ObjectiveTo investigate the effects of metformin on the immune functions of immature dendritic cells （imDCs） and the underlying mechanisms. MethodsMouse bone marrow-derived imDCs were treated with different concentrations of metformin. The working concentration and treatment time of metformin in this study were determined based on the results of cell apoptosis and cell viability assays. The effects of metformin on the phagocytic capacity of imDCs was evaluated using an antigen endocytosis assay. The expression of cluster of differentiation 205 （CD205）， the polymerization of filamentous actin （F-actin）， and the underlying regulatory mechanisms were investigated through flow cytometry， laser confocal fluorescence microscopy， and Western blot. ResultsThe working concentrations of metformin were 1， 2， 4 mmol/L for 24 h determined by the apoptosis and cell viability assays.Metformin significantly suppressed the phagocytic capacity of imDCs， down-regulated the expression of the mannose receptor CD205 on the cell surface， which was closely associated with phagocytic function； metformin inhibited the RhoA-ROCK1-LIMK1-Cofilin signaling pathway， which inhibited the polymerization of F-actin and disturbed its dynamic remodeling of imDCs. ConclusionMetformin can inhibit the expression of CD205 and disrupt the remodeling of F-actin， thereby suppressing the antigen-capturing capacity of imDCs.

BACKGROUND:Mechanical alignment is the"gold standard"alignment technique in total knee arthroplasty,but regardless of advances in prosthetic materials and robotic-assisted navigation,mechanical alignment-total knee arthroplasty still has a patient dissatisfaction rate of about 20％.OBJECTIVE:To evaluate the early efficacy of navigation-assisted total knee arthroplasty using functional alignment.METHODS:A total of 44 consecutive cases(50 knees)that underwent computer navigation-assisted total knee arthroplasty with functional alignment from October 2019 to June 2023 were retrospectively analyzed,including 12 males(14 knees)and 32 females(36 knees).A total of 46 consecutive cases(50 knees)that underwent navigation-assisted total knee arthroplasty with mechanical axis alignment by the same surgical team during the same period were selected as controls,including 5 males(5 knees)and 41 females(45 knees).The tibial osteotomy angle,tibial plateau osteotomy amount,femoral osteotomy angle,distal femoral,posterior and anterior osteotomy amount,and joint line movement were observed in the two groups of patients.Preoperative and postoperative flexion and extension gap internal and external laxity,hip-knee-ankle angle,mechanical lateral distal femoral angle,mechanical medial proximal tibial angle,joint line convergence angle,sagittal femoral component angle,posterior tibial slope,arithmetic hip-knee-ankle angle,joint line obliquity,coronal plane alignment of the knee classification,Western Ontario and McMaster Universities Osteoarthritis Index,and Hospital for Special Surgery score and forgotten joint score were compared between the two groups.RESULTS AND CONCLUSION:(1)The intraoperative tibial plateau osteotomy angle in the functional alignment group was greater than that in the mechanical axis alignment group,and the proportion of gap imbalance(2％)was smaller than that in the mechanical axis alignment group(18％).The differences were all significant(P＜0.05).(2)The hip-knee-ankle angle,mechanical medial proximal tibial angle,arithmetic hip-knee-ankle angle,and joint line obliquity in the functional alignment group were smaller than those in the mechanical axis alignment group postoperatively,and the differences were significant(P＜0.05).(3)The most common coronal plane alignment of the knee classification before surgery was type Ⅰ(80％in the functional alignment group and 42％in the mechanical axis alignment group).(4)The proportion of joint line obliquity＜177°(44％)in the functional alignment group was greater than that in the mechanical axis alignment group(14％)postoperatively.(5)Hospital for Special Surgery score at 1 month,6 months,and last follow-up after surgery was higher in the functional alignment group than that in the mechanical axis alignment group;the differences were statistically significant(P＜0.05).The Western Ontario and McMaster Universities Osteoarthritis Index 1 month after surgery was lower in the functional alignment group than that in the mechanical axis alignment group;the difference was statistically significant(t=-2.85,P=0.005).There was no significant difference in postoperative range of motion and forgotten joint score between the two groups(P＞0.05).(6)It is indicated that navigation-assisted total knee arthroplasty using functional alignment optimizes early clinical efficacy.The functional alignment technique has advantages in restoration of constitutional alignment and joint line obliquity and avoids soft tissue release compared to mechanical alignment technique.

Aim To explore the predictive value of stress hyperglycemia ratio(SHR)for in-hospital mortality and mechanical complications in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods This study constituted a retrospective investigation that collected 995 patients diagnosed with acute STEMI at Suining Central Hospital from June 2019 to July 2023.Comparisons of baseline data were conducted using t-test,Mann-Whitney U test and chi-square test;Logistic regression was used to analyze the association between SHR and the risk of in-hospital mortality and mechanical complications in acute STEMI patients;Restricted cubic spline analysis based on the Logistic re-gression model was utilized to explore non-linear relationship between SHR and the risk of in-hospital mortality and mechan-ical complications;ROC curve was used to evaluate the diagnostic efficacy of SHR;Subgroup analysis was used to assess the predictive efficacy of SHR in each subgroup.Results Patients with high SHR had a significantly higher cardiovas-cular mortality(P=0.007).High SHR was an independent risk factor for in-hospital all-cause mortality(Model 1:OR=3.085,95％ CI:1.719～5.538,P＜0.001;Model 2:OR=2.738,95％ CI:1.4439～5.132,P=0.002),cardiovascular mortality(Model 1:OR=3.406,95％ CI:1.869～6.228,P＜0.001;Model 2:OR=3.053,95％ CI:1.595～5.817,P＜0.001),ventricular aneurysm(Model 1:OR=3.203,95％CI:1.665～6.069,P＜0.001;Model2:OR=3.93,95％CI:1.785～8.663,P＜0.001),cardiac rupture(Model 1:OR=2.461,95％ CI:1.389～4.312,P=0.002;Model 2:OR=2.302,95％ CI:1.214～4.274,P=0.009)and composite endpoint(Model 1:OR=3.719,95％ CI:2.226～6.332,P＜0.001;Model 2:OR=2.919,95％ CI:1.576～5.405,P＜0.001)in patients with acute STEMI.SHR was positively correlated in a linear relationship with the risk of in-hospital all-cause mortality(P for non-linearity=0.250),cardiovascular mortality(P for non-linearity=0.129),ventricular aneurysm(P for non-linearity=0.588),cardiac rupture(P for non-linearity=0.787)and composite endpoint(P for non-linearity=0.399).The SHR had excellent diagnostic efficacy for in-hospital all-cause mortality(AUC=0.694),cardiovascular mortality(AUC=0.697),ventricular aneurysm(AUC=0.706),cardiac rupture(AUC=0.667)and composite endpoint(AUC=0.730),meanwhile SHR predicted efficacy consistently across subgroups.Conclusions High SHR is an independent risk factor for in-hospital all-cause mortality,cardiovascular mortality and cardiac mechanical complications in patients with a-cute STEMI.SHR holds significant predictive value for the prognosis of patients with STEMI.

Accurate characterization of the chemical composition of complex traditional Chinese medicine(TCM)is an essential foundation for the modern scientific interpretation of TCM principles.Mass spectrometry is the most dominant technique in current research on the material basis of TCM,offering the highest sensitivity and the richest information provision.Establishing mass spectrometry databases represents the most effective approach to facilitating the structural analysis of TCM chemical components.This paper systematically searches and reviews literature published from January 2005 to January 2025 through online databases such as China National Knowledge Infrastructure,PubMed,and Web of Science,using"mass spectrometry database"and"traditional Chinese medicine"as keywords.It reviews the current status of seven TCM chemical component mass spectrometry databases and seven natural product mass spectrometry databases.The key advancements of these mass spectrometry databases for natural products are summarized,detailing their characteristics,search methodologies,included information,and data sources.Additionally,challenges related to data quality,standardization,timely updates,database interaction,retrieval functionality,and data sharing and security are discussed in depth.Furthermore,the paper explores prospective development directions for TCM mass spectrometry databases,emphasizing the importance of open data sharing,technological innovation,and data security.Through this analysis,the paper aims to offer theoretical guidance and practical recommendations for the precise identification of TCM components,as well as for the construction and application of these databases.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Aim To explore the predictive value of stress hyperglycemia ratio(SHR)for in-hospital mortality and mechanical complications in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods This study constituted a retrospective investigation that collected 995 patients diagnosed with acute STEMI at Suining Central Hospital from June 2019 to July 2023.Comparisons of baseline data were conducted using t-test,Mann-Whitney U test and chi-square test;Logistic regression was used to analyze the association between SHR and the risk of in-hospital mortality and mechanical complications in acute STEMI patients;Restricted cubic spline analysis based on the Logistic re-gression model was utilized to explore non-linear relationship between SHR and the risk of in-hospital mortality and mechan-ical complications;ROC curve was used to evaluate the diagnostic efficacy of SHR;Subgroup analysis was used to assess the predictive efficacy of SHR in each subgroup.Results Patients with high SHR had a significantly higher cardiovas-cular mortality(P=0.007).High SHR was an independent risk factor for in-hospital all-cause mortality(Model 1:OR=3.085,95％ CI:1.719～5.538,P＜0.001;Model 2:OR=2.738,95％ CI:1.4439～5.132,P=0.002),cardiovascular mortality(Model 1:OR=3.406,95％ CI:1.869～6.228,P＜0.001;Model 2:OR=3.053,95％ CI:1.595～5.817,P＜0.001),ventricular aneurysm(Model 1:OR=3.203,95％CI:1.665～6.069,P＜0.001;Model2:OR=3.93,95％CI:1.785～8.663,P＜0.001),cardiac rupture(Model 1:OR=2.461,95％ CI:1.389～4.312,P=0.002;Model 2:OR=2.302,95％ CI:1.214～4.274,P=0.009)and composite endpoint(Model 1:OR=3.719,95％ CI:2.226～6.332,P＜0.001;Model 2:OR=2.919,95％ CI:1.576～5.405,P＜0.001)in patients with acute STEMI.SHR was positively correlated in a linear relationship with the risk of in-hospital all-cause mortality(P for non-linearity=0.250),cardiovascular mortality(P for non-linearity=0.129),ventricular aneurysm(P for non-linearity=0.588),cardiac rupture(P for non-linearity=0.787)and composite endpoint(P for non-linearity=0.399).The SHR had excellent diagnostic efficacy for in-hospital all-cause mortality(AUC=0.694),cardiovascular mortality(AUC=0.697),ventricular aneurysm(AUC=0.706),cardiac rupture(AUC=0.667)and composite endpoint(AUC=0.730),meanwhile SHR predicted efficacy consistently across subgroups.Conclusions High SHR is an independent risk factor for in-hospital all-cause mortality,cardiovascular mortality and cardiac mechanical complications in patients with a-cute STEMI.SHR holds significant predictive value for the prognosis of patients with STEMI.

Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.