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.

Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

Objective:To investigate the clinical characteristics, treatment and prognosis of juvenile dermatomyositis (JDM) complicated by sever gastrointestinal hemorrhage in children.Methods:A retrospective analysis was conducted on 4 JDM patients with sever gastrointestinal hemorrhage admitted to our hospital, from January 2017 to January 2025. Data including demographics, clinical manifestations, laboratory and imaging findings, treatment courses, and outcomes were reviewed.Results:The cohort comprised 4 patients (2 males, 2 females), with onset ages of 6.1, 6.2, 10.0 and 8.0 years. All presented with rash and fatigue and were diagnosed with severe refractory JDM (strongly positive anti-NXP2 antibodies). Sever gastrointestinal hemorrhage occurred 18, 12, 51, and 2 months after JDM diagnosis. Two cases had confirmed gastrointestinal infections due to contaminated food. Abdominal pain was the initial gastrointestinal symptom and black stool was observed in all cases, hemoglobin levels dropped below 60 g/L (case 1-4 decreased to 38, 59, 60 and 43 g/L respectively). All patients exhibited intestinal wall thickening. Active bleeding sites included the duodenum (3 cases: 2 cases near the duodenal papilla, 1 cases with diffuse duodenal oozing). Emergency endoscopic hemostasis was performed in 3 cases. One patient with diffuse duodenal bleeding required additional glucocortieoid pulse therapy after failed interventional embolization. Three patients stabilized following aggressive treatment of JDM, while 1 case died due to duodenal perforation.Conclusions:Anti-NXP2 antibody-positive JDM patients are prone to gastrointestinal involvement, particularly in chronic cases. Duodenal bleeding is common, with vascular erosion and deep mucosal ulcers posing life-threatening risks. For children with positive anti-NXP2 antibodies who present with abdominal pain and thickened intestinal walls, early endoscopic examination should be conducted as soon as possible to detect digestive tract lesions and provide timely treatment. Patients with severe digestive tract bleeding usually require active treatment for the underlying disease combined with endoscopic hemostasis therapy. Under timely treatment, the prognosis is relatively favorable.

Objective:To summarize the experience and effect of extracorporeal cardiopulmonary resuscitation (ECPR) in acute myocardial infarction (AMI) with in-hospital cardiac arrest (IHCA).Methods:The data of 70 patients with AMI-IHCA-ECPR in extracorporeal life support center of the first affiliated hospital of Nanjing medical university from January 2017 to December 2024 were retrospectively analyzed. The patients were grouped by Survival/death at 90 days, with/without combined intra-aortic balloon pump (IABP). Age, sex, Charlson comorbidity index, initial rhythm, Gensini score, ECPR initial blood gas pH and lactate value, no-flow time, time from cardiac arrest to extracorporeal membrane oxygenation (ECMO) initiation (CA-Pump On time), ECMO treatment time, 90-day survival rate were analyzed.Results:Among the 70 patients with AMI-IHCA-ECPR, 22 (31.4%) patients survived at 90 days, of whom 19 (86.4%) patients had good neurological outcomes. About 50% of AMI-IHCA-ECPR patients had severe multi-vessel coronary artery lesions, and there was no significant difference in survival outcomes among different vascular lesions. In the IABP group, the success rate of ECMO withdrawal was low, the duration of ECMO treatment was long, and the combination of IABP did not reduce the mortality. Compared with the death group, the 90-day survival group had a lower Gensini score, a higher ECPR initial blood gas pH and a lower lactic acid value.Conclusions:AMI-IHCA-ECPR combined with IABP did not show significant survival benefits, and about 50% of patients had severe lesions of multiple coronary arteries. It is difficult to evaluate the prognosis based on a single offender vessel. It is recommended to evaluate the outcome of patients by quantification of the severity of coronary artery lesions by Gensini score.

Bone-related diseases are a group of inflammatory diseases characterized by abnormal bone resorption and formation,with a wide variety of diseases involving age,inflammation,obesity,genetics,radiation,and other pathogenic factors.In recent years,se-nescent cells have become an important mechanism for age-related diseases,and their role in bone-related diseases has attracted the at-tention of researchers.Senescent cells are gradually being used as therapeutic targets for bone-related diseases.In this paper,we pres-ent a review of the mechanism of senescent cells in various types of bone-related diseases,which will provide new strategies for the pre-vention and treatment of bone diseases.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To explore clinical characteristics of multiple sclerosis(MS)patients in Suzhou,and to analyze main factors affecting their prognosis.Methods:General data,clinical symptoms,cerebrospinal fluid and imaging examinations of 51 MS patients admitted to Department of Neurology of the Second Hospital of Soochow University from July 31,2009 to July 31,2021 were retrospectively analyzed,and main factors affecting their prognosis were discussed.Results:Average age of onset of 51 MS patients was(43.3±15.6)years old,female accounted for 56.9%,male/female=1/1.3.Adult onset MS(AOMS)accounted for 62.8%,male/female=1/1.7;late onset MS(LOMS)accounted for 37.2%,male/female=1/0.9.Relapsing remitting MS(RRMS)accounted for 76.5%,and chronic onset accounted for 60.8%.Average annual recurrence rate was 8.8%.The first symptoms were numbness and weakness of limbs.Dizziness and numbness were more common in patients without recurrence after diagnosis of MS,and limb weak-ness and numbness were more common in patients with recurrence.Among lesions of MRI,62.7%(32/51)of periventricular involve-ment,52.9%(27/51)of spinal cord involvement,51.0%(26/51)of infratentorial involvement.Proportion of subtentorial and spinal cord(cervical,thoracic)involved were significantly higher in patients with recurrent MS than without recurrence.Values of albumin,IgG,IgA and IgM in cerebrospinal fluid increased with increase of recurrence times.EDSS score of male was higher than female,and LOMS score was higher than AOMS.MS patients without relapse had a low EDSS score,and median EDSS score at current follow-up was 0(0,1.00)score.MS score with relapse was relatively high,and median EDSS score at current follow-up was 2.75(0.25,7.25)score.Conclusion:MS patients with chronic onset are more common,with a high proportion of LOMS,and proportion of males increases with increasing age of onset.High EDSS score at first onset,cervical,thoracic and subtentorial lesions,increased values of cerebrospinal fluid albumin,IgG,IgA,IgM,age at first onset(50+years old),male associate with poor MS prognosis.

Objective:To investigate the effects of paclitaxel combined with Ipatasertib on the proliferation,migration and epitheli-al-mesenchymal transition(EMT)of oral squamous cell carcinoma(OSCC)SCC-9 cells in vitro.Methods:SCC-9 cells were treated with paclitaxel and Ipatasertib repectively and in combination.CCK-8 test and EdU assay were used to detect cell proliferation ca-pacity.Cellular migration was detected by Transwell and scratch method.The protein expressions of E-cad,N-cad,Vimentin,AKT and NF-κB were detected by Western blot.Results:Paclitaxel of 0.5-32 μmol/L combined with Ipatasertib of 2.5 μmol/L(IC50)showed synergistic inhibitory effect on the proliferation of SCC-9 cells,the combination of paclitaxel and ipatasertib more significantly inhibited the migration,down-regulated the protein expression of AKT,NF-κB,N-cad and Vimentin,and up-regulated the protein expression of E-cad.Conclusion:The combination of paclitaxel and Ipatasertib may have synergistic inhibitory effects on the prolif-eration,migration and EMT of OSCC cells,the function may be ralated with the inhibition of PI3K/AKT signaling pathway.