1.Safety and efficacy of donor-derived chimeric antigen receptor T-cell therapy in patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation
Yaqi ZHUO ; Sanfang TU ; Xuan ZHOU ; Jilong YANG ; Lijuan ZHOU ; Rui HUANG ; Yuxian HUANG ; Meifang LI ; Bo JIN ; Bo WANG ; Shiqi LI ; Zhongtao YUAN ; Lihua ZHANG ; Lin LIU ; Sanbin WANG ; Yuhua LI
Chinese Journal of Hematology 2024;45(1):74-81
Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.
2.Expression and significance of ubiquitin-specific proteases 20 and hypoxia inducible factor-1α in breast cancer
Lingyu FANG ; Jinghua HU ; Junfeng WEN ; Shiqi HAN ; Yali WANG ; Lulan PU ; Jingjia LI ; Yi YANG ; Shishan DENG ; Lingmi HOU ; Fangfang ZHOU
The Journal of Practical Medicine 2024;40(16):2270-2276
Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P<0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P<0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P<0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P<0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P<0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.
3.Effect of Aqueous Extract of Scrophularia ningpoensis on AMPK Activity in INS-1 Cells under High Glucose Exposure
Xu GUO ; Jun ZHOU ; Xiaohan LI ; Shiqi CHEN ; Yanguo GAO ; Yonghong ZHANG ; Qibin WANG ; Tao ZHENG ; Li CHEN
Herald of Medicine 2024;43(6):850-854
Objective To investigate the effect of aqueous extract of Scrophularia ningpoensis(AESN)on AMP-activated protein kinase(AMPK)activity in INS-1 cells under high glucose(HG)conditions.Methods INS-1 cells were cultured in HG medium and treated with different concentrations of AESN.The influences of AESN on cell viability and pyroptotic body formation were detected using the CCK-8 assay.Western blotting was used to observe the effects of AESN on AMPK expression and phosphorylation.The effect of AESN on AMPK activity was measured using time-resolved fluorescence resonance energy transfer(TR-FRET)assay.Results Compared with normal glucose controls,INS-1 cells exposed to HG showed decreased cell viabilities and increased formation of pyroptotic bubbles using CCK-8 assay.Western blotting results indicated that HG exposure led to a decrease in intracellular AMPK phosphorylation levels.However,co-incubation with AESN under HG exposure AESN treatment increased the cell viabilities and phosphorylation of AMPK and decreased the pyroptotic bubbles formation in a concentration-dependent manner.In addition,the results of TR-FRET revealed that AESN treatment effectively increased AMPK activity in a concentration-dependent manner.Conclusion AESN has an activating effect on AMPK activity in HG-treated INS-1 cells.
4.Hotspots and trends of nutrition research in global preschool children from 2012 to 2022 based on Citespace visual analysis
Jiawen ZHANG ; Ziling ZHAO ; Shiqi CHEN ; Tianjin ZHOU ; Yanlin LI ; Yuci LIU ; Min LUO
Chinese Journal of Child Health Care 2024;32(4):433-439
【Objective】 To review the scientific research advances in the field of preschool children′s nutrition from 2012 to 2022, in order to provide reference for relevant policy formulation and further scientific exploration in this area. 【Methods】 High-quality literature published both domestically and internationally between 2012 and 2022 was retrieved through Web of Science (WOS) and China National Knowledge Infrastructure (CNKI) database. Excel and CiteSpace software were applied to visualize the research hotspots and frontier trends. 【Results】 A total of 1 816 English articles and 110 Chinese articles were included in the analysis. The cooperation network density of research institutions and authors was found to be low. Excluding the search terms, the top three English keywords were vitamin A (0.74), intervention (0.67), obesity prevention (0.55); the top three Chinese keywords were "anemia" (0.41), "obesity" (0.38), and "nutritional status" (0.18). In Chinese and English clusters, "anemia" and "physical activity" ranked first, respectively. The latest burst words identified were "dietary pattern" and "diet quality". 【Conclusions】 The number of English literature published in the field of preschool children′s nutrition is increasing, but it has shown a downward trend in the past three years in China. There are few studies in this field in China. The research hotspots primarily focus on the nutritional status of preschool children, with less attention paid to intervention research and methodological exploration. Further research in the field of preschool children′s nutrition in China may need to focus on the external determinants of preschool children′s nutrition, such as parental education, diet and food supply.
5.Molecular markers of postoperative recurrence and malignant transformation in low-grade gliomas and their predictive value
Xuzhao LI ; Shiqi ZHOU ; Haibin LENG ; Dakuan GAO ; Lixin XU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):284-291
【Objective】 To identify the risk factors for recurrence and malignant transformation (MT) in patients with low-grade glioma (LGG) after surgery. 【Methods】 The data of 163 patients who underwent LGG resection and subsequent follow-up from March 2009 to April 2019 were retrospectively collected. Patients who did not experience recurrence or MT after surgery were included in the control group (85 cases), those who experienced recurrence after surgery were included in the observation 1 group (44 cases), and those who experienced MT after surgery were included in the observation 2 group (34 cases). Based on the clinical data of the three groups of patients, their clinical characteristics were analyzed, and the risk factors and predictive value for recurrence and MT were explored using Logistic regression model and receiver operating characteristic (ROC) curve. 【Results】 There were significant differences between the control group and the observation 1 group in preoperative seizure, preoperative Karnofsky performance status (KPS) score, and surgical approach (P<0.05). There were significant differences between the control group and the observation 2 group in gender, preoperative KPS score, tumor size, and surgical approach (P<0.05). There were significant differences between the control group and the observation 1 group in isocitrate dehydrogenase (IDH) mutation, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, tumor suppressor protein p53, mouse double minute 2 (MDM2), vascular endothelial growth factor (VEGF), or epidermal growth factor receptor (EGFR) (P<0.05). There were significant differences between the control group and the observation 2 group in PCNA, MMP-9, cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, or VEGF (P<0.05). Logistic regression analysis showed that IDH mutation, MMP-9, and PCNA were independent risk factors for LGG recurrence (P<0.05), while VEGF, MMP-9, and PCNA were independent risk factors for LGG MT (P<0.05). The area under curve (AUC) of PCNA, MMP-9 and IDH mutation for predicting LGG MT after surgery was 0.744, 0.790, and 0.799, respectively. The AUC of PCNA, MMP-9, and VEGF for predicting LGG recurrence after surgery was 0.729, 0.750, and 0.900, respectively. 【Conclusion】 This study found that IDH mutation, MMP-9 and PCNA were independent risk factors for LGG recurrence, while VEGF, MMP-9 and PCNA were independent risk factors for LGG MT by retrospectively analyzing the clinical data and protein expression of 163 patients with LGG after surgery. These proteins have high accuracy in predicting LGG recurrence and MT after surgery. Therefore, the proteins may play an important role in the biological behavior and treatment effect of LGG, and can be used as reference indicators for prognosis evaluation and individualized treatment of LGG patients after surgery.
6.Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019
Jiamin QIU ; Fangfang ZENG ; Chen CHENG ; Huiyan WEN ; Shiqi HUANG ; Dan LIU ; Jinlei QI ; Peng YIN ; Maigeng ZHOU ; Ying XU ; Zhiping LIU ; Qingsong MEI ; Heng XIAO ; Zheng XIANG ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2024;45(3):365-372
Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.
7.Research Progress and Perspectives of Antibody-drug Conjugates Targeting Trophoblast Cell Surface Antigen-2 in Advanced Non-small Cell Lung Cancer
XU JINGYAN ; LIU JIAQI ; MEI SHIQI ; ZHOU QING
Chinese Journal of Lung Cancer 2024;27(10):763-776
Non-small cell lung cancer(NSCLC)remains a significant global health burden,and there is an urgent need for new treatment options.Trophoblast cell surface antigen-2(TROP-2),a target closely associated with NSCLC prog-nosis,has become a research hotspot in recent years.Notably,TROP-2-targeted antibody-drug conjugates(ADCs)have made groundbreaking advances in NSCLC therapy.Clinical studies have demonstrated that certain TROP-2 ADCs can significantly improve progression-free survival in previously treated patients with advanced or metastatic NSCLC,regardless of the presence of actionable genomic alterations.These agents have shown promising potential in both frontline and subsequent treatment settings.In terms of safety,while adverse effects affecting the hematologic,respiratory,and gastrointestinal systems are gener-ally manageable,close clinical monitoring and timely management are still required.In conclusion,TROP-2 ADCs hold great promise in the treatment of NSCLC.
8.Visualization of mTOR Pathway Regulated by Traditional Chinese Medicine: A Bibliometric Analysis Based on Multiple Software
Xiaoshan HUI ; Shichao LU ; Yongmei LIU ; Shiqi WANG ; Siyuan ZHOU ; Jinsheng ZHANG ; Jie WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(1):155-162
ObjectiveTo summarize the research progress of mammalian target of rapamycin (mTOR) pathway regulated by traditional Chinese medicine(TCM) and provide reference for visualization and quantitative analysis of related research based on multiple software linkage. MethodLiterature related to TCM regulation of mTOR pathway in Web of Science was taken as the research object. Citespace,VOSviewer,and carrort2 were used for biliometric analysis and visualization of the literature. ResultA total of 245 papers that met the requirements were retrieved,and the visual analysis showed that the papers presented a fluctuating increase year by year after 2010,and numerous research results emerged in 2018. China had the most publications. Institutions with a large number of publications were mainly in Beijing and Shanghai,and most of the regional cooperation was centered in Beijing and Nanjing. According to the research direction and focus,it was found that the intervention of TCM in mTOR pathway in recent years mainly concentrated on the anti-tumor,anti-apoptotic and anti-inflammatory aspects, and TCM interfered with mTOR pathway to regulate cell apoptosis,autophagy,proliferation,and death. AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinases(PI3K)/protein kinase B(Akt)/mTOR pathway were the current and future research hotspots. ConclusionResearch on the regulation of mTOR pathway by TCM had a good prospect,and the in-depth study might provide new ideas and guidance for the treatment of cardiovascular diseases,tumor and other major diseases.
9.Analyzing the influencing factors of quality control assessment of pure tone audiometry among noise exposed personnel in Guangzhou City from 2021 to 2022
Yinan HE ; Hailin ZHOU ; Jiabin LIANG ; Shiqi MAI ; Xing RONG ; Zhi WANG
China Occupational Medicine 2023;50(5):502-506
{L-End}Objective To explore the status of quality control assessment of pure tone audiometry (PTA) and to analyze its influencing factors in occupational medical examination (OME) institutions in Guangzhou City. {L-End}Methods A total of 41 OME institutions in Guangzhou City were selected as the research subjects from 2021 to 2022 using random sampling method, and its status of on-site quality and PTA quality for individuals exposed to noise were assessed. {L-End}Results A total of 205 rectification items were identified among the 41 OME institutions from 2021 to 2022. Among them, 19, 28, 30, and 28 OME institutions did not meet the requirements of organizational structure, quality management system, quality control of OME, and health examination information reporting, respectively. A total of 1 095 OME reports for individuals exposed to noise were assessed, with 820 reports having correct results and conclusions, resulting in an accuracy rate of 74.9%. The results of the multiple logistic regression analysis showed that OME institutions without meeting the requirements for the quality management system had a higher risk of failing the PTA quality control assessment and having inaccurate hearing test results compared with those meeting the requirements (all P<0.05). OME institutions with a filing period less than one year had a higher risk of having inaccurate hearing test results than those with a filing period of one year or more (P<0.05). OME institutions not meeting the requirements for quality control of OME had a higher risk of having abnormal OME conclusions than those meeting the requirements (P<0.05). OME institutions not meeting the requirements for health examination information reporting had a higher risk of having abnormal conclusions in suspected occupational disease than those meeting the requirements (P<0.05). OME institutions not meeting the requirements for the quality management system had a higher risk of having abnormal conclusions of occupational contraindications than those meeting the requirements (P<0.05). {L-End}Conclusion The quality of PTA in OME institutions in Guangzhou City needs to be improved. And a well-established quality management system for OME is beneficial for improving the quality of PTA.
10.Executive function in adolescent patients with major depressive episode with psychotic symptoms and childhood trauma
Shiqi SONG ; Jianbo LIU ; Mengxiao YAN ; Minsi ZHOU ; Ming GAO ; Wentai FENG ; Jianping LU
Sichuan Mental Health 2023;36(3):202-208
BackgroundThere are differences in executive function between major depressive episode patients with or without psychotic symptoms, and childhood trauma may affect the executive function of patients with major depressive episode. Previous research studies predominantly focused on adult patients with major depressive episode, with a lack of studies specifically focusing on adolescent patients with major depressive episode. ObjectiveTo investigate the differences in executive function among adolescent patients with major depressive episode, with or without psychotic symptoms and childhood trauma. MethodsA total of 112 hospitalized adolescent patients with major depressive episode who met the criteria of the International Classification of Diseases, tenth edition (ICD-10) were included in the study. The participants were recruited from the Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital during the period from August 2020 to November 2021. Additionally, 27 healthy controls were recruited through public advertisements. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess executive function through the administration of the Motor Screening Task (MOT), Spatial Working Memory(SWM) and Rapid Visual Information Processing (RVP) modules. Childhood Trauma Questionnaire-Short Form (CTQ-SF) was used to assess the trauma type. ResultsCompared with healthy controls, adolescent patients with major depressive episode had a longer mean delay (Z=-3.407, P=0.001) in the MOT task. In the SWM task, the patients had a higher total number of intergroup error responses (Z=-3.291, P=0.001), a higher total number of intragroup error responses (Z=-3.461, P=0.001), more total number of double error responses (Z=-3.218, P=0.001), a higher total error responses (Z=-3.312, P=0.001), higher strategy scores (Z=-2.437, P=0.015) and longer average delay time (Z=-2.055, P=0.040). In the RVP task, the patients had fewer hits (Z=-3.196, P=0.001), more misses (Z=-3.179, P=0.001), fewer rejections (Z=-2.772, P=0.006), lower hit probability (Z=-3.187, P=0.001) and lower A´ scores (Z=-3.070, P=0.002).Compared with adolescent patients with major depressive episode without psychotic symptoms, those with psychotic symptoms had a lower total number of double error responses (Z=-2.566, P=0.010) in SWM task. Compared with adolescent patients with major depressive episode who did not experience emotional neglect, those who experienced emotional neglect had longer average delay time (Z=-3.183, P=0.001) in MOT task, fewer total hits (Z=-2.445, P=0.014), more total missed reports (Z=-2.467, P=0.014), lower hit probability (Z=-2.445, P=0.014) and lower A´scores (Z=-2.089, P=0.037) in RVP task. Adolescent patients with major depressive episode who had experienced emotional abuse had longer average delay time in MOT task than those who had not experienced emotional abuse (Z=-2.552, P=0.011). ConclusionAdolescent patients with major depressive episode exhibit abnormalities in a majority of executive function domains. Specifically, those without psychotic symptoms and with childhood trauma demonstrate significantly impaired executive function. [Funded by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (number, SZGS013), Basic and Applied Basic Research Fund of Guangdong Province (number, 2019A1515110047), Shenzhen Science and Technology Planning Project (number, JCYJ20190809155019338)]

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