1.Plasma and hepatic free fatty acid, tricarboxylic acid cycle, and ketone bodies metabolic profiles in progressive Gao-Binge model
Anqin LI ; Luxin PANG ; Yuanyuan CHAI ; Qinwei YU ; Zhenzhou JIANG ; Luyong WANG
Journal of China Pharmaceutical University 2025;56(2):196-206
To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.
2.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
3.Analysis of immunogenicity of African swine fever virus p37 recombinant protein in mice
Ying HUANG ; Wenzhu ZHAI ; Chunhao TAO ; Yuheng HE ; Zhen WANG ; Yuanyuan CHU ; Zhongbao PANG ; Hongfei ZHU ; Hong JIA
Chinese Journal of Veterinary Science 2025;45(5):889-895
The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P<0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P<0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.
4.Brucellosis and tuberculosis:comparative analysis of clinical characteristics and features of co-infection
Yilin WANG ; Zihan TANG ; Yuanyuan SHANG ; Yu PANG ; Jun FAN
Chinese Journal of Zoonoses 2025;41(10):1055-1060
This study compared the clinical characteristics of brucellosis,tuberculosis,and their co-infections,to improve dif-ferential diagnosis and disease management.A retrospective analysis was conducted on 41 patients with brucellosis,38 co-infected pa-tients,and 95 patients with tuberculosis admitted to Beijing Chest Hospital,Capital Medical University,between January 2017 and December 2024.Clinical manifestations,laboratory findings,and complications were analyzed statistically.Brucellosis and tuberculo-sis shared clinical similarities,such as presentation with prolonged fever.However,patients with brucellosis tended to exhibit muscle pain,night sweats,and loss of appetite,whereas patients with tuberculosis frequently presented with cough,sputum production,and lymphadenopathy.Co-infected patients had a higher fever incidence,and elevated hs-CRP and ESR levels.Whereas spinal spondyli-tis was more frequent in brucellosis,pulmonary infections and pleural effusion were predominant in tuberculosis.Co-infected patients exhibited characteristics of both diseases,and showed more severe systemic inflammation and prolonged illness.In conclusion,al-though elevated hs-CRP and ESR might aid in differentiation,pathogen detection is crucial for accurate diagnosis.Strengthening screening in patients with persistent fever and systemic inflammation may improve early identification,optimize treatment,and en-hance outcomes.
5.Analysis of immunogenicity of African swine fever virus p37 recombinant protein in mice
Ying HUANG ; Wenzhu ZHAI ; Chunhao TAO ; Yuheng HE ; Zhen WANG ; Yuanyuan CHU ; Zhongbao PANG ; Hongfei ZHU ; Hong JIA
Chinese Journal of Veterinary Science 2025;45(5):889-895
The aim of this study is to explore the immunogenicity of African swine fever virus p37 recombinant protein in mice.C57BL/6J mice were immunized subcutaneously in the abdomen using p37 recombinant protein as antigen.The second immunization was performed 21 d after the first immunization.Serum-specific antibody levels were detected by ELISA;serum cytokine levels were detected using a multifactor assay technique;mice splenic lymphocytes were isolated 7 d after sec-ondary immunization,and the number of splenic lymphocytes secreting IFN-γ after recombinant protein stimulation was detected by ELISpot;and the ratio of CD4+T cells to CD8+T cells was detected by flow cytometry.The results of indirect ELISA showed that p37 recombinant protein could stimulate mice to produce high levels of specific antibodies;ELISpot showed that p37 recom-binant protein could significantly stimulate splenic lymphocytes to produce IFN-γ(P<0.001)and activate cellular immune responses;the results of flow cytometry showed that it could signifi-cantly stimulate the differentiation of T-lymphocytes to CD4+T-lymphocytes(P<0.001).In ad-dition,serum levels of IL-2,IL-4,IFN-γ,and TNF-α immune-related cytokines were significantly higher after the second immunization.Immunization of mice with p37 recombinant protein induced strong humoral and cellular immune responses with good immunogenicity,providing reference for the subsequent epitope identification and functional study of p37 protein and the antigen screening of ASF mRNA vaccine.
6.Brucellosis and tuberculosis:comparative analysis of clinical characteristics and features of co-infection
Yilin WANG ; Zihan TANG ; Yuanyuan SHANG ; Yu PANG ; Jun FAN
Chinese Journal of Zoonoses 2025;41(10):1055-1060
This study compared the clinical characteristics of brucellosis,tuberculosis,and their co-infections,to improve dif-ferential diagnosis and disease management.A retrospective analysis was conducted on 41 patients with brucellosis,38 co-infected pa-tients,and 95 patients with tuberculosis admitted to Beijing Chest Hospital,Capital Medical University,between January 2017 and December 2024.Clinical manifestations,laboratory findings,and complications were analyzed statistically.Brucellosis and tuberculo-sis shared clinical similarities,such as presentation with prolonged fever.However,patients with brucellosis tended to exhibit muscle pain,night sweats,and loss of appetite,whereas patients with tuberculosis frequently presented with cough,sputum production,and lymphadenopathy.Co-infected patients had a higher fever incidence,and elevated hs-CRP and ESR levels.Whereas spinal spondyli-tis was more frequent in brucellosis,pulmonary infections and pleural effusion were predominant in tuberculosis.Co-infected patients exhibited characteristics of both diseases,and showed more severe systemic inflammation and prolonged illness.In conclusion,al-though elevated hs-CRP and ESR might aid in differentiation,pathogen detection is crucial for accurate diagnosis.Strengthening screening in patients with persistent fever and systemic inflammation may improve early identification,optimize treatment,and en-hance outcomes.
7.The impact of central obesity on breast cancer risk and the significance of dietary factors
Yu ZHANG ; Chunwei LI ; Yongchao WANG ; Yuanyuan BAO ; Qi LI ; Lin LI ; Yi PANG ; Chunli GUO ; Yuchen FAN ; Xiangchao MENG ; Kang YU
Chinese Journal of Clinical Nutrition 2024;32(2):65-70
Objective:To explore the influence of central obesity on the risk of breast cancer and the possible role of dietary factors in its prevention.Methods:This study is a case-control study including a total of 212 participants, of whom 63 were with breast cancer, 71 were with breast nodules, and 80 were healthy controls. We used bioelectrical impedance analysis to measure body composition,and adopted the food frequency questionnaire to investigate dietary intake of participants.Results:The visceral adipose tissue ( OR=1.03, 95% CI: 1.003 to 1.077) and trunk fat mass ( OR=1.470, 95% CI: 1.104 to 2.184) were independently associated with the increased risk of breast cancer. Dietary patterns characterized by low dietary intake of beans and dairy products ( OR=1.300, 95% CI: 1.044 to 1.619) and high intake of cereals and red meat ( OR=2.254, 95% CI: 1.705 to 2.982) will increase the risk of breast cancer. Moreover, high meat intake ( β=0.268, 95% CI: 0.034 to 0.503) would advance the accumulation of visceral fat, while high bean intake ( β=-0.485, 95% CI: -0.865 to -0.104) would inhibit. Conclusions:Central obesity is an independent risk factor for breast cancer. Insufficient intake of beans and excessive intake of red meat are identified as factors that can exacerbate central obesity in breast cancer patients.
8.Construction of evaluation index system for clinical practice effectiveness of undergraduate nursing students based on improved Miller's pyramid theory
Fang LIN ; Yuanyuan PANG ; Jing CHEN ; Jiehong LI ; Yuhong SUN
Chinese Journal of Modern Nursing 2024;30(18):2457-2463
Objective:To construct an evaluation index system for clinical practice effectiveness of undergraduate nursing students, so as to provide a basis for the evaluation of clinical practice effectiveness of undergraduate nursing students.Methods:Based on the improved Miller's pyramid theory, a preliminary evaluation index system for clinical practice effectiveness of nursing undergraduate students was formed by literature analysis and semi-structured interview method. From April to July 2023, purposive sampling was used to select 20 experts in nursing education, clinical nursing teaching, and other fields. After two rounds of Delphi expert consultation, a final evaluation index system for clinical practice effectiveness of undergraduate nursing students was formed, and the weights of each index were determined.Results:After two rounds of consultation, the effective response rates of the questionnaire were 95.00% (19/20) and 100.00% (19/19), respectively. The expert authority coefficients were 0.86 and 0.88, and the Kendall harmony coefficients were 0.226 and 0.183 ( P<0.01). The final established evaluation index system for clinical practice effectiveness of undergraduate nursing students included five primary indicators, 13 secondary indicators, and 56 tertiary indicators. Conclusions:Based on the improved Miller's pyramid theory, the evaluation index system for clinical practice effectiveness of undergraduate nursing students constructed is scientific, reliable, and practical, which can provide reference for the evaluation of clinical practice for undergraduate nursing students.
9.Increased Incidence of Severe Adverse Events in Non-Small Cell Lung Cancer Patients with Previous Tuberculosis Episode Treated with PD-1 Inhibitors
Zhang HUI ; Yuan JINFENG ; Xu YUANYUAN ; Yang MENGJIE ; Lyu JIALIN ; Yang XINJIE ; Sheng SHUYAN ; Qian ZHE ; Wang QUNHUI ; Pang YU ; Hu YING
Biomedical and Environmental Sciences 2024;37(7):785-789
Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.
10.Efficacy and Safety of Combined Bedaquiline and Delamanid Use among Patients with Multidrug-Resistant Tuberculosis in Beijing,China
Guo CAN ; Nie LIHUI ; Song YANHUA ; Liu RONGMEI ; Wu XIAOGUANG ; Shang YUANYUAN ; Zhang XUXIA ; Pang YU ; Gao MENGQIU
Biomedical and Environmental Sciences 2024;37(10):1195-1203
Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQ-containing regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients. Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM. Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups. Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.

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