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.

OBJECTIVE: To investigate the effectiveness of arthroscopic double fixation and enhanced suture of long head of biceps tendon (LHBT) in situ for repairing rotator cuff tear. METHODS: A retrospective analysis was conducted on 31 patients with rotator cuff tears and LHBT injuries admitted between June 2022 and November 2023. All patients underwent arthroscopic double fixation and enhanced suture of LHBT in situ. There were 12 males and 19 females, with an average age of 61.6 years (range, 53-76 years). There were 10 cases of acute injury and 21 cases of chronic injury. According to DeOrio and Cofield classification criteria, the degree of rotator cuff tear rated as medium-sized tears in 3 cases, large tears in 12 cases, and massive tears in 16 cases. Associated injuries included 5 cases of shoulder joint adhesions, 12 cases of subscapularis muscle tears, and 31 case of shoulder impingement syndromes. The shoulder range of motion (ROM) (forward flexion, abduction, lateral external rotation, lateral internal rotation) and pain/function scores [visual analogue scale (VAS) score, University of California Los Angeles (UCLA) shoulder score, Constant-Murley score] were recorded before operation and at last follow-up. MRI at last follow-up were taken to evaluate the rotator cuff healing and structural integrity. RESULTS: All 31 surgeries were successfully completed with operation time ranging from 90 to 210 minutes (mean, 144 minutes). The 3-5 anchors (mean, 3.8 anchors) were used during operation. All incisions healed by first intention. All patients were followed up 12-29 months (mean, 18.5 months). At 3 months after operation, 2 cases developed joint adhesions, 3 had internal rotation limitations, and 2 experienced residual pain at the intertubercular groove, all resolved with conservative management. No Popeye deformity occurred during follow-up. At last follow-up, shoulder ROM (forward flexion, abduction, lateral external rotation, lateral internal rotation) and pain/function scores (VAS, UCLA, and Constant-Murley scores) showed significant improvements compared to preoperative values ( P<0.05). At last follow-up, MRI evaluation showed that the rotator cuff healing rate reached 90.3% according to the Sugaya classification criteria. LHBT exhibited normal morphology, course, and continuity without dislocation. Surrounding synovial sheath showed no thickening or effusion. CONCLUSION Arthroscopic double fixation and enhanced suture of LHBT in situ for repairing rotator cuff tear can significantly reduce shoulder joint pain, improve ROM, and achieve a high rotator cuff healing rate.
Humans ; Male ; Middle Aged ; Arthroscopy/methods* ; Rotator Cuff Injuries/physiopathology* ; Female ; Retrospective Studies ; Aged ; Range of Motion, Articular ; Suture Techniques ; Treatment Outcome ; Rotator Cuff/surgery* ; Shoulder Joint/physiopathology* ; Tendons/surgery*

Objective Zinc finger protein 335 (Zfp335) plays a crucial role in the early development of thymic T cells and the differentiation of peripheral T cell subpopulations. The objective of this study is to investigate the role and underlying mechanisms of Zfp335 in the regulation of regulatory T cell (Treg) within tumor immunity. Methods The Zfp335 gene was specifically knocked out in Treg using tamoxifen (Zfp335^fl/fl FOXP3^creERT2), and the MC38 tumor model was established. On the 7th day after tumor inoculation, tumor size was observed and measured. Tumor size was monitored and recorded daily starting from day 7 post-inoculation. On day 12, tumors were harvested, and the proportions of CD4⁺ T cells, CD8⁺ T cells, and Treg were analyzed by flow cytometry. Additionally, the mitochondrial function of effector regulatory T cell (eTreg) was assessed. Results From day 10 post-tumor inoculation, tumor volume in the Zfp335^CKO group was significantly reduced compared to that of the wild-type (WT) group. Furthermore, the infiltration of CD4⁺ and CD8⁺ T cells, along with their respective effector cells, was significantly higher in the Zfp335^CKO group than in the WT group. The proportions of CD4⁺ and CD8⁺ T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were also significantly increased in the Zfp335^CKO group compared to that of the WT group. In addition, the percentage of CD8⁺ T cells secreting granzyme B (GzmB) was significantly higher in the Zfp335^CKO group than that in the WT group. In contrast, the proportion of Treg and inducible T cell co-stimulator (ICOS)⁺ Treg in the Zfp335^CKO group was significantly lower than that in the WT group. Finally, the expression level of Mitotracker Deep Red in eTreg from the Zfp335^CKO group was significantly reduced compared to that in the WT group. Conclusion During tumorigenesis, the specific deletion of Zfp335 impairs Treg activation, which is related to decreased mitochondrial function in eTreg. In Zfp335^CKO mice. Tumors exhibit increased infiltration of effector T cells, accompanied by elevated levels of cytotoxic cytokines, ultimately enhancing resistance to tumor progression.
Animals ; T-Lymphocytes, Regulatory/metabolism* ; Mice ; CD8-Positive T-Lymphocytes/immunology* ; Neoplasms/genetics* ; Cell Line, Tumor ; Mice, Inbred C57BL ; Mice, Knockout ; DNA-Binding Proteins/genetics* ; Female

OBJECTIVE: To investigate the factors affecting ferric chloride (FeCl₃) - induced carotid artery thrombosis model experiment. METHODS: After the common carotid artery was damaged by FeCl₃, the injured vessels were dissected for fixation, embedding, frozen section, and then processed HE staining. The carotid thrombus area ratio was calculated. We examined the effect of FeCl₃ concentration (5%, 10% and 15%), reaction time (2, 4 and 6 min), and recipient mouse age (4-5, 6-8 and 10 weeks) on the formation and stability of arterial thrombosis model. The model was injected through the post-glomus venous plexus of mouse eyeball with 0.075 μg/g and 0.1 μg/g R300 to verify the accuracy of the FeCl₃-induced model on thrombus formation by adjusting the platelet number. RESULTS: HE staining showed that thrombus formation induced by 10% and 15% FeCl₃ was more stable, dense and larger than 5% FeCl₃-induced thrombosis. 10% FeCl₃ induced the formation of dense and large thrombosis after 4 and 6 minutes of vascular endothelium injury, while the thrombosis induced for 2 minutes were looser and smaller in area. Mouse age can not affect thrombus formation and stability, because there were no significant differences in the formation of dense thrombus and thrombus area induced by 10% FeCl₃ among three different age groups of mice. CONCLUSION Many factors affect the formation and stability of arterial thrombosis model induced by FeCl₃. This optimal experimental conditions for construction of a stable carotid artery thrombosis model are 10% FeCl₃, 4 minutes for injury, and 6-8 week old mice.
Animals ; Mice ; Ferric Compounds/adverse effects* ; Chlorides ; Disease Models, Animal ; Carotid Artery Thrombosis/chemically induced* ; Male

OBJECTIVE: To observe the effect of Guilu Taohong Formula on semen quality in varicocele (VC) models of rats, and to explore its possible mechanism. METHODS: Forty-eight male SD rats were randomly divided into four groups (sham group, model group, Guilu Taohong Formula group and L-carnitine group). After the establishment of models, the rats were treated with intragastric administration for eight consecutive weeks. The general condition of the rats was observed. After the gavage, the testicular and epididymal indices were calculated. Semen quality was assessed using an automatic semen analyzer. Apoptosis of testicular cells was assessed by TUNEL staining. And the expression levels of B-cell lymphocytoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine aspartate protease-3 (caspase-3) in testicular tissue were detected by Western blot. RESULTS: Compared with the sham group, testicular index, epididymal index, sperm concentration, the percentage of progressive motility of sperm (PR%) and the expression level of Bcl-2 decreased in model group(P<0.01). An increased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were observed in model group as well(P<0.01). Compared with the model group, the testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 in Guilu Taohong Formula group increased significantly (P<0.05, P<0.01). A decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins were detected in Guilu Taohong Formula group as well(P<0.01). Similarly, the L-carnitine group showed increased testicular index, epididymal index, sperm concentration, PR% and the expression level of Bcl-2 protein (P<0.05, P<0.01), where showed decreased apoptosis rate of spermatogenic cells and the expression levels of Bax and caspase-3 proteins compared with model group (P<0.01, P<0.05). CONCLUSION Guilu Taohong Formula improves semen quality in VC model rats and reduces the apoptosis rate of spermatogenic cells in testicular tissue, which may be related to the promotion of Bcl-2 protein expression and the inhibition of Bax and caspase-3 protein expression levels.
Male ; Animals ; Varicocele/drug therapy* ; Rats ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Semen Analysis ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Disease Models, Animal ; Spermatozoa/drug effects* ; Testis/drug effects*

OBJECTIVE: The aim of this study is to explore the clinical efficacy and safety of endocrinotherapy combined with Shenqi Pills on hormone-sensitive prostate cancer (HSPC). METHODS: Eighty patients who were diagnosed with HSPC and renal-yang deficiency at the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine and the Hospital of Traditional Chinese Medicine of Mayang Miao Autonomous County from 1st April 2021 to 30th April 2024 were randomly divided into 2 groups. The patients in the control group were treated with androgen deprivation therapy (ADT). And the patients in treatment group were treated with Shenqi Pills orally on the basis of the control group. The baseline data of the two groups were analyzed. After 36 months of treatment, the differences between the two groups were compared in terms of overall survival (OS), prostate-specific antigen (PSA) level, PSA response rate, Functional Assessment Scale for Prostate Cancer Therapy (FACT-P), Chinese medicine evidence scores, testosterone level and safety. RESULTS: A total of 80 study subjects were included in this study, including 42 cases in the treatment group and 38 cases in the control group. There was no statistical difference in the baseline data between the two groups before treatment (P>0.05). At the end of the observation period, a statistically significant difference in OS was found in the treatment group compared to the control group in the subgroup of patients with a disease duration ranged of 0-6 months (P<0.05). There was no statistically significant difference in PSA levels in the treatment group at 3 months (P>0.05). And the differences in the proportion of PSA50 (98.1% vs 91.4%), PSA90 (92.9% vs 84.6%) and the proportion of decrease in PSA (56.7% vs 33.8%) in the treatment group were found compared to those in the control group after 6 months of tre atment. After 12 months of treatment, the scores of FACT-4 and renal-yang deficiency in the treatment group were (95.28±7.93) and (15.73±5.70) respectively, compared to the scores in the control group (［85.46±10.12］ and ［18.20±4.27］ (P<0.05). However, there was no significant difference in serum testosterone (［0.60±0.24］ nmol/L vs ［1.09±2.10］ nmol/L) between the two groups (P>0.05). After 24 months of treatment, there were significant differences in in the FACT-4 total score (［97.95±7.54］ vs ［80.33±8.58］), renal-yang deficiency syndrome score (［14.64±5.15］ vs ［24.94±8.75］) between the treatment group and the control group (P<0.05). However, there was no significant difference in serum testosterone ( ［0.73±1.01］ nmol/L vs ［0.59±0.25］ nmol/L) between the two groups (P> 0.05). Better therapeutic results were showed in the treatment group in terms of total FACT-P score, physical situation score, social and family situation score, emotional state score, functional state score, additional score and renal-yang deficiency symptom score (P<0.05). After treatment, there was no serious adverse reaction in the course of treatment, and no obvious abnormality was found in the liver and kidney function of the patients from two groups. CONCLUSION Endocrinotherapy combined with Shenqi Pills is safe and effective in HSPC and can reduce the risk of death in HSPC patients, and the earlier the intervention, the longer the overall survival of the patients. In addition, this treatment regimen can increase the PSA response rate, improve patients' quality of life, and reduce the renal-yang deficiency syndrome score without the risk of elevating serum testosterone levels.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Prostatic Neoplasms/drug therapy* ; Androgen Antagonists/therapeutic use* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Treatment Outcome ; Testosterone

BACKGROUND: Hypertension is associated with an increased risk of calcific aortic valve stenosis (CAVS). However, the directionality of causation between blood pressure traits and aortic stenosis is unclear, as is the benefit of antihypertensive drugs for CAVS. METHODS: Using genome-wide association studies (GWAS) summary statistics, we performed bidirectional two-sample univariable mendelian randomization (UVMR) to assess the causal associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) with CAVS. Multivariable mendelian randomization (MVMR) was conducted to evaluate the direct effect of hypertension on CAVS, adjusting for confounders. Drug target mendelian randomization (MR) and summary-level MR (SMR) were used to estimate the effects of 12 classes of antihypertensive drugs and their target genes on CAVS risk. Inverse variance weighting was the primary MR method, with sensitivity analyses to validate results. RESULTS: UVMR showed SBP, DBP, and PP have causal effects on CAVS, with no significant reverse causality. MVMR confirmed the causality between hypertension and CAVS after adjusting for confounders. Drug-target MR analyses indicated that calcium channel blockers (CCBs), loop diuretics, and thiazide diuretics via SBP lowering exerted protective effects on CAVS risk. SMR analysis showed that the CCBs target gene CACNA2D2 and ARBs target gene AGTR1 were positively associated with CAVS risk, while diuretics target genes SLC12A5 and SLC12A1 were negatively associated with aortic stenosis risk. CONCLUSIONS Hypertension has a causal relationship with CAVS. Managing SBP in hypertensive patients with CCBs may prevent CAVS. ARBs might exert protective effects on CAVS independent of blood pressure reduction. The relationship between diuretics and CAVS is complex, with opposite effects through different mechanisms.

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.