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 investigate the therapeutic effects and mechanisms of Xuefu Zhuyu Mixture(XFZY)in rats with coronary heart disease(CHD).Methods A CHD rat model was established.Successfully modeled rats were randomly divided into five groups(n=12 each):model group,Lipitor group,low-dose XFZY group(7.02 g·kg-1·d-1),high-dose XFZY group(14.04 g·kg-1·d-1),and high-dose XFZY+RS09[Toll-like receptor 4(TLR4)agonist]group(14.04 g·kg-1·d-1 XFZY+intraperitoneal RS09),with an additional normal control group(n=12).After treatment,following treatment completion,all rats underwent echocardiography to assess left ventricular end-diastolic diameter(LVDd),end-systolic diameter(LVDs),ejection fraction(LVEF),and fractional shortening(FS).Myocardial histopathology and vascular remodeling indices were evaluated via hematoxylin-eosin(HE)staining,while myocardial fibrosis was examined using Masson's trichrome staining.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify inflammatory cytokine levels[tumor necrosis factorα(TNF-α),interleukin(IL)-1β,and IL-6]in myocardial tissues.Immunohistochemical analysis determined protein expression of B-cell lymphoma-2(Bc12)and Caspase 3 in myocardial tissues.Western Blot was performed to measure myocardial protein expression levels of TLR4,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-AKT),total AKT,phosphorylated mammalian target of rapamycin(p-mTOR),and total mTOR.Results Compared with the normal group,rats in the model group exhibited severe myocardial tissue damage,along with significantly elevated collagen volume fraction,LVDs,LVDd,myocardial levels of IL-6,TNF-α and IL-1β,cardiomyocyte apoptosis ratio,aortic media thickness,and protein expression of Caspase 3,TLR4,PI3K,p-AKT/AKT and p-mTOR/mTOR in myocardial tissue(P＜0.05).Conversely,LVEF,FS,aortic luminal diameter,and Bcl-2 protein content were significantly reduced,the difference being statistically significant(P＜0.05).Compared to the model group,both low-and high-dose XFZY groups as well as the Lipitor group demonstrated attenuated myocardial lesions,with significant reductions in collagen volume fraction,LVDs,LVDd,myocardial IL-6,TNF-α,IL-1β levels,cardiomyocyte apoptosis ratio,aortic media thickness,and protein expression of Caspase 3,TLR4,PI3K,p-AKT/AKT and p-mTOR/mTOR(P＜0.05).Concurrently,LVEF,FS,aortic luminal diameter,and Bcl-2 protein content were significantly increased,the difference being statistically significant(P＜0.05).No statistically significant differences were observed between the high-dose XFZY group and the Lipitor group for any aforementioned parameters(P＞0.05).However,rats treated with high-dose XFZY plus RS09 showed aggravated myocardial injury with manifested interstitial fibrosis,alongside significantly intensified inflammatory response,cardiomyocyte apoptosis,and vascular remodeling compared to the high-dose XFZY alone group(all P＜0.05).Conclusion XFZY alleviates CHD symptoms by suppressing TLR4/PI3K/AKT/mTOR pathway activation,thereby reducing myocardial inflammation,fibrosis,apoptosis,and vascular remodeling.

Objective To investigate the effects of acupoint application at Tianshu(ST25)combined with kidney-warming and spleen-invigorating therapy on clinical efficacy,intestinal function,and the expressions of Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in patients with ulcerative colitis(UC).Methods A total of 100 UC patients with depletion and deficiency of spleen-kidney complicated with internal accumulation of pathogenic dampness syndrome,treated in the Department of Proctology,Shanghai Municipal Hospital of Traditional Chinese Medicine Affilated to Shanghai University of Traditional Chinese Medicine from June 2022 to June 2024,were selected and randomly divided into four groups(Groups A,B,C,D)using a random number table method,with 25 patients in each group.Group A received standard mesalazine treatment.Group B received Kidney-Warming and Spleen-Invigorating Formula(composed of Psoraleae Fructus,Myristicae Semen,Euodiae Fructus,Schisandrae Chinensis Fructus,Codonopsis Radix,Poria,Atractylodis Macrocephalae Rhizoma,etc.)combined with standard mesalazine treatment.Group C received acupoint application at Tianshu(the medicinal paste for application composed of Caryophylli Flos,Cinnamomi Cortex,Atractylodis Macrocephalae Rhizoma,Euodiae Fructus,Coptidis Rhizoma,etc.)combined with standard mesalazine treatment.Group D received Kidney-Warming and Spleen-Invigorating Formula+acupoint application at Tianshu+standard mesalazine treatment.All groups were treated continuously for 12 weeks.The time for disappearance of clinical symptoms was compared among the four groups.Serum immune cytokines[β-defensin-1,total immunoglobulin A(IgA),interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α)],peripheral blood levels of TLR4 and NF-κB,protein expression levels of TLR4 mRNA and NF-κB p65 mRNA in intestinal mucosal tissue,and changes in intestinal microbiota were observed before and after treatment.The clinical efficacy of the four groups was evaluated.Results(1)Compared to the other three groups,Group D had the shortest time for disappearance of clinical symptoms such as abdominal pain,diarrhea,mucopurulent bloody stools,and tenesmus(P＜0.05).The time for disappearance of various clinical symptoms in Groups B and C was similar(P＞0.05)but was shorter than that in Group A(P＜0.05).(2)After treatment,the serum levels of β-defensin-1,IgA,IL-6,and TNF-α in all four groups were significantly lower than those before treatment(P＜0.05).Post-treatment intergroup comparisons showed statistically significant differences(P＜0.01),with Group D exhibiting the greatest reduction,significantly lower than the other three groups(P＜0.05).The levels in Groups B and C were similar(P＞0.05)but were lower than those in Group A(P＜0.05).(3)After treatment,the peripheral blood levels of TLR4 and NF-κB,and the protein expression levels of TLR4 mRNA and NF-κB p65 mRNA in intestinal mucosal tissue showed a decreasing trend in all four groups(P＜0.05).Post-treatment intergroup comparison results were statistically significant(P＜0.01),with Group D showing the greatest reduction,significantly lower than the other three groups(P＜0.05).All above levels in Groups B and C were similar(P＞0.05)but were lower than those in Group A(P＜0.05).(4)After treatment,the relative contents of Bifidobacterium and Lactobacillus increased(P＜0.05),while those of Saccharomyces and Clostridium decreased(P＜0.05)in Groups B,C,and D.Post-treatment intergroup comparison results were statistically significant(P＜0.01).Group D showed a significant increase in Bifidobacterium and Lactobacillus and a significant decrease in Saccharomyces and Clostridium,with the magnitude of change significantly greater than that in the other three groups(P＜0.05).The quantities of these bacteria in Groups B and C were similar(P＞0.05),but the improvement was significantly greater than that in Group A(P＜0.05).(5)After 12 weeks of treatment,Group D had the highest total effective rate at 100.00％(25/25).The total effective rates of Groups B and C were similar,both at 84.00％(21/25),but were higher than that of Group A(56.00％,14/25).The intergroup difference was statistically significant(x2=16.310,P＜0.01).Conclusion The comprehensive treatment regimen of acupoint application at Tianshu combined with Kidney-Warming and Spleen-Invigorating Formula,on the basis of standard mesalazine treatment,has a positive impact on UC patients with depletion and deficiency of spleen-kidney complicated with internal accumulation of pathogenic dampness syndrome.This treatment method can effectively improve clinical symptoms,regulate β-defensin-1 and IgA levels,enhance immune defense function,downregulate the expression levels of TLR4 and NF-κB,and alleviate inflammatory response.Compared to monotherapies,it is more effective on improving treatment outcomes.

OBJECTIVE: To investigate the effectiveness of using 3 hollow compression screws combined with 1 screw off-axis fixation under the guidance of three-dimensional (3D) printed guide plate with mortise-tenon joint structure (mortise-tenon joint plate) for the treatment of Pauwels type Ⅲ femoral neck fractures. METHODS: A clinical data of 78 patients with Pauwels type Ⅲ femoral neck fractures, who were admitted between August 2022 and August 2023 and met the selection criteria, was retrospectively analyzed. The operations were assisted with mortise-tenon joint plates in 26 cases (mortise-tenon joint plate group) and traditional guide plates in 28 cases (traditional plate group), and without guide plates in 24 cases (control group). There was no significant difference in the baseline data of gender, age, body mass index, cause of injury, and fracture side between groups ( P>0.05). The operation time, intraoperative blood loss, frequency of intraoperative fluoroscopy, incision length, incidence of postoperative deep vein thrombosis of lower extremity, pain visual analogue scale (VAS) score at 1 week after operation, and Harris score of hip joint at 3 months after operation were recorded and compared. X-ray re-examination was taken to check the quality of fracture reduction, fracture healing, and the shortening length of the femoral neck at 3 months after operation, and the incidences of internal fixation failure and osteonecrosis of the femoral head during operation. RESULTS: Compared with the control group, the operation time, intraoperative blood loss, and frequency of intraoperative fluoroscopy reduced in the two plate groups, and the quality of fracture reduction was better, but the incision was longer, and the differences were significant ( P<0.05). The operation time and intraoperative blood loss were significantly higher in the traditional plate group than in the mortise-tenon joint plate group ( P<0.05), the incision was significantly longer ( P<0.05); and the difference in fracture reduction quality and the frequency of intraoperative fluoroscopy was not significant between two plate groups ( P>0.05). There was 1 case of deep vein thrombosis of lower extremity in the traditional plate group and 1 case in the control group, while there was no thrombosis in the mortise-tenon joint plate group. There was no significant difference in the incidence between groups ( P>0.05). All patients were followed up 12-15 months (mean, 13 months). There was no significant difference in VAS score at 1 week and Harris score at 3 months between groups ( P>0.05). Compared with the control group, the fracture healing time and the length of femoral neck shortening at 3 months after operation were significantly shorter in the two plate groups ( P<0.05). There was no significant difference between the two plate groups ( P>0.05). There was no significant difference in the incidences of non-union fractures, osteonecrosis of the femoral head, or internal fixation failure between groups ( P>0.05). CONCLUSION For Pauwels type Ⅲ femoral neck fractures, the use of 3D printed guide plate assisted reduction and fixation can shorten the fracture healing time, reduce the incidence of postoperative complications, and be more conducive to the early functional exercise of the affected limb. Compared with the traditional guide plate, the mortise-tenon joint plate can reduce the intraoperative bleeding and shorten the operation time.
Humans ; Femoral Neck Fractures/diagnostic imaging* ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Bone Screws ; Adult ; Aged ; Treatment Outcome ; Printing, Three-Dimensional ; Operative Time

B and T lymphocyte attenuator (BTLA) is an inhibitory immune checkpoint, which typically interacts with herpesvirus entry mediator (HVEM) and plays a crucial role in regulating immune balance. BTLA interacts with its ligand HVEM in a cis manner on the surface of the same immune cell to maintain immune tolerance, while trans interactions on the surface of different immune cells mediate immunosuppressive effects. Dysregulation of the BTLA/HVEM axis can impair the functions of immune cells, particularly T lymphocytes, promoting immune escape of tumor cells and ultimately leading to tumor progression. Researchers have found that BTLA and HVEM are abnormally expressed in various tumors and are associated with prognosis, suggesting that they may be potential targets for tumor immunotherapy. This review summarizes the molecular structures of BTLA and HVEM, immunomodulatory mechanisms, recent advances in hematologic malignancies, potential inhibitors of BTLA/HVEM interaction, and their applications in immunotherapy for hematologic malignancies.
Humans ; Receptors, Tumor Necrosis Factor, Member 14/chemistry* ; Receptors, Immunologic/immunology* ; Hematologic Neoplasms/genetics* ; Immunotherapy/methods* ; Animals

LC-MS/MS methods for the quantitative determination of mecobalamin and ceftriaxone in rat plasma were established, and utilized to assess the pharmacokinetic behaviors of the two drugs in rats and to determine whether there were pharmacokinetics-based drug-drug interactions between them. Methanol was used as a protein precipitant to process rat plasma samples. For mecobalamin, acetonitrile containing 0.1% formic acid was used as the organic phase, while an aqueous solution of 0.1% formic acid and 2 mmol/L ammonium acetate served as the aqueous phase. For ceftriaxone, the organic phase was acetonitrile with 0.1% formic acid, and the aqueous phase was a 1% formic acid aqueous solution. LC-MS/MS quantitative analysis methods for both drugs were developed under the positive ion mode, followed by comprehensive methodological validation. Single-dose administration (either alone or in combination) was carried out via caudal vein injection. The dosing regimens were 0.03, 0.1, and 0.3 mg/kg for mecobalamin and 90 mg/kg for ceftriaxone. The results of methodological validation indicated that mecobalamin exhibited good linearity in the range of 3−3000 ng/mL (r = 0.9991), and ceftriaxone showed excellent linearity in the range of 0.5~500 μg/mL (r = 1). The selectivity, precision, accuracy, extraction recovery, matrix effect, and stability of the analytical methods for both substances met the relevant requirements. The pharmacokinetic study revealed that, compared with single-drug administration, the average plasma concentration-time profiles of the two drugs almost overlapped during single-dose combined administration. Statistical analysis, specifically one-way analysis of variance, demonstrated no significant differences in major pharmacokinetic parameters (t1/2, AUC0−∞, etc.) (P > 0.05). This study confirmed that no pharmacokinetic-based drug-drug interactions occurred when mecobalamin and ceftriaxone were co-administered in rats. The findings of this research offer a reliable pharmacokinetic foundation for the rational clinical co-use of these two drugs, thus providing valuable insights into optimizing therapeutic strategies.

Objective:To discuss the role of changes of serum total bile acid(TBA)levels induced by long-term high-fat diet in the occurrence of supraventricular arrhythmia(SVA)in the apolipoprotein E knockout(ApoE-/-)mice,and to clarify its mechanism.Methods:Twenty ApoE-/-mice were randomly divided into normal diet group and high-fat diet(HFD)group(n=10);after 20 weeks of feeding,surface electrocardiogram was used to detect cardiac electrophysiology of the mice in various groups;echocardiography was used to detect cardiac systolic function and structure in the mice in various groups;enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of blood lipids,total bile acid(TBA)and inflammatory factors in the mice in various groups;hematoxylin-eosin(HE)staining was used to detect cardiac inflammatory response in the mice in various groups;Masson staining was used to observe myocardial fibrosis degree in the mice in various groups.Results:Compared with normal diet group,4 cases of junctional premature beat(JPB)/junctional tachycardia(JT),1 case of premature atrial contraction(PAC)and 1 case of premature ventricular contraction(PVC)were found in HFD group,while only 1 case of JPB/JT and 1 case of PAC were found in normal diet group.Compared with normal diet group,the heart rate of the mice in HFD group was significantly decreased(P<0.05);the QRS and QT intervals were significantly prolonged(P<0.05);the ejection fraction(EF)and fractional shortening(FS)were significantly decreased(P<0.05);the end-diastolic volume(EDV)was increased(P<0.05),but there was no significant difference in end-systolic volume(ESV)between groups(P>0.05);the left ventricular internal diameter at end-diastole(LVIDd)and left ventricular internal diameter at end-systole(LVIDs)were significantly increased(P<0.05).There were no significant differences in plasma total cholesterol(TC),triglyceride(TG),high-density lipoprotein(HDL-c)and low-density lipoprotein(LDL-c)levels and body weight between normal diet group and HFD group(P>0.05).Compared with normal diet group,the TBA level of the mice in HFD group was significantly increased(P<0.05).There were no significant differences in interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and C-X-C motif chemokine ligand 1(CXCL-1)levels between HFD group and normal diet group.Compared with normal diet group,the interleukin-1β(IL-1β)level in HFD group showed an increasing trend,but there was no significant difference between groups(P>0.05).The HE staining results showed that the inflammatory cell infiltration was similar between HFD group and normal diet group.The Masson staining results showed that compared with normal diet group,the fibrosis of the mice in HFD group showed an increasing trend,but there was no significant difference in myocardial fibrosis area between groups(P>0.05).Conclusion:Long-term high-fat diet may increase serum TBA level in ApoE-/-mice,which may induce SVA.

Objective:To investigate the risk factors for aggravation of type 2 diabetic foot ulcer and the correlation between the level of infection and the severity of the disease,as well as the association of the detection rate of bacteria and the types of bacteria with disease severity in patients with type 2 diabetic foot ulcer,and to provide individualized guidance for the prevention,diagnosis,and treatment of type 2 diabetic foot.Methods:A retrospective analysis was performed for the data of 150 patients with type 2 diabetic foot who were treated in Department of Endocrinology,The First Affiliated Hospital of Kunming Medical University,from October 2021 to June 2023,and according to the Wagner grade of diabetic foot,these patients were divided into mild group A(35 patients with Wagner grade 2),moderate group B(58 patients with Wagner grade 3),and severe group C(57 patients with Wagner grade 4).The clinical data of the three groups were analyzed.Results:The severity of type 2 diabetic foot ulcer was correlated with white blood cell count,neutrophil count,platelet count,monocyte count,globulin,alkaline phosphatase,neutrophil-lymphocyte ratio,monocyte-lymphocyte ratio,platelet-lymphocyte ratio,high-sensitivity C-reactive protein,procalcitonin,interleukin-6,erythrocyte sedimentation rate,hemoglo-bin,albumin/globulin ratio,lymphocyte count,cholinesterase,albumin,fasting blood glucose,gamma-glutamyl transferase,glycated he-moglobin,blood uric acid,high-density lipoprotein cholesterol,total cholesterol,triglycerides,and low-density lipoprotein cholesterol(P<0.05).The multivariate ordinal logistic regression analysis showed that the neutrophil-lymphocyte ratio and erythrocyte sedi-mentation rate were independent risk factors for the progression of Wagner grade of diabetic foot(P<0.05).For groups A,B,and C,the detection rate of bacteria in foot ulcer secretion tended to increase with the severity of diabetic foot,with the highest detection rate in group C,followed by groups B and A.A total of 31 types of bacteria were detected in the three groups,and the proportion of Gram-positive bacteria was higher than that of Gram-negative bacteria,with Staphylococcus aureus accounting for the highest proportion of 27.72%in all samples.Conclusion:High-sensitivity C-reactive pro-tein,procalcitonin,interleukin-6,and erythrocyte sedimentation rate increase with the progression of the Wagner grade of diabetic foot,and neutrophil-lymphocyte ratio and erythrocyte sedimentation rate are independent risk factors for the progression of the Wagner grade of diabetic foot.The detection rate of bacteria in foot ulcer secretion tends to increase with the Wagner grade of diabetic foot,and Gram-positive bacteria account for a higher proportion than Gram-negative bacteria,with Staphylococcus aureus accounting for the highest proportion.

Objective To explore the mediating role of mobile phone dependency and self-rated health in the relationship between adverse childhood experiences(ACEs)and mental health among young adults.Methods A cross-sectional study was conducted using cluster random sampling among 1 611 young adults(mean age 26.30 years)from a region in Hainan Province.Participants completed the childhood trauma questionnaire(short form),the mobile phone addiction index,the depression-anxiety-stress scale(simplified Chinese version),and a self-rated health questionnaire.Pearson correlation analysis and mediation effect analysis were employed to examine the relationships among ACEs,mobile phone dependency,self-rated health,and mental health.Results ACEs,mobile phone dependency,and self-rated health were all significantly correlated with mental health(all P＜0.01).ACEs had a direct negative effect on mental health(direct effect=0.221,95%confidence interval[CI]0.150-0.293).Furthermore,ACEs exerted indirect effects on mental health through 3 pathways:the independent mediation of mobile phone dependency(indirect effect=0.081,95%CI 0.035-0.130),the independent mediation of self-rated health(indirect effect=0.034,95%CI 0.011-0.062),and the chain mediation of mobile phone dependency and self-rated health(indirect effect=0.009,95%CI 0.004-0.015).Conclusion ACEs have a significant impact on the mental health of young adults,with mobile phone dependency and self-rated health serving as key mediators.Interventions aimed at reducing mobile phone dependency and improving health status may help mitigate the negative impact of childhood trauma on mental health,thereby promoting psychological well-being in this population.