As the population is aging rapidly,the incidence of Alzheimer's disease(AD)is increasing year by year.The World Health Organization stresses that early prevention plays a key role in reducing the incidence of AD.Subjective cognitive decline(SCD)is an early window of AD development,and timely intervention can effectively slow down the progression of the disease or prevent it from developing into dementia,thus reducing the burden on the society.White matter hyperintensity(WMH)can effectively reflect white matter changes and provide strong evidence to identify SCD.In this paper,we review the recent research progress in WMH and SCD,reveal the problems in the current research on WMH,explain the correlation between WMH and SCD in terms of physiopathology and cognitive function,and put forward several suggestions for the future research.
Humans ; White Matter/pathology* ; Cognitive Dysfunction/pathology* ; Alzheimer Disease/pathology* ; Magnetic Resonance Imaging

Objective To investigate the prevalence status and influencing factors of metabolic syndrome (MS) in adult patients with hypopituitarism (HP) during hospitalization. Methods The data of adult HP patients who received treatment in the hospital were collected from March 2021 to March 2024. The prevalence status of MS in adult HP patients was counted, and logistic regression analysis was adopted to analyze the influencing factors of MS in adult HP patients. Results Among the 308 adult HP patients in this study, 121 cases developed MS and 187 cases did not develop MS, and they were included in the MS group (n=148) and the non-MS group (n=232). The incidence of MS in adult HP patients was 38.95% (148/380). Compared with the non-MS group, the levels of high-density lipoprotein cholesterol, serum total cholesterol and low-density lipoprotein cholesterol in the MS group were higher, the waist circumference was larger, and the growth hormone was lower (P<0.05). After logistic regression analysis, it was found that high-density lipoprotein cholesterol (OR=1.069, 95%CI: 1.010-1.132, P=0.021), total serum cholesterol (OR=1.065, 95%CI: 1.014-1.119, P=0.012), low-density lipoprotein cholesterol (OR=1.055, 95%CI: 1.005-1.108, P=0.031), waist circumference (OR=1.063, 95%CI: 1.006-1.123, P=0.030) and growth hormone (OR=1.077, 95%CI: 1.019-1.138, P=0.009) could independently affect the occurrence of MS in adult HP patients (P<0.05). Conclusion Adult HP patients during hospitalization are often complicated with MS. High-density lipoprotein cholesterol, serum total cholesterol, low-density lipoprotein cholesterol, waist circumference, and growth hormone are factors affecting the occurrence of MS in adult HP patients.

As a member of the Citrus genus of the Rutaceae family, Citrus changshan-huyou(CSHY) is mainly produced in Quzhou city, Zhejiang province. Modern research shows that different medicinal parts of CSHY(immature fruit, mature fruit peel, flower buds, leaves, seeds, etc.) are abundant in flavonoids, terpenes, coumarins, phenolic acids, and volatile oils. Their pharmacological activities include respiratory system protection, liver protection, anti-inflammation, anti-hyperlipidemia, anti-hyperglycemia, and antioxidation. Based on the summarization of 374 chemical components in different medicinal parts of CSHY identified in the past 20 years, this study reviewed their pharmacological actions and mechanisms and further analyzed the current status of quality control of different medicinal parts of CSHY, aiming to provide reference for the resource development and exploitation and the quality control research of different medicinal parts of CSHY.
Citrus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Plants, Medicinal/chemistry* ; Quality Control ; Animals

OBJECTIVE: To evaluate the clinical effect and safety of acupuncture manipulation on treatment of intractable facial paralysis (IFP), and verify the practicality and precision of the Anzhong Facial Paralysis Precision Scale (Eyelid Closure Grading Scale, AFPPS-ECGS). METHODS: A multicentre, single-blind, randomized controlled trial was conducted from October 2022 to June 2024. Eighty-nine IFP participants were randomly assigned to an ordinary acupuncture group (OAG, 45 cases) and a characteristic acupuncture group (CAG, 44 cases) using a random number table method. The main acupoints selected included Yangbai (GB 14), Quanliao (SI 18), Yingxiang (LI 20), Shuigou (GV 26), Dicang (ST 4), Chengjiang (CV 24), Taiyang (EX-HN 5), Jiache (ST 6), Fengchi (GB 20), and Hegu (LI 4). The OAG patients received ordinary acupuncture manipulation, while the CAG received characteristic acupuncture manipulation. Both groups received acupuncture treatment 3 times a week, with 10 times per course, lasting for 10 weeks. Facial recovery was assessed at baseline and after the 1st, 2nd and 3rd treatment course by AFPPS-ECGS and the House-Brackmann (H-B) Grading Scale. Infrared thermography technology was used to observe the temperature difference between healthy and affected sides in various facial regions. Adverse events and laboratory test abnormalities were recorded. The correlation between the scores of the two scales was analyzed using Pearson correlation coefficient. RESULTS: After the 2nd treatment course, the two groups showed statistically significant differences in AFPPS-ECGS scores (P<0.05), with even greater significance after the 3rd course (P<0.01). Similarly, H-B Grading Scale scores demonstrated significant differences between groups following the 3rd treatment course (P<0.05). Regarding temperature measurements, significant differences in temperatures of frontal and ocular areas were observed after the 2nd course (P<0.05), becoming more pronounced after the 3rd course (P<0.01). Additionally, mouth corner temperature differences reached statistical significance by the 3rd course (P<0.05). No safety-related incidents were observed during the study. Correlation analysis revealed that the AFPPS-ECGS and the H-B Grading Scale were strongly correlated (r=0.86, 0.91, 0.93, and 0.91 at baseline, and after 1st, 2nd, and 3rd treatment course, respectively, all P<0.01). CONCLUSIONS Acupuncture is an effective treatment for IFP, and the characteristic acupuncture manipulation enhances the therapeutic effect. The use of the AFPPS-ECGS can more accurately reflect the recovery status of patients with IFP. (Trial registration No. ChiCTR2200065442).
Humans ; Acupuncture Therapy/methods* ; Facial Paralysis/therapy* ; Female ; Male ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Aged

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

The rapid development of artificial intelligence (AI), especially generative AI (GenAI), has already brought, and will continue to bring, revolutionary changes to our daily production and life, as well as create new opportunities and challenges for diagnostic and therapeutic practices in the medical field. Haihe Hospital of Tianjin University collaborates with the National Supercomputer Center in Tianjin, Tianjin University, and other institutions to carry out research in areas such as smart healthcare, smart services, and smart management. We have conducted research and development of a full-process disease diagnosis and treatment assistance system based on GenAI in the field of smart healthcare. The development of this project is of great significance. The first goal is to upgrade and transform the hospital's information center, organically integrate it with existing information systems, and provide the necessary computing power storage support for intelligent services within the hospital. We have implemented the localized deployment of three models: Tianhe "Tianyuan", WiNGPT, and DeepSeek. The second is to create a digital avatar of the chief physician/chief physician's voice and image by integrating multimodal intelligent interaction technology. With generative intelligence as the core, this solution provides patients with a visual medical interaction solution. The third is to achieve deep adaptation between generative intelligence and the entire process of patient medical treatment. In this project, we have developed assistant tools such as intelligent inquiry, intelligent diagnosis and recognition, intelligent treatment plan generation, and intelligent assisted medical record generation to improve the safety, quality, and efficiency of the diagnosis and treatment process. This study introduces the content of a full-process disease diagnosis and treatment assistance system, aiming to provide references and insights for the digital transformation of the healthcare industry.
Artificial Intelligence ; Humans ; Delivery of Health Care ; Generative Artificial Intelligence

Objective To establish a chromatography-tandem mass spectrometry method for detecting chlorfenapyr and its metabolite tralopyril in blood,and to investigate the toxicokinetics in rats.Methods Chlorfenapyr(8 mg/kg)was administered orally to rats,and blood samples were collected from rats'canthus vein at 5 min,15 min,30 min,1 h,3 h,6 h,12 h,24 h and 48 h after administration.The blood samples were extracted using 100 μL of 5%formic acid solution and 400 μL of acetonitrile.Chlorfena-pyr was qualitatively and quantitatively detected by triple quadrupole gas chromatography-tandem mass spectrometry(GC-MS/MS)and tralopyril was detected by triple quadrupole liquid chromatography-tandem mass spectrometry(LC-MS/MS).The DAS 3.0 software was used to fit the toxicokinetic equa-tions and calculate the toxicokinetic parameters.Results Chlorfenapyr was detectable from 5 min to 24 h with a peak time of 1 h.Tralopyril was detectable from 15 min to 48 h with a peak time of 3 h.The toxicokinetic process of chlorfenapyr in rat blood conformed to a first-order absorption one-compartment open model,with the toxicokinetic equation described as C=e-0.265t-e-0.175t.Tralopyril con-formed to the first-order absorption three-compartment model,and the toxicokinetic equation was C=47 361.069e-2.209t-35 404.962e-1.486t+11 956.363e-0.512t.In the equations,C stands for the concentration of the target substance in the blood,e is the natural constant(≈2.718 28),and t stands for time.Conclu-sion This study optimized the detection method for chlorfenapyr and its metabolite tralopyril in blood.The toxicokinetic equations and parameters of chlorfenapyr and tralopyril can provide a reference for the estimation of oral intake time of chlorfenapyr.

This study used kidney metabolomics to investigate the underlying mechanisms of Guilingji (GLJ) on mild cognitive impairment (MCI) rats. The rats were randomly divided into 6 groups (n = 8), i.e., control group, model group, positive drug (Ginkgo biloba tablet, donepezil) group, GLJ group (low and high dose group). The MCI rat model was replicated using subcutaneous injection of D-galactose into the back of the neck along with a semi-high-fat diet for a total of 8 weeks, and drug was administered from the 5th week for 4 weeks. The kidney function and renal pathological changes of each group of rats were tested. And LC-MS based kidney metabolomics coupled with multivariate data analysis were conducted to explore the potential biomarkers, and corresponding metabolic pathways were then determined. After administration of GLJ, the level of urea nitrogen was decreased compared with those of the model group, and the abnormalities of morphology in kidney tissues were improved. The positive drugs (ginkgo biloba tablet and donepezil) had no significant modulating effect on renal function indexes. Ginkgo biloba tablet can lessen the pathological injury of kidney tissue, and donepezil had no improvement on renal histopathology. A total of 23 MCI related differential metabolites were identified in kidney, and 17 metabolites were signifcantly restored by GLJ compared with those of the model group. Additionally, we found that the cysteine and methionine metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism were significantly involved in the regulatory effect of GLJ. The results illuminate the "cong shen zhi nao" mechanism of GLJ, and also provide a research basis for the clinical use of GLJ for the treatment of MCI. The animal experiment of this study was approved by the Ethics Committee of Shanxi University (approval number: 2020DW121).

Pulmonary fibrosis， chronic obstructive pulmonary disease， acute lung injury， asthma， and infectious pneumonia are common pulmonary inflammatory diseases worldwide. There is evidence that mitochondria produce a large amount of reactive oxygen species （ROS） when stimulated by inflammation， leading to oxidative stress that affects the onset and progression of pulmonary inflammatory diseases. With in-depth research， traditional Chinese medicine （TCM） has made significant progress in the treatment of pulmonary inflammatory diseases. An increasing amount of evidence indicates that single TCM and their active components， as well as TCM compound formulas， can improve mitochondrial oxidative stress status through multi-target and multi-pathway mechanisms， thereby effectively treating pulmonary inflammatory diseases. Currently， there is a lack of systematic review and summary of TCM research in this field both domestically and internationally. Therefore， this article aims to summarize and conclude the mechanisms by which TCM regulates mitochondrial oxidative stress to intervene in pulmonary inflammatory diseases， providing a scientific basis for its clinical application and offering new ideas and references for in-depth research on the prevention and treatment of pulmonary inflammatory diseases with TCM.