1.Incidence and risk factors of pneumonia in patients with thoracic tumors receiving radiotherapy combined with immunotherapy
Wenjie ZHANG ; Jing WANG ; Wei SHI ; Hu QIU ; Yongshun CHEN
Chinese Journal of Radiation Oncology 2025;34(9):914-920
Objective:To evaluate the incidence and risk factors of pneumonia in patients with thoracic cancer treated with immunotherapy combined with radiotherapy (RT).Methods:The clinic data of 265 patients with thoracic cancer who received RT and at least 2 cycles of immunotherapy at Renmin Hospital of Wuhan University between January 2020 and January 2024 were retrospectively analyzed. Patients were divided into 2 groups according to treatment sequence: 100 patients with sequential immunotherapy after RT, 165 patients with RT after immunotherapy, including sequential RT after immunotherapy (119 cases) and concurrent RT with immunotherapy (46 cases). The occurrence and grading of treatment-related pneumonia were determined by clinical symptoms, signs, and chest CT findings. The relationship between interval time window of different treatment methods and pneumonia was analyzed by Pearson correlation analysis. χ2 test was used for univariate analysis of risk factors, and logistic regression for multivariate analysis. Results:In the sequential immunotherapy after RT group, the incidence of pneumonia was 12.0% (12/100), with grade ≥2 pneumonia in 4.0% (4/100). The interval time between RT and immunotherapy, has a strong negative correlation with pneumonia incidence and grade ≥2 pneumonia incidence ( r=-0.88, -0.79; both P<0.001). When immunotherapy was initiated ≥7 weeks after RT, the incidence of pneumonia significantly decreased to 5% ( P=0.020), with no grade ≥2 cases. In the immunotherapy followed by sequential / concurrent RT cohort, the incidence of pneumonia was significantly higher in the concurrent subgroup compared with the sequential subgroup [65% (30/46) vs. 44.5% (53/119), P=0.027], and the comparison of the incidence of grade ≥2 pneumonia was the same [33% (15/46) vs. 14.3% (17/119), P=0.014]. The interval time window of RT after immunotherapy was strongly negatively correlated with the incidence of pneumonia and grade ≥2 pneumonia ( r=-0.77, -0.83; both P<0.001). When RT was initiated ≥4 weeks after immunotherapy, the incidence of pneumonia significantly decreased ( P<0.001). Pneumonia incidence differed significantly across RT target sites (intrapulmonary vs. extrapulmonary), total dose (<60 Gy vs. ≥ 60 Gy), and fractionation regimen (conventional vs. hypofractionation) ( P < 0.001, = 0.008, = 0.031), but was not associated with age, gender, smoking history, type of immune checkpoint inhibitor (anti-programmed death-1 vs. anti-programmed death ligand-1), or the number of prior immunotherapy cycles (all P > 0.05). Multivariate analysis identified RT within the lung and interval time of RT after immunotherapy ≤ 4 weeks as independent risk factors for the incidence of pneumonia (both P < 0.001). Conclusions:The interval window between RT and immunotherapy is a critical determinant of pneumonia incidence. Delaying immunotherapy for more than 7 weeks after RT, or delaying RT for more than 4 weeks after immunotherapy, can significantly reduce the risk of radiation-related pneumonia.
2.Research progress on the molecular mechanism of the relationship between macrophages and acute ischemic stroke
Yongshun ZHANG ; Feng ZHAO ; Meng SUN ; Zhiqiang LI
Chinese Journal of Cerebrovascular Diseases 2025;22(4):285-290
The relationship between macrophages and acute ischemic stroke is currently a research hotspot.Previous studies have shown that macrophages in the central nervous system,vascular wall,and circulatory system can affect acute ischemic stroke through different mechanisms such as exacerbating inflammatory responses,phagocytosis,or inducing ferroptosis of vascular endothelial cells.In addition,during the occurrence of acute ischemic stroke,macrophages in the vascular wall and circulating system play a significant role through exosomes.This article reviewed the pathogenic mechanisms of macrophages in acute ischemic stroke,with the aim of providing a reference for in-depth research on the relationship between macrophages and acute ischemic stroke and the development of precise treatment plans.
3.Research progress on the molecular mechanism of the relationship between macrophages and acute ischemic stroke
Yongshun ZHANG ; Feng ZHAO ; Meng SUN ; Zhiqiang LI
Chinese Journal of Cerebrovascular Diseases 2025;22(4):285-290
The relationship between macrophages and acute ischemic stroke is currently a research hotspot.Previous studies have shown that macrophages in the central nervous system,vascular wall,and circulatory system can affect acute ischemic stroke through different mechanisms such as exacerbating inflammatory responses,phagocytosis,or inducing ferroptosis of vascular endothelial cells.In addition,during the occurrence of acute ischemic stroke,macrophages in the vascular wall and circulating system play a significant role through exosomes.This article reviewed the pathogenic mechanisms of macrophages in acute ischemic stroke,with the aim of providing a reference for in-depth research on the relationship between macrophages and acute ischemic stroke and the development of precise treatment plans.
4.Research progresses in coronary CT angiography of coronary atherosclerotic plaques
Mengyuan BAO ; Yongshun WU ; Xinwei ZHANG ; Linxin ZHANG ; Yan XING
Chinese Journal of Interventional Imaging and Therapy 2025;22(9):613-616
Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.
5.Research progresses in coronary CT angiography of coronary atherosclerotic plaques
Mengyuan BAO ; Yongshun WU ; Xinwei ZHANG ; Linxin ZHANG ; Yan XING
Chinese Journal of Interventional Imaging and Therapy 2025;22(9):613-616
Coronary CT angiography(CCTA)plays an important role in study of coronary atherosclerotic plaques,which can be used to assess plaque composition and vulnerability,hence predicting major adverse cardiovascular events.Furthermore,CCTA combined with radiomics analysis is helpful for optimizing cardiovascular risk stratification.The research progresses in CCTA of coronary atherosclerotic plaques were reviewed in this article.
6.Incidence and risk factors of pneumonia in patients with thoracic tumors receiving radiotherapy combined with immunotherapy
Wenjie ZHANG ; Jing WANG ; Wei SHI ; Hu QIU ; Yongshun CHEN
Chinese Journal of Radiation Oncology 2025;34(9):914-920
Objective:To evaluate the incidence and risk factors of pneumonia in patients with thoracic cancer treated with immunotherapy combined with radiotherapy (RT).Methods:The clinic data of 265 patients with thoracic cancer who received RT and at least 2 cycles of immunotherapy at Renmin Hospital of Wuhan University between January 2020 and January 2024 were retrospectively analyzed. Patients were divided into 2 groups according to treatment sequence: 100 patients with sequential immunotherapy after RT, 165 patients with RT after immunotherapy, including sequential RT after immunotherapy (119 cases) and concurrent RT with immunotherapy (46 cases). The occurrence and grading of treatment-related pneumonia were determined by clinical symptoms, signs, and chest CT findings. The relationship between interval time window of different treatment methods and pneumonia was analyzed by Pearson correlation analysis. χ2 test was used for univariate analysis of risk factors, and logistic regression for multivariate analysis. Results:In the sequential immunotherapy after RT group, the incidence of pneumonia was 12.0% (12/100), with grade ≥2 pneumonia in 4.0% (4/100). The interval time between RT and immunotherapy, has a strong negative correlation with pneumonia incidence and grade ≥2 pneumonia incidence ( r=-0.88, -0.79; both P<0.001). When immunotherapy was initiated ≥7 weeks after RT, the incidence of pneumonia significantly decreased to 5% ( P=0.020), with no grade ≥2 cases. In the immunotherapy followed by sequential / concurrent RT cohort, the incidence of pneumonia was significantly higher in the concurrent subgroup compared with the sequential subgroup [65% (30/46) vs. 44.5% (53/119), P=0.027], and the comparison of the incidence of grade ≥2 pneumonia was the same [33% (15/46) vs. 14.3% (17/119), P=0.014]. The interval time window of RT after immunotherapy was strongly negatively correlated with the incidence of pneumonia and grade ≥2 pneumonia ( r=-0.77, -0.83; both P<0.001). When RT was initiated ≥4 weeks after immunotherapy, the incidence of pneumonia significantly decreased ( P<0.001). Pneumonia incidence differed significantly across RT target sites (intrapulmonary vs. extrapulmonary), total dose (<60 Gy vs. ≥ 60 Gy), and fractionation regimen (conventional vs. hypofractionation) ( P < 0.001, = 0.008, = 0.031), but was not associated with age, gender, smoking history, type of immune checkpoint inhibitor (anti-programmed death-1 vs. anti-programmed death ligand-1), or the number of prior immunotherapy cycles (all P > 0.05). Multivariate analysis identified RT within the lung and interval time of RT after immunotherapy ≤ 4 weeks as independent risk factors for the incidence of pneumonia (both P < 0.001). Conclusions:The interval window between RT and immunotherapy is a critical determinant of pneumonia incidence. Delaying immunotherapy for more than 7 weeks after RT, or delaying RT for more than 4 weeks after immunotherapy, can significantly reduce the risk of radiation-related pneumonia.
7.Short term clinical efficacy and influencing factors of ustekinumab monoclonal antibody in the treatment of Crohn's disease
Rui WANG ; Changqin LIU ; Cui ZHANG ; Qinglu YANG ; Jiaolan YANG ; Pengyun YIN ; Xiaohui LI ; Yongshun SUN ; Zhanju LIU ; Xiaomin SUN
The Journal of Practical Medicine 2024;40(7):989-995
Objective To analyze the short-term clinical efficacy and influencing factors of ustekinumab monoclonal antibody(UST)in the treatment of Crohn′s disease(CD).Methods Retrospective cohort study was used to collect the clinical data of CD patients treated with UST in the 10th People′s Hospital affiliated to Tongji University from December 2020 to October 2022.The main analysis is the short-term clinical efficacy and influencing factors of UST treatment for CD at weeks 8 and 16,And analyze the endoscopic response rate of some patients.Results A total of 91 CD patients who first used UST were included.The 8-week clinical response rate of UST treat-ment for CD was 61.5%,and the clinical response rate was 45%;The clinical response rate at 16 weeks was 71.4%,and the clinical response rate was 54.9%.56 cases underwent endoscopic re-examination in our hospital,and the endoscopic response rate at 16 weeks was 41.1%.Univariate analysis showed that fistula(including anal fistula,personal history of anal fistula,and intestinal skin fistula)is associated with clinical remission in Crohn′s disease patients at 8/16 weeks.Further multivariate COX regression analysis showed that the presence of a history of anal fistula surgery was an independent protective factor affecting clinical remission in CD patients treated with UST at 8 weeks(HR = 0.04,95%CI:0.00~0.38;P = 0.005)and 16 weeks(HR = 0.04,95%CI:0.01~0.34;P = 0.003)compared to those without fistula;Narrow lesions are an independent risk factor for 16 week clinical remission in CD patients compared to non-narrow and non-penetrating lesions(HR = 1.75,95%CI:1.08~2.84;P = 0.023).No patients were found to have stopped medication due to serious adverse reactions.Conclusions UST can improve the clinical remission and response of CD patients at 8/16 weeks,and has good short-term clinical efficacy.CD patients with a personal history of anal fistula are recommended to use UST monoclonal antibodies,while patients with stenotic lesions should be cautious in using UST monoclonal antibodies.Whether the patient has undergone surgical treatment in the past,as well as whether UST has been used on the first or non-first line,has no significant impact on clinical remission.
8.Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity.
Yongshun ZHANG ; Lan YANG ; Yangsen OU ; Rui HU ; Guangsheng DU ; Shuang LUO ; Fuhua WU ; Hairui WANG ; Zhiqiang XIE ; Yu ZHANG ; Chunting HE ; Cheng MA ; Tao GONG ; Ling ZHANG ; Zhirong ZHANG ; Xun SUN
Acta Pharmaceutica Sinica B 2024;14(1):350-364
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.
9.Introduction to the revision of Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene
Lihua XIA ; Ying ZHANG ; Xiaofeng DENG ; Shanyu ZHOU ; Yongshun HUANG ; Xiying LI ; Qifeng WU ; Muwei CAI ; Xiaowen LUO ; Fengling ZHAO
China Occupational Medicine 2024;51(1):37-42
With the development of clinical related disciplines, the update and establishment of relevant standards/guidelines at home and abroad, GBZ 185-2006 Diagnostic Criteria for Occupational Medicamentose-like Dermatitis due to Trichloroethylene (hereinafter referred to as “GBZ 185-2006”) was unable to meet clinical needs. Therefore, the GBZ 185-2006 was revised based on the principles of evidence-based medicine, in accordance with relevant laws/regulations and relevant standards/guidelines in combination with review of research data on occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) home and abroad, and the development of clinical practice and clinical related disciplines. The main modifications include: adding terms and definitions of OMDT, modifying the description of clinical manifestations of the diagnostic principles, adjusting the description of latency, deleting the diagnostic requirement of the incidence probability, adding the specific allergen patch test as the etiological diagnostic index, standardizing the application scope, operating procedure and precautions of the specific allergen patch test. In addition, the relevant content of “Basic Characteristics and Clinical Types of Skin Damage of Medicamentose-like Dermatitis due to Trichloroethylene” in Appendix A is improved, the treatment principles are revised, and the content of new progress in treatment, artificial liver application, are added. The revised GBZ 185-2024 Diagnostic Standard for Occupational Medicamentose-like Dermatitis due to Trichloroethylene is more scientific and practical, and can provide technical basis for the standardized diagnosis and treatment of OMDT in medical and health institutions.
10.Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.
Fuhua WU ; Shuang LUO ; Yongshun ZHANG ; Yangsen OU ; Hairui WANG ; Zhaofei GUO ; Chunting HE ; Shuting BAI ; Penghui HE ; Min JIANG ; Xiaoyan CHEN ; Guangsheng DU ; Xun SUN
Acta Pharmaceutica Sinica B 2023;13(5):2219-2233
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.

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