1.Recent advances in the application of three dimensional reconstruction techniques in surgical treatment of early lung cancer
Tao LONG ; Zhengbing REN ; Aizhong SHAO ; Zhicheng HE ; Weibing WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):121-128
Lung cancer is the leading cause of death worldwide. With the prevalence of CT screening and early diagnosis and treatment of lung cancer in China, more and more patients with early-stage lung cancer characterized with ground-glass opacity are discovered and urgently require treatment, which poses a significant challenge to surgeons. As an emerging technology, three dimensional reconstruction technology plays a crucial auxiliary role in clinical work. This review aims to briefly introduce this technology, focusing on its latest advances in surgical applications in early lung cancer screening, malignant risk assessment, and perioperative period application and medical education.
2.Comparision of aripiprazole and risperidone in improving psychiatric symptoms among chronic schizophrenia patients
Jianfeng WANG ; Bangwen LIU ; Yanyan ZHANG ; Yanping XUE ; Liang GUO ; Yanhai WU
Sichuan Mental Health 2025;38(2):108-114
BackgroundAtypical antipsychotics have been widely used in patients with chronic schizophrenia, and aripiprazole and risperidone are the most commonly used drugs. The mechanism of action of the two is different, while previous studies have provided insufficient credible evidence from multiple perspectives to support the comparative efficacy of the two drugs in improving symptoms in patients with chronic schizophrenia. ObjectiveTo compare the efficacy of aripiprazole and risperidone on the improvement of symptoms, prepulse inhibition (PPI), cognitive functioning and neurotrophic factors in patients with chronic schizophrenia, so as to provide effective treatment regimens for these patients. MethodsA total of 86 patients with chronic schizophrenia attending the psychiatry department of the Third People's Hospital of Fuyang from March 2021 to March 2023 and fulfilling the diagnostic criteria of International Classification of Diseases, tenth edition (ICD-10) were enrolled and grouped using random number table method, each with 43 cases. Aripiprazole group was given oral aripiprazole once daily at an initial dose of 5 mg for one week and then gradually increased to a maximum dose of 25 mg. Risperidone group received oral risperidone twice daily at an initial dose of 0.5 mg for one week and then gradually increased to a maximum dose of 3 mg. Treatment in both groups lasted 3 months. Before treatment and 3 months after treatment, Patients were required to complete Positive and Negative Symptom Scale (PANSS), detection of both strong and weak PPIs in a startle modification passive attention paradigm, Wisconsin Card Sorting Test (WCST) and the measurement of neurotrophic factors at baseline and after treatment. The adverse reactions were recorded. Analysis of covariance was used to test the difference between the PANSS score, PPI, WCST and neurotrophic factor levels of the groups, with the pretest used as the covariate. Results3 months after treatment, no statistical difference was found in the scores of PANSS general psychopathology subscale, positive symptom subscale, negative symptom subscale and total score between two groups after treatment (F=0.621, 0.815, 0.743, 0.752, P>0.05). There were no statistically significant differences between the two groups in PPI inhibition rate, single intense stimulus amplitude, single intense stimulus latency, prepulse inhibition amplitude, or prepulse inhibition latency (F=0.174, 0.001, 0.183, 0.171, 0.001, P>0.05). There was no statistically significant difference in the total number of WCST tests between two groups (F=0.512, P>0.05), whereas aripiprazole group reported significantly larger total numbers of categories completed and correct responses as well as smaller total numbers of random errors and perseverative errors compared to risperidone group (F=3.737, 4.621, 4.892, 5.130, P<0.05). A significant increase in brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) along with a reduction in glial fibrillary acidic protein (GFAP) were documented in risperidone group when compared to risperidone group (F=4.414, 3.781, 6.319, P<0.05). No significant difference was demonstrated in the incidence of adverse reactions between the two groups (χ2=0.261, P>0.05). ConclusionAripiprazole may be more beneficial than risperidone in improving cognitive functioning and neurotrophic factor levels in patients with chronic schizophrenia. [Funded by Scientific Research Project of Fuyang Municipal Health Commission in 2021 (number, FY2021-147)]
3.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
4.Mining and analysis of ADE signals of two camptothecin topoisomerase 1 inhibitors
Zhenjiang WU ; Jianjun LIU ; Xiangyu BAI ; Maofan YANG ; Wenhai FAN ; Pan WANG ; Junsong YANG
China Pharmacy 2024;35(9):1133-1138
OBJECTIVE To mine and analyze the adverse drug events (ADE) signals of two camptothecin topoisomerase 1 inhibitors, i.e. irinotecan and topotecan, and to provide reference for clinical medication safety. METHODS Based on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database, ADE report data for the aforementioned two drugs were extracted from January 1, 2004 to March 31, 2023. After processing the data, signal mining was conducted by using the reporting odds ratio in conjunction with the Bayesian confidence propagation neural network, followed by analysis. RESULTS A total of 14 738 relevant ADE reports were screened, among which 11 483 were associated with irinotecan and 3 255 with topotecan. The ADE reports for irinotecan were predominantly male, whereas for topotecan, they were predominantly female; the age of patients using the two drugs mainly concentrated in 45-<75 years old. A total of 847 signals were detected, involving 24 system organ classes (SOCs). Among them, 565 signals of irinotecan were detected, involving 24 SOCs, primarily concentrating on gastrointestinal disorders, general disorders and administration site conditions, blood and lymphatic system disorders; the most frequently reported ADE was diarrhea, and the ADE with the strongest signal intensity was cholinergic syndrome. A total of 282 signals of topotecan were detected, involving 22 SOCs, primarily concentrating on general disorders and administration site conditions, investigations, blood and lymphatic system disorders, and gastrointestinal disorders; the most frequently reported ADEs were death and anemia, and the ADE with the strongest signal intensity was febrile bone marrow aplasia. ADE signals for irinotecan such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and those for topotecan such as iris atrophy, retinal degeneration, vitreous hemorrhage, were not documented in their respective drug instruction. CONCLUSIONS ADEs of irinotecan and topotecan primarily involve the digestive and hematologic systems, warranting close clinical monitoring. Cholinergic syndrome caused by irinotecan should be concerned. In addition, patients receiving irinotecan should also be monitored for ADE such as metastatic colorectal cancer, peripheral sensory neuropathy, steatohepatitis, and proteinuria; for patients using topotecan, enhanced surveillance of ocular diseases is recommended to ensure medication safety.
5.Development of the Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School Students and its reliability and validity
LUO Caifeng,WU Jing,XU Jianou,L Fei,SUN Jiaxuan,SHANG Bin,ZHANG Xuting
Chinese Journal of School Health 2024;45(6):775-779
Objective:
To develop the Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary Schools Students, and to determine its reliability and validity, in order to provide a basis for developing targeted strategies to promote family-school-community cooperation in the area of nutritional education.
Methods:
Based on overlapping spheres of influence theory, the initial scale was developed through a qualitative and literature review, discussion with Delphi experts and a pilot survey from July 2022 to July 2023. From July to September 2023, a total of 125 primary school parents, 118 primary school teachers and 113 community personnel were selected from six cities in Jiangsu Province by convenient sampling methods, who were investigated to test the reliability and validity of the scale and to develop a formal scale.
Results:
The final Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School students consisted of 3 dimensions and 19 items. The exploratory analysis extracted three metric factors, with a contribution ratio of 69.07% to the accumulated variance. The mean scale component effectiveness was 0.94, and the coefficient of association between the respective dimensions and the scale ranged from 0.80 to 0.91.The overall Cronbach α coefficient for the scale was 0.95, the folded half reliability was 0.87, and the retest reliability was 0.98.
Conclusion
The Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School Students has good reliability and validity, and can be used to measure the degree of the family-school-community cooperation dilemma regarding nutritional education in primary school students.
6.Eosinophil infiltration in cervical lesion and cervical cancer tissues and their clinical significances
Yanyan LU ; Xiangbo XU ; Yamei WU ; Yuqi LIU ; Han WANG ; Lijuan YANG ; Zhenjiang WANG ; Zishen XIAO ; Yanbo LIU
Journal of Jilin University(Medicine Edition) 2024;50(6):1691-1702
Objective:To discuss the differences in eosinophil(EOS)infiltration in cervical tissue and its relationship with cervical-related diseases,and to clarify the effect of EOS on the occurrence and development of cervical intraepithelial neoplasia(CIN)and cervical cancer.Methods:The clinical data of 256 patients with cervical diseases were collected and divided into cervical cancer group(n=46,including 26 cases of squamous cell carcinoma,15 cases of adenocarcinoma,and 5 cases of adenosquamous carcinoma),chronic cervicitis group(n=50),CIN stage Ⅰ group(n=50),CIN stage Ⅱ group(n=50),CIN stage Ⅲ group(n=30),and normal group(adjacent normal cervical tissue,n=30)based on their conditions.Colposcopy was used to observe the morphology of cervical tissue of the patients in various groups;thin-layer liquid-based cytology test(TCT)was used to observe the morphology of the cervical exfoliated cells in various groups;hybrid capture-chemiluminescence method was used to detect the human papillomavirus(HPV)infection in cervical tissue of the patients in various groups;HE staining was used to observe the pathomorphology of cervical tissue of the patients in various groups;Congo red staining was used to detect the numbers of EOS infiltration in cervical tissue of the patients in various groups;Pearson correlation analysis was used to analyze the correlation between the number of EOS infiltration and the malignancy degree of cervical cancer.Results:The cervical surface of the patients in normal group was smooth and pink,with uniformly distributed capillaries;the cervical surface of the patients in chronic cervicitis group showed red inflammatory changes,with some accompanied by Nabothian cysts and varying degrees of erosion and ulcers;the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups showed epithelial ulcers,thickening,and irregular morphology,with mosaic and punctate vessels;the cervical surface of the patients in cervical cancer group showed raised areas with neoplasms and necrotic ulcers,and they were fragile and prone to bleeding.After acetic acid staining,no obvious changes of the patients in normal group were observed.The cervix of the patients in chronic cervicitis group showed slight white changes that lasted for a short time;in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,irregular thin acetowhite epithelium with map-like borders was observed,with increasingly acetowhite reactions and larger areas as the stages advanced.The cervix of the patients in cervical cancer group showed thick acetowhite epithelium that lasted longer,with rigid and clear contours.After iodine staining,the cervix of the patients in normal group was brown,with uniform coloration;the cervix of the patients in chronic cervicitis group showed poor coloration in inflammatory lesion areas;the cervix of the patients in CIN stage Ⅰ group showed iodine coloration in metaplastic areas,while the cervix of the patients in CIN stage Ⅲ group showed poor coloration in larger lesion areas;the cervix of the patients in cervical cancer group showed irregular surfaces with cauliflower-like growth and no coloration after iodine staining,appearing orange-yellow or mustard yellow.The TCT observation results showed there were no heteromorphic cells and few inflammatory cells in cervical exfoliated cells of the patients in infiltration in normal group;there were numerous neutrophils and EOS in exfoliated cervical cells without heteromorphic cells in chronic cervicitis group.The heteromorphic binucleated cells with high nuclear-cytoplasmic ratios and deeply stained nuclei were observed in cervical exfoliated cells of the patients in CIN stage Ⅰ and CIN stage Ⅱ groups.More heteromorphic cells with high nuclear-cytoplasmic ratios and irregular nuclear membranes were showed in cervical exfoliated cells of the patients in CIN stage Ⅲ group.The cervical exfoliated cells of the patients in cervical cancer group showed large and prominent nucleoli,clustering into syncytial changes.Compared with normal group,the atypial of cervical exfoliated cells in CIN stage Ⅰ,CIN stage Ⅱ,CIN stage Ⅲ,and cervical cancer groups was increased.The hybrid capture-chemiluminescence results showed that compared with normal and chronic cervicitis groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅰ,CIN stage Ⅱ,and CIN stage Ⅲ groups,the numbers of HPV infection and TCT heteromorphic cells of the patients in cervical cancer group were increased(P<0.05).The HE staining results showed normal cell morphology and structure in normal group,with infiltration of inflammation cells such as neutrophils,monocytes,macrophages,EOS,and lymphocytes;in chronic cervicitis group,the infiltration of inflammatory cells was increased;in CIN group,the cervical cells showed slightly larger nucleoli and heteromorphic cells,with inflammatory cells mainly distributing around the hetermomorphic cells;in cervical cancer group,the cervical cells showed large and deeply stained nucleoli with significant atypia,and the infiltration of inflammatory cells around the cancer cells was increased.Compared with normal group,the numbers of inflammatory cells and EOS infiltration in cervical tissue of the patients in chronic cervicitis group were increased(P<0.05),and the numbers of inflammatory cells and EOS infiltration of the patients in CIN group were increased(P<0.05);compared with chronic cervicitis group,the number of inflammatory cells and EOS infiltration of the patients in CIN group were decreased(P<0.05);compared with chronic cervicitis group and CIN group,the numbers of inflammatory cells and EOS infiltration of the patients in cervical cancer group were increased(P<0.05).The EOS in cervical cancer tissue was mainly distributed around the cancer nests;compared with CIN stage Ⅰ group,the numbers of EOS infiltration in CIN stage Ⅱ and CIN stage Ⅲ groups were increased(P<0.05);compared with CIN stage Ⅱ group,the number of EOS infiltration in CIN stage Ⅲ group was increased(P<0.05).The higher the malignancy degree of the tumor,the more EOS infiltration was observed,and the number of EOS infiltration was positively correlated with the invasion depth of cervical cancer(r=0.533 0,P<0.01).Conclusion:HPV infection and EOS infiltration play a role in promoting the and occurrence development of cervical precancerous lesions and cervical cancer.
7.Research progress on relationship between frailty and brain health
Zhaojun JING ; Jin WU ; Xihu YANG ; Peng JIANG
Journal of Clinical Medicine in Practice 2024;28(13):131-136
Frailty is related to the aging of the elderly, characterized by the decline of multi-system physiological functions and the increase of susceptibility. Both frailty and brain function decline are associated with age increase, and brain health can affect the postoperative outcomes and long-term quality of life in elderly patients. This paper provided a review on the relationship between frailty and brain health, specifically elaborating on the relationships of frailty with olfactory function decline, sleep disorders, and cognitive function, and aimed to remind medical staffs to pay attention to the frailty and brain function status of elderly patients, strengthen early evaluation and intervention, and improve the quality of life of elderly patients.
8.Levels of neutrophil extracellular traps in neonates with acute respiratory distress syndrome.
Hong XIANG ; Ze-Ming WU ; Hai CHEN ; Hai-Jin ZHU ; Ming CHANG
Chinese Journal of Contemporary Pediatrics 2023;25(4):357-361
OBJECTIVES:
To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS.
METHODS:
The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively). The control group was selected from jaundice neonates who were observed in the neonatal department of the hospital during the same period, and they had no pathological factors causing neonatal jaundice. Peripheral blood samples were collected on day 1, day 3, and day 7 after admission for the ARDS group, and on the day of admission for the control group. Serum cf-DNA levels were measured using a fluorescence enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using enzyme-linked immunosorbent assay. A Pearson correlation analysis was used to evaluate the correlation of serum cf-DNA levels with serum IL-6 and TNF-α levels.
RESULTS:
A total of 50 neonates were enrolled in the ARDS group, including 15 neonates with mild ARDS, 25 with moderate ARDS, and 10 with severe ARDS. Twenty-five neonates were enrolled in the control group. Compared with the control group, the serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased (P<0.05). Compared with the mild ARDS group, the serum levels of cf-DNA, IL-6, and TNF-α in the moderate and severe ARDS groups were significantly increased (P<0.05), and the increase was more significant in the severe ARDS group (P<0.05). The serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased on day 3 after admission and significantly decreased on day 7 after admission compared with those on day 1 after admission (P<0.05). The Pearson correlation analysis showed that there was a positive correlation between serum cf-DNA levels and IL-6 levels as well as TNF-α levels in 50 neonates with ARDS (P<0.05).
CONCLUSIONS
There is an excessive expression of NETs in neonates with ARDS, and dynamic monitoring of serum cf-DNA levels has certain clinical value in evaluating the severity and early diagnosis of ARDS in neonates.
Infant, Newborn
;
Humans
;
Extracellular Traps
;
Prospective Studies
;
Tumor Necrosis Factor-alpha
;
Interleukin-6
;
Prognosis
;
ROC Curve
;
Respiratory Distress Syndrome
;
DNA
9.Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice.
Shuang WU ; Qiubing CHEN ; Yalan WANG ; Hao YIN ; Yuan WEI
Journal of Zhejiang University. Medical sciences 2023;52(3):306-317
OBJECTIVES:
To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice.
METHODS:
siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR.
RESULTS:
Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01).
CONCLUSIONS
The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.
Animals
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Female
;
Mice
;
Antioxidants/metabolism*
;
Cholesterol/metabolism*
;
Ethanol/pharmacology*
;
Glutathione/pharmacology*
;
Inflammation
;
Lipids/pharmacology*
;
Liver
;
Malondialdehyde/pharmacology*
;
Mice, Inbred C57BL
;
Oxidative Stress
;
Reactive Oxygen Species/metabolism*
;
RNA, Small Interfering/pharmacology*
;
Superoxide Dismutase
;
Triglycerides/metabolism*
;
Cytochrome P-450 CYP2E1/metabolism*
10.Clinical study of cytokine models to predict organ functional impairment after treatment with chimeric antigen receptor T cells in children with B-lineage lymphocytic leukemia
Keke RUN ; Fan YANG ; Xiaochen LIN ; Yue ZHANG ; Yunhong DAI ; Shuiyan WU ; Fang FANG ; Zhenjiang BO ; Ying LI ; Jun LU
Chinese Pediatric Emergency Medicine 2023;30(5):340-346
Objective:To explore the predictive value of peripheral blood cytokine models on organ functional impairment after chimeric antigen receptor T(CAR-T) cell therapy in children with B-lineage lymphocytic leukemia.Methods:The clinical data of 44 children with acute B-lineage lymphoblastic leukemia who received CAR-T cell therapy at Children′s Hospital of Soochow University from September 2018 to October 2020 were retrospectively analyzed.Peripheral blood cytokines, including interleukin(IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, interferon(IFN)-γ and IL-17A, were measured daily for 14 days after receiving CAR-T cell therapy.The trend of peripheral blood cytokine levels was analyzed at the endpoint of organ function recovery or death within 14 days after CAR-T cell treatment.Receiver operating characteristic curve was used to establish a mathematical prediction model to predict the occurrence of organ damage in the children.Results:Of the 44 children, 31 cases were boys and 13 cases were girls, with a median age of 7.96 (5.19, 11.48)years.Cytokine release syndrome(CRS) response occurred in 95.5% (42/44) children, with 88.1% (37/42) had a grade 1-3 CRS response, and 16.7% (7/42) had a severe grade 4-5 CRS response.Using IL-6>3 892.95 pg/mL as cut-off value, the area under the curve(AUC) for predicting acute respiratory failure was 0.818, with a sensitivity of 0.8 and a specificity of 0.735, while combining IFN-γ>414.4 pg/mL, IL-6>3 892.95 pg/mL and IL-2>27.05 pg/mL were the three cut-off values, with an AUC of 0.741, sensitivity of 0.6 and specificity of 0.912 for predicting acute respiratory failure. Using IFN-γ>1 699.5 pg/mL as cut-off value, the AUC for predicting shock was 0.908, with a sensitivity of 0.722 and a specificity of 1.With IL-6>4 607.3 pg/mL as cut-off value, the AUC for predicting liver injury was 0.964, with a sensitivity of 1 and a specificity of 0.906, while combining both IL-6>4 607.3 pg/mL and IFN-γ>1 446.2 pg/mL as cut-off values, the AUC for predicting liver injury was 0.977, with a sensitivity of 1 and a specificity of 0.906.Combining both IL-6>6 972.2 pg/mL and IFN-γ>3 981.5 pg/mL predicted a positive predictive value of 62.5% and a negative predictive value of 94.4% for grade 4-5 CRS response, with an AUC of 0.846, a predictive sensitivity of 0.714 and a specificity of 0.838, and all children had a combination of two or more organ function injuries.Conclusion:The combination of IL-6 and IFN-γ can effectively predict the incidence of liver injury and cytokine release syndrome.The combination of peripheral blood cytokines IFN-γ, IL-6 and IL-2 can be used to predict the incidence of acute respiratory failure after the treatment of CAR-T cells in children with acute B-lineage lymphoblastic leukaemia.IFN-γ single index can be used to predict the incidence of shock.The combination of IL-6 and IFN-γ can be used to predict the incidence of liver injury and the severity of CRS.


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