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 analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia. METHODS: A retrospective study was conducted on 7 patients diagnosed by Yangjiang People's Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People's Hospital of Yangjiang (Ethics No: 20240001). RESULTS: For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A2, whilst another had significantly decreased Hb A and Hb A2, in addition with the appearance of a Hb H band. The content of Hb Bart's in four neonates was ≥ 0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c.2delT, HBA2: c.1A>G, HBA2: c.1A>T, and HBA1: c.2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c.427T>C (Hb CS) and HBA2: c.2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c.1A>G and Southeast Asian type deletion. CONCLUSION Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c.1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.
Humans ; Phenotype ; Codon, Initiator/genetics* ; Female ; Male ; Retrospective Studies ; alpha-Globins/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobin A/genetics* ; Adult ; Mutation

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.

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.

Objective:To analyze the correlation between variants in the start codon of the α-globin gene and phenotypes of thalassemia, so as to provide a basis for the diagnosis and prevention of α-thalassemia.Methods:A retrospective study was conducted on 7 patients diagnosed by Yangjiang People′s Hospital and Guangzhou Hybribio Co. Ltd., from June 2019 to October 2022. Routine blood tests and hemoglobin electrophoresis were carried out. Potential variants were identified through polymerase chain reaction (PCR) combined with Reverse dot blotting (RDB), Gap-PCR, and Sanger sequencing. This study has been approved by the Medical Ethics Committee of People′s Hospital of Yangjiang (Ethics No: 20240001).Results:For the 7 patients, results of blood routine test of one case was unknown, and that of another was normal. The remaining 5 cases had presented with microcytic hypochromic anemia. The results of hemoglobin electrophoresis showed that one case had normal Hb A and slightly lower Hb A 2, whilst another had significantly decreased Hb A and Hb A 2, in addition with the appearance of a Hb H band. The content of Hb Bart′s in four neonates was ≥0.4%. The remaining one case had no result. Genetic testing has identified 4 rare start codon mutations, namely HBA2: c. 2delT, HBA2: c. 1A>G, HBA2: c. 1A>T, and HBA1: c. 2T>C. Among these, Patient 1 had harbored compound heterozygous variants of HBA2: c. 427T>C (Hb CS) and HBA2: c. 2delT. Patient 4 had harbored compound heterozygous variants of HBA2: c. 1A>G and Southeast Asian type deletion. Conclusion:Heterozygotes with HBA start codon variants usually present as silent or mild thalassemia, and the symptoms of anemia may deteriorate when combined with other α-thalassemia variant. The HBA2: c. 1A>T start codon variant was unreported previously in China. The detection of start codon variants has helped to clarify the causes of anemia, genetic counseling, and guidance for reproduction.

Objective:To investigate the clinical characteristics of left-sided infective endocarditis (IE) without underlying valvular heart diseases (VHD).Methods:This was a retrospective study. Clinical data of 206 patients with left-sided IE (age: (50.4±16.1) years; 144 males (69.9%)) discharged from Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2011 to May 2021 were retrospectively analyzed, including 129 cases with underlying VHD (IE+VHD group) and 77 cases without underlying VHD (IE group). The 6-month survival rate of patients after discharge was analyzed with Kaplan-Meier survival curve; and the 6-month survival rates of the patients with different sizes of endocardial vegetation and different treatment modalities in the IE group were further analyzed with log-rank method.Results:The proportions of patients with age ≥65 years old, arrhythmia and aortic valve involvement, and the in-hospital mortality in the IE group were significantly lower than those in the IE+VHD group ( P<0.05). However, the proportion of patients with fever and speech vague/limb movement disorder/headache, those with mitral valve involvement in the IE group were significantly higher than those in the IE+VHD group ( P<0.05). The median value of C-reactive protein (CRP) in the IE group was significantly higher than that in the IE+VHD group ( P<0.05). Nevertheless, the median value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the IE group was significantly lower than that in the IE+VHD group ( P<0.05). There were as no significant differences in the positive rates of bacterial/fungal blood cultures and the proportion of patients with mitral and aortic valve involvement of endocardial vegetation between the two groups (all P>0.05). Kaplan-Meier survival curve analysis showed that there was no significant difference in 6-month survival rate of patients between the IE group and IE+VHD group (88.7% vs. 93.6%, log-rank χ2=0.887, P=0.346). In the IE group, the 6-month survival rate after discharge in patients with maximum diameter of vegetation ≤10 mm was higher than that in patients with maximum diameter of vegetation >10 mm (96.3% vs. 80.7%, log-rank χ2=4.111, P=0.043). There was no significant difference in 6-month survival rate between patients treated with antibiotics combined with surgery and those treated with antibiotics alone (96.2% vs. 78.6%, log -rank χ 2=2.976, P=0.084). Conclusion:Compared to left-sided IE patients with underlying VHD, patients without underlying VHD are likely to have a younger age, more mitral valve involvement and lower in-hospital mortality; for those patients with maximum diameter of vegetation ≤10 mm there is a higher survival rate, and antibiotics combined with surgery may help to improve the survival rate.

Objective:To compare the clinical manifestations,laboratory results,and imaging features between pyogenic spondylitis(PS) and tuberculous spondylitis(TS).Methods:This was a cross-sectional study. A total of 88 patients with infectious diseases of spine(IDS) admitted to Shanghai Sixth People′s Hospital from January 2021 to December 2023 were analyzed,including 61 PS cases(PS group) and 27 TS cases(TS group). The clinical manifestations,laboratory results,and imaging features were compared between two groups. The factors associated with PS were analyzed by multivariate logistic regression. The diagnostic efficacy for pathogen identification was compared between metagenomics next-generation sequencing(mNGS) and bacterial culture methods in PS and TS patients.Results:Compared with the TS group,the PS group had a higher age-adjusted Charlson comorbidity index(aCCI)[3.0(1.5,4.0) points vs. 2.0(1.0,3.0) points, Z=-2.189, P=0.029],shorter onset time of disease[1.0(0.8,3.0) months vs. 6.0(2.0,12.0) months,Z=-4.353, P<0.001],and higher median blood leukocyte counts and serum ferritin(SF) level(7.2×10 9/L vs. 6.3×10 9/L, Z=-2.652, P=0.008; 571.3 ng/ml vs. 266.0 ng/ml, Z=-4.773, P<0.001). The proportions of lumbar spine involvement,non-collapsed involved vertebrae,and bone bridges formed were all higher in the PS group compared to the TS group[68.8%(99/144) vs. 41.4%(29/70), χ2=14.628, P<0.001; 68.9%(42/61) vs. 18.5%(5/27), χ2=19.055, P<0.001; 41.0%(25/61) vs. 7.4%(2/27), χ2=9.921, P=0.002]. The proportions of thoracic spine involvement,severe vertebral collapse,severe narrowing of the involved intervertebral space,sequestrum,and paravertebral soft tissue calcification were all higher in the TS group compared to the PS group[52.9%(37/70) vs. 18.1%(26/144), χ2=27.463, P<0.001; 55.6%(15/27) vs. 13.1%(8/61), χ2=17.462, P<0.001; 74.1%(20/27) vs. 37.7%(23/61), χ2=9.907, P=0.002; 74.1%(20/27) vs. 18.0%(11/61), χ2=25.761, P<0.001; 51.9%(14/27) vs. 6.6%(4/61), χ2=23.599, P<0.001]. Multivariate logistic regression analysis indicated that a symptom duration<5.5 months( OR=30.644,95% CI: 2.022-464.529, P<0.05) and a leukocyte count>7.35×10 9/L( OR=48.653,95% CI: 2.045-1 157.721, P<0.05) indicated a higher likelihood of PS; while the vertebral collapse indicated a higher likelihood of TS( OR=0.025,95% CI: 0.001-0.638, P<0.05). The most common pathogen in the PS group was Staphylococcus aureus(31 cases,50.8%),followed by Streptococcus species(10 cases,16.4%). The positive rates of mNGS testing in the PS and TS groups were 84.1%(37/44) and 12/13,respectively,which were higher than those of conventional bacterial culture[77.8%(42/54)] and Mycobacteriumtuberculosis culture(2/11). Conclusions:Compared with the TS patients,the PS patients have shorter onset time,higher aCCI scores,higher blood leukocyte counts and SF levels,less vertebral collapse and intervertebral space narrowing,and more bone bridge formation. The TS patients have more dead bones and calcifications. The mNGS has a higher diagnostic efficacy than bacterial cultures for PS and TS.

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.