Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

BACKGROUND:Hydrogels have become a research hotspot due to their unique advantages in the biomedical field due to their superior mechanical and biological properties.At present,related research involves tissue engineering,wound dressing and so on. OBJECTIVE:To review the advantages and properties of hydrogels and the research progress of their application in the repair of oral and maxillofacial defects,discuss the current limitations and challenges of hydrogels in application and promotion,and provide new ideas for future research directions. METHODS:Relevant literature was searched in PubMed,CNKI,and WanFang database by computer.The search terms were"hydrogel,oral and maxillofacial defects,mechanical properties,tissue engineering,wound dressing"in Chinese and"hydrogel,oral and maxillofacial defects,mechanical properties,guided tissue regeneration,wound dressing"in English.Preliminary screening was carried out by reading titles and abstracts,and articles not related to the topic of the article were excluded.According to the inclusion and exclusion criteria,108 articles were finally included for the result analysis. RESULTS AND CONCLUSION:(1)The hydrogel has good biological activity,mechanical controllability,and stimulation response.(2)Polymer,metal,and ceramic hydrogel composites have appropriate mechanical properties,biodegradability,and controlled release rate,which are suitable for maxillofacial bone tissue engineering.(3)Fibrin-based hydrogel could fill the hollow nerve conduit through the nerve defect area and promote the regeneration and growth of axons to restore the function of maxillofacial nerve.(4)Controlling the interaction between nanomaterials and hydrogels can improve the formation of muscle fiber oriented structure to promote maxillofacial muscle tissue regeneration.(5)Polysaccharide hydrogel has gradually become the first choice for repairing irregular periodontal defects due to its ability to control drug delivery,carry bioactive molecules,and combine with other materials to produce the best scaffold matching the extracellular matrix.(6)Calcium phosphate or calcium carbonate-based hydrogels can be used to fill irregular or fine tissue defects and remineralize hard tissues.The self-assembled hydrogels are simple to prepare and have good biological activity.(7)Salivary gland-derived extracellular matrix-like gel is expected to participate in the treatment of many salivary gland diseases.(8)Hydrogels can be used as wound dressings in combination with biological adhesives,acellular biomaterials,antimicrobials,antioxidants,or stem cells to treat various wounds.(9)Fibrin-based hydrogel has the most potential in the repair of oral and maxillofacial defects.It has excellent biocompatibility,flexibility,and plasticity.It can combine with cells,extracellular matrix proteins,and various growth factors,and promote the osteogenic differentiation of mesenchymal stem cells,axon regeneration and growth,angiogenesis,myotube differentiation,salivary gland tissue regeneration,and periodontal tissue regeneration.It has a broad prospect in the repair of oral and maxillofacial defects.However,its therapeutic effect depends on the function of the substance carried.The complex preparation process,its safety and long-term efficacy,and the special anatomical oral and maxillofacial structure is the problem that hinders its promotion,which also provides directions for future research.

Objective To investigate the clinical value of metagenomic next-generation sequencing(mNGS)in the detection of pathogenic microorganisms in pediatric infectious diseases and to analyze the clinical characteristics of relevant cases.Methods A retrospective analysis was conducted on 30 pediatric patients who underwent mNGS pathogen detection in Hangzhou Red Cross Hospital from January 2023 to January 2024,along with 30 patients who did not undergo mNGS testing as the control group.Clinical information,including age,gender,hospital stay,symptoms and signs,routine blood tests,C-reactive protein(CRP),imaging findings,mNGS pathogen detection results,and patient outcomes,was collected.The differences between mNGS and conventional microbiological testing(CMT)results were compared,and the impact of mNGS testing on infection treatment and hospitalization duration was analyzed.Results Among the 30 patients who underwent mNGS testing,21 were male and 9 were female;with an age range of 1 year 5 months to 12 years 9 months,mean age:(7.15±3.13)years.The mNGS test identified 9 viruses,10 Gram-positive bacteria,5 Gram-negative bacteria,3 fungi,and 5 specific pathogens.Based on the test results,12 patients had their anti-infective treatment plans adjusted,with an average hospital stay of(10.63±3.15)days.In the control group,7 patients had their treatment plans adjusted,with an average hospital stay of(12.64±2.79)days.The average hospital stay was significantly shorter in the mNGS group compared to the control group(P<0.05).Conclusions The clinical symptoms and signs of pediatric infectious diseases often lack specificity,and CMT methods are suboptimal.mNGS exhibits high sensitivity for pathogen detection and demonstrates significant value in etiological diagnosis and therapeutic guidance when CMT fails to identify pathogens.However,interpretation of mNGS results requires integration with clinical presentations and other auxiliary diagnostic findings.

Objective To investigate the current status of cleaning,disinfection,and sterilization management of dental instruments in medical institutions in Henan Province,analyze potential issues in hospital infection control,and propose targeted nursing strategies.Methods A convenience sampling method was used to survey the cleaning,disinfection,and sterilization management of dental instruments in 352 medical institutions in Henan Province from February to April 2024.A self-made questionnaire was designed,covering aspects such as the handling model and personnel configuration for dental instruments,training for cleaning,disinfection,and sterilization personnel,configuration and maintenance of cleaning and disinfection equipment,use and management of small pressure steam sterilizers,and reprocessing status of dental instruments.Results A total of 352 questionnaires were distributed,with 348 valid responses.Among the 34 primary medical institutions,only 10(29.41％)had a centralized cleaning,disinfection,and sterilization model for dental instruments;13(38.24％)had dedicated personnel for cleaning,disinfection,and sterilization of dental instruments;25(73.53％)were equipped with pressure water guns.Compari-sons among medical institutions of different levels showed statistically significant differences(P＜0.001).In the 348 medical institutions,194(55.75％)arranged pre-job training for nursing personnel;143(41.09％)performed mainte-nance on cleaning and disinfection equipment once a year;52(14.94％)did not perform pre-treatment on contaminated dental instruments after use.Among the 104 institutions using small pressure steam sterilizers,21(20.19％)used Type N small pressure steam sterilizers.Conclusion The centralized management rate of dental instruments and the basic equipment configuration rate in primary medical institutions in Henan Province are relatively low.There are issues such as insufficient personnel training,neglect of equipment maintenance,improper management of small pressure steam sterilizer usage,and incomplete reprocessing procedures in medical institutions at all levels.It is recommended that nursing managers further strengthen the training of nurses in the disinfection supply center,standardize the cleaning,disinfection,and sterilization workflow for dental instruments,in order to prevent and control hospital infections.

OBJECTIVE To investigate the epidemiological characteristics,clinical features and distribution of pathogens isolated from the burn wound patients with infections in a northwestern hospital from 2014 to 2023 so as to provide bases for prevention and treatment of burn wound infections in the northwestern region.METHODS The epidemiological characteristics,clinical features and distribution of pathogenic isolated from the burn wound patients with infections who were treated in the 940th Hospital of Joint Logistic Support Force from 2014 to 2023 were retrospectively analyzed.RESULTS A total of 2122 burn wound patients were enrolled in the study,397(18.71％)of whom had infections,including 306(14.42％)patients with community-acquired infections and 91(4.29％)patients with hospital-acquired infections.The proportion infections was higher among the patients aged no less than 60 years old(63/154)than among the patients aged less than 14 years old(231/983)and the pa-tients aged between 14 and 60 years old(103/985)(x2=108.840,P＜0.001).The proportion of infections was higher among the patients with the burn wound depth no less than grade Ⅲ(146/458)than among the patients with the burn wound depth no less than grade Ⅱ(251/1664)(x2=66.600,P＜0.001).The proportion infections was higher among the patients with burn wounds in limbs(370/1881)than among the patients with burn wounds in other sites(1153/1987)(x2=47.244,P＜0.001).The isolation rates of methicillin-resistant Staphy-lococcus epidermidis and carbapenem-resistant Pseudomonas aeruginosa strains showed downward trends from 2014 to 2023,the isolation rates of carbapenem-resistant Klebsiella pneumoniae and the third generation cephalo-sporins-resistant Escherichia coli showed upward trends,however,there were no significant differences.CONCLUSIONS The patients with no less than 60 years of age,no lower than grade Ⅲ of burn wound depth and burn wounds in limbs are more likely to have burn wound infections.S.aureus is the predominant species of pathogens causing the infections.The isolation rates of carbapenem-resistant K.pneumoniae strains and the third generation cephalosporins-resistant E.coli strains show upward trends.It is necessary to take targeted prevention and treatment measures for the burn wound infections.

This study was aimed at exploring the mechanism underlying the effects of nitidine chloride against Talaromyces marnef-fei through network pharmacology analysis.We collected NC and TM action targets from various databases;constructed a protein-protein interaction(PPI)network by using common drug and disease targets;and performed KEGG pathway and GO enrichment analy-ses.In vitro cellular experiments were conducted to test the antibacterial ability of NC at various concentrations,qPCR was used to de-tect the mRNA expression of genes in the target pathway,and WB was used to examine the expression of proteins associated with tar-get signaling pathways in cells.We identified 153 target genes for NC and 2 095 target genes for TM,among which 23 targets over-lapped.By integrating the PPI network with KEGG enrichment analysis,we selected key target genes in the MAPK signaling pathway,such as FLT1,FLT3,CD38,and PRF1.The CFU results indicated that NC had favorable antibacterial capability.Moreover,qPCR demonstrated that NC downregulated the mRNA expression of FLT1,FLT3,and RPS6KA3,and upregulated the mRNA expression of MAP3K8.WB findings indicated that NC downregulated the expression of RSK2,VEGF,and FLT3 proteins,and upregulated the ex-pression of MAP3K8 protein.NC may exert its anti-TM effects by downregulating the expression of RSK2,VEGF,and FLT3 proteins,thereby inhibiting MAPK pathway activation.The potential targets and signaling pathways underlying NC's anti-TM action may pro-vide new insights to guide the clinical application of NC.

BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P＜0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P＞0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.