1.Role of naringenin in the prevention and treatment of autoimmune hepatitis and its molecular mechanism
Changwen LIN ; Qiuyi REN ; Mengjie ZHENG ; Huan YAN ; Jia LI ; Jiaxin FENG ; Haiying LIN ; Faming SHU ; Xiaoling ZHOU ; Dewen MAO ; Fuli LONG
Journal of Clinical Hepatology 2026;42(6):1419-1425
Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease mediated by T lymphocytes, and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound, naringenin (NAR) shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis, targeted inhibition of inflammatory pathways, antioxidation, regulating hepatocyte metabolism and apoptosis, improving mitochondrial function, and regulating intestinal flora. However, the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH, explores the potential signaling pathways involved in this process, and analyzes existing challenges in its translation and application and future research directions, so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.
2.Recommendations for the clinical use of anti-amyloid-β monoclonal antibody for Alzheimer's disease(2025)
Nan ZHI ; Jinwen XIAO ; Rujing REN ; Binyin LI ; Jintao WANG ; Jieli GENG ; Wenwei CAO ; Yaying SONG ; Hualong WANG ; Shuguang CHU ; Guoping PENG ; Jun LIU ; Xiaoyun LIU ; Fang YUAN ; Wen WANG ; Ronghua DOU ; Xia LI ; Ling YUE ; Wenshi WEI ; Xiaoling PAN ; Xiangyang ZHU ; Dian HE ; Weinü FAN ; Jingping SHI ; Nan ZHANG ; Hui ZHAO ; Qin CHEN ; Cuibai WEI ; Xiaochun CHEN ; Gang WANG
Journal of Chongqing Medical University 2025;50(9):1133-1140
In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.
3.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
4.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
5.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
6.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
7.Expression and clinical significance of CXCR3 on effector T cells in the peripheral blood of patients with Alzheimer′s disease
Zhuangzhuang REN ; Shuangshuang JIA ; Xiaoling ZHONG ; Yufeng ZHANG ; Tingting LI ; Feng QIU
Chinese Journal of Internal Medicine 2025;64(4):339-343
Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.
8.Expression and clinical significance of CXCR3 on effector T cells in the peripheral blood of patients with Alzheimer′s disease
Zhuangzhuang REN ; Shuangshuang JIA ; Xiaoling ZHONG ; Yufeng ZHANG ; Tingting LI ; Feng QIU
Chinese Journal of Internal Medicine 2025;64(4):339-343
Objective:This study investigated the expression of C-X-C motif chemokine receptor 3 (CXCR3) on CD45RO? T cells in the peripheral blood of patients with Alzheimer′s disease (AD) and its association with clinical features.Methods:A total of 41 AD patients and 30 age-and sex-matched healthy controls (HCs) were recruited from the Department of Neurology at the Medical Division of PLA General Hospital between September 2022 and March 2024. Flow cytometry was used to quantify CXCR3 expression on CD45RO? T cell subsets in peripheral blood. Dementia severity in AD patients was assessed using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Spearman correlation analysis examined the relationship between CD45RO?CXCR3? T cell levels and cognitive function in the AD group. Receiver operating characteristic (ROC) curve analysis determined the predictive utility of CD45RO?CXCR3? T cells for AD, quantified by the area under the curve (AUC).Results:Compared to healthy controls, AD patients exhibited significantly elevated levels of CD8?CD45RO?CXCR3? T cells [17.8% (7.2%, 40.3%) vs. 8.2% (5.1%, 12.3%), Z=-2.59, P<0.05]. However, no significant differences were observed for CD4?CD45RO?CXCR3? T cells, CD4?CD45RO?CXCR3? T cells, or CD8?CD45RO?CXCR3? T cells ( P>0.05). Spearman correlation analysis revealed a negative correlation between CD8?CD45RO?CXCR3? T cell levels and cognitive scores (MMSE: r=-0.72, P<0.05; MoCA: r=-0.70, P<0.05). ROC analysis demonstrated an AUC of 0.81 for CD8?CD45RO?CXCR3? T cells in predicting AD, with a sensitivity of 59.0% and specificity of 93.3%. Conclusions:CXCR3 expression is significantly upregulated on CD8?CD45RO? T cells in AD patients, and its levels correlate with cognitive impairment severity. These findings suggest that CD8?CD45RO?CXCR3? T cells may serve as a potential biomarker for AD diagnosis and progression monitoring.
9.Effect of Icariin Regulating mTOR/Akt/CREB Pathway on High Glucose Induced Autophagy and Apoptosis in Podocytes
Mingxia LI ; Qian YANG ; Haixia QIAO ; Xiaoling WANG ; Liyuan JIA ; Limei HU ; Weidong REN
Herald of Medicine 2024;43(1):19-25
Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P<0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P<0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P<0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P<0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P<0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P<0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P<0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.
10.Epidemiological characteristics of human respiratory syncytial virus among acute respiratory infection cases in 16 provinces of China from 2009 to 2023
Aili CUI ; Baicheng XIA ; Zhen ZHU ; Zhibo XIE ; Liwei SUN ; Jin XU ; Jing XU ; Zhong LI ; Linqing ZHAO ; Xiaoru LONG ; Deshan YU ; Bing ZHU ; Feng ZHANG ; Min MU ; Hui XIE ; Liang CAI ; Yun ZHU ; Xiaoling TIAN ; Bing WANG ; Zhenguo GAO ; Xiaoqing LIU ; Binzhi REN ; Guangyue HAN ; Kongxin HU ; Yan ZHANG
Chinese Journal of Preventive Medicine 2024;58(7):945-951
Objective:To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023.Methods:The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed.Results:A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M ( Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant ( P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age ( P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion:Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.

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