BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

ObjectiveTo identify the pathogen species responsible for the wilt disease of Tetradium ruticarpum in Chongqing， investigate there biological characteristics， and screen effective fungicides， so as to provide a theoretical basis for disease control in production. MethodsThe pathogen was isolated via the tissue culture method. Pathogenicity was verified according to Koch's postulates. The pathogen was identified based on morphological characteristics and multi-gene phylogenetic analysis. The mycelial growth rate method was used for biological characterization of the pathogen and fungicide screening. ResultsThe pathogen colonies were nearly circular with irregular edges， white， short， velvety aerial hyphae， and pale purple undersides. Macroconidia were colorless， sickle-shaped， with 3-5 septa， while microconidia were transparent， elliptical， aseptate or with 1-2 septa. Multi-gene phylogenetic analysis showed that the pathogen clustered in the same clade as Fusarium fujikuroi with 100% support， which， combined with morphological characteristics， identified the pathogen causing wilt of T. ruticarpum in Chongqing as F. fujikuroi. The optimal conditions for the mycelial growth of F. fujikuroi were mung bean agar （MBA） with glucose as the carbon source， beef extract and yeast powder as nitrogen sources， 28 ℃， pH 7.0， and alternating light/dark conditions. The optimal conditions for sporulation were potato dextrose agar （PDA） with glucose as the carbon source， beef extract as the nitrogen source， 28 ℃， pH 7.0， and complete darkness. Among chemical fungicides， phenazine-1-carboxylic acid exhibited the strongest inhibitory effect on F. fujikuroi. Shenqinmycin and tetramycin were the most effective bio-fungicides. ConclusionThis study is the first to report F. fujikuroi as the causal agent of wilt disease in T. rutaecarpa. The chemical fungicide phenazine-1-carboxylic acid and the bio-fungicides shenqinmycin and tetramycin showed strong inhibitory effects against F. fujikuroi.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective To investigate the correlations of interleukin-1 β(IL-1β)level and per-centage of CD16+CD56+natural killer(NK)cells in peripheral blood with severity of disease in pa-tients with pulmonary tuberculosis.Methods A total of 150 patients with active pulmonary tubercu-losis(APTB)in the Suqian First People's Hospital from January 1,2021 to September 1,2023 were selected as APTB group,and 150 patients with inactive pulmonary tuberculosis(IPTB)in the same period were selected as IPTB group.Level of IL-1 β and percentage of CD16+CD56+NK cells in pe-ripheral blood of patients with different disease severities were compared,and their correlations with severity of disease were analyzed.Results In the APTB group,level of IL-1 β in the peripheral blood was significantly higher than that in the IPTB group,while the percentage of CD16+CD56+NK cells was significantly lower(P＜0.001).In the mild,moderate,and severe groups,level of IL-1 βshowed a significant gradual increasing trend in peripheral blood,while the percentage of CD16+CD56+NK cells showed a significant gradual decreasing trend(P＜0.001).After treatment,the level of IL-1β in the peripheral blood decreased significantly,while the percentage of CD16+CD56+NK cells increased significantly in the APTB group(P＜0.001).Correlation analysis revealed that level of IL-1β in the peripheral blood of patients with pulmonary tuberculosis was positively correlated with severity of disease(r=0.732,P＜0.001),while the percentage of CD16+CD56+NK cells was negatively correlated with severity of disease(r=-0.612,P＜0.001).Conclusion Level of IL-1β in the peripheral blood is elevated while the percentage of CD16+CD56+NK cells is de-creased in patients with pulmonary tuberculosis,which is closely related to the severity of APTB.

In the era of rational molecular design of fusion proteins,linker selection has garnered significant attention as a critical determinant of construct functionality.Suboptimal selection of linkers may result in such structural perturbations as protein misfolding,reduced expression yields,and compromised bioactivity.Consequently,the strategic selection of linkers tailored to specific objectives of molecular design by optimizing spatial orientation,maintaining domain autonomy or enabling post-translational modifications has emerged as a pivotal research frontier.Given these challenges,this review outlines the common properties of linkers,ways of classification,and the functional-structural interplay in current applications.Furthermore,we propose context-dependent selection frameworks for therapeutic proteins,biosensors,and enzyme cascades,which can serve as a systematic methodology to guide linker optimization in next-generation fusion protein engineering.

To summarize the clinical practice of continuous medical service for patients at Shanghai Children′s Medical Center, affiliated with Shanghai Jiao Tong University School of Medicine, from September 2023 to December 2024, following the approval of its extended care qualification. This study utilized a mixed-methods research design that integrates quantitative and qualitative approaches. The quantitative study included a total of 117 subjects, with an age range of 18 to 35 years, an average age of 21.56 years, and a median age of 19 years; there were 59 males and 58 females. The disease types covered four major categories: childhood leukemia and solid tumors (68 cases), congenital structural malformations (25 cases), congenital hereditary metabolic diseases (4 cases), and rare diseases (20 cases). Among the subjects, 57.26% (67 cases) were first-time visitors to SCMC. The patients came from 20 provinces, autonomous regions, and municipalities across the country, with 88.03% (103 cases) from outside Shanghai. The treatment outcomes showed improvement or cure in 80.34% (94 cases) of the subjects, and there were no medical complaints. In addition, a qualitative study was conducted to deeply explore the experiences, confusions, and challenges of receiving or implementing continuous medical services from the perspectives of patients and their families, as well as medical staff. According to the inclusion and exclusion criteria, a total of 44 subjects were included in the study, among them, there were 12 patients, 12 family members who were taking care of the patients in SCMC, and 20 corresponding medical staff members. The results of the qualitative study showed that trust in the attending physicians of the children′s specialty hospital, a good doctor-patient relationship, satisfactory treatment outcomes, and support from medical insurance policies are the main driving forces for patients over 18 years old to receive continuous treatment at children′s specialty hospitals. The medical staff of the hospital also believed that this model can promote patient benefits. In conclusion, under the policy support of the Shanghai Municipal Health Commission, the "Six Fixed" Model for continuous treatment established by SCMC has achieved certain positive results in practice. This provides practical references for the development of continuous treatment in China and offers new strategies for the application of preventive medicine in the field of children′s health.

Objective: To investigate the trend in disease burden of interstitial lung disease (ILD) in China from 1990 to 2021, so as to provide a reference for formulating prevention and control strategies for chronic respiratory diseases. Methods: Based on the Global Burden of Disease 2021 database, data on the number of incident cases, incidence, standardized incidence, number of deaths, mortality, standardized mortality, number of disability-adjusted life years (DALY), DALY rate, and standardized DALY rate of ILD in China were collected. The incidence, mortality, and DALY rate were used to analyze the disease burden of ILD. The estimated annual percentage change (EAPC) was employed to assess the trend in standardized incidence, standardized mortality, and standardized DALY rate of ILD from 1990 to 2021. Rate decomposition analysis was applied to identify the main contributing factors affecting the trend in disease burden. Results: In 2021, China reported 48 514 cases, 7 674 deaths, and 222 288 person-years of DALY due to ILD, representing increases of 155.43%, 159.70%, and 97.34%, respectively, compared with 1990. From 1990 to 2021, the standardized incidence and standardized mortality of ILD in China showed upward trends (EAPC=1.106% and 0.239%, both P<0.05), while the standardized DALY rate showed a downward trend (EAPC=-0.230%, P<0.05). From 1990 to 2021, the standardized incidence and standardized mortality among males showed upward trends (EAPC=1.199% and 0.520%, both P<0.05), while the trend in the standardized DALY rate was not statistically significant (P>0.05). Among females, the standardized incidence of ILD showed an upward trend (EAPC=0.966%, P<0.05), while the standardized mortality and standardized DALY rate showed downward trends (EAPC=-0.306% and -0.760%, both P<0.05). In 2021, the incidence, mortality, and DALY rate of ILD in China increased with age, peaking in the group aged ≥95 years at 14.84/105, 13.90/105, and 124.71/105, respectively. Across all age groups aged ≥55 years, the incidence, mortality, and DALY rate of ILD were consistently higher in males than in females. The increase in the number of incident cases, deaths, and DALY due to ILD in China from 1990 to 2021 was primarily influenced by population aging, with contribution rates of 42.65%, 68.25%, and 69.79%, respectively. Conclusions From 1990 to 2021, the incidence and mortality risk of ILD in China showed upward trends, while the disability risk demonstrated a downward trend. Males bore a heavier disease burden of ILD, and aging was identified as the primary factor contributing to the increased burden of ILD in China.

To summarize the clinical practice of continuous medical service for patients at Shanghai Children′s Medical Center, affiliated with Shanghai Jiao Tong University School of Medicine, from September 2023 to December 2024, following the approval of its extended care qualification. This study utilized a mixed-methods research design that integrates quantitative and qualitative approaches. The quantitative study included a total of 117 subjects, with an age range of 18 to 35 years, an average age of 21.56 years, and a median age of 19 years; there were 59 males and 58 females. The disease types covered four major categories: childhood leukemia and solid tumors (68 cases), congenital structural malformations (25 cases), congenital hereditary metabolic diseases (4 cases), and rare diseases (20 cases). Among the subjects, 57.26% (67 cases) were first-time visitors to SCMC. The patients came from 20 provinces, autonomous regions, and municipalities across the country, with 88.03% (103 cases) from outside Shanghai. The treatment outcomes showed improvement or cure in 80.34% (94 cases) of the subjects, and there were no medical complaints. In addition, a qualitative study was conducted to deeply explore the experiences, confusions, and challenges of receiving or implementing continuous medical services from the perspectives of patients and their families, as well as medical staff. According to the inclusion and exclusion criteria, a total of 44 subjects were included in the study, among them, there were 12 patients, 12 family members who were taking care of the patients in SCMC, and 20 corresponding medical staff members. The results of the qualitative study showed that trust in the attending physicians of the children′s specialty hospital, a good doctor-patient relationship, satisfactory treatment outcomes, and support from medical insurance policies are the main driving forces for patients over 18 years old to receive continuous treatment at children′s specialty hospitals. The medical staff of the hospital also believed that this model can promote patient benefits. In conclusion, under the policy support of the Shanghai Municipal Health Commission, the "Six Fixed" Model for continuous treatment established by SCMC has achieved certain positive results in practice. This provides practical references for the development of continuous treatment in China and offers new strategies for the application of preventive medicine in the field of children′s health.

BackgroundAttention deficit hyperactivity disorder （ADHD） is a neurodevelopmental disorder characterized by age-inappropriate inattention， excessive activities incongruous with setting， and emotional impulsivity. Subthreshold ADHD （sADHD） is clinically defined as the presence of ADHD symptoms that do not meet the full diagnostic criteria for ADHD. Children with sADHD exhibit deficits in executive function， demonstrate more conduct， learning， and anxiety-related problems compared to typically developing children， and show even poorer working memory performance than children diagnosed with ADHD. Currently， there is limited epidemiological research on sADHD in China， with few studies simultaneously investigating the prevalence of both ADHD and sADHD in children. ObjectiveTo investigate the prevalence of ADHD and sADHD among children aged 6–13 years in Chongqing， analyzing their distribution characteristics within this population， with the aim of providing references for developing preventive measures against both ADHD and sADHD. MethodsFrom October to November 2023， a total of 3 398 students in grades 1–6 from six primary schools in Jiangbei District， Chongqing were selected using a stratified cluster random sampling method. The occurrence of ADHD and sADHD was evaluated by using the short version （18-item version） of the Swanson， Nolan， and Pelham IV rating scales （SNAP-IV） and the Chinese vision of Schedule for Affective Disorder and Schizophrenia for School-aged Children-Present and Lifetime Version （K-SADS-PL）. ResultsThe ADHD detection rate among children in Chongqing was 1.90% （95% CI： 0.014–0.024）. Boys showed a significantly higher ADHD detection rate than girls （χ²=7.733， P=0.005）. No statistically significant differences were found in ADHD detection rates across different grades or age groups （χ²=7.347， 12.362， P>0.05）. The sADHD detection rate was 6.32% （95% CI： 0.054–0.072）. Similarly， boys exhibited significantly higher sADHD detection rates than girls （χ²=21.005， P<0.01）. Significant differences emerged across different grades （χ²=20.559， P=0.001）， while no statistically significant difference was observed in age groups （χ²=12.070， P=0.060）. ConclusionThe ADHD detection rates were comparable across all grade levels and age groups from 6–13 years old. Second-grade children demonstrated notably higher sADHD rates compared to other grades， while boys demonstrated higher prevalence rates than girls for both ADHD and sADHD. ［Funded by Science and Health Joint Medical Research Project in Jiangbei District， Chongqing City in the Second Half of 2023 （number， 2023JBKWLH022）］