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.

One of the most common adverse reactions associated with cancer and its treatment is sarcopenia,a syndrome primarily caused by the disruption of muscle homeostasis,leading to excessive muscle atrophy and decreased muscle strength.For cancer patients,sarcopenia reflects not only a state of muscle mass loss but also serves as an important factor affecting treatment efficacy and survival rates.However,cancer-related sarcopenia often has a more insidious onset,is not visible to the naked eye,and is easily overlooked.Therefore,it is necessary to recognize the dangers of sarcopenia throughout the cancer treatment process and to identify low muscle mass early.In recent years,as healthcare professionals have increasingly focused on sarcopenia,research on cancer-related sarcopenia has gradually deepened,with new advancements in its assessment,diagnosis,intervention,and impact on anti-cancer treatment.This article provides a review of these key areas to offer a theoretical basis for the clinical practice of cancer-related sarcopenia.

Objective To look for cognitive assessment paradigms and electrocardiographic(ECG)characteristics sensitive to mental fatigue through an experimental study.Methods Data were collected from 10 healthy students of the University of Shanghai for Science and Technology who participated in the 4-day National Undergraduate Electronics Design Contest,including their Stanford sleepiness scale(SSS)scores,sleep duration,cognitive task performance,and ECG signal data.Ten ECG features,including time-domain,frequency-domain,and information-domain characteristics,were extracted during cognitive tasks.The cognitive task performance and ECG features sensitive to changes in mental fatigue were analyzed.Results Significant differences were observed in SSS scores(x2=23.116,P＜0.001)and sleep duration(x2=19.608,P＜0.001)across the 4 d.For cognitive task performance,word-color congruent accuracy and word-color incongruent accuracy in the Stroop task and Single-visual target stimulus accuracy and Visual target-auditory non-target stimulus accuracy in the audiovisual competition task all showed significant negative correlations with SSS scores(all P＜0.05).Regarding ECG features,Poincaré plot SD2 during the Stroop task was positively correlated with sleep duration(P＜0.05),while Poincaré plot SD2 during the 2-back task was positively correlated with mental fatigue assessment scores and was negatively correlated with sleep duration(both P＜0.05).Conclusion The accuracy of the Stroop task and audiovisual competition task is a cognitive ability indicator sensitive to mental fatigue,while the Poincaré plot SD2 during Stroop and 2-back tasks is an ECG indicator sensitive to mental fatigue.

Objective To provide a comprehensive description and summary of the clinical characteristics of eosinophilic granulomatosis with polyangiitis(EGPA)in order to enhance understanding of this disease.Methods A total of 33 EGPA patients treated in Zhongshan Hospital,Fudan University,between Jan 2017 and Aug 2022 were included in this retrospective analysis.The diagnosis was based on the 1990 American College of Rheumatology(ACR)classification criteria for EGPA.Clinical manifestations,laboratory examinations,and treatment outcomes of the patients were analyzed.Results Among the 33 EGPA patients,there were 22 males(66.7%)and 11 females(33.3%),with an average age of diagnosis being(47.42±15.83)years old.The most common initial department visited by patients was the rheumatology department(23 cases,69.7%),followed by the respiratory medicine department(6 cases,18.2%).Skin involvement manifested as rash,ulcers,necrosis or gangrene was observed in most cases(23 cases,69.7%),followed by asthma(17 cases,51.5%),infiltrative pneumonia(14 cases,42.4%),peripheral neuropathy(9 cases,27.3%),thrombosis formation(9 cases,27.3%).The mean absolute value of eosinophils in all patients was measured as(3.43±3.52)×109/L,with eight patients(24.2%)testing positive for antineutrophil cytoplasmic antibody(ANCA).Compared with ANCA-negative patients,ANCA-positive individuals exhibited significantly higher Birmingham Vasculitis Activity Score(BVAS)and eosinophil count,as well as a higher incidence rate of renal involvement(P<0.05).Glucocorticoid therapy was administered in thirty-two patients(97%),while biologics or tofacitinib were given to eleven patients(33.3%),among them six received tofacitinib treatment,of which five achieved disease remission.Conclusion EGPA exhibits a wide range of clinical manifestations,and ANCA-positive patients tend to exhibit higher disease activity levels.A multidisciplinary diagnosis and treatment system for EGPA should be established.

Objective:To investigate the clinical outcomes of nephron-sparing surgery (NSS) for tuberous sclerosis complex(TSC) -associated renal angiomyolipoma (RAML). Methods:This retrospective case-series study analyzed the clinical data of 15 TSC-RAML patients who underwent NSS at the Department of Urology, Peking Union Medical College Hospital between April 2013 and July 2024. The cohort included 4 males and 11 females. The age at TSC diagnosis was (28.5±14.5) years (range: 5 to 62 years), and the age at first surgery was (33.3±10.8) years (range: 18 to 62 years). The maximum tumor diameter( M(IQR)) was 6.4(7.9)cm (range: 3.5 to 31.5 cm). Patient baseline characteristics, surgical approach, TSC-RAML staging, imaging findings, and laboratory data were collected. Relationships between variables were analyzed using Generalized Estimating Equations with post-hoc tests. Results:A total of 18 surgical procedures were performed on the 15 patients. These included 7 open surgeries, 9 laparoscopic surgeries, and 2 laparoscopic procedures converted to open surgery. The mean preoperative serum creatinine level was (70.2±14.2) μmol/L (range: 50 to 101 μmol/L), which increased to (99.2±29.8) μmol/L (range: 47 to 171 μmol/L) on postoperative day 1. However, at one year postoperatively, serum creatinine was (76.8±13.5)μmol/L (range: 55 to 106 μmol/L),showed no significant difference from preoperative levels ( P>0.05). At the 6-month postoperative follow-up, the Utrecht Interventional Classification stage for all treated tumors had decreased to grade 1 or 2. At the 12-month follow-up (available for 13 patients), 11 patients showed no disease progression. Conclusions:NSS is a viable treatment option for rigorously selected patients with high-stage TSC-RAML. Although NSS causes transient renal function impairment, it provides effective tumor burden control. In stringently selected patients with high-stage disease and under long-term follow-up, NSS is associated with limited long-term renal impairment.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Objective To investigate the establishment and evaluation of an idiopathic pulmonary fibrosis(IPF)mouse model induced by the intratracheal infusion of bleomycin(BLM)of different concentrations.Methods Male C57BL/6J mice were randomly divided into a control group,Model-L group(1.5 mg/kg,BLM),Model-M group(2.5 mg/kg,BLM),and Model-H group(3.5 mg/kg,BLM).An IPF mouse model was constructed by one-time intratracheal infusion of BLM.The general status,body mass,survival rate,and lung coefficient of mice in different groups were compared.Pathological changes in lung tissue,the hydroxyproline content,fibrosis markers and inflammatory factor levels were observed.Results Compared with the control group,the survival rate decreased and body weight showed a downward trend in the low-,medium-,and high-dose model groups,with significant increases in lung coefficients.Inflammatory infiltration(P＜0.01)and collagen deposition(P＜0.0001)were observed in the lung tissues of all model groups.Hydroxyproline levels in lung tissue and serum were significantly elevated(P＜0.05).The mRNA levels of fibrosis markers α-Sma,Fn1,and Col1a1 were upregulated(P＜0.001),with significant increases in corresponding protein expression(P＜0.05).The mRNA expression of the inflammatory factor Tgfb1 also increased(P＜0.0001).Conclusion 1.5,2.5 and 3.5 mg/kg BLM can induce an IPF model in C57BL/6J mice.Based on the results observed for survival rate,body mass,lung coefficient changes,lung tissue gross and pathological changes,and fibrosis-related biomarkers,2.5 mg/kg BLM is the optimal concentration for inducing an IPF mouse model.

Epilepsy is a chronic neurological disease caused by abnormal synchronous discharge of the brain, which is characterized by recurrent and transient neurological abnormalities, mainly manifested as loss of consciousness and limb convulsions, and can occur in people of all ages. At present, anti-epileptic drugs (AEDs) are still the main means of treatment, but their efficacy is limited by the problem of drug resistance, and long-term use can cause serious side effects, such as cognitive dysfunction and vital organ damage. Although surgical resection of epileptic lesions has achieved certain results in some patients, the high cost and potential risk of neurological damage limit its scope of application. Therefore, the development of safe, accurate and personalized non-invasive treatment strategies has become one of the key directions of epilepsy research. In recent years, photobiomodulation (PBM) has gained significant attention as a promising non-invasive therapeutic approach. PBM uses light of specific wavelengths to penetrate tissues and interact with photosensitive molecules within cells, thereby modulating cellular metabolic processes. Research has shown that PBM can enhance mitochondrial function, promote ATP production, improve meningeal lymphatic drainage, reduce neuroinflammation, and stimulate the growth of neurons and synapses. These biological effects suggest that PBM not only holds the potential to reduce the frequency of seizures but also to improve the metabolic state and network function of neurons, providing a novel therapeutic avenue for epilepsy treatment. Compared to traditional treatment methods, PBM is non-invasive and avoids the risks associated with surgical interventions. Its low risk of significant side effects makes it particularly suitable for patients with drug-resistant epilepsy, offering new therapeutic options for those who have not responded to conventional treatments. Furthermore, PBM’s multi-target mechanism enables it to address a variety of complex etiologies of epilepsy, demonstrating its potential in precision medicine. In contrast to therapies targeting a single pathological mechanism, PBM’s multifaceted approach makes it highly adaptable to different types of epilepsy, positioning it as a promising supplementary or alternative treatment. Although animal studies and preliminary clinical trials have shown positive outcomes with PBM, its clinical application remains in the exploratory phase. Future research should aim to elucidate the precise mechanisms of PBM, optimize light parameters, such as wavelength, dose, and frequency, and investigate potential synergistic effects with other therapeutic modalities. These efforts will be crucial for enhancing the therapeutic efficacy of PBM and ensuring its safety and consistency in clinical settings. This review summarizes the types of epilepsy, diagnostic biomarkers, the advantages of PBM, and its mechanisms and potential applications in epilepsy treatment. The unique value of PBM lies not only in its multi-target therapeutic effects but also in its adaptability to the diverse etiologies of epilepsy. The combination of PBM with traditional treatments, such as pharmacotherapy and neuroregulatory techniques, holds promise for developing a more comprehensive and multidimensional treatment strategy, ultimately alleviating the treatment burden on patients. PBM has also shown beneficial effects on neural network plasticity in various neurodegenerative diseases. The dynamic remodeling of neural networks plays a critical role in the pathogenesis and treatment of epilepsy, and PBM’s multi-target mechanism may promote brain function recovery by facilitating neural network remodeling. In this context, optimizing optical parameters remains a key area of research. By adjusting parameters such as wavelength, dose, and frequency, researchers aim to further enhance the therapeutic effects of PBM while maintaining its safety and stability. Looking forward, interdisciplinary collaboration, particularly in the fields of neuroscience, optical engineering, and clinical medicine, will drive the development of PBM technology and facilitate its transition from laboratory research to clinical application. With the advancement of portable devices, PBM is expected to provide safer and more effective treatments for epilepsy patients and make a significant contribution to personalized medicine, positioning it as a critical component of precision therapeutic strategies.

ObjectiveTo study the effects of applying different microbial fertilizers on the growth and rhizosphere soil environment of Codonopsis pilosula and provide a theoretical basis for ecological cultivation of this medicinal plant. MethodsSeven groups were designed， including CK （no application of microbial fertilizer）， T1 （Trichoderma longibrachiatum fertilizer）， T2 （Bacillus subtilis fertilizer）， T3 （Trichoderma viride fertilizer）， T4 （compound microbial fertilizer）， T5 （C. pilosula stems and leaves fermented with compound microbial fertilizer）， and T6 （Scutellaria baicalensis stems and leaves fermented with T. viride fertilizer）. The physiological indicators， yield， and quality of C. pilosula and the physicochemical properties， enzyme activities， and microbial diversity in the rhizosphere soil of different fertilizer treatments were measured. ResultsGroup T1 showed slight decreases in soluble protein content （SPC） and superoxide dismutase （SOD）. Groups T2-T6 showed increases in physiological indicators such as proline （Pro）， soluble solids content （SSC）， SPC， catalase （CAT）， and peroxidase （POD） and a decrease in malondialdehyde （MDA） in C. pilosula leaves. All the fertilizer treatments increased the yield of C. pilosula and the total polysaccharide content in the roots. T1， T2， T3， T4， and T5 increased the total flavonoid content in the roots. Meanwhile， T4 increased the total saponin content in the roots. All the fertilizer treatments reduced the pH and increased the electric conductivity （EC）， soil organic matter （SOM）， and alkaline nitrogen （AN） in the soil. T2 and T5 increased the available phosphorus （AP）， and T3， T4， T5， and T6 increased the available potassium （AK） in the soil. All the fertilizer treatments increased the activities of urease， sucrase， and CAT in the soil. Except that T1 decreased the bacterial diversity in the soil， other fertilizer treatments significantly increased bacterial and fungal diversity in the soil. Different fertilizer treatments significantly affected the composition of bacterial and fungal communities in the soil. At the phylum level， the dominant bacterial phyla included Proteobacteria， Acidobacteriota， and Bacteroideta， and the dominant fungal phyla were Ascomycota， Mortierellomycota， and unclassified_fungi in the rhizosphere soil of C. pilosula after bacterial fertilizer treatment. At the genus level， unclassified Gemmatimonadaceae， Sphingomonas， and unclassified Vicinamibacteraceae were the dominant bacterial genera， while unidentified， unclassified Fungi， and unclassified Sordariomycetes were the dominant fungal genera in the rhizosphere soil. The results of redundancy analysis indicated that the main physicochemical factors affecting changes of microbial communities in the rhizosphere soil of C. pilosula were pH， EC， AK， AN， AP， and soil organic matter （SOM） in the soil. The correlation heatmap showed that Bryobacter had significantly positive correlations with EC， AK， and AN. There was a significantly negative correlation between Fusarium and SOM. In summary， applying an appropriate amount of microbial fertilizer can promote the growth and improve the rhizosphere soil environment of C. pilosula. ConclusionThe compound microbial fertilizer and the C. pilosula stems and leaves fermented with compound microbial fertilizer can improve the soil nutrients， growth， development， yield， and quality of C. pilosula， and thus they can be applied to the artificial cultivation of C. pilosula.