1.A Review of the Data-Driven Policy Making of Medical Financial Assistance for Rare Diseases: Current Situation, Trends and Opportunities
Yuehan DUAN ; Zhiyu FAN ; Qianhui LI ; Zhaiwen PENG
JOURNAL OF RARE DISEASES 2025;4(1):39-45
The inherent clinical uncertainties, substantial costs, and small patient cohorts of orphan drugs limit the applicability of randomized controlled trial (RCT)-based health technology assessments (HTAs) in guiding coverage criteria, sustainable financing models, and equitable reimbursement frameworks for medical financial assistance policies for rare diseases.The digital transformation in healthcare system leads to solutions to the challenges in designing the policy by using data-driven decision-making. This article summarizes the decision-making issues in policy design, discusses the current status and trends of digital transformation, and analyzes the important new opportunities for AI-driven policy design for medical financial assistance policies for rare diseases. Decision-making that is digital intelligence driven and using techniques such as big data analytics and real-world research methods will enhance targeting efficiency, improve the quality of financing, and realize the performance-based reimbursement in the medical financial assistance, providing significant value in facilitating the policy reform and development for rare diseases healthcare.
2.Resection of mediastinal tumor combined with persistent left superior vena cava: A case report
Zongjun XIANG ; Fan ZHANG ; Lei LI ; Yongguo LU ; Xiaoming LI ; Haide MU ; Xiaowei ZHOU ; Linqi YANG ; Zhiyu WAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(07):1044-1046
Persistent left superior vena cava is a rare venous variant that is often combined with cardiovascular malformations. In thoracic surgery, especially mediastinal tumor resection, neglect of this variant may make the surgery difficult and risky, and careful preoperative imaging interpretation and adequate preoperative evaluation play an important role in the perioperative safety of the patient. In this paper, we reported a case of a 17-year-old female patient with a persistent left superior vena cava combined with mediastinal tumors. She was successfully discharged 5 days after thoracoscopic surgery, and after 3 years of postoperative follow-up, no tumor recurrence was observed.
3.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.
4.Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum.
Xue ZHANG ; Jing HAN ; Yudong WANG ; Li FENG ; Zhisong FAN ; Yu SU ; Wenya SONG ; Lan WANG ; Long WANG ; Hui JIN ; Jiayin LIU ; Dan LI ; Guiying LI ; Yan LIU ; Jing ZUO ; Zhiyu NI
Protein & Cell 2025;16(6):491-496
5.Analysis of influencing factors for early tumor recurrence and efficacy of adjuvant chemotherapy in gallbladder carcinoma patients after curative-intent resection: a nationwide, multicenter clinical study
Dong ZHANG ; Qi LI ; Wei GUO ; Fan HUANG ; Yi ZHU ; Kecan LIN ; Dalong YIN ; Wei CHEN ; Rui DING ; Ping YUE ; Yunfeng LI ; Zhiyu CHEN ; Zhimin GENG
Chinese Journal of Digestive Surgery 2024;23(1):125-133
Objective:To investigate the influencing factors for early tumor recurrence and the efficacy of adjuvant chemotherapy in gallbladder carcinoma (GBC) patients after curative-intent resection.Methods:The retrospective case-control study was conducted. The clinicopathological data of 506 patients with GBC in 11 medical centers, including The First Affiliated Hospital of Xi'an Jiaotong University et al, from January 2016 to December 2020 were collected. There were 168 males and 338 females, aged (62±11)years. All patients underwent curative-intent resection of GBC, and they were divided into patients with and without early recurrence based on time to postoperative recurrence. Observation indicators: (1) treatment; (2) follow-up and survival of patients; (3) analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC; (4) efficacy of postoperative adjuvant chemotherapy. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and Log-Rank test was used for survival analysis. Results:(1) Treatment. Of 506 patients, there were 112 cases with postoperative adjuvant chemotherapy, and 394 cases without postopera-tive adjuvant chemotherapy. They underwent 5(range, 3-9)cycles of postoperative adjuvant chemo-therapy. (2) Follow-up and survival of patients. All 506 patients underwent postoperative follow-up, with the follow-up time of 55(range, 34-93)months. During the follow-up, there were 248 patients with tumor recurrence, including 158 cases of early recurrence and 90 cases of late recurrence, and there were 258 patients without tumor recurrence. Of 506 patients, 275 cases survived, and 231 cases died of multiple organ failure caused by tumor recurrence and metastasis. The postoperative recurr-ence-free survival time, overall survival time were 52(range,1-93)months, 62(range, 2-93)months. The 1-, 3-, 5-year disease-free survival rates and 1-, 3-, 5-year overall survival rates of the 506 pati-ents were 68.8%, 53.8%, 47.9% and 78.3%, 58.7%, 51.6%, respectively. Results of survival analysis showed that the median overall survival time of 158 patients with postoperative early recurrence and 348 patients without postoperative early recurrence (including 90 cases of late recurrence and 258 cases of no tumor recurrence) were 9(range, 2-73)months and unreached, showing a significant difference between them ( χ2=456.15, P<0.05). (3) Analysis of influencing factors for early tumor recurrence after curative-intent resection of GBC. Results of multivariate analysis showed that carcinoembryonic antigen (CEA) >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 were independent risk factors influencing early tumor recurrence after cura-tive-intent resection of GBC ( odds ratio=2.74, 6.20, 1.81, 2.93, 4.82, 95% confidence interval as 1.62-4.64, 1.82-21.12, 1.15-3.08, 1.68-5.09, 1.91-12.18, P<0.05), while postoperative adjuvant chemo-therapy was an independent protect factor ( odds ratio=0.39, 95% confidence interval as 0.21-0.71, P<0.05). (4) Efficacy of postoperative adjuvant chemotherapy. The median overall survival time of 394 patients without postoperative adjuvant chemotherapy and 112 patients with postoperative adjuvant chemotherapy were 57(range, 2-93)months and unreached, showing a significant differ-ence between them ( χ2=9.38, P<0.05). Of the 158 patients with postoperative early recurrence after curative-intent resection of GBC, 135 cases didn't receive adjuvant chemotherapy and 23 cases received adjuvant chemotherapy, with the overall survival time of 8(range, 2-73)months and 17(range, 8-61)months, respectively, showing a significant difference between them ( χ2=7.68, P<0.05). Conclusions:CEA >5.0 μg/L, poorly differentiated tumor, liver invasion, and tumor N staging as stage N1-N2 are independent risk factors influencing early tumor recurrence after curative-intent resection of GBC, while postoperative adjuvant chemotherapy is an independent protect factor. Postoperative adjuvant chemotherapy can prolong the overall survival time of patients with post-operative tumor early recurrence.
6.Clinical application and progress of yttrium 90 microsphere selective internal radiation therapy in primary hepatic cancer
Hui ZHANG ; Ying FU ; Binbin TAN ; Minghua SHAO ; Ping LIU ; Chao FAN ; Hailei CHEN ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2024;23(2):242-247
Primary hepatic cancer is one of the major problems that need to be solved urgently in the field of public health, seriously endangering the life and health of Chinese people. Its treatment mode is multidisciplinary participation and synergy of multiple therapeutic methods. Even though there are many common clinical treatments for liver cancer in China, its therapeutic outcome is still unsatisfactory. yttrium-90 has been applied for more than 20 years, and a large amount of foreign clinical data have been accumulated. Combining the latest literature and clinical practice, the authors describe the clinical application and research progress of yttrium-90 micro-sphere selective internal radiation therapy in primary liver cancer.
7.Spatial distribution pattern of local tumor progression analysis after microwave ablation of hepatocellular carcinoma based on three-dimensional magnetic resonance imaging
Fangying FAN ; Wenzhen DING ; Fangyi LIU ; Zhigang CHENG ; Zhiyu HAN ; Xiaoling YU ; Ping LIANG ; Jie YU
Chinese Journal of Hepatology 2024;32(3):208-213
Objective:To investigate the spatial distribution pattern of local tumor progression (LTP) for hepatocellular carcinoma (HCC) ≤5 cm after microwave ablation.Methods:A retrospective analysis was performed on 169 HCCs with matched MRI before and after ablation from December 2009 to December 2019. A tumor MRI was reconstructed using three-dimensional visualization technology. LTP was classified as contact or non-contact, early or late stage, according to whether LTP was in contact with the edge of the ablation zone and the occurrence time (24 months). The tumor-surrounded area was divided into eight quadrants by using the eight-quadrant map method. An analysis was conducted on the spatial correlation between the quadrant where the ablative margin (AM) safety boundary was located and the quadrant where different types of LTP occurred. The t-test, or rank-sum test, was used for the measurement data. 2-test for count data was used to compare the difference between the two groups.Results:The AM quadrant had a distribution of 54.4% LTP, 64.2% early LTP stage, and 69.1% contact LTP, suggesting this quadrant was much more concentrated than the other quadrants ( P ?0.001). Additionally, the AM quadrant had only 15.2% of non-contact type LTP and 17.1% of late LTP, which was not significantly different from the average distribution probability of 12.5% (100/8%) among the eight quadrants ( P = 0.667, 0.743). 46.6% of early contact type LTP was located at the ablation needle tip, 25.2% at the body, and 28.1% at the caudal, while the location distribution probabilities of non-early contact LTP were 34.8%, 31.8%, and 33.3%, respectively. Conclusion:LTP mostly occurs in areas where the ablation safety boundary is the shortest. However, non-contact LTP and late LTP stages exhibit the feature of uniform distribution. Thus, this type of LPT may result from an inadequate non-ablation safety boundary.
8.Influence of curative-intent resection with textbook outcomes on long-term prognosis of gall-bladder carcinoma: a national multicenter study
Zhipeng LIU ; Zimu LI ; Yule LUO ; Xiaolin ZHAO ; Jie BAI ; Yan JIANG ; Yunfeng LI ; Chao YU ; Fan HUANG ; Zhaoping WU ; Jinxue ZHOU ; Dalong YIN ; Rui DING ; Wei GUO ; Yi ZHU ; Wei CHEN ; Kecan LIN ; Ping YUE ; Yao CHENG ; Haisu DAI ; Dong ZHANG ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2024;23(7):926-933
Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.
9.Influencing factors of textbook outcomes in liver surgery after radical resection of gallbladder carcinoma: a national multicenter study
Zhipeng LIU ; Xuelei LI ; Haisu DAI ; Weiyue CHEN ; Yuhan XIA ; Wei WANG ; Xianghao YE ; Zhihua LONG ; Yi ZHU ; Fan HUANG ; Chao YU ; Zhaoping WU ; Jinxue ZHOU ; Dong ZHANG ; Rui DING ; Wei CHEN ; Kecan LIN ; Yao CHENG ; Ping YUE ; Yunfeng LI ; Tian YANG ; Jie BAI ; Yan JIANG ; Wei GUO ; Dalong YIN ; Zhiyu CHEN
Chinese Journal of Digestive Surgery 2023;22(7):866-872
Objective:To investigate the influencing factors of textbook outcomes in liver surgery (TOLS) after radical resection of gallbladder carcinoma.Methods:The retrospective case-control study was conducted. The clinicopathological data of 530 patients who underwent radical resection of gallbladder carcinoma in 15 medical centers, including the First Affiliated Hospital of Army Medical University et al, from January 2014 to January 2020 were collected. There were 209 males and 321 females, aged (61±10)years. Patients underwent radical resection of gallbladder carcinoma, including cholecystectomy, hepatectomy, invasive bile duct resection, and lymph node dissection. Observation indicators: (1) situations of TOLS; (2) influencing factors of TOLS. Measure-ment data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. The univariate analysis was conducted using the corresponding statistical methods based on data type, and variables with P<0.10 were included in multivariate analysis. Multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Situations of TOLS. All 530 patients underwent radical resection of gallbladder carcinoma, and there were 498 cases achieving R 0 resection, 508 cases without ≥grade 2 intra-operative adverse events, 456 cases without postoperative grade B and grade C biliary leakage, 513 cases without postoperative grade B and grade C liver failure, 395 cases without severe com-plications within postoperative 90 days, 501 cases did not being re-admission caused by severe com-plications within postoperative 90 days. Of the 530 patients, 54.53%(289/530) of patients achieved postoperative TOLS, while 45.47%(241/530) of patients did not achieve postoperative TOLS. (2) Influencing factors of TOLS. Results of multivariate analysis showed that American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy were independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma ( odds ratio=2.65, 1.87, 5.67, 5.65, 2.55, 3.34, 95% confidence interval as 1.22?5.72, 1.18?2.95, 2.51?12.82, 2.83?11.27, 1.41?4.63, 1.88?5.92, P<0.05). Conclusion:American Society of Anesthesiologists classification >grade Ⅱ, preoperative jaundice, T staging as T3?T4 stage, N staging as N2 stage, liver resection as right hemi-hepatectomy, and neoadjuvant therapy are independent factors influencing TOLS in patients undergoing radical resection of gallbladder carcinoma.
10.Short-term efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy for the treatment of non-small cell lung cancer
Yixing LI ; Heng ZHAO ; Bohao LIU ; Jizhao WANG ; Yanpeng ZHANG ; Chendong GUO ; Chuchen ZHAO ; Kun FAN ; Hongyi WANG ; Runyi TAO ; Zhiyu WANG ; Jia ZHANG ; Junke FU ; Guangjian ZHANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(03):369-374
Objective To explore the short-term efficacy and safety of pembrolizumab combined with chemotherapy in the neoadjuvant treatment of non-small cell lung cancer. Methods The clinical data of 11 male patients with non-small cell lung cancer who underwent pembrolizumab combined with neoadjuvant chemotherapy in the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from December 2019 to June 2021 were retrospectively analyzed. The average age of the patients was 52.0-79.0 (62.0±6.9) years. The imaging data and pathological changes before and after neoadjuvant treatment were compared, and adverse reactions during neoadjuvant treatment were recorded. Objective remission rate (ORR) and main pathological remission rate (MPR) and pathological complete remission rate (pCR) were the main observation endpoints. Results After preoperative neoadjuvant therapy with pembrolizumab combined with platinum or paclitaxel, all patients successfully underwent thoracoscopic radical resection of lung cancer. The ORR was 72.7%, and the MPR was 81.8%. Among them, 45.5% of patients achieved pCR. The main adverse reactions were hypoalbuminemia, decreased appetite and nausea. The mortality rate within 30 days after surgery was 0, and no tumor metastasis was observed. Conclusion Pembrolizumab combined with neoadjuvant chemotherapy is safe and feasible to treat non-small cell lung cancer, and the short-term efficacy is beneficial.

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