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.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.
4.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.
5.Research on pharmaceutical management provisions in the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals in Hubei Province (2024 Edition)
Linlin ZHAO ; Yuanyuan LU ; Maochang LIU ; Fan JIN ; Liangfang PANG ; Wei FU
China Pharmacy 2024;35(23):2858-2862
OBJECTIVE To study pharmaceutical management provisions in the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals in Hubei Province (2024 Edition) (hereinafter referred to as 2024 Edition of Hubei Maternal and Child Health Care Standards). METHODS The formulation of pharmaceutical management clauses and management rules in the 2024 Edition of Hubei Maternal and Child Health Care Standards was elaborated and compared with the pharmaceutical management clauses in the Evaluation Standards for Third-level Maternal and Child Health Care Hospitals (2016 Edition) to find out their similarities and differences; the basis for the formulation of unique pharmaceutical management clauses was analyzed, so as to propose further improvement suggestions. RESULTS & CONCLUSIONS Compared with the Evaluation Standards for Third- level Maternal and Child Health Care Hospitals (2016 Edition), the similarities in pharmaceutical management in the 2024 Edition of Hubei Maternal and Child Health Care Standards were mainly reflected in the relevant laws, regulations, rules and personnel requirements that should be followed, the full process management of drug procurement, reserve, storage and recall, drug dispensing and formulation management, etc. The unique provisions of the 2024 Edition of Hubei Maternal and Child Care Standards were mainly reflected in the establishment of children’s medication working group, the establishment of a list of children’s specific drugs, the development of surplus drug management system, and the management of off-label drug use, etc. The formulation of unique provisions for pharmaceutical management not only conformed to the newly released policy requirements in recent years, but also combined the characteristics and actual situation of maternal and child health care hospitals. 2024 Edition of Hubei Maternal and Child Health Care Standards should be further improved in terms of strengthening detail management and enhancing the rational application management of traditional Chinese medicine.
6.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.
7.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.
8.Etiological analysis on a foodborne disease outbreak caused by two serotypes of Salmonella
Aixia YAN ; Ying KANG ; Yao CUI ; Wenxuan ZHAO ; Shoufei LI ; Miao WANG ; Yuanyuan WANG ; Luotong WANG ; Fengshuang WANG ; Bo PANG ; Ying LI
Chinese Journal of Epidemiology 2023;44(9):1440-1446
Objective:To understand the etiological characteristics of 2 serotypes of Salmonella strains isolated from a foodborne disease outbreak. Methods:A total of 11 anal swabs of the cases, 13 suspected contaminated food and 10 environmental samples were collected from a foodborne disease outbreak occurred on September 8, 2022 in a school. The anal swabs were enriched with selenite brilliant green enrichment broth (SBG) and brain heart infusion broth (BHI) respectively. PCR detection and culture of common intestinal pathogens were carried out. The suspected food samples were tested according to national standards for food safety. Multiple suspected Salmonella colonies were obtained and selected for serotype determination and whole genome sequencing. Serotypes were determined based on the whole-genome sequence, and clustering analysis was performed based on core genome single nucleotide polymorphism (SNP). Results:The positive rates of Salmonella in anal swabs and suspected food samples were 9/11 and 5/13 respectively. Both Salmonella Uganda and Salmonella Idikan were isolated from 4 anal swabs and 4 suspected food samples. For the remaining samples, only Salmonella Uganda or Salmonella Idikan was isolated in each sample. The positive rate of Salmonella in 11 anal swabs of the cases after BHI enrichment for 12 h and 24 h were all 9/11 in real-time PCR, same to the culture results. Salmonella Uganda and Salmonella Idikan formed two independent and genetically distant lineages in the clustering tree based on core genome SNP, and 0-14 and 0-23 SNP were observed in Salmonella Uganda and Salmonella Idikan respectively. Conclusions:This foodborne disease outbreak was probably caused by Salmonella Uganda and Salmonella Idikan, which both exhibited strong genetic diversity. The PCR based pathogen screening strategy plus pathogen enrichment for cases' annal swabs can be used in the routine outbreak investigation.
9.Study of influencing factors of seasonal influenza virus infection in pregnant women in Suzhou, 2015-2018
Qian FENG ; Yuanyuan ZHANG ; Lin BAO ; Yuanyuan PANG ; Yayun TAN ; Pengwei CUI ; Jun ZHANG ; Liling CHEN
Chinese Journal of Epidemiology 2023;44(11):1748-1755
Objective:To explore the influencing factors of seasonal influenza among pregnant woman in Suzhou from 2015 to 2018.Methods:Based on the data of the influenza follow-up cohort of pregnant women in Suzhou from 2015 to 2018, the basic and clinical characteristics of the cohort were described, and the influencing factors of laboratory-confirmed influenza cases in pregnant women were analyzed by unconditional logistic regression.Results:A total of 19 006 pregnant women were recruited, in whom 479 cases of influenza were laboratory confirmed. Influenza A (H3N2) (42.8%) was the main sub-type. In pregnant women with exposure risk in influenza season, unconditional univariate logistic analysis showed that pregnant women or their husbands had registered permanent residence in Suzhou, pregnant women worked as childminder or nanny, had more than 2 permanent residents in the family except themselves, had medical insurance in Suzhou, had fertility insurance in Suzhou, were in the third trimester at the time of enrollment, had cough in the past month, were pregnant for the first time, had children, before and after pregnancy, spent more time outdoors than before, wore masks more often than before and had changed the frequency of gathering were all related to influenza virus infection in pregnant women. Among them, the first pregnancy, increasing the time of outdoor activity, increasing the frequency of wearing masks, and changing the frequency of gathering were important protective factors. Unconditional multivariate logistic regression analysis showed that the number of permanent residents at home was >2 (a OR=1.24, 95% CI: 1.01-1.52) and being in the third trimester, (a OR=1.56, 95% CI: 1.26-1.91) were the risk factors for maternal infection with influenza virus. Conclusion:Pregnant women with a large number of permanent residents and late pregnancy should pay attention to preventing seasonal influenza.
10.Investigation of 2019-nCoV reinfection in previously infected people in Suzhou
Yuanyuan ZHANG ; Hui HANG ; Qian XU ; Cheng LIU ; Yayun TAN ; Pengwei CUI ; Lin BAO ; Hui LIU ; Shanshan LU ; Feng XU ; Yuanyuan PANG ; Ge TIAN ; Jun ZHANG ; Jie ZHU ; Liling CHEN
Chinese Journal of Epidemiology 2023;44(11):1756-1761
Objective:To understand the reinfection rate of 2019-nCoV in the previously infected population in Suzhou and compare the illness severity and prognosis of the reinfection cases with the first-time infection cases.Methods:A questionnaire survey was conducted in the persons with previous 2019-nCoV infection reported in Suzhou from January 22, 2020 to November 8, 2022 to collect the information about the incidence of reinfection of 2019-nCoV in this population from December 8, 2022 to January 18, 2023. The persons who were infected with 2019-nCoV for the first time were selected by marching the residence, age and gender at ratio of 1∶2 from 2019-nCoV infection community follow-up cohort of Suzhou. By χ2 test, the clinical symptoms and prognosis of the reinfection case and the first-time infection cases were compared. Results:The reinfection rate of 2019-nCoV was 13.01% (147/1 130) in Suzhou. No reinfection was found within 1-6 months after the first-time infection, the rate of reinfection was 10.59% (95/897) in those with interval of 7-12 months between the reinfection and the first-time infection and 45.61% (52/114) in those with the interval ≥24 months. The lowest reinfection rate was 9.09% (1/11) in those who had completed 4 doses of 2019-nCoV vaccination. The main symptoms of the reinfection cases were similar to those of the first-time infection cases. Except for dry cough, nausea/poor appetite and other symptoms, there were significant differences in other clinical symptoms between the two groups ( P<0.05). In the reinfection cases, fever had shorter duration with lower body temperature. The hospital visit rate in the reinfection cases was 4.08% (6/147), lower than that in the cases with the first-time infection (11.56%, 34/294). The time for negative nucleic acid (antigen) test result and recovery from illness after the reinfection were shorter than those after the first-time infection. Conclusions:Reinfection occurred in some people who had been infected with 2019-nCoV. The interval between the reinfection and the first-time infection and the completion of the 4 doses of booster vaccination were the factors influencing the reinfection rate. The hospital visit rate in the reinfection cases was lower than that in the cases with the first-time infection. The reinfection had similar symptoms and shorter illness duration compared with the first-time infection.

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