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 characterize the sequence polymorphism of HLA-A, -B, and -C loci in the northern Han Chinese population and to evaluate their selection signals and phylogenetic patterns based on long-read sequencing data. Methods: A total of 408 unrelated healthy blood donors were enrolled. Long-read sequencing of HLA-A, -B, and -C loci was performed using the PacBio Sequel II platform. The Ewens-Watterson neutrality test, sliding-window nucleotide diversity (π) and Tajima′s D analyses were conducted, together with genetic distance heatmaps, principal coordinates analysis (PCoA), and maximum likelihood phylogenetic analysis to assess polymorphism distribution, selection signals, and phylogenetic structure across the three loci. Results: The analyzed sequence lengths for the HLA-A, -B, and -C loci were 3 257 bp, 3 794 bp, and 3 831 bp, respectively; the numbers of locus-specific sequence types were 44, 82, and 56, with corresponding locus-specific sequence type diversities of 0.905 2, 0.964 9, and 0.939 8, respectively. The Ewens-Watterson test showed no significant deviation from neutrality (P>0.05). Sliding-window analysis revealed elevated π and Tajima′s D values in exons 2 and 3 as well as in certain intronic regions of HLA-A and HLA-B, whereas HLA-C exhibited relatively lower overall diversity. Genetic distance heatmaps, PCoA, and phylogenetic analysis consistently showed clear clustering in HLA-A and HLA-C, while HLA-B displayed the highest phylogenetic heterogeneity. Conclusion: HLA-A, -B, and -C gene sequences in the northern Chinese Han population exhibit high levels of polymorphism and marked regional heterogeneity. HLA-B shows greater diversity, stronger signals of selection, and more complex phylogenetic structure compared with HLA-A and HLA-C.

OBJECTIVE To investigate the relationship between 23-site chip genetic screening failures and the results of newborns hearing screening,and to provide clinical reference for the diagnosis and treatment of genetic screening failures.METHODS There were 1 916 newborns born in the Beijing area from November 2022 to May 2024,who did not pass the 23-site chip genetic screening tests and underwent newborn hearing screening with definite initial screening results.Chi-square test was used to analyze the relationship between different mutation types and genotypes and the initial hearing screening results.RESULTS The overall neonatal hearing screening failure rate was 5.27%(101/1 916),with a higher failure rate of 61.54%(56/91)for homozygous and compound heterozygous mutations than the failure rate of 2.54%(45/1 772)for heterozygous mutations,0%(0/34)for digenic gene heterozygous mutations,and 0(0/19)for mtDNA 12S rRNA mutations,with a statistically significant difference(P<0.001).Among the homozygous and compound heterozygous mutations,the failure rates of homozygous and compound heterozygous for GJB2 gene and SLC26A4 gene were 59.76%(49/82)and 77.78%(7/9),respectively,with no statistically significant difference between the two groups(P=0.488).The homozygous and compound heterozygous for GJB2 gene were divided into three groups based on genotype:c.109G>A homozygous mutations,c.109G>A compound heterozygous mutations,and other homozygous and compound heterozygous mutations.The hearing screening failure rates of the three groups,from highest to lowest,were as follow:other homozygous and compound heterozygous mutations(88.89%,8/9),c.109G>A homozygous mutations(65.12%,28/43),and c.109G>A compound heterozygous mutations(43.33%,13/30),with a statistically significant difference(P=0.029).The failure rates of heterozygous for GJB2 gene,SLC26A4 gene and GJB3 gene were 2.86%(40/1 398),1.25%(4/321)and 1.89%(1/53),respectively,with no statistically significant difference among the three groups(P=0.241).The failure rate of hearing screening for individuals with GJB2 heterozygotes of different genotypes and individuals with SLC26A4 heterozygotes of different genotypes did not show statistically significant differences.CONCLUSION The failure rate of newborn hearing screening for homozygous and compound heterozygous mutation of 23-site chip genetic screening is higher than that of other mutation types,verifying the effectiveness of the newborn hearing screening program.Some newborns of homozygous and compound heterozygous mutation can pass the hearing screening,especially those with the c.109G>A homozygous and compound heterozygous mutation,who need clinical follow-up.

The morbidity and mortality associated with diphtheria have been effectively managed through mass immunization strategies. Nevertheless, recent outbreaks of diphtheria have been reported in various regions of Africa and Asia. In addition to infections among children, there has been a notable increase in cases among middle-aged and elderly individuals, underscoring the necessity of continued vigilance in the control of diphtheria. This paper reviewed the epidemiology of diphtheria, the current application of vaccines, and immunization strategies, with the aim of providing evidence for the prevention and control of this disease.

Objective To investigate the sequencing results of the SLC26A4 gene in 34 nuclear families and the genetic diagnosis on the offspring in the nuclear families who have been screened for SLC26A4 gene single-allele mutation in the deafness genetic screening,to provide a basis for genetic consulting.Methods A retrospective anal-ysis was performed on the results of SLC26A4 gene testing in 34 nuclear families,in which the offspring with SLC26A4 gene single-allele mutation in deafness genetic screening of each nuclear family.The offspring of 34 nucle-ar families with the second mutation site detected by sequencing,their audiological results were included in the anal-ysis;and if they suffered from hearing loss,the results of temporal bone CT or inner ear MRI were also included in the analysis.Results The sequencing results of 34 nuclear families showed that there were 23 offsprings(67.65％,23/34)with SLC26A4 gene single-allele mutation,and one parent was SLC26A4 gene single-allele mutation.There were 11 offsprings(32.35％,11/34)with second site,among which 7 offsprings(63.64％,7/11)with SLC26A4 gene complex heterozygous mutations,and their parents were SLC26A4 gene single-allele mutations.Among the 7 offsprings with SLC26A4 gene complex heterozygous mutation,3 cases were with hearing loss,all of which were diagnosed as large vestibular aqueduct syndrome,and the other 4 cases were normal.While 4 offsprings(36.36％,4/11)with SLC26A4 gene double heterozygous mutation(cis mutation),and one parent was SLC26A4 gene double heterozygous mutation.The hearing 4 offsprings with SLC26A4 gene double heterozygous mutations were normal.Among the 34 nuclear families,3 pairs of parents were SLC26A4 gene single-allele mutation,and both mutation sites were pathogenic,risk of reproducing children with hereditary hearing loss was 25％.Conclusion The detec-tion sites of deafness gene chip are limited.Using gene sequencing technology to sequence the nuclear family can fur-ther clarify the gene mutation type in offspring and provide guidance for parents to reproduce.

With the deepening understanding of the pathogenesis of psoriasis, small-molecule drugs targeting the key Janus kinase (JAK) -tyrosine kinase (TYK) 2 pathway have gained increasing interest. TYK2-related pathways play an important role in the pathogenesis of psoriasis, while they are not involved in modulating broad biological effects, making them one of the potential therapeutic targets for the efficient and safe treatment of psoriasis. How to improve the selectivity and specificity of TYK2 inhibitors to minimize adverse reactions associated with the inhibition of other pathways has been one of the key directions for development of drugs targeting TYK2 in recent years. This review summarizes the role of TYK2 pathway in the pathogenesis of psoriasis, the modes of action of TYK2 inhibitors (competitive or allosteric inhibition), and the latest clinical research progress.

Objective:To investigate the current status of the implementation of home-based phototherapy (HBPT) in patients with vitiligo, and to analyze management needs among patients receiving HBPT.Methods:A questionnaire survey was conducted on the application of HBPT among patients with vitiligo who visited the outpatient clinic of the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from December 2021 to November 2022. Additionally, the popularization and usage of HBPT as well as needs of patient management were investigated and analyzed in these vitiligo patients.Results:A total of 496 valid questionnaires were collected from 496 patients with vitiligo (241 males [48.5%] and 255 females [51.5%]) . Their ages at visit ranged from 2 to 67 (30.87 ± 12.36) years. The most commonly affected sites were the head and face (52.2%) , followed by hair (32.1%) , hands and feet (31.4%) , trunk (30.2%) , limbs (24.3%) , neck (19.5%) , and perineum (9.9%) . Among the participants, 320 (64.5%) were currently using or had used HBPT, and 352 (70.8%) expressed a willingness to learn more about HBPT usage guidelines and health education. Regarding the repigmentation outcomes after HBPT: among 312 patients, 54 (17.3%) reported complete recovery, 64 (20.5%) were markedly improved, 142 (45.5%) experienced improvement, and 52 (16.7%) showed no response. Adverse reactions occurred in 223 patients (71.5%) , of whom 28 (9.0%) experienced severe adverse reactions. The most desired guiding information was the adjustment method for phototherapy dosage and treatment duration (184/352, 52.3%) ; the most effective way to receive health education information was through verbal education by medical staff (177/352, 50.3%) .Conclusion:For vitiligo patients who were willing to accept and use HBPT, the most desired guiding information was the adjustment method for phototherapy dosage and treatment duration, and verbal health education by medical staff appeared to be the main way to obtain health education information.

Objective:To analyze the mediating effect of cardiovascular health status (CVH) on the association between educational level and cardiovascular disease (CVD).Methods:The participants were from Shanghai Suburban Adult Cohort and Biobank, and questionnaire survey, physical examination, blood biochemistry were conducted from 2016 to 2020 for baseline information collection, and follow up was conducted until March 31, 2024 based on the medical data, CVD incidence data and death surveillance data at different levels. The associations of educational level, CVH and time to CVD onset of the study population were analyzed using the accelerated failure time model to analyze the mediating effects of CVH, health behaviors, and health factors in the association of educational level and time to CVD onset. The mediating effects of educational level, gender, and age moderated associations were also analyzed.Results:A total of 57 312 participants were included, with 2 780 new cases of CVD during a median follow-up of 6.71 (6.71-6.72) years, and a mean incidence density of 7.77/1 000 person-years (95% CI: 7.48/1 000 person-years -8.06/1 000 person-years). In total, the less educational level and the lower CVH, the higher CVD incidence density ( P<0.05). The results of accelerated failure time models showed that the time ratio for CVD-free survival was 1.15 (95% CI: 1.06-1.24) and 1.33 (95% CI: 1.10-1.60) for moderate and high educational level, respectively. The results of the mediation effect analysis showed that the association between moderate and high educational level and time to CVD onset was 29.60% (20.50%-50.00%) and 36.10% (23.80%-59.00%), 9.97% (5.07%-20.00%) and 13.84% (6.84%-29.00%), 15.24% (9.64%-27.00%) and 17.55% (11.58%-33.00%) of mediators mediated by CVH, health behaviors, health factors, respectively. Among them, there was an exposure-mediated interaction of educational level and a positive moderating effect of age. Conclusion:CVH, health behaviors and health factors had a proportionate mediating effect in the association between educational level and risk of CVD development.

Objective:To understand the coverage and information consistency rate of National Immunization Program (NIP) vaccines among children born during 2020-2021 in Zhejiang Province, Chongqing City, and Shanxi Province (3 provinces) of China .Methods:A simple random sampling method was used to randomly select 3 counties (districts) from each of the 3 provinces, 5 townships from each county (district), and 5 villages from each township. Vaccination information for seven NIP vaccines was collected for children born between 2020 and 2021 in each village. The vaccination coverage, timely coverage, and consistency rates between the survey data and the Immunization Planning Information System data were analyzed.Results:A total of 1 117 children were investigated. The vaccination coverage for each dose of NIP vaccine ranged from 99.10% to 100.00%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 99.19% to 100.00%, 98.92% to 100.00%, and 99.20% to 100.00%, respectively. The timely coverage of each dose of NIP vaccine ranged from 89.79% to 99.82%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 94.09% to 99.73%, 89.52% to 99.73%, and 78.55% to 100.00%, respectively. The consistency rate of information on each dose of NIP vaccine ranged from 94.36% to 99.91%, with those in Zhejiang Province, Chongqing City, and Shanxi Province ranging from 97.85% to 99.73%, 98.92% to 100.00%, and 86.06% to 100.00%, respectively.Conclusions:Coverage of NIP vaccines was generally high among children born during 2020-2021 in the 3 provinces of China, but there were regional differences in the timely coverage of some vaccine doses and the vaccination information consistency rate. It is necessary to strengthen the timely vaccination of children's vaccine booster doses and optimize the management of vaccination services.

Objective:To evaluate the protective effectiveness (VE) of the acellular pertussis vaccine (aPV) against pertussis in children aged 2 months to 6 years.Methods:A test-negative case-control study was conducted among children aged 2 months to 6 years who sought medical care for cough and underwent pertussis nucleic acid testing at sentinel surveillance hospitals in Zhejiang Province in 2024. Cases were defined as those with positive pertussis nucleic acid test results, while controls were test-negative individuals matched 1∶1 based on propensity scores using the caliper matching method. Conditional logistic regression models were used to calculate odds ratios ( ORs) and VEs. Results:Among the 658 participants, 31.76% (209 cases) tested positive for pertussis. After propensity score matching, 203 cases and 203 controls were included in the analysis. The VE of 1-2, 3, and 4 doses of aPV against pertussis was 52.46% (95% CI:-39.82%-83.84%), 65.22% (95% CI: 6.86%-87.02%), and 72.21% (95% CI: 34.33%-88.24%), respectively. For pertussis-related hospitalization, the VE of 1-3 and 4 doses was 80.95% (95% CI:31.38%-94.71%) and 86.79% (95% CI: 51.89%-96.37%). The VE for those who completed 4 doses of vaccination and had intervals of less than 2 years, 2 years, 3 years, and 4 years or more after vaccination were 91.15% (95% CI: 67.61%-97.58%), 84.70% (95% CI: 43.71%-95.84%),56.23% (95% CI:-47.58%-87.02%), and 49.92% (95% CI:-83.74%-86.35%), respectively. Conclusion:The VE of aPV against pertussis in children aged 2 months to 6 years increases with the number of doses administered, and it is more effective in preventing hospitalization due to pertussis. The VE declines rapidly over time after the last dose. It is recommended to follow the new pertussis immunization program for timely and full vaccination.