Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

This review summarizes recent advances in neoadjuvant immunotherapy for advanced gastric cancer.Through literature search in PubMed,Web of Science,and CNKI databases from 2020 to 2023,we systematically analyzed the mechanisms,clinical applications,and bio-marker research.Programmed death-1(PD-1)inhibitors combined with chemotherapy significantly improve patient outcomes,while mi-crosatellite instability(MSI),programmed death-ligand 1(PD-L1)expression,and tumor mutational burden(TMB)have been identified as important predictive biomarkers.Multi-omics analysis shows great potential in identifying optimal responders,with pyroptosis-related gene scoring system(PRS)positively correlating with anti-tumor immune infiltration.Metabolic reprogramming and epigenetic regulation in the tumor microenvironment play key roles in immune evasion,while emerging targets such as Claudin 18.2 and combination targeting strategies further enhance therapeutic efficacy.Despite significant progress,precise patient selection and overcoming resistance mechan-isms remain major challenges.Future research should focus on biomarker validation,personalized treatment strategy development,tumor microenvironment dynamic analysis,and novel combination therapy exploration to improve clinical outcomes.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

Objective:To compare and analyze the differences in the measurement of intra-abdominal pressure in different positions of critically ill patients treated with extracorporeal membrane oxygenation (ECMO) combined with prone position integration, with a view to finding a more optimal intra-abdominal pressure monitoring strategy, which can provide a theoretical basis for clinical diagnosis and treatment.Methods:Forty critically ill patients who underwent ECMO combined with prone position integrated treatment in the department of Intensive Care Medicine of the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2023 were selected by convenience sampling method using an own-control trial. The differences in intra-abdominal pressure between supine position with head elevated at 0°, 15°and 30°and prone position with head high and foot low slopes at 0°, 15°and 30°were compared and analyzed. Heart rate, respiration, mean arterial pressure and oxygen saturation were also compared in patients in different positions.Results:There were 29 males and 11 females in 40 patients with the age of (62.58 ± 17.99) years.The intra-abdominal pressure in supine position with head elevated at 30° was (12.45 ± 3.43) mmHg(1 mmHg=0.133 kPa), which was higher than that of 0° and 15° of (9.38 ± 2.52) and (10.70 ± 2.95) mmHg, and the differences were statistically significant ( t=4.56, 2.45, both P<0.05);the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05); the intra-abdominal pressure in prone position with head-high-foot-low slope of 30° was (12.92 ± 4.19) mmHg, which was higher than that of 0°and 15°of (9.67 ± 2.80), and (11.01 ± 3.10) mmHg, and the differences were statistically significant ( t=4.08, 2.32, both P<0.05); the difference in intra-abdominal pressure between 0° and 15° was not statistically significant ( P>0.05).The differences in intra-abdominal pressure between groups of supine bed head elevation 0°, 15°, 30°and prone position with head high and foot low slopes 0°, 15°, 30°were not statistically significant (all P>0.05). The differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the supine position with head elevated at 0°, 15°and 30° were not statistically significant when compared within groups (all P>0.05); the differences in heart rate, respiration, mean arterial pressure and oxygen saturation in the prone position with head elevated with feet and feet on low slopes at 0°, 15°and 30°were not statistically significant when compared within groups (all P>0.05); and the differences in supine position with head elevated at 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of heart rate, respiration, mean arterial pressure were not statistically significant (all P>0.05); supine bed head elevation 0°, 15°, 30°and prone head-height-foot-low slope 0°, 15°, 30°of oxygen saturation between the groups, the differences were statistically significant ( Z=6.85, 6.82, 6.68, all P<0.05). Conclusions:Intra-abdominal pressure can be measured in the 15° prone position in critically ill patients treated with ECMO combined with prone position integration; the different positions have little effect on vital signs, but the prone position significantly improves oxygen saturation.

Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.

BACKGROUND:Trunk pressure biofeedback is considered a reliable indicator for assessing core muscle strength.It not only reflects the status of an individual's trunk strength but also has a close relationship with the function of respiratory muscles. OBJECTIVE:To explore the correlation between trunk pressure biofeedback and diaphragmatic function in young adults. METHODS:A total of 80 young adults from Shangrao Normal University,China were enrolled,including 34 males and 46 females,with an average age of(19.83±1.45)years.Diaphragmatic thickness and mobility were measured using a bedside musculoskeletal ultrasound system.Maximum inspiratory pressure was determined using a portable pulmonary function tester.Lumbar and abdominal pressures in prone and supine positions were assessed using a pressure biofeedback device.The degree of correlation between trunk pressure biofeedback and diaphragmatic function was determined using Pearson or Spearman correlation coefficients.A multivariate linear regression analysis was used to determine predictive models for diaphragmatic function. RESULTS AND CONCLUSION:Grouped by sex,age,height,body mass,trunk pressure biofeedback values,diaphragm thickness during quiet inspiration and expiration,diaphragmatic thickening ratio during quiet breathing,diaphragmatic thickness during deep inspiration and expiration,diaphragmatic thickening ratio during deep breathing,diaphragmatic mobility during deep inspiration,and maximum inspiratory pressure were higher in the male group than the female group(all P<0.05).Grouped by physical activity level,trunk pressure biofeedback values and maximum inspiratory pressure were lower in the sedentary group than in the exercise group(both P<0.05).Both anterior and posterior trunk pressure biofeedback were significantly correlated with diaphragmatic thickness during quiet inspiration and expiration,diaphragmatic thickening ratio during quiet breathing,diaphragmatic thickness during deep inspiration and expiration,diaphragmatic thickening ratio during deep breathing,diaphragmatic mobility during deep inspiration,and maximum inspiratory pressure(all P<0.01).Anterior trunk pressure biofeedback entered the predictive model for diaphragmatic thickness during quiet inspiration(F=27.228,P<0.001),during deep inspiration(F=38.615,P<0.001),and along with age for diaphragmatic mobility during deep inspiration(F=15.408,P<0.001).Anterior trunk pressure biofeedback,body mass,and age entered the predictive model for maximum inspiratory pressure(F=22.314,P<0.001).To conclude,there is a strong correlation between trunk pressure biofeedback and diaphragmatic thickness,diaphragmatic mobility,and maximum inspiratory pressure.The rapid and simple measurement of trunk pressure biofeedback can serve as a method for screening the diaphragmatic function in healthy young adults.

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD). Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria. Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR). Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Objective To explore the pharmacologically active components in areca nut that induce oral submucosal fibrosis(OSF)and the possible mechanism.Methods The chemical components in areca nut were analyzed using Thermo QE plus liquid chromatography tandem high-resolution mass spectrometer and Compound discover 3.2 data processing software.The chemical activity of the top 20 compounds was analyzed based on Chinese Pharmacopoeia(2015),PubChem,Chemical book,and SciFinder databases.The potential active components,core targets,biological functions and signaling pathways affecting OSF were analyzed by network pharmacology.The targets of OSF were obtained by integrating Genecards and KEGG databases.The compounds acting on the targets were selected from the Systematic Pharmacology Technology Platform of Traditional Chinese Medicine(TCMSP),and the target-compound,compound-TCM,target-compound-TCM network was constructed.Molecular docking was used to analyze the component-target binding.Immunohistochemistry was used to examine the expressions of key proteins in the PI3K-Akt and MAPK pathways in clinical samples of OSF.Results The core intersection target genes between the top 10 active ingredients in areca nut extract and OSF involved mainly the PI3K-Akt and MAPK pathways.In the clinical samples,the expressions of PI3K protein decreased and the expressions p-PI3K,AKT1 and P-Akt all increased significantly in OSF tissue,where increased JNK protein expression and enhanced activity of c-Jun and c-Fos transcriptional factors were also detected.The OSF patients had significantly elevated plasma levels of IL-6 and IL-8 compared with healthy individuals.Conclusion The main active ingredients including arecoline,arecaine,and guvacine are capable of activating the PI3K-Akt and MAPK pathways to promote the expressions of inflammatory mediators IL-6 and IL-8 and induce collagen hyperplasia,thus leading to the occurrence of oral submucosal fibrosis.