Objective To evaluate the efficacy of Puerariae lobatae radix （PLR） and Anemarrhenae Rhizoma （AR） in preventing and treating Alzheimer’s disease （AD） and explore its potential mechanism of action by LC-MS serum metabolomics strategy. Methods The AD rat model was established by administering aluminum chloride （AlCl₃） and D-galactose （D-gal） for 20 weeks. The traditional Chinese medicine intervention group was given the PLR, AR, and PLR-AR extracts for 8 weeks by gavage. The model effect and efficacy were evaluated by Morris water maze test and biochemical indicators including SOD, NO, and MDA; Metabolomics research based on the UHPLC-Q/TOF-MS method was conducted, and relevant metabolic pathways were analyzed through the MetaboAnalyst online website. Results The learning and memory abilities of AD model rats were significantly decreased compared with the control group, and the levels of oxidative stress and lipid peroxides were significantly increased （P<0.05）, while the SOD content was decreased considerably （P<0.01）. The learning and memory abilities of AD model rats were improved, oxidative stress and lipid peroxidation levels were reversed, and serum SOD content was increased significantly after the intervention of PLR-AR, with better effects than single drugs. Through metabolomics, 70 differential metabolites were identified between the AD model group and the control group, mainly involving 10 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and unsaturated fatty acid biosynthesis, et.al. The intervention of PLR-AR could adjust 47 metabolites, with 20 metabolites showing significant differences （P<0.05）. The significantly adjusted metabolites involve 6 pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis, et al. Conclusion The combination of PLR and AR could significantly improve the learning and memory abilities of AD rat models. The mechanism may be related to the improvement of oxidative stress and lipid peroxidation levels, the increase of serum SOD content, and the regulation of phenylalanine, tyrosine, and tryptophan biosynthesis pathways.

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.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

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: Chronic liver disease (CLD), mainly non-alcoholic fatty liver disease (NAFLD), is a significant public health concern worldwide. This study aims to quantify the burden of NAFLD in CLD globally and within China, using data from the Global Burden of Disease (GBD) Study 2021, providing crucial insights for global and local health policies. METHODS: The study used comprehensive data from the GBD study 2021. It included estimates of prevalence, incidence, mortality, and disability-adjusted life years (DALYs). Age-standardized rates and average annual percent change (AAPC) from 2011 to 2021 were reported. A meticulous decomposition analysis was conducted. RESULTS: In 2021, there were 1582.5 million prevalent cases, 47.6 million incident cases, 1.4 million deaths, and 44.4 million DALYs attributable to CLD, globally. Among these, NAFLD has emerged as the predominant cause, accounting for 78.0% of all prevalent CLD cases (1234.7 million) and 87.2% of incident cases (41.5 million). Correspondingly, NAFLD had the highest age-standardized prevalence (15,017.5 per 100,000 population) and incidence (876.5 per 100,000 population) rates among CLDs. In addition, China's CLD age-standardized prevalence rate was 21,659.5 per 100,000 population, and the age-standardized incidence rate was 752.6 per 100,000 population, higher than the global average. From 2011 to 2021, the global prevalence rate of CLD increased slowly (AAPC = 0.17), consistent with the trend in China (AAPC = 0.23). Furthermore, the prevalence rate of NAFLD rose significantly in China (AAPC = 1.30) compared with the global average (AAPC = 0.91). Decomposition analysis also showed the worldwide increase in deaths and DALYs for NAFLD, which were primarily attributable to population growth and aging. CONCLUSIONS The burden of CLD and NAFLD remains substantial globally and within China in terms of high prevalence and incidence. As such, this underscores the need for targeted prevention and treatment strategies. These findings emphasize the importance of continued surveillance and research to mitigate the growing impact of liver diseases on global and Chinese health systems.
Humans ; Non-alcoholic Fatty Liver Disease/mortality* ; Global Burden of Disease ; China/epidemiology* ; Prevalence ; Male ; Disability-Adjusted Life Years ; Female ; Incidence ; Middle Aged ; Chronic Disease ; Adult ; Quality-Adjusted Life Years ; Liver Diseases/epidemiology* ; Aged

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male