Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.

Objective: To explore the relationship between stigma and mental resilience in adolescent epilepsy patients and associated factors, so as to provide reference for future psychological intervention in adolescent patients with epilepsy. Methods: A total of 295 adolescent patients with epilepsy from Wuhan Mental Health Center were enrolled as participants from February 2021 to October 2024. The stigma was evaluated by Kilifi Stigma Scale for Epilepsy (KSSE), and psychological resilience was evaluated by Connor-Davidson Resilience Scale (CD-RISC). Associated factors of stigma and psychological resilience in adolescent patients with epilepsy were analyzed by multivariate Logistic regression analysis. Results: In the adolescent patients with epilepsy, KSSE score was (10.90±4.13) points, with 138 cases (46.78%) at low level, 154 cases (52.20%) at moderate level and 3 cases (1.02%) at high level. CD-RISC score was (50.19±5.97) points, there were 170 cases (57.63%) at low level and 125 cases (42.37%) at high level. Multivariate Logistic regression analysis showed that disease course >3 years ( OR =2.22), family history of epilepsy ( OR = 4.18) , monthly family income ≤5 000 yuan ( OR =2.05), single parent family ( OR =2.46) and middle and high stigma level ( OR = 1.72) had a higher risk on low level of mental resilience ( P <0.05). The course of disease >3 years ( OR =2.20), family history of epilepsy ( OR =3.54), general seizure ( OR =2.12), monthly family income ≤5 000 yuan ( OR =2.70), low level of mental resilience ( OR =2.03) of adolescent epilepsy patients showed a high risk on moderate high level of stigma ( P <0.05). Conclusions The stigma level is higher, while psychological resilience is lower in adolescent patients with epilepsy. Clinically, targeted intervention should be implemented based on related factors such as stigma in addescent patients with epilepsy.

AIM: To investigate the causal effects of ceramides on retinal vein occlusion(RVO)and elucidate their potential mediating mechanisms using Mendelian randomization(MR)analysis.METHODS: Genome-wide association study(GWAS)data for four ceramide species were utilized as exposures, and RVO GWAS data from the FinnGen database as the outcome. Additionally, GWAS data for 1 400 intermediate metabolites were analyzed to identify potential mediators in the ceramide-RVO pathway.RESULTS: Two ceramide species exhibited significant causal associations with RVO: ceramide(d40:1)[IVW OR(95% CI): 0.750(0.604-0.930), P<0.05] and ceramide(d42:2)[IVW OR(95% CI): 0.771(0.632-0.941), P<0.05], suggesting protective effects. Mediation analysis revealed that ceramide(d40:1)influenced RVO risk through metabolites including 3-methylxanthine, branched/straight-chain/cyclopropyl 10:1 fatty acids, glutamine, and hydroxypalmitoyl sphingomyelin. Similarly, ceramide(d42:2)acted via N-methylhydroxyproline, the same fatty acid group, N1-methyladenosine, and the leucine-to-N-palmitoyl-sarcosinate ratio.CONCLUSION: Ceramides(d40:1)and(d42:2)confer protection against RVO, partially mediated by specific metabolic pathways.

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Objective To analyze the effect and molecular mechanism of phellodendron amurense in the treatment of liver injury based on network pharmacology,and to verify the relevant prediction targets and the protective effect of phellodendron amurense extract-Phellodendron amurense polysaccharide on immune liver injury through mice.Methods TCMSP and Swiss target prediction databases were used to retrieve and screen phellodendron amurenses active components and action targets,and then obtain disease-related targets on GeneCards and OMIM websites,and take compounds and disease intersection targets for protein interaction.Analysis,GO biological function and KEGG signaling pathway enrichment analysis,followed by molecular docking of compounds and key target proteins,and finally established a mouse liver injury model induced by Daodou protein A(Con A)to explore the mechanism of phellodendron amurense extract in the treatment of liver injury.Results 37 active ingredients were screened.The key targets for their treatment were tumor necrosis factor α(TNF-α),serine/threonine protein kinase 1(AKT1),signal transduction and transcription activation factor 3(STAT3),epidermal growth factor receptor(EGFR)anditin.Enzyme 3(CASP3)and other enrichment analysis showed that phellodendron amurense might play a protective role in protecting the liver through molecular mechanisms such as positive regulation of MAPK cas-cade reaction,oxidative stress response and regulatory PI3K-Akt signaling pathway,lipid and atherosclerosis.Ani-mal experiments had found that the gastric treatment of phellodendron amurense polysaccharide could improve the activity of superoxide dismutase(SOD)and catalase(CAT)in liver tissue,reduce the levels of serum alkaline phosphatase(ALP),aspartate aminotransferase(AST)and malonaldehyde(MDA)in liver tissue,and regulate serum inflammatory factor while the expression of intercitin(IL)-6,IL-1 β,tumor necrosis factor α(TNF-α),ac-tivated the expression of transforming growth factor β1(TGF-β1),and reduced TNF-α mRNA expression in liver tissue.Conclusion Phellodendron amurense can intervene in lipid and atherosclerosis pathways by acting on tar-gets such as TNF-α,AKT1,STAT3,EGFR and CASP3 to reduce oxidative stress and inflammatory reactions and achieve liver protection.

Objective An isotemporal substitution model was used to explore the associations between activities including 10 minutes per day of physical activity(PA),sedentary behavior(SB),and sleep(SLP),and depressive symptoms among vocational school students with and without depressive symptoms.Methods Questionnaire survey was conducted on grade one to grade three students attending vocational schools in Shanghai and Jiangsu Province from Dec 2021 to Jan 2022.Fourteen schools were selected using the convenience cluster sampling method.The selected students were categorized into depressive symptoms group and non-depressive symptoms group according to the Centre for Epidemiologic Studies Depression Scale(CES-D)scores.Results A total of 40 339 questionnaires were collected,of which 10 086 were able to clearly remember the time of physical activity in the past week,and 8 149 were valid after data cleaning.According to the valid questionnaires,5 496 students(67.44%)were in the non-depressive symptoms group and 2 653(32.56%)were in the depressive symptoms group.The mean age of the students were(16.70±1.19)years.In the non-depressive symptoms group,substituting moderate physical activity(MPA)for all the other behaviors was negatively associated with CES-D scores,while substituting vigorous physical activity(VPA)for MPA and SB was positively associated with CES-D scores.In the depressive symptoms group,substituting walking,SB,and SLP with MPA was negatively associated with CES-D scores,respectively.The associations of MPA substituted for walking,SB,and SLP with CES-D scores were much stronger in the depressive symptoms group than in the non-depressive symptoms group.Conclusion The detection rate of depressive symptoms was high among vocational students.Substituting MPA for walking,SB,and SLP were negatively associated with CES-D scores,with a stronger association observed in the depressive symptoms group than in the non-depressive symptoms group.

Objective:To improve the teaching quality of Medical Microbiology by optimizing the teaching method,adjusting the teaching content and reforming the assessment model.Methods:The students of grade 2020 and 2021 of the same major were divided into the control group and the reform group.The control group received the traditional teaching method.The reform group received the"online + offline"blended teaching method,which integrates online learning resources and ideological and political education into the theoretical content of the curriculum.And the whole process assessment system was applied to the teaching method.The teaching quality was evaluated by the whole process examination results and questionnaire survey.Results:Compared with the control group,the score in the reform group was significantly improved(P＜0.01).Results of the questionnaire survey showed that students'satisfaction with the mixed teaching method reached 97.5% .The integration of hot issues of microbiology and curriculum ideological and political education significantly improved students'learning interest,and more students wanted to engage in the work of microbiology related fields in the future.Conclusion:The practice results show that optimizing the teaching method,adjusting the teaching content and reforming the assessment mode can stimulate the students'learning interest,improve the students'independent learning ability and improve the teaching quality.

BACKGROUND:Anterior cruciate ligament injury tends to lead to secondary meniscus injury and osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by anterior cruciate ligament injury. OBJECTIVE:To study the effect of partial rupture of the anterior cruciate ligament on the stress of medial and lateral meniscus and articular cartilage of knee joint by finite element analysis. METHODS:The CT and MRI images of the knee joint of a healthy volunteer were selected,and the scan data were imported into Mimics,Geomagic and SolidWorks software.After registration and fusion,four kinds of three-dimensional knee joint models were established:models of intact anterior cruciate ligament,rupture of the posterior external tract of anterior cruciate ligament,rupture of the anterior internal tract of anterior cruciate ligament,and absence of anterior cruciate ligament.Finally,data were imported into Ansys software to apply four different modes of loads to the knee joint:Longitudinal loads of 750 N were applied to the top of the femur;longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia;a longitudinal load of 750 N and a varus moment of 10 Nm were applied to the top of the femur to simulate genu varus;750 N longitudinal load and 4 Nm internal rotation moment were applied to the proximal end of the femur to simulate knee internal rotation.The finite element analysis of biomechanical stress changes of the meniscus and articular cartilage of the knee joint was carried out. RESULTS AND CONCLUSION:(1)In the straight position of the knee joint,when the anterior medial tract of the anterior cruciate ligament was broken and the anterior cruciate ligament was missing under longitudinal loads of 750 N at the top of the femur,the total stress and peak value of meniscus increased significantly,but the stress distribution of the meniscus and the stress of articular cartilage did not change significantly.In longitudinal load of 750 N to the top of the femur and forward thrust of 134 N behind tibia,the fracture of the anterior internal tract of the anterior cruciate ligament increased the tibia forward,the compressive stress of posterior angle of the meniscus increased,and the stress of the articular cartilage did not change significantly.During simulating genu varus,the posterior angular stress of the lateral meniscus decreased,the stress of the medial meniscus increased,and the stress of articular cartilage slightly decreased when anterior cruciate ligament injuries were complete.When the anterior internal tract of the anterior cruciate ligament was broken or absent under knee internal rotation,the equivalent stress peak value of femoral cartilage and tibia cartilage shifted from medial cartilage to lateral cartilage,and the stress peak value of meniscus increased significantly.At this time,the anterior internal tract of the anterior cruciate ligament played a leading role in the rotational stability of the knee joint.(2)These results indicate that the risk of secondary meniscus injury in patients with anterior and medial anterior cruciate ligament band rupture was much higher than that in patients with posterior and external anterior cruciate ligament band rupture when the knee was in the upright standing position,varus and pronation,and there was no significant difference in the impact on articular cartilage.

BACKGROUND:The incidence of medial collateral ligament injuries in the knee joint is easy to lead to secondary meniscus and cartilage damage,and long-term chronic damage can lead to the occurrence of osteoarthritis.At present,there are few studies on the mechanics of meniscus and articular cartilage injury caused by medial collateral ligament rupture. OBJECTIVE:To investigate the effect of different degrees of medial collateral ligament injury on the biomechanics of meniscus and cartilage of knee joint. METHODS:The CT and MRI examinations of the knee joint of a healthy volunteer were performed to obtain the image data.The scanning data were imported into Mimics,Geomagic,and Solidworks software in turn.After registration and fusion,a 3D model of normal knee joint was established.On this basis,models of medial collateral ligament injury in different degrees of knee joint were simulated,which were divided into four groups,including:(1)medial collateral ligament was intact;(2)deep medial collateral ligament fracture;(3)superficial medial collateral ligament fracture;(4)complete rupture of medial collateral ligament.Finally,Ansys software was introduced to apply three modes of loads to the knee joint:(1)10 N·m valvaration torque was applied to the top of the femur.(2)A 4 N·m internal torque was applied to the top of the femur.(3)A 4 N·m external torque was applied to the top of the femur.The effects of four groups of models on knee biomechanics under different loads were analyzed. RESULTS AND CONCLUSION:(1)In the extension position of the knee joint,when a 10 N·m valgus torque was applied to the knee joint,the overall stress of the posterolateral meniscus increased with different degrees of medial collateral ligament injuries,while the stress of the articular cartilage did not change significantly.The peak stress of the posterolateral meniscus increased significantly with superficial medial collateral ligament rupture.(2)In the knee extension position,when a 4 N·m internal rotation torque was applied to the knee joint,the overall stress of the medial and lateral meniscus increased after different degrees of medial collateral ligament injury.When superficial medial collateral ligament rupture occurred,the peak stress of the meniscus shifted from the anterior horn of the medial meniscus to the anterior horn of the lateral meniscus.(3)In the knee extension position,applying a 4 N·m external rotation torque to the knee joint,the peak stress of the posterolateral meniscus increased more significantly than that of the medial meniscus,and the stress of the articular cartilage changed less.(4)These results show that the risk of meniscus injury secondary to superficial medial collateral ligament rupture is much higher than that of deep medial collateral ligament rupture when the knee is in extension,and the lateral meniscus is more vulnerable to injury than the medial meniscus.Both superficial medial collateral ligament and deep medial collateral ligament play an important role in the rotational stability of the knee joint.