Alzheimer's disease (AD) is the leading cause of dementia, and no effective treatment has been developed for it thus far. Recently, the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions. Accordingly, the potential therapeutic effect of pterostilbene (PTS) on AD has been demonstrated in multiple in vivo and in vitro experiments. In this study, we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD. Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms, including anti-oxidative damage, anti-neuroinflammation, anti-apoptosis, cholinesterase activity inhibition, attenuation of β-amyloid deposition, and tau protein hyperphosphorylation. Moreover, PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha (PPAR-α), monoamine oxidase B (MAO-B), silent information regulator sirtuin 1 (SIRT1), and phosphodiesterase 4A (PDE4A). Furthermore, to further elucidate the potential therapeutic mechanisms of PTS in AD, we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins, and the obtained binding energies ranged from -2.83 to -5.14 kJ/mol, indicating that these proteins exhibit good binding ability with PTS. Network pharmacology analysis revealed multiple potential mechanisms of action for PTS in AD. In summary, by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD, it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD, either using PTS or other developed drug interventions.

Objective: To evaluate the safety and efficacy of therapeutic whole blood exchange combined with lymphoplasmapheresis in the treatment of refractory autoimmune hemolytic anemia (AIHA). Methods: A retrospective analysis was performed on the clinical data of AIHA patients who underwent therapeutic whole blood exchange combined with lymphoplasmapheresis at our hospital from March 2022 to May 2025. Efficacy was assessed by comparing changes in hemoglobin, platelet count, and bilirubin levels before and after treatment. Safety was evaluated by analyzing vital signs before and after the procedure, parameters during the exchange, and adverse reactions. Results: A total of 12 AIHA patients were enrolled, completing 19 exchange procedures. The number of procedures per patient ranged from 1 to 3. The median treatment duration was 67 (65-73) minutes, with a median exchange volume of 2 025 (1 851-2 121) mL, comprising 4.5 (4-6) units of red blood cells and 1 350 (1 200-1 400) mL of plasma. Ten patients achieved partial remission, one achieved complete remission, and one showed no response, yielding an response rate of 91% (11/12). After a single session, hemoglobin increased significantly by 17.58±9.85 g/L (P<0.01), while platelets counts decreased by 45 (17.5, 79)×10 /L (P<0.05), and both systolic and diastolic blood pressure showed a significant elevation (P<0.05). However, no statistically significant differences were observed in total bilirubin, indirect bilirubin, white blood cell count, or heart rate. During the procedures, 4 adverse reactions occurred in 3 patients: one child experienced severe heart rate fluctuation twice consecutively, and two adults developed plasma allergies. All reactions resolved spontaneously without pharmacological intervention. Conclusion: The combination of therapeutic whole blood exchange and lymphoplasmapheresis appears to be a safe and effective treatment for refractory AIHA patients.

Objective: To investigate the factors affecting pre-exposure prophylaxis (PrEP) use among men who have sex with men (MSM), so as to provide a basis for improving PrEP uptake among MSM and optimizing HIV prevention and control strategies. Methods: The MSM were recruited at a HIV testing site of the "Danlan Public Welfare" organization in Beijing Municipality using the convenient sampling method from March to May 2024. Sociodemographic information, awareness of basic AIDS knowledge, sexual orientation and behaviors, the use of PrEP and post-exposure prophylaxis (PEP) in the past six months were collected using the questionnaire survey. Multivariable logistic regression model and decision tree model were used to analyze the influencing factors for PrEP use among MSM. Results: A total of 414 participants were surveyed, with a mean age of (33.52±8.50) years. Among them, 345 individuals (83.33%) had a college degree and above. The predominant sexual orientation was homosexual, with 265 individuals, accounting for 64.01%. The majority reported having 1 to 2 same-sex partners in the past six months, with 182 individuals (43.96%). A total of 39 individuals (9.42%) had used PEP in the past six months. A total of 68 individuals (16.43%) had used PrEP during the same period. Multivariable logistic regression analysis revealed that educational attainment (college degree and above, OR=28.200, 95%CI: 3.162-251.519), the number of same-sex partners in the past six months (3-5 partners, OR=3.963, 95%CI: 1.065-14.755; ≥6 partners, OR=7.518, 95%CI: 1.829-30.910), and the use of PEP in the past six months (OR=18.606, 95%CI: 7.587-45.631) were significant factors associated with PrEP use among MSM. The decision tree model identified educational level, sexual orientation, and the number of same-sex partners in the past six months as factors affecting PrEP use among MSM. Among these, the number of same-sex partners in the past six months emerged as the primary influencing factor. The use of PrEP was 38.46% among MSM who had ≥3 same-sex partners in the past six months and identified as homosexual or heterosexual. Conclusion The use of PrEP among MSM is primarily associated with educational level, the number of same-sex partners in the past six months, use of post-exposure prophylaxis (PEP) in the past six months, and sexual orientation.

Objective:To explore the clinical application value of serum N-glycan profiles for evaluating the severity of liver tissue inflammation in patients with chronic hepatitis B (CHB).Methods:A total of 221 CHB patients who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to December 2020 were retrospectively enrolled. The Scheuer scoring system was used to assess the histological inflammation grade of the liver tissue. Serum N-glycan levels were measured using DNA sequencer-assisted N-glycan fingerprinting (NGFP). Using the upper limit of the alanine aminotransferase (ALT) reference value (40 U/L) as a cutoff, logistic regression models were developed to construct diagnostic models under two scenarios: normal ALT or abnormal ALT. Models based on serum N-glycan levels and serum N-glycan levels combined with routine laboratory indicators, were used to non-invasively evaluation of various pathological grades of liver tissue inflammation in CHB patients. The DeLong test was used to compare the diagnostic efficacy of the models by analyzing the areas under the receiver operating characteristic curve (AUC). Glycosylation-related gene expression differences associated with varying degrees of liver inflammation were analyzed using the Gene Expression Omnibus (GEO) database.Results:In CHB patients with normal ALT level, the relative abundances of N-glycan structure peak 1 (NGA2F) and peak 2 (NGA2FB) increased with higher liver inflammation grades, while the relative abundance of peak 5 (NA2) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G A) and its enhanced version (HIS-G A Plus) for identifying significant inflammation and necrosis (≥G2, indicating the initiation of antiviral therapy) were 0.805 (95% CI 0.690-0.899) and 0.904 (95% CI 0.821-0.960), respectively. In CHB patients with ALT>40 U/L, the relative abundances of peaks 1 (NGA2F), 2 (NGA2FB), and 3 (NG1A2F) increased with higher liver inflammation grades, while the relative abundances of peaks 8 (NA3) and 11 (NA4) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G B) and its enhanced version (HIS-G B Plus) for identifying significant inflammation (≥G2) were 0.810 (95% CI 0.727-0.889) and 0.838 (95% CI 0.754-0.901), respectively. With increasing liver inflammation grades, the expression levels of four glycosyltransferase genes (CHST4, FUT8, SLC51B, and ST8SIA4) were significantly upregulated ( P<0.05). Conclusions:Serum N-glycan biomarker models can be used to assist in evaluating the severity of liver tissue inflammation in CHB patients with both normal and abnormal ALT levels.

Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.

Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been devel-oped for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation of β-amyloid deposi-tion,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxi-dase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kj/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple po-tential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.

BACKGROUND:Traditional Chinese medicine has unique advantages in preventing and treating spleen-deficiency and hyperlipidemia.In basic studies,models of spleen-deficiency and hyperlipidemia are commonly found in rats,pigs,and other animals.This has limitations for medical research that can only use mouse models.It is urgent to establish and evaluate mouse models of spleen-deficiency and hyperlipidemia to support basic research on traditional Chinese medicine in preventing and treating spleen-deficiency and hyperlipidemia.OBJECTIVE:To establish a mouse model of spleen-deficiency hyperlipidemia.METHODS:Totally 24 C57BL/6J mice were randomly divided into normal group(n=12)and spleen-deficiency hyperlipemia group(n=12).Mice in normal group were fed basic diet.Mice in the spleen-deficiency hyperlipemia group were prepared with a diet disorder+fatigue internal injury+high-fat feeding method to establish a spleen-deficiency high-fat model.In the first 2 weeks,the mice were forced to swim to their endurance limit on a single day and were only fed cabbage,with free access to water.They were also gavaged with refined lard+high-fat feed on two-day intervals.After 2 weeks,the mice were fed a high-fat diet every day and the diet continued until 12 weeks.The mice were fed with a high-fat diet for 4 and 12 weeks,and their body weight,food intake,gripping strength,fecal water content,small intestinal charcoal propulsion rate,serum D-xylose and gastrin levels,spleen index and thymus index,blood lipid level,total body fat mass,body fat percentage,and liver lipid deposition were tested.RESULTS AND CONCLUSION:(1)Compared with the normal group,the body weight,fecal water content,total body fat mass,body fat percentage,triglyceride and total cholesterol levels of the mice in the spleen-deficiency hyperlipemia group fed with high-fat diet for 4 and 12 weeks were increased(P＜0.05);the daily food intake,gripping force,and D-xylose level of the mice fed with high-fat diet for 4 and 12 weeks were decreased(P＜0.05);the spleen index of the mice fed with high-fat diet for 4 weeks was increased(P＜0.05);the small intestinal carbon propulsion rate,gastrin level,spleen index,and thymus index of the mice fed with high-fat diet for 12 weeks were decreased(P＜0.05);the low-density lipoprotein cholesterol level of the mice fed with high-fat diet for 12 weeks was increased(P＜0.05).(2)The results of liver oil red O staining showed that the lipid deposition in the spleen-deficiency hyperlipemia group after 4 weeks of high-fat diet feeding was slightly more than that in the normal group,and the lipid deposition in the high-fat diet feeding for 12 weeks was significantly more than that in the normal group.(3)The results show that a stable spleen deficiency and hyperlipidemia mouse model can be prepared by the compound method of eating disorders,exhaustion,and high-fat feeding.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

ObjectiveTo explore the mechanism of Huoxue Rongluo prescription （HXRLP） in repairing the blood-brain barrier （BBB） after ischemic stroke （IS）. MethodsMale C57BL/6 mice were randomly divided into sham operation （Sham） group， cerebral infarction model （MCAO） group， environmental circadian disruption with cerebral infarction model （ECD-MCAO） group， low-， medium-， and high-dose HXRLP （HXRLP-L， M， and H） groups （8.5， 17， 34 g·kg^-1·d^-1， respectively）， and positive drug butylphthalide （NBP） group （0.23 mL·d^-1）. In the Sham group， only the exposed blood vessels were isolated without suture insertion. In the other groups， the middle cerebral artery occlusion （MCAO） model of mice was prepared. In the ECD-MCAO group， HXRLP groups， and NBP group， the environmental circadian disruption （ECD） model was prepared. The mice in the Sham group， MCAO group， and ECD-MCAO group were given the same volume of soybean oil by gavage， while those in the other groups were given the corresponding drugs by gavage. Samples were collected after 7 consecutive days of administration. The mNSS score was used to evaluate the repair effect of HXRLP on neurological deficits after IS. Hematoxylin-eosin （HE） staining was used to assess the impact of HXRLP on the pathological damage of brain tissue after IS. 2，3，5-Triphenyltetrazolium chloride （TTC） staining and cerebral blood perfusion status were used to evaluate the repair effect of HXRLP on brain tissue damage after IS. Evans blue staining and transmission electron microscopy were used to evaluate the improvement effect of HXRLP on the permeability injury of BBB after IS. Immunofluorescence （IF） staining was used to observe the expression of von Willebrand Factor （vWF）， brain and muscle Arnt-like 1 （Bmal1）， and Occludin in brain tissue. Western blot was used to detect the protein expression of Bmal1， Occludin， tight junction protein （Claudin-5）， vascular endothelial growth factor （VEGF）， and angiopoietins（Ang）， and related analysis was conducted. ResultsCompared with the Sham group， the MCAO group exhibited significantly aggravated neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01） and significantly reduced cerebral blood perfusion （P0.01）. The expression of Bmal1， vWF， vascular endothelial growth factor A （VEGFA）， and Ang in brain tissue was significantly enhanced （P0.01）， while the expression of Occludin and Claudin-5 was significantly weakened （P0.01）. Compared with the MCAO group， the ECD-MCAO group showed significantly aggravated neurological deficits， cerebral infarction volume， and BBB leakage （P0.01）， obviously worsened brain pathological damage （P0.05）， significantly reduced cerebral blood perfusion （P0.01）， and significantly decreased expression of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. Compared with the ECD-MCAO group， the HXRLP groups of all doses presented significantly improved neurological deficits， cerebral infarction volume， brain pathological damage， and BBB leakage （P0.01）， significantly increased cerebral blood perfusion （P0.01）， and enhanced expression levels of Bmal1， vWF， VEGFA， Ang， Occludin， and Claudin-5 in brain tissue （P0.01）. ConclusionHXRLP can regulate the clock protein Bmal1 and promote the expression of VEGFA， Ang， Occludin， and Claudin-5， thereby improving BBB damage after IS.