1.Differences of gene expression profiles of different subpopulations of exhausted T cells in patients with active pulmonary tuberculosis
Weifang LIN ; Jingyu ZHOU ; Huaxin CHEN ; Siran LIN ; Zhe ZHOU ; Zhangyufan HE ; Yixuan YANG ; Xiaoqian HU ; Yiting TANG ; Yuanyuan LIU ; Lingyun SHAO
Chinese Journal of Infectious Diseases 2024;42(2):91-97
Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.
2.Analysis of patients'satisfaction with mobile medical payment and its influencing factors in ethnic minority areas of Yunnan province
Jumei LI ; Sisi LI ; Jiufu MA ; Defen XIONG ; Lihong YANG ; Chunyan LONG ; Siran FU
Modern Hospital 2024;24(5):765-768,772
Objective This paper aims to explore patient satisfaction with mobile medical payments in ethnic minority areas and its influencing factors.Methods From May to August 2023,565 ethnic minority patients from 6 villages in 4 ethnic minority autonomous counties in Dehong Prefecture and Pu'er City,Yunnan Province,were selected as research subjects,and 186 Han patients in Kunming were selected as controls.The general information questionnaire,the mobile medical payment will-ingness and attitude survey scale,and the medical cost mobile payment satisfaction survey scale were used to investigate their sat-isfaction with actual situation of medical mobile payment.Additionally,this paper discussed influencing factors affecting satisfac-tion.Results The ethnic minority patients exhibited a significantly lower level of satisfaction compared to the Han patients(39.65±10.43 vs.49.54±7.88,P<0.05).ethnic minority patients scored significantly lower on the dimensions of satisfac-tion,such as perceived safety,ease of use and usefulness of mobile medical payment compared to the group of Han patients(all P<0.05).Additionally,they ethnic minority patients showed significantly lower level of willingness and attitude to use mobile medical payment compared to the group of Han patients(P<0.05).The main factors influencing the significant difference in satisfaction with mobile medical payment were ethnic group,number of hospital visits in previous year,first-time use of mobile medical payment,and educational background(P<0.05).Conclusion Ethnic minority patients have a low perception of secur-ity,ease of use,and usefulness of mobile medical payments,as well as a low willingness and characteristics for mobile medical payment.Therefore it is necessary to further enhance their experience and satisfaction.In the development of mobile medical pay-ment services hospitals should fully consider the current situation of"illiteracy""semi-illiteracy"and"lack of resources"in re-mote ethnic areas.They should actively develop service platforms and applications suitable for mobile medical payment in ethnic minority areas to continuously enhance service efficiency and quality.
3.Clinical features of nontuberculous mycobacteria disease patients with positive anti-interferon γ autoantibody
Zhijie QIN ; Siran LIN ; Ting WANG ; Wencan YANG ; Xiaoqian HU ; Shiyong WANG ; Ran SU ; Peidong CHEN ; Lingyun SHAO
Chinese Journal of Infectious Diseases 2024;42(4):233-238
Objective:To investigate the clinical features of nontuberculous mycobacteria (NTM) disease patients with positive anti-interferon γ (IFN-γ) autoantibody.Methods:Forty-three adult human immunodeficiency virus-uninfected patients with NTM disease hospitalized in Huashan Hospital, Fudan University and Jing′an Branch, Huashan Hospital, Fudan University from July 2021 to August 2023 were included. Clinical data and NTM strain information of the patients were collected. The plasma levels of anti-IFN-γ autoantibodies were detected by enzyme-linked immunosorbent assay, and the patients were divided into antibody positive group and antibody negative group. The clinical characteristics and laboratory examination results between the two groups were compared. The independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Multivariate logistic regression analysis was used to determine the correlation factors of positive anti-IFN-γ autoantibodies. Results:Among the 43 patients, 13 cases (30.2%) were positive for anti-IFN-γ autoantibodies and 30 cases (69.8%) were negative. The proportions of patients with NTM disseminated infection (9/13 vs 30.0%(9/30))and combined bacterial infection (5/13 vs 6.7%(2/30)) in antibody positive group were both higher than those in antibody negative group, and the differences were both statistically significant ( χ2=5.74 and 6.73, respectively, both P<0.05). The white blood cell count, platelet count, the proportion of platelet count >350×10 9/L of antibody positive patients were all higher than those of antibody negative group, while the white sphere ratio was lower than that of antibody negative group, with statistical significance ( t=2.42, 3.02, χ2=9.77 and t=3.66, respectively, all P<0.05). Erythrocyte sedimentation rate, C-reactive protein, procalcitonin, globulin, immunoglobulin G, immunoglobulin A and immunoglobulin M in antibody positive patients were all higher than those in antibody negative group, and the differences were all statistically significant ( U=99.50, 112.00, 115.50, 61.50, 76.50, 99.00 and 83.00, respectively, all P<0.05). Mycobacterium abscessus complex (seven cases and 11 cases, respectively) and Mycobacterium avium complex (five cases and 13 cases, respectively) were the main isolated strains in antibody positive and antibody negative patients. Multivariate logistic regression analysis showed that combined with bacterial infection (odds ratio ( OR)=21.83, 95% confidence interval ( CI) 1.94 to 245.71), NTM disseminated infection ( OR=7.64, 95% CI 1.10 to 53.26), platelet count>350×10 9/L ( OR=14.31, 95% CI 1.91 to 107.04) were risk factors for anti-IFN-γ autoantibodies positive (all P<0.05). Conclusions:Patients with positive anti-IFN-γ autoantibodies have higher probability of having elevated levels of systemic inflammation. Anti-IFN-γ autoantibody test is recommended for patients with NTM disease who present with co-bacterial infection, NTM disseminated infection, or elevated platelet count (>350×10 9/L).
4.Expression of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain on CD8 + T cells in silicosis patients with Mycobacterium tuberculosis infection
Yuzhen XU ; Miaoyao LIN ; Jingyu ZHOU ; Qianqian LIU ; Qingluan YANG ; Siran LIN ; Lingyun SHAO ; Wenhong ZHANG ; Lihong LI ; Xitian HUANG ; Yungui ZHANG ; Qiaoling RUAN
Chinese Journal of Infectious Diseases 2021;39(11):670-675
Objective:To explore the expression and clinical significance of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) on the peripheral blood mononuclear cells (PBMC) in silicosis patients with Mycobacterium tuberculosis infection. Methods:August 2018, a total of 78 patients with silicosis (all were quarry workers in Sanmen County, Zhejiang Province) were enrolled and divided into silicosis combined with active pulmonary tuberculosis group (APTB group), silicosis combined with latent tuberculosis infection group (LTBI group), and simple silicosis with non-tuberculosis infection group (non-TB group). Flow cytometry was used to analyze the expressions of TIGIT, programmed death-1 (PD-1) and transcription factor T-bet on PBMC from patients. Mann-Whitney U test and Pearson correlations analysis were used for statistical analysis. Results:Among the 78 patients, eight were in the APTB group, 24 in the LTBI group, and 46 in the non-TB group. The expressions of PD-1 and TIGIT on CD8 + T cells in the APTB group (29.45%(16.78%) and 65.40%(12.12%), respectively) were significantly higher than those in the LTBI group (17.40%(11.17%) and 48.30%(28.75%), respectively; U=23.500 and 43.500, respectively, P=0.000 8 and 0.020 5, respectively) and non-TB group (15.95%(12.46%) and 45.30%(19.75%), respectively; U=64.000 and 69.000, respectively, P=0.002 3 and 0.003 8, respectively), and the differences were all statistically significant. The expression of TIGIT was positively correlated with PD-1 on CD8 + T cells in silicosis patients ( r=0.434 3, P<0.01). The proportion of PD-1 + TIGIT + CD8 + T cells in the APTB group (19.90%(22.67%)) was significantly higher than those in the non-TB group (11.55%(11.29%), U=76.500, P=0.007 1) and LTBI group (11.55%(10.53%), U=41.000, P=0.015 4), while the proportion of PD-1 -TIGIT -CD8 + T cells in the APTB group (30.60%(12.90%)) was significantly lower than non-TB group (48.90%(18.98%), U=58.000, P=0.001 3) and LTBI group (47.20%(24.59%), U=41.000, P=0.015 4). The differences were all statistically significant. The expression of T-bet on the peripheral blood CD8 + T cells in the APTB group (29.45%(16.78%)) was higher than that in the non-TB group (15.95%(12.46%)) and the LTBI group (17.40%(11.17%)), and the differences were both statistically significant ( U=46.500 and 46.000, respectively, P=0.000 3 and 0.028 3, respectively). The expression of T-bet on CD8 + T cells was positively correlated with TIGIT on CD8 + T cells ( r=0.456 7, P<0.01). The expression of T-bet on PD-1 + TIGIT + CD8 + T cells in the APTB group (65.40%(12.12%)) was higher than those in the LTBI group (48.30%(28.75%), U=23.500, P=0.000 8) and non-TB group (45.30%(19.75%), U=65.000, P=0.002 6), and the differences were both statistically significant. Conclusion:The immunosuppressive receptor PD-1 and TIGIT are highly expressed on CD8 + T cells in silicosis patients with active pulmonary tuberculosis, which indicates CD8 + T cells exhaustion in these population, while the highly co-expression of T-bet suggests the exhausted subsets may have reversed potentiality.
5.Correlation of carotid intima-media thickness and cardiac diastolic dysfunction in patients with type 2 diabetes
Xiaofang HONG ; Wanting XU ; Xingsong CHEN ; Baozhu YANG ; Siran XU ; Xiaodan ZHANG
Journal of Chinese Physician 2021;23(11):1623-1627
Objective:This study explored the correlation between carotid intima-media thickness (CIMT) and cardiac diastolic dysfunction in patients with type 2 diabetes mellitus (T2DM).Methods:381 T2DM patients hospitalized in the endocrinology department of the Second Affiliated Hospital of Guangzhou Medical University from January 2019 to January 2020 were selected. According to E/A value, they were divided into normal diastolic function group (149 cases) and incomplete diastolic function group (232 cases); According to the CIMT value, they were divided into CIMT normal group (213 cases) and CIMT thickening group (168 cases). The general data, blood lipid, blood glucose, liver and kidney function, cardiac color Doppler ultrasound and carotid color Doppler ultrasound were compared and analyzed. Multivariate logistic analysis was used to analyze the influencing factors of cardiac diastolic dysfunction in patients with T2DM. Receiver operating characteristic curve (ROC) was used to analyze the ability of CIMT value to predict cardiac diastolic dysfunction in T2DM patients.Results:Multivariate regression analysis showed that age ( OR=1.067, P<0.001), increased CIMT ( OR=1.863, P=0.011) and systolic blood pressure ( OR=1.014, P=0.016) were the risk factors for occurrence of cardiac diastolic dysfunction in patients with T2DM ( P<0.05). ROC analysis demonstrated that the area under the curve (AUC) for cardiac diastolic dysfunction diagnosed by CIMT was 0.625 (95% CI: 0.568-0.683, P<0.001). The cut-off value was 0.875, with a sensitivity of 52.6% and specificity of 69.1%. Conclusions:Increased CIMT is an independent risk factor for cardiac diastolic dysfunction in patients with T2DM. The level of CIMT has certain predictive value for the occurrence of cardiac diastolic dysfunction.
6.Development of Clinical Information Navigation System Based on 3D Human Model.
Siran MA ; Yuanyuan YANG ; Jiecheng GAO ; Zhe XIE
Chinese Journal of Medical Instrumentation 2020;44(6):471-475
A clinical information navigation system based on 3D human body model is designed. The system extracts the key information of diagnosis and treatment of patients by searching the historical medical records, and stores the focus information in a predefined structured patient instance. In addition, the rule mapping is established between the patient instance and the three-dimensional human body model, the focus information is visualized on the three-dimensional human body model, and the trend curve can be drawn according to the change of the focus, meanwhile, the key diagnosis and treatment information and the original report reference function are provided. The system can support the analysis, storage and visualization of various types of reports, improve the efficiency of doctors' retrieval of patient information, and reduce the treatment time.
Diagnosis, Computer-Assisted
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Humans
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Medical Informatics Applications
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Models, Anatomic
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Software
7.Analysis of clinical efficacy of hypofractionated precision radiotherapy for lung metastases
Ruizhi ZHAO ; Jingwei LUO ; Jianping XIAO ; Qingfeng LIU ; Ye ZHANG ; Nan BI ; Hongmei ZHANG ; Xuesong CHEN ; Kai WANG ; Yuchao MA ; Siran YANG ; Junlin YI ; Yexiong LI
Chinese Journal of Radiation Oncology 2020;29(8):639-643
Objective:To evaluate the efficacy and safety of hypofractionated radiotherapy for lung metastases (LMs).Methods:From March 2007 to April 2019, 193 patients with 317 LMs including 124 male and 69 female admitted to our hospital were enrolled. The median age was 58 years old and the median KPS was 80. The primary tumors were mainly distributed in the lung (33.7%), colorectum (21.2%), head and neck (13.5%) and breast (10.9%), respectively. The clinical efficacy and side effects of hypofractionated radiotherapy for LMs were evaluated.Results:The median follow-up time was 59.9 months (95% CI: 55.1-64.6 months). Among 193 patients with 317 LMs, 90.7% of them were treated with 4D-CT, 69.4% for intensity-modulated radiation therapy (IMRT), 28.0% for volumetric-modulated arc therapy (VMAT) and 2.6% for tomotherapy (TOMO), respectively. The median gross tumor volume (GTV) and planning target volume (PTV) were 5.0 cm 3(0.2-142.3 cm 3) and 12.0 cm 3(1.0-200.1 cm 3). The prescription dose regimen was 60 Gy in 4 to 15 fractions. The median dose for PTV was 60 Gy (45-70 Gy) and biological effective dose was 96 Gy (60-150 Gy), respectively. The 1-, 3-and 5-year local control rates (LCR) were 95.7%, 91.3% and 89.9%, respectively. The median time from primary cancer diagnosis to lung metastases was a prognostic factor for LCR ( P=0.027). The overall survival (OS) and progression-free survival (PFS) rates were 90.1%, 60.8%, 46.2%, and 54.3%, 30.3%, 19.9%, respectively. The median time from primary cancer diagnosis to lung metastases and extrapulmonary metastases was the prognostic factor for OS and PFS. No Grade 3 toxicities were seen. Conclusion:Image-guided hypofractionated precision radiotherapy is an efficacious and safe treatment for LMs.
8.A phase Ⅱ trial of comprehensive treatment based on radiotherapy in leptomeningeal metastasis
Siran YANG ; Qingfeng LIU ; Jianping XIAO ; Hongmei ZHANG ; Nan BI ; Ye ZHANG ; Yuchao MA ; Kai WANG ; Xuesong CHEN ; Ruizhi ZHAO ; Xi WU ; Junling LI ; Junlin YI ; Shulian WANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2020;29(9):744-750
Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.
9. The application of whole-brain radiotherapy for non-small cell lung cancer with brain metastases: evolution and revolution
Chinese Journal of Radiation Oncology 2019;28(10):784-787
Whole brain radiotherapy (WBRT) was widely used clinically as the standard therapy for brain metastases (BM). With the development of radiotherapy technology and systemic therapies, the non-small cell lung cancer (NSCLC) patients have prolonged local control rate and median survival time, meanwhile post-radiotherapy intracranial toxicities often lead to serious impacts on the quality of life and neurocognitive function. Therefore, the role WBRT played should have been reevaluated. The purpose of this review is to analyze the clinical application value of WBRT in the context of new treatments for NSCLC with BM, and to predict the main developing directions of WBRT in the future.
10.Case-control study of fractionated stereotactic radiotherapy combined with temozolomide for large brain metastases
Yuchao MA ; Jianping XIAO ; Nan BI ; Hongmei ZHANG ; Yingjie XU ; Ye ZHANG ; Qingfeng LIU ; Lei DENG ; Wenqing WANG ; Feng LIU ; Kai WANG ; Ruizhi ZHAO ; Siran YANG ; Yexiong LI
Chinese Journal of Radiation Oncology 2018;27(4):348-353
Objective To retrospectively analyze and compare the clinical efficacy and safety between fractionated stereotactic radiotherapy (FSRT) combined with and without temozolomide in the treatment of large brain metastases.Methods Between 2009 and 2017,84 patients with large brain metastases (tumor size ≥ 6 cm3) were recruited and assigned into the CRT group (concurrent TMZ and FSRT,n=42) and RT group (FSRT alone,n=42).The radiation dose was 52.0 Gy in 13 fractions or 52.5 Gy in 15 fractions.Patients were reexamined by magnetic resonance imaging (MRI) during treatment.The radiation field would be shrunk if the gross target volume (GTV) was reduced.The clinical efficacy was evaluated at postoperative 2 to 3 months.The primary end-point event was local recurrence-free survival (LRFS) and the secondary end-point events included intracranial progression-free survival (IPFS),progression-free survival (PFS),overall survival (OS),brain metastasis-specific survival (BMSS) and adverse events.The survival rates were assessed with Kaplan-Meier method and log-rank test and monovariate analysis.Results The median GTV in the CRT and RT groups was 16.9 cm3 and 15.7 cm3.During the treatment,75% of the lesions in the CRT group were reduced compared with 34% in the RT group (P=0.000).The local control (LC) rate in the CRT and RT groups was 100% and 98%.The median follow-up time was 16.1 months (range,2.1-105.7 months).In the CRT group,the LRFS (P=0.040),IPFS (P=0.022),PFS (P=0.045),OS (P=0.013) and BMSS (P=0.006) were significantly better than those in the RT group,respectively.In the CRT group,the incidence of grade Ⅰ-Ⅱ gastrointestinal adverse events was 33%,significantly higher compared with 26% in the RT group (P=0.006).No grade Ⅳ-Ⅴ adverse events occurred in both groups.Conclusion Combined application of temozolomide and FSRT can further enhance the LC and survival rates and do not increase the risk of severe adverse events in patients diagnosed with large brain metastases.

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