Objective: To explore the impact of personalized early treatment appliances (ETA) on the relationship between dental and maxillofacial structures in patients with ClassⅡ malocclusion during the replacement phase, and to provide a basis for clinical treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee, and informed consent was obtained from patients. From May 2023 to December 2023, 15 patients with Angle ClassⅡ malocclusion accompanied by mandibular retraction and anterior deep overjet during mixed dentition were enrolled in this study (8 males and 7 females; mean age 8.8 years). Each patient received a customized domestically manufactured ETA that was created based on dental arch dimensions, overjet severity, and occlusal relationships assessed from study models. Patients were instructed to wear the appliance for at least 2 hours during the day and throughout the night. The treatment duration was 6 months, at which time the changes in cephalometric data before treatment (T0) and after treatment (T1) were compared using Uceph software Results: The angle between sella, nasion and supramentale point B (SNB) of the patients increased significantly by (1.03 ± 1.74°) compared to before treatment (P = 0.039). The angle between subspinale point A and supramentale point B (ANB), the distance between point A and point B on the FH plane (wits value), the overjet, and the overbite decreased by (0.47 ± 0.61°), (2.48 ± 2.11) mm, (2.48 ± 3.42) mm, and (0.79 ± 1.40) mm, respectively, compared to before treatment, and the differences were statistically significant (P<0.05). The angle between sella, nasion and subspinale point A (SNA), the angle between the FH and MP planes (FMA), the angle between the long axis of the L1 and MP plane (IMPA), the angle between the MP plane and SN plane (MP-SN), the distance from S to Go divided by the distance from N to Me (S-Go/N-Me), and the distance of the FH plane perpendicular from G point to the Pog point (G Vert Pog) increased compared to before treatment, while the angle between the SGn and FH planes (Y-axis) and the angle between the long axis of the L1 and FH plane (FMIA) decreased compared to before treatment, but there was no statistical difference (P>0.05). Conclusion Personalized, customized ETA orthodontic appliances can effectively improve the sagittal and vertical relationships between the maxilla and mandible in patients with ClassⅡ malocclusion.

As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective:To evaluate the feasibility of non-invasive prenatal testing (NIPT) for the screening of fetal chromosome aneuploidies in twin pregnancies.Methods:A total of 2 745 women with twin-pregnancies were subjected for NIPT screening. Chromosomal karyotyping and chromosomal microarray analysis (CMA) were carried out on amniotic fluid samples from those with a high risk for fetal chromosome aneuploidies, and the diagnosis and pregnancy outcome were followed up. The sensitivity, specificity, positive predictive value and false positive rate of the NIPT were calculated.Results:Compared with other chromosomal abnormalities, NIPT had a higher efficacy for trisomy 21 and sex chromosomal aneuploidy (SCA) in twin pregnancies (with sensitivity being 100%, 100%, and specificity being 99.93%, 99.9%, respectively). It is difficult to evaluate the efficacy for trisomies 18 and 13 due to the limited data. For chromosome microdeletions and microduplications spanning 15 ~ 21 Mb, NIPT also had a certain detection rate. Compared with women with natural conception, NIPT had a higher detection rate for those with twin pregnancies by assisted reproduction ( P < 0.05). Conclusion:It is feasible to use NIPT for the detection of chromosome aneuploidies in women with twin pregnancies.

Objective:To explore the predictive value of serum sorting protein (Sortilin) combined with extracellular matrix metalloproteinase inducible factor (EMMPRIN) for in stent restenosis (ISR) after carotid artery stent placement (CAS).Methods:A total of 197 patients with carotid artery stenosis who underwent CAS treatment at the Capital Medical University Daxing Teaching Hospital from January 2018 to October 2020 were selected as the study subjects. All patients were followed up for 24 months after surgery and were divided into an ISR group (28 cases) and a non ISR group (169 cases) based on the occurrence of ISR. Enzyme linked immunosorbent assay (ELISA) was used to detect and compare the preoperative serum Sortilin and EMMPRIN levels between the two groups. We collected clinical data from patients and analyzed the influencing factors of post CAS ISR using univariate and multivariate logistic regression models. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of serum Sortilin and EMMPRIN for postoperative ISR in CAS.Results:The serum Sortilin, EMMPRIN, age, proportion of concomitant hypertension, degree of preoperative stenosis, neutrophil count (NEUT), platelet count (PLT), white blood cell count (WBC), high-sensitivity C-reactive protein (hs-CRP), triglycerides (TG), and total cholesterol (TC) in the ISR group were higher than those in the non ISR group (all P<0.05). The results of multivariate logistic regression analysis showed that PLT, WBC, and elevated serum Sortilin and EMMPRIN were independent risk factors for the occurrence of ISR after CAS surgery (all P<0.05). ROC curve analysis showed that the AUC under the ROC curve of serum Sortilin and EMMPRIN alone and in combination for predicting postoperative ISR in CAS were 0.735(95% CI: 0.546-0.918), 0.766(95% CI: 0.615-0.910), and 0.839(95% CI: 0.701-0.984), respectively. The predictive efficacy of the combined application was greater than that of the two indicators alone. Conclusions:Patients with postoperative ISR after CAS have abnormally elevated levels of serum Sortilin and EMMPRIN before surgery, which are independent risk factors for postoperative ISR. The combined detection of serum Sortilin and EMMPRIN has good predictive value for the risk of postoperative ISR in CAS.

Objective To observe the effects of Angelicae Sinensis Radix-Paeoniae Radix alba combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on liver inflammation and hepatocytes regeneration in non-alcoholic steatohepatitis(NASH)associated cirrhosis;To discuss its possible mechanism.Methods West diet combined with carbon tetrachloride was used to prepare the NASH related cirrhosis model.The mice were randomly divided into control group,model group,Angelicae Sinensis Radix-Paeoniae Radix alba group,BM-MSCs group,and Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,with 12 mice in each group.After successful modeling,corresponding interventions were given according to grouping for 4 consecutive weeks.HE staining was used to observe the morphology of liver tissue;the contents of serum ALT,AST,TBil,TG,ALB,AFP,as well as the contents of IL-1β,TNF-α and HGF in liver tissue were detected;RT-qPCR was used to detect TLR9,MyD88,TRAF6 and NF-κBp65 mRNA expression in liver cells;primary liver cells were separated,CpG ODN 2216 stimulation was induced in vitro,cells supernatant was extracted,and IL-1β and TNF-α content were detected.Results Compared with the control group,inflammatory cell infiltrated in liver tissue of model group mice,accompanied by hepatocyte necrosis and collagen deposition,forming pseudo lobules;the contents of serum ALT,AST,TBil and TG increased,the content of ALB decreased,the content of HGF in liver tissue decreased,the contents of IL-1β and TNF-α increased,with statistical significance(P<0.05);the mRNA expressions of TLR9,MyD88,TRAF6 and NF-κBp65 in liver cells increased(P<0.05),and the contents of IL-1β and TNF-α in cells supernatant increased after CpG ODN 2216 induction(P<0.05).Compared with the model group,the inflammatory infiltration in liver tissue and necrosis of liver cells were reduced and the degree of liver fibrosis was alleviated in the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group,the liver tissue damage in Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group were slightly improved;except for the TG content in BM-MSCs group,all detection indicators showed significant improvement in each intervention group(P<0.05).Compared with the Angelicae Sinensis Radix-Paeoniae Radix alba group and BM-MSCs group,the Angelicae Sinensis Radix-Paeoniae Radix alba+BM-MSCs group showed statistical significance in related detection indicators(P<0.05),and demonstrated a synergistic effect.Conclusion Angelicae Sinensis Radix-Paeoniae Radix alba combined with BM-MSCs transplantation could effectively improve the liver function and promote liver cell regeneration.The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expressions and function,the inhibition of inflammatory cytokines secretions,and the improvement of liver inflammatory microenviroment.

AIM:To investigate the molecular mechanism of long noncoding RNA(lncRNA)SNHG1 in regu-lating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop.METHODS:CHME-5 human microglia were cultured in vitro,and were divided into 7 groups:blank group,random peptide group,gp120 V3 loop group(HIV-1 gp120 group),HIV-1 gp120+shCon group,HIV-1 gp120+SNHG1 sh2 group,HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1;ferroptosis inhibitor)group,and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 in-hibitor)group.Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h.After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h,the cells were then treated with gp120 V3 loop for 24 h.The levels of inflammato-ry cytokines in the cell supernatants were detected by ELISA.Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),Sirt1 and p53.Microplate reader was used to detect the levels of intracellular ferrous ion(Fe2+)and malondialdehyde(MDA).RESULTS:(1)The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group(P<0.05).Compared with HIV-1 gp120 group,the ex-pression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.05).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significant-ly increased(P<0.01).(2)The results of Western blot showed that compared with blank group,the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated(P<0.01).Com-pared with HIV-1 gp120 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were sig-nificantly up-regulated(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated(P<0.05),but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated(P<0.01),and the expression level of p53 was significantly up-regulated(P<0.05).(3)Compared with blank group,the levels of Fe2+and MDA in HIV-1 gp120 group were significantly increased(P<0.05).Compared with HIV-1 gp120 group,the levels of Fe2+and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,Fe2+and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased(P<0.05).CONCLUSION:Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop,which may be achieved by regulating ferrop-tosis-related signaling molecules through the Sirt1/p53 signaling pathway.

Objective:To screen differentially expressed circular RNA (circRNA) in rat articular chondrocyte injury induced by T-2 toxin, and explore the mechanism of cartilage injury.Methods:Twenty-four SD rats (males, body weight 60 - 80 g) were randomly divided into T-2 toxin group (administrated T-2 toxin 100 ng·g -1·d -1 by gavage) and control group (administrated equal amounts of deionized water by gavage) using a random number table method, 12 rats in each group. After 4 weeks of intervention, the articular cartilage was collected for transcriptome sequencing. Deseq2 software [ P < 0.05 and |log 2(fold change)| > 1, fold change was the multiple of differential expression] was used to identify differentially expressed circRNA. Based on the competing endogenous RNAs (ceRNA) hypothesis, the miRanda software was used to predict the microRNA (miRNA, miR) binding sites of differentially expressed circRNA, and Cytoscape 3.10.0 software was used to plot the circRNA-miRNA interaction network. MiRWalk 3.0, MiRDB, and miRTarBase softwares were used to predict downstream target genes, and Cytoscape 3.10.0 software was used to map the circRNA-miRNA-mRNA interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the biological functions and enrichment pathways of target genes. Results:A total of 19 differentially expressed circRNAs were screened (including 10 upregulated and 9 downregulated). A total of 1 320 miRNAs binding sites and 16 target genes were predicted. Target gene enrichment analysis revealed significant enrichment of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathway ( P < 0.05). Tumour necrosis factor receptor-associated factor 6 (Traf6) and interleukin-1 receptor-associated kinase 1 (Irak1) were enriched in the MAPK and NF-κB signaling pathways, with corresponding miRNA and circRNA of miR-146a-5p and chr2: 94716330|94720889. Conclusion:Nineteen differentially expressed circRNAs in rat articular chondrocyte injury are successfully screened, and chr2: 94716330|94720889 may regulate the MAPK and NF-κB signaling pathways through the miR-146a-5p/Traf6/Irak1 axis, inducing articular chondrocyte injury.