Thyroid-associated ophthalmopathy(TAO)is a rare organ-specific autoimmune disease with an unclear pathogenesis. At present, the treatment still relies mainly on glucocorticoids and traditional immunosuppressants. However, some patients respond poorly to these drugs and experience treatment-related adverse reactions, highlighting the urgent need for novel drugs for TAO treatment. In recent years, with the deepening of research on the pathogenesis of TAO, a multitude of biologics targeting specific targets have emerged. Among them, teprotumumab, which targets the insulin-like growth factor-I receptor(IGF-IR), has been approved by the Food and Drug Administration for the treatment of TAO, and several other biologics are currently in clinical trials. This review provides the latest reference for the clinical prevention, treatment, and research of TAO by summarizing the current clinical research status of biologics targeting IGF-IR, neonatal Fc receptor(FcRn), thyroid-stimulating hormone receptor(TSHR), B cells, cytokines, and other biological agents in TAO and analyzing their impact on clinical treatment and future research trends.

AIM: To analyze the causes of blindness and low vision in patients with visual disability in Yangpu District of Shanghai from 2019 to 2022.METHODS:Cross-sectional study. A total of 1 604 patients who participated in the evaluation of visual disability in Shanghai Yangpu District Kongjiang Hospital, from April 2019 to December 2022 were selected for the study. The grade of visual disability and the main causes of blindness and low vision were determined by trained doctors.RESULTS:A total of 804 patients with visual disabilities were identified, with 87.31% aged 60 and above. The causes of visual disability were high myopic retinopathy(30.47%), age-related macular degeneration(23.26%), glaucoma(17.04%), and diabetic retinopathy(11.07%). Glaucoma(36.96%)is the leading cause of blindness.CONCLUSION: The majority of patients with visual disability are aged 60 years and above. More attention should be paid to the elderly population. Comprehensive prevention, treatment and rehabilitation measures should be applied in different diseases based on classification, so as to early reduce the occurrence of visual disability.

Objectives:Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE.Methods:The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE.Results:Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease ( HR=6.360), positive anti-double-stranded DNA antibodies ( HR=7.203), low level of complement C3 ( HR=25.715), and low level of complement C4 ( HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events ( HR=0.109) were protective factors ( P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS ( HR=0.753, 95% CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions:PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

Gastric cancer is one of the major diseases threatening human health, with a high incidence and a low early diagnostic rate. There are many bottlenecks encountered during its treatment. Consequently, improving the early diagnostic rate and exploring new therapeutic targets are currently urgent challenges that need to be addressed. Telomerase is undetectable in normal tissues, but it exhibits high specificity and sensitivity in most cancers and has a definite correlation with prognosis. It may serve as a serum tumor marker and prognostic indicator. Human telomerase reverse transcriptase (hTERT) gene polymorphism can regulate the susceptibility of people to gastric cancer, and affect the occurrence, development, proliferation and apoptosis of gastric cancer through its target gene. Substances such as resistin, visfatin, G-quadruplex and methylenedioxyaniline can affect the occurrence and development of gastric cancer by regulating telomerase expression. The mechanism by which hTERT regulates tumor invasion and metastasis is currently unclear, so elucidating its mechanism is of great significance.This paper will review the research progress of this mechanism in recent years.

Background and purpose:Long noncoding RNA(lncRNA)can regulate gene transcription,mRNA shear,stabilization and translation,and it is an important regulatory factor in a variety of biological processes.This study aimed to investigate the expression and clinical features of lncRNA FLJ30679 in oral squamous cell carcinoma(OSCC)and its effect on the malignant biological behavior of OSCC.Methods:The expression of FLJ30679 in head and neck squamous cell carcinoma(HNSCC)tissues and normal tissues was analyzed by the UCSC Xena database for expression and prognosis.The expression of FLJ30679 in OSCC cell lines was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).The subcellular localization of FLJ30679 in OSCC cells was detected by RNA nuclear-cytoplasmic fractionation assays.FLJ30679 Smart Silencer was used to establish the FLJ30679 knockdown group(SS-FLJ30679),and overexpression plasmid of FLJ30679 was used to establish FLJ30679 overexpression group(FLJ30679).The effects of altered FLJ30679 expression on the proliferative and migration capacity of OSCC cells were examined by cell counting kit-8(CCK-8)and transwell migration assays.RTFQ-PCR and Western blot were used to determine the effect of altered FLJ30679 expression on the expression of epithelial-mesenchymal transition(EMT)-related genes in OSCC cells.The effects of altered FLJ30679 expression on the phosphoinositide 3-kinase(PI3K)/protein kinase(AKT)pathway were detected by Western blot.Results:Online query of database showed that FLJ30679 expression was higher in HNSCC tissues compared to normal tissues(P＜0.01).HNSCC patients with higher FLJ30679 expression had lower overall survival(P＜0.01).The RTFQ-PCR results showed that FLJ30679 was expressed at a higher level in six OSCC cell lines compared with normal cells,and was predominantly localized in the nucleus.The ability of OSCC cells in the SS-FLJ30679 group to proliferate and migrate was significantly lower compared with the SS-NC group(P＜0.01).OSCC cells in the FLJ30679 overexpression group had significantly higher proliferative and migratory capacities than those in the vector group(P＜0.001).RTFQ-PCR and Western blot results showed that FLJ30679 knockdown resulted in upregulation of mRNA and protein expression levels of E-cadherin(P＜0.01)and downregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.01).FLJ30679 overexpression resulted in downregulation of protein expression levels of E-cadherin(P＜0.01)and upregulation of mRNA and protein expression levels of N-cadherin and vimentin(P＜0.05).Western blot results showed that knockdown of FLJ30679 resulted in decreased protein expression levels of phosphorylated-PI3K(p-PI3K)and phosphorylated-AKT(p-AKT)(P＜0.001),and overexpression of FLJ30679 resulted in increased protein expression levels of p-PI3K and p-AKT(P＜0.01).Conclusion:The expression of FLJ30679 was increased in OSCC tissues and cells.It promoted the proliferation and migration ability of OSCC cells,which may be caused by FLJ30679 promoting EMT via PI3K/AKT pathway.

BACKGROUND/OBJECTIVES: Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear.MATERIALS/METHODS: A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for in vivo assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an in vitro podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively. RESULTS: In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/ LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/ LC3I ratio in podocytes. CONCLUSION Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.

Objective:To evaluate the clinical significance of neoadjuvant immunotherapy combined with chemotherapy in the treatment of larynx preservation in locally advanced hypopharyngeal squamous cell carcinoma. Methods:Patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were eligible. All received 2 cycles of pembrolizumab combined with docetaxel and platinum neoadjuvant induction therapy. After two cycles, the efficacy was evaluated, followed by radical chemoradiotherapy or surgery and adjuvant chemoradiotherapy according to the efficacy. The primary endpoints were objective response rate（ORR） ，larynx-preservation（LP） rate at 3 months post-treatment and the adverse reactions during neoadjuvant therapy. Results:From December 2021 to December 2022, 10 patients with locally advanced HPSCC（cT3-T4aN0-N3M0） were enrolled. After 2 cycles of the neoadjuvant therapy, 2 patients achieved complete response（CR）, 7 patients achieved partial response（PR）, 1 patient was stable disease（SD）, objective response rate（ORR） was 90%, and disease control rate（DCR） was 100%. 5 patients received radical chemoradiotherapy, 5 patients received surgery and adjuvant chemoradiotherapy, four of them received partial laryngectomy and partial hypopharyngeal resection surgery, and one of them received total laryngectomy and partial hypopharyngeal resection surgery. All patients were able to withstand adverse reactions of neoadjuvant therapy and successfully completed the whole treatment of HPSCC without grade 3-4 treatment-related adverse reactions. There was no recurrence or metastasis during 3-18 months of follow-up. 1 patient died of severe pneumonia 3 months after the completion of radical chemoradiotherapy. At 3 months after treatment, the larynx-preservation rate was 80%. Conclusion:Neoadjuvant immunotherapy combined with chemotherapy has good short-term efficacy and the adverse reactions were tolerable. It can improve the larynx-preservation rate of patients with locally advanced HPSCC, thus improving the prognosis and quality of life of patients.
Humans ; Squamous Cell Carcinoma of Head and Neck/etiology* ; Neoadjuvant Therapy ; Quality of Life ; Cisplatin ; Treatment Outcome ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Larynx ; Head and Neck Neoplasms ; Immunotherapy

Thyroid-associated ophthalmopathy(TAO)is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults.Due to the complex clinical manifestations and prolonged course,TAO seriously affect the physical and mental health of patients.The pathogenesis of TAO has not been fully elucidated and the treatment lacks specificity.Therefore,in-depth research on the pathogenesis of TAO is to find effective treatments.In recent years,studies have suggested that there is gut microbiota disorder in TAO,and the risk factors of TAO can promote gut microbiota disorder.Disordered gut microbiota can participate in the occurrence and development of TAO via influencing T cell differentiation,mimicking autoantigens,and influencing host non-coding RNA expression.Modulating the gut microbiota also has therapeutic effects on TAO and is a promising therapeutic approach.

Objective:To explore the value of jellyfish sign, an abnormal ultrasonographic sign, in predicting adverse perinatal outcomes of women with complete placenta previa combined with placenta accreta spectrum disorders (PAS).Methods:This retrospective study analyzed the ultrasound images of 72 singleton gravidas, diagnosed with complete placenta previa combined with PAS, who underwent cesarean section at the First Affiliated Hospital of Nanjing Medical University between January 2020 and February 2023. Based on the presence and absence of the jellyfish sign in ultrasound images, these gravidas were divided into the jellyfish-sign group (15 cases, 20.8%) and the non-jellyfish-sign group (57 cases, 79.2%). The clinical data and perinatal outcomes of the two groups were analyzed. The adverse perinatal outcomes encompassed conditions such as abdominal aorta balloon block, uterine artery embolism, hysterectomy, postpartum hemorrhage, and neonatal intensive care unit (NICU) admission of their neonates. Statistical analysis was performed using two independent samples t-test, the Mann-Whitney U test and the Chi-square (or Fisher's exact) test. Results:(1) The jellyfish-sign group exhibited a higher parity [(1.6±0.7) times vs (1.2±0.6) times, t=2.01] and higher prenatal scores of placenta accreta [(12.3±1.5) scores vs (8.6±2.9) scores, t=6.59] than those in the non-jellyfish-sign group (both P<0.05). Among the 57 cases in the non-jellyfish-sign group, there were 14 cases of placenta creta (24.6%), 40 cases of placenta increta (70.2%), and three cases of placenta percreta (5.3%). Among the 15 cases in the jellyfish-sign group, nine cases were diagnosed with placenta increta, six with placenta percreta, and none with placenta creta. The difference in distribution between the two groups was statistically significant (Fisher's exact test, P<0.001). (2) Intraoperative blood loss [(for those who accepted abdominal aorta balloon block, 1 973±1 057) ml vs (1 211±576) ml, t=2.55], red blood cells transfused [4.0 U (2.0-23.0 U) vs 2.5 U (0.0-11.0 U), Z=－2.53], postoperative hospitalization time [(9.7±2.4) vs (7.5±2.2) d, t=3.36], the incidence of abdominal aorta balloon block [15/15 vs 38.6% (22/57), χ2=17.92], uterine artery embolism [for those who accepted abdominal aorta balloon block, 3/15 vs 1.8% (1/57), Fisher's exact test], and requiring blood transfusion [15/15 vs 63.2% (36/57), Fisher's exact test] were higher in the jellyfish-sign group than those in the non-jellyfish-sign group. However, the non-jellyfish-sign group had lower gestational age at delivery [(33.6±1.5) weeks vs (35.2±1.8) weeks, t=－3.24], and lower neonatal Apgar score at 1 min and 5 min [1 min: 8 scores (3-10 scores) vs 9 scores (4-10 scores), Z=－2.46; 5 min: 9 scores (7-10 scores) vs 10 scores (6-10 scores), Z=－2.02] (all P<0.05). There were no significant differences in emergency surgery rate, 24 h postoperative blood loss, neonatal birth weight, and proportion of NICU admission between the two groups. Additionally, no cases of hysterectomy or death were observed in the two groups. Conclusions:Ultrasound examination revealing jellyfish signs in patients with complete placenta previa and PAS is associated with an increased likelihood of adverse perinatal outcomes. Consequently, the management of these patients should be given greater attention.

Objective: This cross-sectional study explores the serial multiple mediation of the correlation between internet addiction and depression by social support and sleep quality of college students during the COVID-19 epidemic. Methods: We enrolled 2,688 students from a certain university in Wuhu, China. Questionnaire measures of internet addiction, social support, sleep quality, depression and background characteristics were obtained. Results: The prevalence of depression, among 2,688 college students (median age [IQR]=20.49 [20.0, 21.0] years) was 30.6%. 32.4% of the students had the tendency of internet addiction, among which the proportion of mild, moderate and severe were 29.8%, 2.5% and 0.1%, respectively. In our normal internet users and internet addiction group, the incidence of depression was 22.6% and 47.2%, respectively. The findings indicated that internet addiction was directly related to college students’ depression and indirectly predicted students’ depression via the mediator of social support and sleep quality. The mediation effect of social support and sleep quality on the pathway from internet addiction to depression was 41.97% (direct effect: standardized estimate=0.177; total indirect effect: standardized estimate= 0.128). The proposed model fit the data well. Conclusion Social support and sleep quality may continuously mediate the link between internet addiction and depression. Therefore, the stronger the degree of internet addiction, the lower the individual’s sense of social support and the worse the quality of sleep, which will ultimately the higher the degree of depression. We recommend strengthening monitoring of internet use during the COVID-19 epidemic, increasing social support and improving sleep quality, so as to reduce the risk of depression for college students.