ObjectiveTo develop a community-family management model for older adults with mild cognitive impairment (MCI) and to formulate detailed application specifications, and to fully leverage the initiative of communities and families under limited resource conditions, for achieving community-based early detection and early intervention for older adults with MCI. MethodsA systematic literature review was conducted to identify pertinent publications. Corpus-based research methodologies were employed to extract, refine, integrate and synthesize management elements, thereby establishing the specific content and service processes for each stage of the management model. Utilizing the 5W2H analytical framework, essential elements such as management stakeholders, target populations, content and methods for each stage were delineated. The model and its application guidelines were finalized through expert consultation and demonstration. ResultsAn expert evaluation of the management model yielded mean scores of 4.84, 4.32 and 4.84 for acceptability, feasibility and systematicity, respectively. By integrating the identified core elements with expert ratings and feedback, the final iteration of the community-family management model for older adults with MCI was formulated. This model comprised of five stages: screening and identification, comprehensive assessment, intervention planning, monitoring and referral pathways to ensure implementation, and enhanced support for communities, family members and caregivers. Additionally, it included 18 specific application guidelines. ConclusionThe proposed management model may theoretically help delay cognitive decline, improve cognitive function and potentially promote reversal from MCI to normal cognition. It may also enhance the awareness and coping capacity of older adults and their families, strengthen community healthcare professionals' ability to early identify and manage MCI.

ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation， and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group， model group， and Diwu Yanggan Capsule group using a random number table， with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage， and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention； DNA methylation chips were used to analyze the change in DNA methylation in liver tissue， and gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were used for data analysis. In addition， the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB， ADCK2， ERLIN2， SEMA3B， and TPH2 in the liver tissue of rats， and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups， while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group， the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group， the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes， and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation， apoptosis， and microenvironment regulation， such as the calcium ion signaling pathway， the cAMP signaling pathway， and the extracellular factor signaling pathway. Compared with the model group， the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene （P<0.05） and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes （all P<0.05）. Compared with the model group， the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 （all P<0.05）. ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective To investigate extended high-frequency hearing in young adults and to analyse its char-acteristics.Methods A total of 230 freshmen(101 males and 129 females,aged 17-19 years old)from the class of 2023 at the Air Force Medical University underwent audiometric tests,including acoustic impedance,conventional frequency and extended high-frequency audiometry,and distortion product otoacoustic emissions(DPOAE).Ac-cording to the results of extended high-frequency audiometry,the students were divided into normal and abnormal groups,and the hearing thresholds at conventional frequencies were compared between the two groups.Results Of the 230 students,47.83％(110/230)showed abnormal extended high-frequency hearing.The hearing thresholds of the right ear were 1 to 3 dB higher than those of the left ear at most frequencies.The hearing thresholds of the ab-normal group were higher than those of the normal group in the conventional frequencies(P＜0.05).The difference in extended high-frequency thresholds between the two groups increased with higher frequency.Conclusion Ex-tended high-frequency hearing loss occurs earlier,and has a higher prevalence in young adults,and right ear hearing is worse than that of left ear.Extended high-frequency audiometry can be used as a predictive tool for detecting con-ventional frequency hearing loss.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Objective To investigate the effect of withaferin A on aquaporin 4(AQP4)expression and brain edema in rats with traumatic brain injury(TBI).Methods A TBI rat model was established using the modified free-fall Feeney method,following which the rats were divided into model group and low-dose,medium-dose and high-dose withaferin A groups.Another sham operation group was set up,with 15 rats in each group.Withaferin A was administered once a day by intraperitoneal injection for seven consecutive days.The neurological function of the rats was evaluated using the neurological severity score(NSS),the brain water content was measured using the dry-wet spe-cific gravity method,the blood brain barrier permeability was measured using the Evans Blue method,and the histopathological changes of the cerebral cortex were observed by HE staining.Further,the apoptosis level of the hippocampal cells was observed by TUNEL staining and the expression levels of AQP4 mRNA in the cerebral cortex was detected by real-time quantitative PCR.The expression levels of rhe AQP4 protein in the cerebral cortex,and that of Bax,Bcl-2 and cleaved caspase-3 proteins in the hippocampus were detected by Western blotting.Results Medium and high doses of disolanesin A significantly improved the histopathological changes in the cerebral cortex and decreased the neurological impairment,brain water content and blood brain barrier permeability scores in TBI rats.Simultaneously,A QP4 mRNA and protein expression levels in the cerebral cortex,and Bax and cleaved caspase-3 protein expression and apoptosis levels in the hippocampal tissues of TBI rats decreased;however,Bcl-2 protein expression levels increased.Conclusion Withaferin A can reduce brain edema after TBI and improve neurological function.The mechanism may be related to the inhibition of AQP4 expression.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.