1.Development and application on a full process disease diagnosis and treatment assistance system based on generative artificial intelligence.
Wanjie YANG ; Hao FU ; Xiangfei MENG ; Changsong LI ; Ce YU ; Xinting ZHAO ; Weifeng LI ; Wei ZHAO ; Qi WU ; Zheng CHEN ; Chao CUI ; Song GAO ; Zhen WAN ; Jing HAN ; Weikang ZHAO ; Dong HAN ; Zhongzhuo JIANG ; Weirong XING ; Mou YANG ; Xuan MIAO ; Haibai SUN ; Zhiheng XING ; Junquan ZHANG ; Lixia SHI ; Li ZHANG
Chinese Critical Care Medicine 2025;37(5):477-483
The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence
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Humans
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Delivery of Health Care
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Generative Artificial Intelligence
2.Effect of BTK inhibitor BGB-3111 combined with bortezomib on apoptosis of human multiple myeloma cells and its mechanism
Hongjie LI ; Maozhuo LAN ; Xiao WANG ; Ranran FENG ; Yanyan TAO ; Jiaqing LIU ; Haibai SUN
Journal of Jilin University(Medicine Edition) 2025;51(3):599-609
Objective:To discuss the effect of zanubrutinib(BGB-3111)combined with bortezomib(Btz)on the apoptosis of the human multiple myeloma(MM)cells,and to clarify its possible mechanism.Methods:The human MM cell lines U266,PS-R,RPMI8226,KMS28-PE,KMS28-BM,and H929 were cultured in vitro.Western blotting method was used to detect the expression level of Bruton's tyrosine kinase(BTK)protein in various cells;cell counting kit-8(CCK-8)method was used to detect the survival rates of the RPMI8226,U266,and KMS28-BM cells after treated with 0,10,20,30,40,and 50 μmol·L?1 BGB-3111.The RPMI8226,U266,and KMS28-BM cells at the logarithmic growth phase were selected and divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.Flow cytometry was used to detect the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of myeloid cell leukemia 1(MCL-1),B-cell lymphoma-2(Bcl-2),Bcl-2-interacting mediator of cell death(Bim),phosphorylated Bim(p-Bim),P65,phosphorylated P65(p-P65),tumor necrosis factor receptor-associated factor(TRAF)2,and tumor necrosis factor alpha-induced protein 3(A20)in different kinds of cells.The U266 cells were divided into A20 overexpression group(A20-OE group)and empty vector control group(EV group).Each group was further divided into control group,BGB-3111 group,Btz group,and BGB-3111+Btz group.The corresponding plasmids were transfected;Western blotting method was used to detect the transfection efficiency of the cells in various groups;flow cytometry was used to detect the apoptotic rates of the cells in various groups after over-expression of A20.Results:The Western blotting results showed that compared with KMS28-BM cells,the expression levels of BTK protein in the U266,RPMI8226,and H929 cells were significantly increased(P<0.05 or P<0.01).The CCK-8 results showed that compared with 0 μmol·L?1 BGB-3111 group,the survival rates of the RPMI8226 and U266 cells in 10,20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05 or P<0.01),and the survival rates of the KMS28-BM cells in 20,30,40,and 50 μmol·L?1 BGB-3111 groups were significantly decreased(P<0.05).Compared with RPMI8226 and U266 cells,the survival rates of the KMS28-BM cells in 20,30,and 40 μmol·L?1 BGB-3111 groups were significantly increased(P<0.05).Therefore,10 μmol·L?1 BGB-3111 was selected for subsequent experiments.The flow cytometry results showed that compared with control group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05 or P<0.01);compared with BGB-3111 group and Btz group,the apoptotic rates of the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.01);compared with control group,the apoptotic rates of the KMS28-BM cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.01);compared with BGB-3111 group,the apoptotic rate of the KMS28-BM cells in BGB-3111+Btz group was significantly increased(P<0.01);compared with EV group,the apoptotic rates of the cells in A20-OE group in Btz group and BGB-3111+Btz group were significantly increased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111 group,Btz group,and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of Bim protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of MCL-1,p-Bim,and Bcl-2 proteins were significantly decreased(P<0.05).Compared with control group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in Btz group and BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05);compared with BGB-3111 group and Btz group,the expression levels of p-P65 protein in the RPMI8226 and U266 cells in BGB-3111+Btz group were significantly increased(P<0.05),while the expression levels of TRAF2 and A20 proteins were significantly decreased(P<0.05).The flow cytometry results showed that compared with EV group,the expression level of A20 protein in A20-OE group cells was significantly increased(P<0.01).Conclusion:BGB-3111 induces apoptosis in the MM cells by inhibiting BTK activity and enhances the pro-apoptotic effect of Btz.Over-expression of A20 increases the sensitivity of the MM cells to the combined treatment.The antitumor effect may be related to the inhibition of the nuclear factor kappa B(NF-κB)signaling pathway.
3.Mechanism of CD4 +CXCR5 +T cells and programmed necrosis factor in tuberculosis
Haibai SUN ; Ranran FENG ; Dong ZHANG ; Xiao WANG ; Jiaqing LIU
International Journal of Biomedical Engineering 2020;43(2):100-105
Objective:To explore the mechanism of follicular helper T (Tfh) cells, i.e. CD4 +CXCR5 +T cells, and the secreted cytokine programmed death factor 1 (PD-1) in the pathogenesis of tuberculosis, and to explore the significance of Tfh cells and PD-1 in the treatment of tuberculosis. Methods:Flow cytometry was used to detect the changes of Tfh cells and PD-1 in mononuclear cells during the treatment cycle of tuberculosis.Results:Before treatments, the ratio of Tfh cells/CD4 +T cells in peripheral blood mononuclear cells in the pulmonary tuberculosis group was 3.37%±0.45%, which was significantly higher than 2.21%±0.47% of the healthy control group ( P<0.01), and significantly higher than 2.39%±0.38% after treatments ( P<0.01). Before treatments, the ratio of CD4 +CXCR5 +PD-1 +T cells/Tfh cells in the peripheral blood of the tuberculosis group was 25.33%±10.08%, which was significantly higher than 8.42%±2.31% of the healthy control group ( P<0.01), and significantly higher than 11.35%±2.65% after treatments ( P<0.01). After treatments, the levels of Tfh cells and PD-1 in the sputum smear-negative group and the sputum smear-negative group were lower than that before treatments, and the difference between the groups was statistically significant (all P<0.05). Conclusions:The levels of Tfh cells and PD-1 in patients with tuberculosis are significantly higher than those in healthy people, and after drug treatment, the levels of both can be reduced. With the prolongation of the treatment cycle, the sputum smear-transforming group and the non-negative group began to show significant differences. In the course of pulmonary tuberculosis, monitoring changes in Tfh cells and PD-1 levels is helpful for the diagnosis of tuberculosis, and has certain guiding significance for its treatment and outcome.
4.Establishment and evaluation of predictive diagnostic equation for smear negative tuberculosis meningitis
Jiaqing LIU ; Lixia ZHANG ; Haibai SUN ; Zhonghua QIN ; Min WU ; Ming GAO ; Yuming LI
Tianjin Medical Journal 2017;45(4):418-423
Objective To explore a rapid and accurate method for the diagnosis of smear negative tuberculosis meningitis (TBM). Methods Sixty-seven patients with TBM were selected from Tianjin Haihe Hospital from June 2014 to June 2016, and 118 patients with non-tuberculous meningitis (NTBM) in the same period were chosen as control group, including bacterial meningitis (BM) group (n=61) and viral meningitis (VM) group (n=57). The laboratory routine, biochemical and immune indicators were tested with the specimens of both the blood and cerebrospinal fluid of all the patients. The Logistic regression equation was established for the diagnosis of TBM, and the diagnostic efficacy of which was evaluated by the receiver operating characteristic curve (ROC). Results The predictive regression equations of the TBM with BM, VM and NTBM (BM + VM) were obtained when BM group was used as a control: PRE_BM=1/1 +e-(-5.298+0.196 × ESAT-6+ 0.119 × CFP-10-2.968 × PCT+2.206 × ADA_CSF+0.705 × GLU_CSF+0.093 × LDH_CSF), PRE_VM=1/1+e-(-6.907+0.394 × ESAT-6-0.120 × Na+2.633 × ADA_CSF-0.088 × Cl_CSF) and PRE_NTBM=1/1+e-(0.683+0.099×ESAT-6+0.063×CFP-10-2.645×PCT+1.393×ADA_CSF+1.342×TbAb_CSF)respectively. When BM group was served as a control, the sensitivity, specificity, positive and negative predictive values of the regression for the diagnosis of TBM were 97.01%(89.63%-99.64%), 98.36%(91.20%-99.96%), 98.48%(91.84%-99.96%) and 96.77%(88.83%-99.61%), respectively.When VM group was served as a control, which were 94.03%(85.41%-98.35%), 94.74%(85.38%-98.90%), 95.45%(87.29%-99.05%) and 93.10%(83.27%-98.09%), respectively. When NTBM group was served as control, which were 94.03%(85.41%~98.35%), 90.68%(83.93%-95.25%), 85.14%(74.96%-92.34%) and 96.40%(91.03%-99.01%), respectively. Conclusion The predictive regression equation could be used as early diagnostic TBM with high sensitivity and specificity, which should be popularized in clinical practice, while, according to the higher negative predictive value, the negative results of which could be used to rule out of the TBM and non-empirical medication.
5.Evaluating the value of detecting cytokines for diagnosis of tuberculous pleural effusion by liquid array technology
Jiaqing LIU ; Li ZHANG ; Shuang FENG ; Lixia ZHANG ; Haibai SUN ; Gang LIU ; Hongxia XIAO ; Min WU ; Yanqing DU ; Shuye LIU
Chinese Journal of Laboratory Medicine 2015;(8):562-566
Objective To establish a diagnostic model of multiple cytokines for differential diagnosis of tuberculous pleural effusion , and compare its diagnostic accuracy with tuberculosis infected T cells detection ( T-SPOT.TB ) in order to evaluate its diagnostic performance.Methods Case-control study.Totally 147 patients with pleural fluid in Tianjin Haihe Hospital were enrolled and categorized as tuberculous pleural effusion group ( n=95 ) and malignant pleural effusion group ( n=52 ) from December 2011 to June 2013.Pleural effusion cytokines including interferon-γ( IFN-γ) , C-X-C motif chemokine 10 (CXCL-10), tumor necrosis factor-α(TNF-α), vascular endothelial growth factor (VEGF), IL-2, IL-16, IL-17, IL-27 and IL-33 were tested by liquid chip technology and analyzed by Binary Logistic regression and receiver operating characteristic curve (ROC), and the pleural effusion was also detected by tuberculosis infected T cells detection ( T-SPOT.TB) as a control.Results The comparison of the AUC of cytokines is:CXCL-10>IL-27>IFN-γ>IL-33 >IL-17>IL-16>TNF-α>VEGF>IL-2; After that, CXCL-10, IFN-γ, IL-27 and IL-33 were included the Binary Logistic regression model.The regression equation is P=1/1+e-( -16.851+0.390 ×IFN-γ+0.006 ×IL-27+0.020 ×IL-33).The AUC, sensitivity and specificity of the diagnostic model were 99.5%, 96.84%, and 98.08%, respectively.Both AUC and sensitivity of the diagnostic model were superior to those of any single index.Compared with T-SPOT.TB (0.995 ±0.003), the AUC of the diagnostic model (0.921 ±0.023) was significantly greater ( Z=3.235, P <0.01), but no significant difference was found when it comes to diagnostic results consistency (χ2 =0.062 5, P>0.05).The Kappa of the two methods was 0.795, which meant fine agreement of the evaluations of the two raters.Conclusion The application of liquid array technology of high sensitivity and repeatability with high throughput provided a novel insight and method in the clinical diagnosis , treatment and prevention for tuberculous pleural effusion scientifically and accurately.
6.Diagnostic Value of Combined Detection of the Level of IFN-γand IP-10 by Liquid Array Technology in Tuberculous Pleural Effusion
Jiaqing LIU ; Li ZHANG ; Haibai SUN ; Min WU ; Yanqing DU ; Shuang FENG ; Shuye LIU
Tianjin Medical Journal 2014;(9):943-945
Objective To explore the diagnostic value of combined detection of the liquid array technology, interfer-on (IFN)-γand IFN-γ-inducible protein (IP)-10 in the rapid, accurate diagnosis and differential diagnosis of tuberculous pleural effusions. Methods Patients with transudative pleural effusions were divided into tuberculous pleural effusion group (n=52) and malignant pleural effusion group (n=38). The method of T-SPOT.TB was used to detect the number of effec-tor T cells sensitized to Mycobacterium tuberculosis and spot forming cells (SFCs). The liquid array technology was used to detect the level of IFN-γand IP-10. Logistic regression was used to analyze and compare the diagnostic value of the two-method combination. Results The diagnostic sensitivity, specificity and the area under the ROC curve (AUC) of T-SPOT. TB were 90.38%, 84.21%, and 0.938 (95%CI:0.867-0.978), respectively. The diagnostic sensitivity, specificity and AUC of combined detection of IFN-γand IP-10 were 98.08%, 97.37%, and 0.995 (95%CI:0.951-1.000), respectively. There was no significant difference in the diagnostic sensitivity and specificity between the two methods, and the diagnostic agreement for the two diagnostic methods was fine (Kappa=0.703). The difference of AUC between the methods was significantly differ-ent (Z=1.996, P<0.05). The method of combined detection of IFN-γand IP-10 showed the larger AUC (AUC=0.995). Con-clusion The combined diagnosis meets the clinical needs of rapid, accurate diagnosis and differential diagnosis for tuber-culous pleural effusion by simultaneously assaying the level of IFN-γand IP-10 using the liquid array technology.

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