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 ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

Objective To analyze the genomic characteristics of Klebsiella pneumoniae carrying blaNDM-1 and Atlanta subterranean carry-ing blaIMP-4 isolated from the stool sample of the same patient and elucidate their resistance mechanisms.Methods The minimum in-hibitory concentrations(MIC)of the isolated strains were detected by the micro-broth dilution method.The NG-Test CARBA-5 was used to detect the phenotype of carbapenemases.The genomic characteristics of the strains were analyzed by the whole genome sequen-cing(WGS)and bioinformatics analysis.Results The isolated Klebsiella pneumoniae was resistant to most antibiotics.Atlanta subter-ranean was resistant to meropenem and ertapenem,but sensitive to imipenem.The two strains were susceptible to polymyxin,tigecy-cline,amikacin,ciprofloxacin,and aztreonam.The WGS analysis showed that Klebsiella pneumoniae belonged to ST1040 type and car-ried 8 resistance genes,including blaNDM-1,aac(6')-Ib-cr.v2,aadA16,aadA2,qnrS1,arr-3,sul1 and dfrA27,and 4 plasmid repli-cons such as lncR,lncU,lncFIA(Hl1)and lncFIB(K).Atlanta subterranean carried two resistance genes(blaIMP-4 and qnrS1)and 1 plasmid replicon(lncN).The analysis results of virulence factors showed that Klebsiella pneumoniae carried virulence factors such as fimbrium,capsule,and siderophore.Atlanta subterranean carried virulence factors such as fimbrium,flagella,lipopolysaccharides,and endotoxins.Conclusion The Atlanta subterranean producing blaIMP-4 enzyme and Klebsiella pneumoniae producing blaNDM-1 enzyme are isolated from the stool sample of the same patient,and their genomic characteristics are analyzed.The emergence of new carbapen-em-resistant strains poses a huge challenge to clinical treatment and infection prevention and control.The screening and detection of carbapenemase genes should be strengthened.

In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural-cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Humans ; Neoplasms/metabolism* ; Receptors, Neurotransmitter/physiology* ; Animals ; Tumor Microenvironment/physiology*

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective To analyze the genomic characteristics of Klebsiella pneumoniae carrying blaNDM-1 and Atlanta subterranean carry-ing blaIMP-4 isolated from the stool sample of the same patient and elucidate their resistance mechanisms.Methods The minimum in-hibitory concentrations(MIC)of the isolated strains were detected by the micro-broth dilution method.The NG-Test CARBA-5 was used to detect the phenotype of carbapenemases.The genomic characteristics of the strains were analyzed by the whole genome sequen-cing(WGS)and bioinformatics analysis.Results The isolated Klebsiella pneumoniae was resistant to most antibiotics.Atlanta subter-ranean was resistant to meropenem and ertapenem,but sensitive to imipenem.The two strains were susceptible to polymyxin,tigecy-cline,amikacin,ciprofloxacin,and aztreonam.The WGS analysis showed that Klebsiella pneumoniae belonged to ST1040 type and car-ried 8 resistance genes,including blaNDM-1,aac(6')-Ib-cr.v2,aadA16,aadA2,qnrS1,arr-3,sul1 and dfrA27,and 4 plasmid repli-cons such as lncR,lncU,lncFIA(Hl1)and lncFIB(K).Atlanta subterranean carried two resistance genes(blaIMP-4 and qnrS1)and 1 plasmid replicon(lncN).The analysis results of virulence factors showed that Klebsiella pneumoniae carried virulence factors such as fimbrium,capsule,and siderophore.Atlanta subterranean carried virulence factors such as fimbrium,flagella,lipopolysaccharides,and endotoxins.Conclusion The Atlanta subterranean producing blaIMP-4 enzyme and Klebsiella pneumoniae producing blaNDM-1 enzyme are isolated from the stool sample of the same patient,and their genomic characteristics are analyzed.The emergence of new carbapen-em-resistant strains poses a huge challenge to clinical treatment and infection prevention and control.The screening and detection of carbapenemase genes should be strengthened.

Objective:To investigate the role of ubiquitin-specific protease 21 (USP21) in enterovirus group A type 71 (EV-A71) infection.Methods:Peripheral blood mononuclear cells (PBMC) were obtained from a cohort of 24 children infected with EV-A71 and 24 healthy children. Expression of USP21 was determined by real-time fluorescence quantitative PCR (qPCR). Additionally, the impact of USP21 overexpression or knockout on EV-A71 replication was evaluated using a combination of qPCR and western blot (WB) analysis. Furthermore, WB was employed to measure the levels of EV-A71 structural protein VP1, phosphorylated interferon regulatory factor 3 (IRF3) and other key molecules in the RIG-I-like receptor (RLR) signaling pathway. Co-immunoprecipitation (Co-IP) was utilized to investigate the effects of USP21 on the ubiquitin levels of EV-A71 nonstructural protein 2A protease (2A pro). Results:In comparison to healthy children, the expression of USP21 mRNA in PBMC of children infected with EV-A71 was notably elevated. The overexpression of USP21 significantly enhanced the cytopathic effects induced by EV-A71, upregulated levels of VP1 mRNA and protein, and facilitated EV-A71 replication, leading to a decrease in cell activity with increasing levels of USP21 transfection. Following the knockout of the USP21 gene, the VP1 mRNA levels were significantly declined in comparison to the control group. Furthermore, the overexpression of USP21 was found to have no impact on the transcriptional activity of EV-A71 2A pro. However, it was observed to enhance the expression of 2A pro protein, reduce the ubiquitination of 2A pro, suppress the protein levels of mitochondrial antiviral signaling protein (MAVS) and melanoma differentiation-associated gene 5 (MDA5), as well as decrease the phosphorylation of IRF3. Additionally, the induction of IFN-β mRNA by EV-A71 infection was downregulated. Conclusions:USP21 has been shown to enhance the replication of EV-A71 through the downregulation of 2A pro ubiquitination, suppression of MAVS and MDA5 protein expression, and inhibition of the interferon signaling pathway.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Objective:To investigate the potential source of infection for a cluster outbreak of human brucellosis in Yantai City, Shandong Province.Methods:The information of a human brucellosis cluster outbreak case in Yantai City, Shandong Province in 2022 was collected, the strains were isolated and cultured, and DNA was extracted. BCSP31-PCR was used for species identification, and AMOS-PCR was used for species type identification. Multiple locus variable-number tandem-repeat analysis (MLVA)-16 was used for clustering analysis, and the results were compared with the public database MLVAbank and the monitoring data of Brucella in Shandong Province in 2022. At the same time, whole genome single nucleotide polymorphism (wgSNP) typing was used to analyze the 53 Brucella strains that had completed whole genome sequencing in Shandong Province in 2022, and the wgSNP phylogenetic tree was constructed. Results:According to BCSP31-PCR and AMOS-PCR identification, the three strains related to the cluster outbreak of brucellosis in Yantai City, Shandong Province in 2022 were all Brucella melitensis biotype. The results of MLVA-16 typing showed that the MLVA-16 typing of the three isolated strains was completely consistent, with 16 tandem repeat loci of 1-5-3-13-2-2-3-2-4-41-8-4-4-3-6-5, belonging to the Eastern Mediterranean clade. Compared with MLVAbank, the MLVA-16 typing of two strains isolated from Kazakhstan was consistent with the results of this study. Compared with the monitoring data of Brucella in Shandong Province in 2022, it was found that the MLVA-16 typing of 11 isolated strains was consistent with the results of this study, which were isolated from Zaozhuang, Linyi, Taian, Yantai, and Weifang cities, respectively. The results of wgSNP typing showed that the distance between the 11 strains and the strains of the current outbreak was less than 7 single nucleotide polymorphisms, and the strains were isolated from Taian, Zibo, Linyi, Binzhou, Jinan, Jining, Yantai and Weihai cities, respectively. Conclusion:After tracing the source of a human brucellosis cluster outbreak in Yantai City, Shandong Province in 2022, it is speculated that the strains of Brucella melitensis isolated from Linyi, Taian and Yantai cities are closely related, indicating that sheep in these areas have homology.