkun SUN ; Wenzheng CHEN ; Jie ZHU ; Dan SHEN ; Qingshan DU ; Fan ZHANG ; Kan LIU ; Xu ZHANG
Chinese Journal of Urology 2022;43(7):518-522
Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.
7.Clinical characteristics of esophageal reflux after total gastrectomy
Zhiyuan ZHENG ; Yancheng CUI ; Jing ZHANG ; Chao SHEN ; Yushi ZHOU ; Xin LIU ; Yingjiang YE ; Qiwei XIE ; Mujun YIN ; Xiaodong YANG ; Kewei JIANG ; Zhidong GAO ; Zhifeng WANG ; Lili ZHAO ; Shan WANG ; Bin LIANG
Chinese Journal of General Surgery 2021;36(4):267-271
Objective:To observe the clinical characteristics of esophageal reflux after total gastrectomy (ERATG), and to explore the mechanism of occurrence.Methods:Fourteen gastric cancer patients who underwent total gastrectomy were prospectively enrolled in this study. The postoperative symptoms were observed and recorded and 24 h MII-pH with pH monitoring was performed to investigate the characteristics of postoperative reflux.Results:After total gastrectomy patients were with different degrees of ERATG as heartburn, appetite loss, chest tightness and belching. The overall nature of ERATG is mainly weak acid, with a pH between 4 and 7. ERATG involved esophageal-jejunal anastomosis and a length of esophagus 7 cm above the anastomosis. Patients with typical reflux symptoms had a lower pH minimum in the upright position than those without typical symptoms[(4.76±0.71) vs.(5.68±0.37), t=2.866, P<0.05]. Patients with typical reflux symptoms had a higher frequency of reflux of mixed liquid and liquid-air reflux than those without typical symptoms[liquid(31.25±29.76) vs.(4.50±9.14), t=0.011, P<0.05; liquid-air(19.50±12.99) vs.(2.00±2.61), t=0.004, P<0.05]. Conclusion:ERATG is mainly a upward reflux of weakly acidic gas, with typical symptoms of heartburn, appetite loss, chest tightness and belching. Patients with typical symptoms usually have lower pH in the upright position.
8.Diagnostic value of tumor markers in peritoneal lavage fluid for peritoneal metastasis of colorectal cancer
Xin LIU ; Yushi ZHOU ; Qiwei XIE ; Mujun YIN ; Xiaodong YANG ; Kewei JIANG ; Zhiyuan ZHENG ; Bin LIANG ; Yingjiang YE ; Shan WANG
Chinese Journal of General Surgery 2020;35(8):593-597
Objective:To determine the diagnostic value of tumor markers in peritoneal lavage fluid from colorectal cancer patients for tumor peritoneal metastasis.Methods:A total of 227 colorectal cancer patients who undergoing surgical treatment were included. 300 ml of peritoneal lavage fluid was irrigated immediately upon laparotomy for traditional cytology (PLC) testing, 134 patients were tested for tumor marker of peritoneal lavage fluid (pTM). Univariate analysis was performed to determine the risk factors for peritoneal metastasis; pTM ROC curve was used to determine the best cutoff value; paired chi-square test was used to compare the difference between PLC and pTM detection.Results:The positive rate of PLC was 12.3% (28/227). Age>65, stage T3 + , lymph node metastasis, mucinous adenocarcinoma and increased serum CA125, CA19-9 are related to peritoneal metastasis; The best cutoff value of pTM for peritoneal metastasis : pCEA 17.095 ng/dl, sensitivity 58.3%, specificity 93.9%; pCA19-9 4.515 U/ml, sensitivity 83.3%, specificity 80.0%; pCA125 303.2 U/ml, sensitivity 58.3%, specificity 95.7%; pCA-724 3.01 U/ml, sensitivity 66.7%, specificity 95.7%; The best cutoff value of pTM for peritoneal micrometastasis: pCA19-9 3.43 U/ml, sensitivity 100%, specificity 72.2%. The positive rate of pCA19-9 was 29.85%, which was higher than that of PLC (χ 2=2.00, P<0.05). Conclusion:Peritoneal metastasis of colorectal cancer is related to tumor T stage, lymph node metastasis, tumor pathological type, and increased serum CA125 and CA19-9; pTM has diagnostic value for peritoneal metastasis of colorectal cancer.
9.Application of high-resolution melting analysis of segmental duplication in the prenatal diagnosis of common trisomies
Wenyan XU ; Qiwei GUO ; Ping HU ; Yuning ZHU ; Xuemei ZHANG ; Xinyi ZHENG ; Haixia ZHANG ; Yulin ZHOU
Chinese Journal of Laboratory Medicine 2020;43(7):745-750
Methods:A total of 1 152 amniotic fluid samples were collected from pregnant women who underwent prenatal diagnosis in the Nanjing Maternity and Child Health Care Hospital, Women′s Hospital School of Medicine Zhejiang University, West China Second University Hospital, Sichuan University/West China Women′s and Children′s Hospital, and Xiamen Maternal and Child Health Hospital from September 2014 to August 2016. These samples were examined with SD-HRM and karyotyping simultaneously. Clinical sensitivity and specificity of SD-HRM were calculated, and Kappa values were measured to evaluate the consistency of detection results of the two methods.Results:A total of 161 cases of trisomy 21, 60 cases of trisomy 18, and 5 cases of trisomy 13 were detected by SD-HRM in 1 152 prenatal samples, sensitivity and specificity were both up to 100%, and Kappa values is equal to 1 which were consistent with the results of karyotype analysis.Conclusion:SD-HRM is validated to be highly accurate for the prenatal diagnosis of common trisomies, which is promising in the clinical practice.
10.Detection of intraperitoneal free cancer cells in gastric cancer patients undergoing gastrectomy and its relationship with short-term prognosis
Dafang LIU ; Chao SHEN ; Yushi ZHOU ; Zhiyuan ZHENG ; Xin LIU ; Yingjiang YE ; Qiwei XIE ; Mujun YIN ; Xiaodong YANG ; Kewei JIANG ; Haipeng XIAN ; Xiaotao ZHAO ; Bin LIANG ; Shan WANG
Chinese Journal of General Surgery 2018;33(5):376-380
Objective To evaluate different methods in detecting intraperitontal free cancer cells (IFCCs) in patients with gastric cancer and to clarify the relationship between positive IFCCs and short-term prognosis.Methods A total of 119 gastric cancer patients who underwent surgical treatment were enrolled.Peritoneal lavage was performed with 300-400 ml saline respectively at three points of time:immediately after abdominal cavity entry;when surgical operation was completed;when extensive intraoperative peritoneal lavage was done.The IFCCs were detected with methods of traditional centrifugal cytology,membrane cytology,ICC and RT-PCR.The survival curve of patients with gastric cancer was drawn using Kaplan-Meier method.Results The positive rate of PLC was 16.8%,20.7% and 11.2% respectively at 3 timepoints (P < 0.05).The positive rates of ICC were 28.6%,38.8% and 20.7% respectively at 3 timepoints.The positive rates of RT-PCR were 39.3%,69.5% and 50.8% respectively at 3 time points.The positive rate of IFCCs detected through RT-PCR was higher than that of PLC and ICC (P < 0.05).The short-term prognosis of patients with positive IFCCs was worse than those with negative results detected with any three method at the timg point immediately after opening the abdomen (P < 0.05).At the timg point immediately after removing the tumors,the short-term prognosis of patients with positive IFCCs detected with PLC was worse (P < 0.05).Conclusion The short-term prognosis was poor in patients with positive IFCCs.It is the best time to detect IFCCs before radical resection.Surgical procedures increase the risk of shedding of IFCCs.


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