The molecular mechanism of verbascoside(OC1) in promoting acetylcholine(ACh) release in the pathogenesis of Alzheimer's disease(AD) was studied. Adrenal pheochromocytoma cells(PC12) of rats induced by β-amyloid protein(1-42)(Aβ_(1-42)) were used as AD models in vitro and were divided into control group, model group(Aβ_(1-42) 10 μmol·L~(-1)), OC1 treatment group(2 and 10 μg·mL~(-1)). The effect of OC1 on phosphorylated proteins in AD models was analyzed by whole protein phosphorylation quantitative omics, and the selectivity of OC1 for calcium channel subtypes was virtually screened in combination with computer-aided drug design. The fluorescence probe Fluo-3/AM was used to detect Ca~(2+) concentration in cells. Western blot analysis was performed to detect the effects of OC1 on the expression of phosphorylated calmodulin-dependent protein kinase Ⅱ(p-CaMKⅡ, Thr286) and synaptic vesicle-related proteins, and UPLC/Q Exactive MS was used to detect the effects of OC1 on ACh release in AD models. The effects of OC1 on acetylcholine esterase(AChE) activity in AD models were detected. The results showed that the differentially modified proteins in the model group and the OC1 treatment group were related to calcium channel activation at three levels: GO classification, KEGG pathway, and protein domain. The results of molecular docking revealed the dominant role of L-type calcium channels. Fluo-3/AM fluorescence intensity decreased under the presence of Ca~(2+) chelating agent ethylene glycol tetraacetic acid(EGTA), L-type calcium channel blocker verapamil, and N-type calcium channel blocker conotoxin, and the effect of verapamil was stronger than that of conotoxin. This confirmed that OC1 promoted extracellular Ca~(2+) influx mainly through its interaction with L-type calcium channel protein. In addition, proteomic analysis and Western blot results showed that the expression of p-CaMKⅡ and downstream vesicle-related proteins was up-regulated after OC1 treatment, indicating that OC1 acted on vesicle-related proteins by activating CaMKⅡ and participated in synaptic remodeling and transmitter release, thus affecting learning and memory. OC1 also decreased the activity of AChE and prolonged the action time of ACh in synaptic gaps.
Animals ; Rats ; Glucosides/administration & dosage* ; Acetylcholine/metabolism* ; Alzheimer Disease/genetics* ; PC12 Cells ; Phenols/chemistry* ; Neurotransmitter Agents/metabolism* ; Drugs, Chinese Herbal ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics* ; Humans ; Phosphorylation/drug effects* ; Calcium/metabolism* ; Polyphenols

PURPOSE: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

OBJECTIVE: To investigate the clinical effect of minimally invasive technique in the treatment of moderate and severe gluteal muscle contracture. METHODS: A retrospective study was conducted on 85 patients (170 sides) with bilateral gluteal muscle contracture admitted from January 2016 to December 2019. All patients were treated with minimally invasive release of tendon knife. There were 32 males and 53 females, ranging in age from 15 to 37 years old, with an average age of (22.3±6.3) years old. Operation time, intraoperative blood loss, incision length, first postoperative ambulation time, complication rate, recurrence rate, and Harris hip score (HHS) were analyzed and evaluated. RESULTS: The average follow-up time was (16.2±4.6) months, ranging from 12 to 30 months. The operation time ranged from 7 to 15 min, with an average of (10.2±3.1) min. Intraoperative blood loss ranged from 2 to 20 ml, with an average of (8.4±2.2) ml. The incision length ranged from 0.6 to 2.0 cm, with an average of (0.8±0.3) cm. The time to postoperative ambulation ranged from 12 to 28 h, with an average of (20.0±3.2) h. All patients achieved primary wound healing without sciatic nerve injury or recurrence. HHS hip function scores ranged from 90 to 98, with an average score of (96.2±1.4). Complications included intraoperative tendon blade tip fracture in two cases (removed under fluoroscopic guidance) and subcutaneous hematoma in three cases-two resolved with compression and one with open evacuation.. Twenty-nine patients exhibited transient swaying gait postoperatively, of which 24 patients returned to normal after 4 weeks and 5 patients returned to normal after 6 weeks. CONCLUSION Minimally invasive tendon blade release is a safe and effective technique for treating gluteal muscle contracture, offering minimal trauma, rapid recovery, and excellent cosmetic and functional outcomes. However, it exhibits a low risk of blade tip fracture and sciatic nerve injury, warranting experienced surgical handling.
Humans ; Male ; Female ; Adult ; Minimally Invasive Surgical Procedures/methods* ; Adolescent ; Retrospective Studies ; Buttocks/surgery* ; Young Adult ; Contracture/surgery* ; Tendons/surgery* ; Muscle, Skeletal/surgery*

Objective This research was performed to identify rodent-borne pathogens in Hekou Port,Yunnan Province.Methods Rodents were captured using cages and dissected to collect their lungs,liver,spleen,and other viscera.Eight pathogens,including Yersinia pestis,Leptospira,Bartonella,and Anaplasmataceae,were identified using polymerase chain reaction amplification.Amplified pathogen sequences from positive samples were sequenced,and BLAST homology searches were conducted using GenBank to confirm pathogen identities.A phylogenetic tree of the identified pathogens was constructed using the neighbor joining method.Results The total of 31 rodents,identified as Rattus tanezumi,R.norvegicus,and Mus musculus,were captured.Among these,R.tanezumi was the dominant species,accounting for 64.52％of the total.Two pathogens,Leptospira interrogans and Neoehrlichia mikurensis,were detected,with positivity rates of 9.68％and 29.03％,respectively.No other pathogens were detected.The overall positivity rate for rodent-borne pathogens was 35.48％.Conclusions The single 16S rRNA gene fragment is insufficient for the molecular identification of all Neoehrlichia species.Accurate species identification should be based on a combined analysis of multiple genes.The prevalence of rodent-borne pathogens in Hekou Port indicates the necessity for enhanced surveillance of rodent-borne diseases and implementation of additional prevention and control measures in border ports.

Objective:In this study, we aimed to investigate the short-term efficacy and safety of perioperative administration of the PD-1 inhibitor tislelizumab combined with the SOX regimen (oxaliplatin plus S-1) in patients with locally advanced gastric cancer, and to identify factors influencing therapeutic outcomes.Methods:In this retrospective cohort study, we analyzed clinical data of 166 patients who had undergone perioperative therapy and D2 radical gastrectomy in the Department of General Surgery, First Medical Center of Chinese PLA General Hospital between September 2021 and September 2023. The cohort comprised 140 men and 26 women, of median age 62 years (range: 30-75). The patients were allocated to two groups: 62 receiving tislelizumab plus SOX (combination therapy group), and 104 SOX alone (chemotherapy-only group). Primary outcomes included pathological complete response rate, treatment-related adverse events, and complications of surgery. Secondary outcomes comprised major pathological response rate, tumor regression grade (Grades 1-2 denoting favorable response, Grade 3 moderate, and Grades 4-5 poor response), R0 resection rate, and short-term survival outcomes (1-year disease-free and overall survivals). Risk factors associated with pCR in the combination group were also analyzed.Results:The combination therapy group exhibited significantly higher rates of pCR (25.8% vs. 8.7%, χ 2=8.93, P=0.003) and Grade 1 tumor regression (25.8% vs. 16.3%, χ 2=15.32, P=0.001) than the chemotherapy-only group. There were no statistically significant differences in major pathological response rates (41.9% vs. 39.4%), R0 resection rates (96.8% vs. 97.1%,), treatment- related adverse events (48.4% vs. 42.3%,), surgical complications (9.7% vs. 12.5%), 1-year disease-free survival (82.3% vs. 78.8%), or 1-year overall survival (93.5% vs. 91.3%), There were no statistically significant differences (all P>0.05). Multivariate logistic analysis identified neural invasion as an independent risk factor for reduced pCR in the combination group (OR=0.10, 95%CI:0.01-0.85, P=0.035). Conclusions:Perioperative tislelizumab combined with SOX chemotherapy improves pathological response rates in patients with locally advanced gastric cancer and has favorable short-term efficacy and safety profiles. Neural invasion may diminish the therapeutic efficacy of immunotherapy.

Objective To explore the effects of dodecanoylcarnitine(DA)and myristoleic acid(MA)on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms.Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4.The expression levels of DA,MA,and sphingosine-1-phosphate(S1P)in the cell supernatant were detected by ELISA.MLE-12 cells were separately intervened with DA and MA.RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α(TNF-α)and the level of intracellular reactive oxygen species(ROS).Additionally,Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase(p-38 MAPK)and src homology 2 domain-containing phosphatase 1(SHP-1).To explore the role of S1PR2 in the effects of DA and MA,MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013,and the above experiments were repeated.Results IL-4 stimulation significantly upregulated the levels of DA,MA,and S1P in MLE-12 cells(P<0.05).DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group(P<0.05),along with elevated ROS levels(P<0.05).Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells.Notably,JTE-013 pre-treatment completely reversed these effects(P<0.05).Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor,promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway.This study reveals the core regulatory role of S1PR2 in this pathway as well.

Objective To explore the effects of dodecanoylcarnitine(DA)and myristoleic acid(MA)on the function of mouse alveolar epithelial cell line MLE-12 and their underlying mechanisms.Methods An inflammatory model was established by stimulating MLE-12 cells with IL-4.The expression levels of DA,MA,and sphingosine-1-phosphate(S1P)in the cell supernatant were detected by ELISA.MLE-12 cells were separately intervened with DA and MA.RT-PCR and flow cytometry were used to detect the expression changes of inflammatory factors IL-6 and tumor necrosis factor-α(TNF-α)and the level of intracellular reactive oxygen species(ROS).Additionally,Western blot was performed to detect the expression of key proteins such as p38 mitogen-activated protein kinase(p-38 MAPK)and src homology 2 domain-containing phosphatase 1(SHP-1).To explore the role of S1PR2 in the effects of DA and MA,MLE-12 cells were pretreated with the S1PR2 inhibitor JTE-013,and the above experiments were repeated.Results IL-4 stimulation significantly upregulated the levels of DA,MA,and S1P in MLE-12 cells(P<0.05).DA/MA treatment groups exhibited significantly increased expression of IL-6 and TNF-α compared with the control group(P<0.05),along with elevated ROS levels(P<0.05).Western blot analysis revealed that DA/MA promoted SHP-1 dephosphorylation and phosphorylated p38 MAPK activation in MLE-12 cells.Notably,JTE-013 pre-treatment completely reversed these effects(P<0.05).Conclusion Asthma-related metabolites DA and MA exacerbate the inflammatory and oxidative stress responses of MLE-12 cells by activating the S1PR2 receptor,promoting the dephosphorylation of SHP-1 and the activation of the p-p38 MAPK pathway.This study reveals the core regulatory role of S1PR2 in this pathway as well.

Objective:In this study, we aimed to investigate the short-term efficacy and safety of perioperative administration of the PD-1 inhibitor tislelizumab combined with the SOX regimen (oxaliplatin plus S-1) in patients with locally advanced gastric cancer, and to identify factors influencing therapeutic outcomes.Methods:In this retrospective cohort study, we analyzed clinical data of 166 patients who had undergone perioperative therapy and D2 radical gastrectomy in the Department of General Surgery, First Medical Center of Chinese PLA General Hospital between September 2021 and September 2023. The cohort comprised 140 men and 26 women, of median age 62 years (range: 30-75). The patients were allocated to two groups: 62 receiving tislelizumab plus SOX (combination therapy group), and 104 SOX alone (chemotherapy-only group). Primary outcomes included pathological complete response rate, treatment-related adverse events, and complications of surgery. Secondary outcomes comprised major pathological response rate, tumor regression grade (Grades 1-2 denoting favorable response, Grade 3 moderate, and Grades 4-5 poor response), R0 resection rate, and short-term survival outcomes (1-year disease-free and overall survivals). Risk factors associated with pCR in the combination group were also analyzed.Results:The combination therapy group exhibited significantly higher rates of pCR (25.8% vs. 8.7%, χ 2=8.93, P=0.003) and Grade 1 tumor regression (25.8% vs. 16.3%, χ 2=15.32, P=0.001) than the chemotherapy-only group. There were no statistically significant differences in major pathological response rates (41.9% vs. 39.4%), R0 resection rates (96.8% vs. 97.1%,), treatment- related adverse events (48.4% vs. 42.3%,), surgical complications (9.7% vs. 12.5%), 1-year disease-free survival (82.3% vs. 78.8%), or 1-year overall survival (93.5% vs. 91.3%), There were no statistically significant differences (all P>0.05). Multivariate logistic analysis identified neural invasion as an independent risk factor for reduced pCR in the combination group (OR=0.10, 95%CI:0.01-0.85, P=0.035). Conclusions:Perioperative tislelizumab combined with SOX chemotherapy improves pathological response rates in patients with locally advanced gastric cancer and has favorable short-term efficacy and safety profiles. Neural invasion may diminish the therapeutic efficacy of immunotherapy.

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Objective To investigate the risk factors of microcirculation obstruction(MVO)after reperfusion in patients with acute myocardial infarction(AMI).Methods Forty-one patients with AMI who received treatment with myocardial reperfusion were retrospectively selected.Cardiac magnetic resonance(CMR)was used to determine whether the patients had MVO.The patients were divided into MVO and non-MVO groups.The basic data,laboratory examination and CMR parameters of patients were collected and compared between the groups,and the risk factors related to MVO were screened out by logistic regression analysis.Results Delayed myocardial enhancement was observed in all 41 patients,among which 11 cases(26.8%)were with MVO.A total of 206 delayed myocardial enhancement segments were observed,of which 77 segments combined with MVO and 129 segments without MVO.AMI patients with MVO had a higher rate of transmural myocardial infarction,greater infarct volume,left ventricular myocardial mass(LVMM)and edema degree,as well as lower ejection fraction of left and right ventricles(P<0.05).Multivariate logistic regression analysis indicated that infarct volume[odds ratio(OR)=1.116,95%confidence interval(CI)1.017-1.224,P=0.020]was an independent risk factor for MVO after AMI reperfusion.Conclusion Infarct volume is an independent risk factor for MVO after AMI reperfusion,and MVO is associated with left and right ventricular function impairment.