1.FGF21 overexpression upregulates SIRT1/GPX4 to inhibit ferroptosis and relieve CCl4 mouse acute liver injury
Xutao LING ; Qianqian HUANG ; Lun ZHANG ; Fang XIE ; Nan BAI ; Yingxia WANG ; Haoran HUA ; Haoze WANG ; Wenjing DAI ; Kexin LI ; Jianqing WANG
Acta Universitatis Medicinalis Anhui 2026;61(6):1053-1060
ObjectiveTo investigate the protective effect of liver-targeted fibroblast growth factor 21 (FGF21) overexpression against CCl₄-induced acute liver injury (ALI) and its association with silent information regulator 1/glutathione peroxidase 4 (SIRT1/GPX4) expression and ferroptosis-related markers. MethodsFemale ICR mice (8 weeks old) were randomly divided into Control, CCl₄, adeno-associated virus (AAV)-FGF21, and AAV-FGF21 + CCl4 groups. Liver-targeted FGF21 overexpression was achieved via tail vein injection of AAV8-FGF21 virus with green fluorescent protein (GFP) labeling. ALI was induced by intraperitoneal injection of CCl₄ (0.3 mL/kg), with sample collection at 12 hours. Body weight and liver weight were recorded to calculate the liver weight/body weight. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using a biochemical analyzer. FGF21 expression in liver tissues was detected by immunofluorescence. Hepatic histopathology was evaluated by HE staining. RT-qPCR was performed to assess mRNA expression of ferroptosis and iron metabolism-related genes (ACSL4, PTGS2, HJV, FPN, GPX4), FGF21, and SIRT1. Protein expression of FGF21, SIRT1, and GPX4 were determined by Western blot. Iron content, malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activity in liver homogenate were quantified using assay kits. ResultsCompared with the Control group, the FGF21 mRNA and protein expression elevated in CCl4 group; serum ALT/AST levels and liver weight/body weigh increased. The HE staining results showed that the liver cell membranes were ruptured. The mRNA levels of ACSL4 and PTGS2, the iron content and MDA levels all increased (P<0.01). The mRNA levels of SIRT1, GPX4, HJV, and FPN, the GSH level and SOD activity all decreased (P<0.05), and the protein levels of SIRT1 and GPX4 both decreased (P<0.05). Compared with the CCl4 group, the serum levels of ALT and AST in the AAV-FGF21 + CCl4 group were decreased (P<0.01), and the liver/body ratio of mice decreased (P<0.01). The results of HE staining showed that the degree of liver injury was alleviated. The mRNA levels of ACSL4 and PTGS2, iron content and MDA level all decreased (P<0.01), while the mRNA levels of SIRT1, GPX4, HJV, FPN, GSH level and SOD activity all increased (P<0.05). The protein levels of SIRT1 and GPX4 both increased (P<0.05). ConclusionFGF21 overexpression is associated with enhanced SIRT1/GPX4 expression and suppression of ferroptosis features, thereby contributing to the alleviation of CCl4-induced ALI.
2.Design, synthesis and pharmacological evaluation of 1,2,3,4-tetrahydrobenzofuro2,3-cpyridine derivatives as p21-activated kinase 4 inhibitors for treatment of pancreatic cancer.
Yang LI ; Yan FANG ; Xiaoyu CHEN ; Linjiang TONG ; Fang FENG ; Qianqian ZHOU ; Shulun CHEN ; Jian DING ; Hua XIE ; Ao ZHANG
Acta Pharmaceutica Sinica B 2025;15(1):438-466
The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC50 values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.
3.Cognition status quo of wild mushroom poisoning and its influencing factors among students in Guizhou Province
ZHOU Qianqian, ZUO Peipei, TIAN Jigui, WU Anzhong, GUO Hua, ZHU Shu
Chinese Journal of School Health 2025;46(3):335-338
Objective:
To assess the awareness and associated factors of wild mushroom poisoning among students in Guizhou Province, so as to provide a scientific foundation for wild mushroom poisoning prevention and control among students.
Methods:
By a multi stage stratified cluster random sampling method, 1 162 students from Guizhou Province were selected in May 2024. The questionnaire survey was administered to evaluate knowledge regarding wild mushroom poisoning. Data were analyzed employing the χ 2 test and Logistic regression model.
Results:
Among the nine questions assessing awareness of wild mushroom poisoning, only three had the awareness rate exceeding 70%. Binary Logistic regression analysis revealed that students who "actively learn about the prevention of wild mushroom poisoning" ( OR=0.48, 95%CI =0.26-0.92) and "spread knowledge about wild mushroom poisoning to others" ( OR=0.47, 95%CI =0.33-0.69) scored higher on the wild mushroom poisoning knowledge questions ( P <0.05). Conversely, students with a habit of consuming wild mushrooms ( OR=1.52, 95%CI =1.15-2.02) scored lower ( P < 0.05 ). 42.3% of the students suggested that scientific dissemination and publicity about wild mushrooms should be intensified.
Conclusions
The awareness rate of wild mushroom poisoning knowledge among students in Guizhou Province requires further attention. Comprehensive knowledge should be disseminated systematically through various channels to further improve students awareness of the prevention and control of wild mushroom poisoning.
4.A multicenter retrospective clinical study of a simplified comprehensive geriatric assessment system in elderly patients with diffuse large B-cell lymphoma
Jiayan LENG ; Yihong CAI ; Xueping GE ; Nanping ZHAO ; Qianqian SU ; Zhuxia JIA ; Jun QIAN ; Bingzong LI ; Haiying HUA ; Xuzhang LU ; Huayuan ZHU ; Jianyong LI ; Wenyu SHI
Chinese Journal of Hematology 2025;46(2):126-133
Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.
5.Status of cancer management in community health service institutions in Shanghai from the perspective of proactive health
Qianqian ZHANG ; Hua JIN ; Wanyu LI ; Dehua YU
Chinese Journal of General Practitioners 2025;24(4):458-464
Objective:To investigate the current status of the implementation of active health management in tumor care in community health service institutions in Shanghai.Methods:This cross-sectional study was conducted in July 2022. A questionnaire was designed based on tumor management practices according to active health principles was designed and distributed to all 247 community health service institutions in 16 administrative districts of Shanghai. Data were collected on tumor screening, establishment of health records for tumor patients, and follow-up practices.Results:Of the 247 questionnaires distributed, 239 were returned, with 228 valid responses (effective response rate: 92.3%). Of the 228 institutions, 72 (31.6%) were located in urban areas, 101 (44.3%) in suburban areas, and 55 (24.1%) in rural areas. Tumor screening was performed by 89.0% (203/228) of the institutions, mainly for colorectal, lung, liver, breast, and gastric cancers. Health records for tumor patients were established by 92.5% (211/228) of institutions. Follow-up of tumor patients was conducted by 99.1% (226/228) of institutions, with 29.6% (67/226) performing 1-2 annual follow-ups. Telephone follow-up was used by 99.1% (224/226) of institutions, while 42.5% (96/226) adjusted the frequency of follow-up based on patients′ Karnofsky Performance Status scores. Targeted health education for patients and families was provided by 84.6% (193/228) of institutions, including exercise guidance (78.8%, 152/193) and psychological support (76.2%, 147/193). No statistically significant differences were observed among urban, suburban, and rural institutions in tumor screening, health record establishment, follow-up frequency, assessment content, follow-up methods, and tumor health education and content (all P>0.05). Conclusions:The coverage of tumor screening in Shanghai′s community health service institutions remains incomplete, the quality of follow-up needs to be improved, and health education programs are not comprehensive. There were no regional differences in tumor screening, health record establishment, follow-up practices, or tumor health education among urban, suburban, and rural populations.
6.The correlation between functional level and the cost of stroke rehabilitation during hospitalization
Qianqian SUN ; Yulin SHI ; Hua TANG ; Rui LI ; Suchen ZHAO ; Luwen ZHANG ; Yumeng FENG ; Dengfeng WAN ; Tiebin YAN
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(4):325-330
Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.
7.The correlation between functional level and the cost of stroke rehabilitation during hospitalization
Qianqian SUN ; Yulin SHI ; Hua TANG ; Rui LI ; Suchen ZHAO ; Luwen ZHANG ; Yumeng FENG ; Dengfeng WAN ; Tiebin YAN
Chinese Journal of Physical Medicine and Rehabilitation 2025;47(4):325-330
Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.
8.A multicenter retrospective clinical study of a simplified comprehensive geriatric assessment system in elderly patients with diffuse large B-cell lymphoma
Jiayan LENG ; Yihong CAI ; Xueping GE ; Nanping ZHAO ; Qianqian SU ; Zhuxia JIA ; Jun QIAN ; Bingzong LI ; Haiying HUA ; Xuzhang LU ; Huayuan ZHU ; Jianyong LI ; Wenyu SHI
Chinese Journal of Hematology 2025;46(2):126-133
Objective:To evaluate the predictive value of simplified geriatric assessment (sGA) in elderly Chinese patients diagnosed with diffuse large B-cell lymphoma (DLBCL) .Methods:It retrospectively analyzed the relationships of sGA with the clinical characteristics, outcome, and prognosis of 219 patients aged ≥60 years who were newly diagnosed with DLBCL at six hospitals in Jiangsu province between January 2018 and December 2022.Results:The median age of 219 patients was 68 years (60-87 years). According to the sGA system criteria, 101 (46.1%), 103 (47.0%), and 15 (6.8%) elderly patients with DLBCL were categorized as fit, unfit, and frail, respectively. The most common adverse reactions after chemotherapy were hematologic, and the incidence of grade >2 hematologic adverse reactions was similar among the three groups (47.5% vs 41.7% vs 46.7%, respectively; χ2=0.712, P=0.700). Compared with the fit and unfit groups, the frail group showed tendencies toward for higher proportions of grade >2 gastrointestinal, pulmonary, and infectious adverse reactions ( P>0.05 for all). The fit, unfit, and frail groups had respective remission rates of 74.3%, 46.6%, and 20.0% ( χ2=25.249, P<0.001) ; disease progression rates of 5.9%, 11.7%, and 26.7% ( χ2=6.763, P<0.05) ; 2-year overall survival rates of 92.1% (95% CI 86.6% to 97.9%), 77.6% (95% CI 69.5% to 86.6%), and 70.1% (95% CI 49.4% to 99.6%) ( P<0.05) ; and 2-year progression-free survival rates of 76.8% (95% CI 67.0% to 84.8%), 69.7% (95% CI 61.8% to 82.0%), and 65.7% (95% CI 53.3% to 100%) ( P=0.399) . Conclusion:sGA can effectively predict treatment adverse effects and efficacy, disease progression, and long-term survival in elderly DLBCL.
9.Status of cancer management in community health service institutions in Shanghai from the perspective of proactive health
Qianqian ZHANG ; Hua JIN ; Wanyu LI ; Dehua YU
Chinese Journal of General Practitioners 2025;24(4):458-464
Objective:To investigate the current status of the implementation of active health management in tumor care in community health service institutions in Shanghai.Methods:This cross-sectional study was conducted in July 2022. A questionnaire was designed based on tumor management practices according to active health principles was designed and distributed to all 247 community health service institutions in 16 administrative districts of Shanghai. Data were collected on tumor screening, establishment of health records for tumor patients, and follow-up practices.Results:Of the 247 questionnaires distributed, 239 were returned, with 228 valid responses (effective response rate: 92.3%). Of the 228 institutions, 72 (31.6%) were located in urban areas, 101 (44.3%) in suburban areas, and 55 (24.1%) in rural areas. Tumor screening was performed by 89.0% (203/228) of the institutions, mainly for colorectal, lung, liver, breast, and gastric cancers. Health records for tumor patients were established by 92.5% (211/228) of institutions. Follow-up of tumor patients was conducted by 99.1% (226/228) of institutions, with 29.6% (67/226) performing 1-2 annual follow-ups. Telephone follow-up was used by 99.1% (224/226) of institutions, while 42.5% (96/226) adjusted the frequency of follow-up based on patients′ Karnofsky Performance Status scores. Targeted health education for patients and families was provided by 84.6% (193/228) of institutions, including exercise guidance (78.8%, 152/193) and psychological support (76.2%, 147/193). No statistically significant differences were observed among urban, suburban, and rural institutions in tumor screening, health record establishment, follow-up frequency, assessment content, follow-up methods, and tumor health education and content (all P>0.05). Conclusions:The coverage of tumor screening in Shanghai′s community health service institutions remains incomplete, the quality of follow-up needs to be improved, and health education programs are not comprehensive. There were no regional differences in tumor screening, health record establishment, follow-up practices, or tumor health education among urban, suburban, and rural populations.
10.Relationship between serum 25-hydroxyvitamin D and handgrip strength in middle-aged and elderly people in five cities of Western China
Ting JING ; Hua JIANG ; Ting LI ; Qianqian SHEN ; Lan YE ; Yindan ZENG ; Wenxin LIANG ; Gang FENG ; Szeto Man-Yau IGNATIUS ; Yumei ZHANG
Journal of Peking University(Health Sciences) 2024;56(3):448-455
Objective:To explore the association between serum 25-hydroxyvitamin D[25(OH)D]and handgrip strength in middle-aged and elderly people in 5 cities of Western China.Methods:Based on the data of a cross-sectional survey conducted in the 5 cities of Western China from February to July 2023,the relevant demographic characteristics of people were collected by questionnaire,handgrip strength was collected by physical examination,and serum 25(OH)D was detected by HPLC-MS/MS.The association between the serum 25(OH)D and handgrip strength was analyzed using Logistic regres-sion and Chi-square test for between-group comparisons models.Results:The prevalence of 25(OH)D deficiency and insufficiency among the middle-aged and elderly people in the 5 cities of Western China was 52.9%and 34.5%,respectively.The people who were older,female,and sampled in winter had lower serum 25(OH)D levels(P<0.05).The prevalence of loss of handgrip strength among the mid-dle-aged and elderly people was 25.3%.The prevalence of handgrip strength loss was higher in the aged 65-80 participants with 25(OH)D deficiency(45.0%)than in those with 25(OH)D insufficiency(32.6%)and 25(OH)D sufficiency(20.6%).The highest prevalence of loss of handgrip strength was found in the aged 75-80 participants with 25(OH)D deficiency(62.1%),followed by the 25(OH)D insufficient group(11.1%,P<0.05).The study found that middle-aged and elderly people with 25(OH)D deficiency had a 1.4-fold increased risk of handgrip strength loss compared with those with 25(OH)D sufficiency(OR=2.403,95%CI:1.202-4.804,P=0.013).No significant association was found between 25(OH)D insufficiency and handgrip strength status in the middle-aged and elderly people.For every 5 μg/L increase in total serum 25(OH)D,the risk of handgrip strength loss reduced by 13.1%(OR=0.869,95%CI:0.768-0.982,P=0.025).For every 5 μg/L increase in serum 25(OH)D2,the risk of handgrip strength loss reduced by 24.1%(OR=0.759,95%CI:0.582-0.990,P=0.042).No significant association was found between serum 25(OH)D3 levels and the risk of hand-grip strength loss.The risk of handgrip strength loss in middle-aged and elderly people was reduced by 25.2%for each incremental increase in the total serum 25(OH)D levels(deficient,insufficient and suf-ficient)(OR=0.748,95%CI:0.598-0.936,P=0.011).The risk of handgrip loss was reduced by 40.0%for each incremental increase in serum 25(OH)D levels in the aged 65-80 and aged 65-69 participants,and by 80.0%for each incremental increase in 25(OH)D levels in the aged 75-80 parti-cipants.Conclusion:Serum total 25(OH)D and 25(OH)D2 levels are associated with handgrip strength status in middle-aged and elderly people in the 5 cities of Western China.


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