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.

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.

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.

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.

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.

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.

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.

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.

The theory of "supplementation/drainage for bitter-desire of the five viscera" originated from Elementary Questions （《素问》）， which is an important origin of the theory of supplementation and drainage prescription. By exploring the connotation of the theory of "supplementation/drainage for bitter-desire of the five viscera"， and adopting the archaeological method of literature research， we collected the relevant writings on the theory of "supplementation/drainage for bitter-desire of the five viscera" by the representative physicians of Yishui school， such as ZHANG Yuansu， LI Gao， WANG Haogu， LUO Tianyi， LI Zhongzi， etc.， combed through the inheritance and development of this theory， and explored the contribution of Yishui school on this. It was found that all the physicians of Yishui school， on the basis of inheriting the theory of "supplementation/drainage for bitter-desire of the five viscera"， combined with their own clinical practice to develop this theory， and promoted the application and development of this theory in clinic， such as ZHANG Yuansu's theories of cold-heat deficiency-excess in viscera and bowels， and the theory of viscera and bowels prescription， and LI Gao's theory of ascending and descending， floating and sinking， supplementing and draining in visceral qi， and other academic thoughts rooted in the theory of "supplementation/drainage for bitter-desire of the five viscera" of Elementary Questions. By clarifying the inheritance and development of this theory by physicians of Yishui school， we can deeply understand the connotation and the embedded rules of prescription of this theory， which can not only guide the clinical medication in traditional Chinese medicine， but also provide reference value to the research on the academic thoughts of the Yishui school and the theory of fsupplementation/drainage for bitter-desire of the five viscera.

ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum （ER） stress and reducing urinary protein in the rat model of diabetic nephropathy （DN）. MethodSeventy-five SD rats were randomized into normal， model， low-， medium-， and high-dose （4.37， 8.73， 17.46 g·kg^-1， respectively） modified Shengjiangsan， and irbesartan （0.014 g·kg^-1） groups， with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage， once a day， for 8 consecutive weeks. After the last administration， the levels of glucose （GLU） in the blood， 24-hour urinary protein （24 h-UTP）， and superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in the renal tissue were measured. Hematoxylin-eosin staining， periodic acid-Schiff staining， and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin， podocin， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， and activating transcription factor 4 （ATF4） in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 （Sirt1）， phosphorylated （p）-protein kinase RNA-like endoplasmic reticulum kinase （PERK）， and p-eukaryotic translation initiation factor 2 alpha （eIF2α） in rat kidneys. ResultCompared with the normal group， the modeling caused pathological damage to the kidneys， elevated the levels of GLU and 24 h-UTP （P<0.05）， up-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and down-regulated the protein level of Sirt1 （P<0.05） in rat kidneys. Compared with the model group， modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels （P<0.05）， alleviated the pathological damage in the renal tissue， down-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and up-regulated the protein level of Sirt1 （P<0.05）. ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue， thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.