Alzheimer's disease (AD), a progressive dementia, is one of the most common neurodegenerative diseases. Clinical trial results of amyloid-β (Aβ) and tau regulators based on the pretext of straightforward amyloid and tau immunotherapy were disappointing. There are currently no effective strategies for slowing the progression of AD. Herein, we spotlight the dysregulation of lipid metabolism, particularly the elevation of ceramides (Cers), as a critical yet underexplored facet of AD pathogenesis. Our study delineates the role of Cers in promoting microglial pyroptosis, a form of programmed cell death distinct from apoptosis and necroptosis, characterized by cellular swelling, and membrane rupture mediated by the NLRP3 inflammasome pathway. Utilizing both in vivo experiments with amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and in vitro assays with BV-2 microglial cells, we investigate the activation of microglial pyroptosis by Cers and its inhibition by icariin (ICA), a flavonoid with known antioxidant and anti-inflammatory properties. Our findings reveal a significant increase in Cers levels and pyroptosis markers (NOD-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, gasdermin D (gasdermin D (GSDMD)), and interleukin-18 (IL-18)) in the brains of AD model mice, indicating a direct involvement of Cers in AD pathology through the induction of microglial pyroptosis. Conversely, ICA treatment effectively reduces these pyroptotic markers and Cer levels, thereby attenuating microglial pyroptosis and suggesting a novel therapeutic mechanism of action against AD. This study not only advances our understanding of the pathogenic role of Cers in AD but also introduces ICA as a promising candidate for AD therapy, capable of mitigating neuroinflammation and pyroptosis through the cyclooxygenase-2 (COX-2)-NLRP3 inflammasome-gasdermin D (GSDMD) axis. Our results pave the way for further exploration of Cer metabolism disorders in neurodegenerative diseases and highlight the therapeutic potential of targeting microglial pyroptosis in AD.

Objective This study aimed to explore the effect of pituitary tumor-transforming gene 1(PTT-G1)on the invasion and proliferation of oral squamous cell carcinoma(OSCC)cell lines under the action of miR-362-3p.Methods The bioinformatics online database was used to query the expression of PTTG1 in head and neck squamous cell carcinoma(HNSCC).The expression of PTTG1 in the Cal-27,HN-30,and HOK cell lines was detected by Western blot.A wound-healing assay was used to determine the effect of PTTG1 on the migration ability of the OSCC cells.The Transwell assay was used to examine the changes in cell-invasion ability.5-ethynyl-2'-deoxyuridine(EdU)cell-proliferation assay was used to detect changes in cell-proliferation ability.Bioinformatics approach predicted the upstream miRNA of PTTG1.The targeting relationship between miR-362-3p and PTTG1 was examined by the dual luciferase assay,and quantitative real-time polymerase chain reaction(qRT-PCR)was used to determine the expression of miRNA in OSCC tissues.Results The ENCORI database showed that PTTG1 expression was up-regulated in OSCC tissues.Western blot confirmed that PTTG1 expression was up-regulated in Cal-27 and HN-30 cells than HOK cells.PTTG1 knockout can inhibit the migration,invasion,and prolif-eration of Cal-27 and HN-30 cells(P<0.05).Bioinformatics prediction websites predicted that the upstream miRNA of PTTG1 was miR-362-3p,and PTTG1 can bind to miR-362-3p.Results of qRT-PCR showed that miR-362-3p expression was downregulated in OSCC tissues compared with normal tissue(P<0.05).Transwell and EdU experiments confirmed that miR-362-3p knockdown can promote the invasion and proliferation of Cal-27 and HN-30 after PTTG1 knockdown.Conclusion miR-362-3p can inhibit the invasion and proliferation of Cal-27 and HN-30 cells by targeting PTTG1.

OBJECTIVE:To systematically evaluate the efficacy of transcranial direct current stimulation on the motor function of patients with Parkinson's disease,and to compare the efficacy of transcranial direct current stimulation at different targets on the motor function of patients with Parkinson's disease,so as to provide a theoretical basis for the target selection of transcranial direct current stimulation in clinical practice. METHODS:Cochrane Library,PubMed,Web of Science,CNKI,VIP,WanFang Data were retrieved for randomized controlled trials on the improvement of motor function in patients with Parkinson's disease by transcranial direct current stimulation published from the database inception to January 2023.The keywords were"Parkinson,transcranial direct current stimulation"in English and Chinese.The quality of the included studies was evaluated using the Cochrane 5.1.0 risk of bias assessment tool and the PEDro scale.Meta-analysis of outcome indicators was performed using RevMan 5.4 and Stata 17.0 software. RESULTS:Fifteen randomized controlled trials were finally included,and the PEDro scale showed that all were high-quality or very high-quality studies.Meta-analysis showed that transcranial direct current stimulation significantly improved Unified-Parkinson Disease Rating Scale part III score[mean difference(MD)=-2.49,95%confidence interval(CI):-4.42 to-0.55,P<0.05),step frequency score(MD=0.07,95%CI:0.03-0.11,P<0.05)and step speed score(MD=0.02,95%CI:0.00-0.05,P<0.05),but not for Berg Balance Scale scores(MD=2.57,95%CI:-0.74 to 5.87,P>0.05).Network Meta-analysis probability ranking:In terms of Unified-Parkinson Disease Rating Scale part III scores,the probability ranking results of target stimulation efficacy were dorsal lateral prefrontal cortex(52.4%)>primary motor cortex(45.8%)>central point of the brain(1.8%)>conventional rehabilitation(0%);in terms of gait frequency scores,the probability probability ranking results of target stimulation efficacy were cerebellum(50.1%)>central point of the brain(45.8%)>dorsal lateral prefrontal cortex(3.9%)>primary motor cortex(0.2%)>conventional rehabilitation(0%);in terms of gait speed scores,the probability ranking results of target stimulation efficacy were cerebellum(64.8%)>dorsal lateral prefrontal cortex(23.8%)>central point of the brain(9.4%)>primary motor cortex(1.7%)>conventional rehabilitation(0.4%);in terms of Berg Balance Scale scores,the probability ranking results of target stimulation efficacy were cerebellum(77.4%)>dorsal lateral prefrontal cortex(20.7%)>central point of the brain(0.7%)>conventional rehabilitation(0.2%). CONCLUSION:Transcranial direct current stimulation significantly improves motor function of patients with Parkinson's disease,with better motor coordination in the dorsolateral prefrontal cortex and better walking and balance in the cerebellum.

Objective To establish an HPLC method for the determination of alkaloids(epiberberine,coptisine,palma-tine,berberine)and catalpol in different ratios(1∶1,1∶10)of ancient and modern Qianjin Huanglian Pills,and to compare the differences in their contents.The content differences were compared to preliminarily evaluate the differences in the efficacy of Qianjin Huanglian Pills in the treatment of diabetes under different preparation processes and different ratios.Methods The alkaloid solvent was methanol∶ hydrochloric acid(100∶1).The detection conditions were as follows:C18 column,acetonitrile-0.05 mol·L-1 potassium dihydrogen phosphate solution(50∶50),detection wavelength 345 nm,column temperature 30℃,flow rate 1 mL·min-1,injection volume 10 μL.The catalpol solution was methanol∶ water(20∶80).The detection conditions were as follows:chromatographic column C18 column,methanol-0.1%phosphoric acid solution(1∶ 99),detection wavelength 210 nm,column temperature 30℃,flow rate 1 mL·min-1,injection volume 10 μL.Results The established method was spe-cific,and the separation effect of the five components was good.It exhibited a good linear relationship(R2＞0.999)in their respec-tive linear ranges.The repeatability,precision,stability,and sample recovery rate all met the requirements.The content of four alka-loids in the ancient method 1∶1 was the highest,and the content of catalpol was the lowest.The content of four alkaloids in the ancient method 1∶10 was the lowest;the content of 1∶1 in the present method was higher than that in the ancient method 1∶10,and the content of berberine in the present method 1∶10 was slightly lower than that in the present method 1∶1,and the rest were higher than that in the present method 1∶1.The PCA results showed that the chemical composition contents of the four kinds of Qianjin Huanglian pills were very different.Conclusion The method is simple,accurate,and reproducible,making it suitable for the quality control of Qianjin Huanglian Pills.It provides a theoretical basis for exploring the difference in efficacy of Qianjin Huanglian Pills.

Objective:To investigate the potential mechanism of miR-1298-5p in non-small cell lung cancer(NSCLC)to regu-late the MSH2 gene and its effect on the biological behavior of tumor cells and the tumor immune microenvironment.Methods:Bioin-formatics was used to identify the key genes and miRNA involved in NSCLC.Cell proliferation was detected by CCK-8 assay,and cell invasion and migration were detected by Transwell assay.Levels of inflammatory factors were detected by ELISA assay.Western blot was used to measure the expression of MSH2 in cells,and fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expressions of miR-1298-5p and MSH2 gene in NSCLC cells.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-1298-5p and MSH2.Spearman correlation analysis was performed to correlate miR-1298-5p with immune cells and immune factors in the tumor immune microenvironment.Results:The level of miR-1298-5p was down-regulated in NSCLC cells compared with normal lung tissue cells.miR-1298-5p overexpression inhibited the proliferation,migration and inva-sion of NSCLC cells.MSH2 was confirmed to be a target gene of miR-1298-5p using luciferase reporter gene assay.Furthermore,down-regulation of miR-1298-5p in NSCLC cells could be reversed by silencing MSH2.miR-1298-5p expression levels were negatively corre-lated with the levels of Treg,IL-10,and TGF-β,and positively correlated with the levels of CD3+T,CD4+T,CD8+T,NK cells,IL-2,and IFN-γ.Conclusion:miR-1298-5p negatively regulates MSH2 to inhibit the proliferation,invasion and migration of NSCLC cells and improve the tumor immune microenvironment.

The PCR-amplified severe fever with thrombocytopenia syndrome virus(SFTSV)Gn-DⅢ-Ⅲ gene was inserted into the pET-30a(+)prokaryotic expression vector to generate the re-combinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ.The plasmid was transformed into E.coli BL21(DE3)for Gn-DⅢ-m protein expression and the expression conditions were optimized.The Gn-DⅢ-Ⅲ protein purified with Ni-NTA column affinity chromatography was applied as the captured antigen to establish an indirect ELISA method for the detection of SFTSV antibody.The results demonstrated that the recombinant plasmid pET-SFTSV-Gn-D Ⅲ-Ⅲ was successfully constructed as identified by PCR and sequencing.The recombinant protein SFTSV Gn-D m-Ⅲ was soluble ex-pression in E.coli under the optimal induction conditions of 0.4 mmol/L IPTG at 25 ℃ for 4 h,and the protein purity was 91.77％after purification by Ni-NTA column.The optimal reaction con-ditions for the indirect ELISA of SFTSV antibody were as follows:coating antigen concentration(5 μg/mL),primary antibody(incubation at 37 ℃ for 1.5 h),and secondary antibody(diluted 1:10 000 and incubated at 37 ℃ for 1 h).The established method had no cross-reactivity with Rift Valley fever virus(RVFV),Ebola virus(EBOV),and tick-borne encephalitis virus(TBEV)posi-tive sera.The method had a high sensitivity,with P/N＞2.1 for SFTSV-positive sera diluted to 81920.Coefficients of variation for intra-and inter-batch reactions were less than 10％.Detection of four SFTSV-infected human clinical serum samples showed the serum samples from patients in re-mission were tested as positive(P/N＞2.1),while serum samples from patients with multiple or-gan failure were detected as negative(P/N＜2.1).The results indicated that the SFTSV Gn-D Ⅲ-Ⅲ protein was successfully expressed and purified,and it was used as the coating protein to estab-lish an indirect ELISA assay for SFTSV antibody,which possesses good specificity,sensitivity and reproducibility.This method might be applied to detect human SFTSV clinical serum samples.

Objective:To investigate the mediating role of self-regulatory fatigue between psychological distress and patient activation among elderly patients undergoing PCI, in order to establish a foundation for enhancing patient activation in this population.Methods:A cross-sectional study was conducted on 267 elderly patients hospitalized in the Department of Geriatrics at Qilu Hospital, Shandong University, for PCI treatment of coronary artery disease from March to August 2023.The study utilized the Patient Self-Regulation Fatigue Scale(SRF-S), the Positivity Scale(PAM), and the Kessler Scale of Psychological Distress(K10)to evaluate self-regulation fatigue, positivity, and psychological distress in the patients.Additionally, a structural equation model was developed to investigate the relationships among these variables.Results:The study found that the scores of PAM, SRF-S, and K10 were as follows: (56.49±9.52), (42.74±8.11), and(23.42±4.45)respectively.Patient activation showed a negative correlation with self-regulatory fatigue and psychological distress, while self-regulatory fatigue was positively correlated with psychological distress.Furthermore, self-regulatory fatigue was identified as playing a partial mediating role between psychological distress and patient activation, with a mediating effect of 0.198, which accounted for 53.8% of the total effect.Conclusions:self-regulatory fatigue serving as a mediating factor between psychological distress and patient activation.Clinicians should prioritize addressing self-regulatory fatigue to enhance the efficacy of patient activation interventions.

BACKGROUND: Exosomes derived from breast cancer have been reported to play a role in promoting cell proliferation, migration, and angiogenesis, which has the potential to accelerate the healing process of diabetic wounds. The aim of this investigation was to examine the function of exosomes originating from 4T1 mouse breast carcinoma cells (TEXs) in the process of diabetic wound healing. METHODS: The assessment of primary mouse skin fibroblasts cell proliferation and migration was conducted through the utilization of CCK-8 and wound healing assays, while the tube formation of HUVECs was evaluated by tube formation assay. High-throughput sequencing, RT-qPCR and cell experiments were used to detect the roles of miR-126a-3p in HUVECs functions in vitro. The in vivo study employed a model of full-thickness excisional wounds in diabetic subjects to explore the potential therapeutic benefits of TEXs. Immunohistochemical and immunofluorescent techniques were utilized to evaluate histological changes in skin tissues. RESULTS: The findings suggested that TEXs facilitate diabetic wound healing through the activation of cell migration, proliferation, and angiogenesis. An upregulation of miR-126a-3p has been observed in TEXs, and it has demonstrated efficient transferability from 4T1 cells to HUVEC cells. The activation of the PI3K/Akt pathway has been attributed to miR-126a-3p derived from TEXs. CONCLUSIONS The promotion of chronic wound healing can be facilitated by TEXs through the activation of cellular migration, proliferation, and angiogenesis. The activation of the PI3K/Akt pathway by miR-126a-3p originating from TEXs has been discovered, indicating a potential avenue for enhancing the regenerative capabilities of wounds treated with TEXs.

Alzheimer's disease is the most common cause of dementia.Current treatment options for Alzheimer's disease are very limited, and non-drug treatment is receiving more and more attention.Cognitive intervention is a relatively new non-drug treatment for Alzheimer's disease.A large number of previous studies have confirmed that cognitive intervention can prevent and mitigate clinical symptoms of Alzheimer's disease.In this review, we systematically introduce cognitive intervention as a prevention tool for Alzheimer's disease and its ability to alleviate clinical symptoms of the disease, and put forward suggestions for the future application of cognitive intervention in Alzheimer's disease.

Objective:To investigate the correlation between paraspinal muscle atrophy, morphological changes of facet joints and adjacent segment disease (ASDis) after lumbar fusion operation.Methods:A retrospective study was conducted among 195 patients who underwent posterior lumbar fusion again for ASDis at this institution from January 2014 to December 2020, including 29 patients with ASDis whose initial surgical fusion segment was L 4,5. According to Roussouly's staging, there were 5 cases of type I, 9 cases of type II, 10 cases of type III, and 5 cases of type IV. Another 29 cases were selected from patients without ASDis after lumbar fusion as a control group. The control group was paired 1∶1 with the ASDis group according to gender, fusion segment, and Roussouly typing of the lumbar spine. The cross-sectional area (CSA) and fat infiltration (FI) of paravertebral muscle, facet joint angle (F-J) and pedicle facet (P-F) angle before the first (second) operation were measured and compared between the two groups. Then logistic regression analysis was used to determine the predictors of ASDis after posterior lumbar fusion. Finally, the receiver operation characteristic (ROC) curve was described, and the area under the curve (AUC) and cut-off point were calculated. At the same time, the paraspinal muscle atrophy before the second operation in ASDis group was measured. Results:The average follow-up time of 98 patients was 59.25±6.38 months (range, 49-73 months). The average body mass index (BMI) of ASDis group was 24.76±3.64 kg/m 2, which was higher than that in control group (22.24±2.92 kg/m 2) ( t=2.481, P=0.041). The average CSA and relative cross-sectional area (rCSA) of paraspinal muscle in ASDis group were 3 214.32± 421.15 mm 2 and 1.69±0.36 respectively, which were less than 3 978.91±459.87 mm 2 and 2.26±0.29 in control group ( t=10.22, P=0.012; t=9.47, P=0.038). The FI degree of paraspinal muscle in ASDis group (21.95%±5.89%) was significantly higher than that in control group (14.64%±7.11%) ( t=7.32, P=0.002). The F-J angle in ASDis group was 35.06°±3.45°, which was less than 38.39°±4.67° in control group ( t=4.76, P=0.027). The P-F angle in ASDis group was 117.39°±8.13°, which was greater than 111.32°±4.78° in control group ( t=5.25, P=0.031). Multivariate logistic regression analysis showed that higher BMI ( OR=1.34, P=0.038), smaller rCSA of paraspinal muscle ( OR=0.02, P=0.017) and higher FI of paraspinal muscle ( OR=1.58, P=0.032) were the risk factors of postoperative ASDis. The ROC curve showed that the AUC of BMI was 0.680 and the cut-off point was 22.58 kg/m 2; The AUC of the FI of paraspinal muscle was 0.716 and the cut-off point was 15.69%; The AUC of rCSA of paraspinal muscle was 0.227 and the cut-off point was 1.92. For ASDis patients, the paraspinal muscle before the second operation had a higher degree of FI (25.47%±6.59% vs. 21.95%±5.89%, t=3.99, P=0.042) and a smaller rCSA (1.52±0.28 vs. 1.69±0.36, t=3.85, P=0.038) than that before the first operation. The difference between the FI degree of paraspinal muscle before the second operation and the first operation was negatively correlated with the occurrence time of ASDis ( r=-0.53, P=0.039) , and the difference of rCSA was positively correlated with the occurrence time of ASDis ( r=0.64, P=0.043) . Conclusion:When BMI >22.58 kg/m 2, FI of paraspinal muscle >15.69%, and rCSA of paraspinal muscle <1.92, it suggests that ASDis is more likely to occur after operation. And the more obvious paraspinal muscle atrophy after the first operation, the earlier ASDis may occur. Morphological changes of facet joints cannot be used as an index to predict the occurrence of ASDis.