Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Osteosarcoma (OS) is the most prevalent primary malignant bone tumor affecting children and adolescents. Despite ongoing research efforts, the 5-year survival rate has remained stagnant for many years, highlighting the critical need for novel drug development to enhance current treatment protocols. Ziyuglycoside II (ZYG II), a triterpenoid saponin extracted from S. officinalis, has recently demonstrated antitumor properties. This study evaluates the antitumor effect of ZYG II on osteosarcoma and elucidates its mechanism of action through the co-regulation of p53 and estrogen-related receptor gamma (ESRRG), which inhibits disease progression. The research employs in vitro experiments using multiple established osteosarcoma cell lines, as well as in vivo studies utilizing a nude mouse model of orthotopic xenograft osteosarcoma. Additionally, ESRRG shRNA was used to construct stable ESRRG-reducing OS cell lines to investigate the molecular mechanism by which ZYG II exerts its anti-osteosarcoma effects through the co-regulation of ESRRG and p53. Results indicate that ZYG II administration led to decreased OS cell viability and reduced tumor volumes. Furthermore, cell cycles were arrested at the G₀/G₁ phase, while the proportion of apoptotic cells increased. Expression of p53, ESRRG, p21, Bax, Cleaved Caspase-9, and Cleaved Caspase-3 proteins increased, while expression of CDK4, Cyclin D1, and Bcl-2 proteins decreased. Multiple ZYG II and ESRRG docking patterns were simulated through molecular docking. Comparing the pharmacodynamic response of ZYG II to OS cell lines with reduced ESRRG and normal expression demonstrated that ZYG II inhibits osteosarcoma progression, induces cell cycle arrest, and promotes cell apoptosis through the coordination of p53 and ESRRG. In conclusion, ZYG II inhibits osteosarcoma progression, leads to cell cycle arrest, and promotes cell apoptosis through synergistic regulation of p53 and ESRRG.
Osteosarcoma/physiopathology* ; Tumor Suppressor Protein p53/genetics* ; Humans ; Animals ; Saponins/chemistry* ; Bone Neoplasms/physiopathology* ; Signal Transduction/drug effects* ; Cell Line, Tumor ; Mice, Nude ; Mice ; Apoptosis/drug effects* ; Receptors, Estrogen/genetics* ; Mice, Inbred BALB C ; Female ; Male ; Xenograft Model Antitumor Assays

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Objective:To develop a prototype artificial intelligence immunofluorescence image recognition system for classification of antinuclear antibodies in order to meet the growing clinical requirements for an automatic readout and classification of immunof luorescence patterns for antinuclear antibody (ANA) images.Methods:Immunofluorescence images with positive results of ANA in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from April 2020 to December 2021 were collected. Three senior technicians independently and in parallel interpreted the Immunofluorescence images to determine the ANA results. Then the images were labeled according to the ANA International Consensus on Fluorescence Patterns (ICAP) classification criteria. There were 7 labeled groups: Fine speckled, Coarse speckled, Homogeneous, nucleolar, Centromere, Nuclear dots and Nuclear envelope. Each group was randomly divided into training dataset and validation dataset at a ratio of 9∶1 by using random number table. On the deep learning framework PyTORCH 1.7, the convolutional neural network (CNN) training platform was constructed based on ResNet-34 image classification network, and the automatic ANA recognition system was established. After the model was established, the test set was set up separately, the judgment results of the model were output by ranking the prediction probability, with the results of the 2 senior technicians was taken as "golden standard". Parameters such as accuracy, precision, recall and F1-score were used as indicators to evaluate the performance of the model.Results:A total of 23138 immunofluorescence images were obtained after segmentation and annotation. A total of 7 models were trained, and the effects of different algorithms, image processing and enhancement methods on the model were compared. The ResNet-34 model with the highest accuracy andswas selected as the final model, with the classification accuracy of 93.31%, precision rate of 91%, and recall rate of 90% and F1-score of 91% in the test set. The overall coincidence rate between the model and manual interpretation was 90.05%, and the accuracy of recognition of nucleolus was the highest, with the coincidence rate reaching 100% in the test set.Conclusion:The current AI system developed based on deep learning of the ANA immunofluorescence images in the present study showed the ability to recognize ANA pattern, especially in the common, typical, simple pattern.

Objective:To analyze the clinical effect of navigation-assisted cosmetic incision for reduction and internal fixation in treating unilateral B-type zygomatic fracture.Methods:A retrospective cohort study was performed on clinical data of 35 patients with unilateral type B zygomatic fracture treated from January 2018 to December 2019 in First Affiliated Hospital of Fujian Medical University. There were 20 males and 15 females at age range of 5-62 years [(38.7±11.3)years]. Navigation-assisted cosmetic incision for reduction and internal fixation was performed for 17 patients (navigation group), and empirical incision to reduction and internal fixation was performed for 18 patients (convention group). The length of bony zygomatic process (zygomatic process) and width of zygomatic temporal point (frontal width) of the bilateral zygomatic bone were measured on the horizontal axis of CT at 1 week after operation. The absolute values of the difference of bony zygomatic process degree and frontal bony width between affected side and the healthy side were compared between the two groups. The patients′ satisfaction and occurrence of complications such as lower eyelid ectropion, incision infection and facial nerve injury were compared between the two groups at half a year after operation.Results:All patients were followed up for 6-24 months [(9.3±1.2)months]. The absolute difference of bony zygomatic process was 0.60(0.25, 0.85) mm in navigation group, and was 0.75 (0.20, 1.98)mm in convention group ( P>0.05). The absolute difference of frontal bony width was (0.37±0.11)mm in navigation group, and was (2.47±0.63)mm in convention group ( P<0.01). Satisfaction rates by both objective evaluation and subjective evaluation in navigation group were better than that in convention group at half a year after operation (both P<0.05). Navigation group showed lower eyelid ectropion in 1 patient and incision infection in 1 patient. Convention group showed facial nerve injury in 1 patient and incision infection in 2 patients. There was no significant difference in the incidence of complications between navigation group [12%(2/17)] and conventional group [17%(3/18)] ( P>0.05). Conclusion:For unilateral type B zygomatic fracture, navigation-assisted cosmetic incision for reduction and internal fixation can more accurately restore the frontal width, and improve satisfaction rate as compared with empirical reduction and internal fixation.

The coronal process of ulna is an important stable structure in front of the elbow joint, which is composed of the tip of the coronal process, towering tubercle and anterior medial face. The fracture of the coronal process is often accompanied by the fracture and dislocation of the elbow joint, which leads to the instability of the elbow joint. The coronoid process has the advantages of small size, special shape, complex surrounding soft tissue structure, and plays an important role in the stability of the elbow joint. The selection of safe, minimally invasive and well exposed surgical approach is a necessary condition for safe and effective internal fixation. The choice of surgical approach must comprehensively consider the concomitant injury and choose the best surgical approach. This article mainly describes the normal anatomical structure of the coronal process and around the elbow joint, analyzes the biomechanics and stability of the coronal process in the elbow joint, and reviews the latest progress in surgical treatment.

Objective:To assess the clinical characteristics and grafts status by coronary angiography(CAG) in symptomatic patients with prior coronary artery bypass graft(CABG).Methods:A retrospective descriptive study of symptomatic patients with prior CABG who underwent CAG was performed, 1 136 patients were included and analyzed. The mean age was(62.5±8.7) years, 76.4% were male. There was a high prevalence of risk factors like hypertension(75.0%), dyslipidemia(48.2%), diabetes(46.1%) and smoking history(62.8%).Results:The mean duration after CABG was (4.65±3.39) years. 94.5% of patients had chest pain. 12.9% of patients had all diseased grafts and 28.7% had all patent grafts. The proportion of diseased SVG was higher than that of diseased arterial grafts. The proportion of diseased grafts anastomosed to RCA territory was higher than that of grafts anastomosed to LCX territory or LAD territory. 52.5% of patients received percutaneous coronary intervention(PCI) revascularization, and 88.3% of PCI was performed in native vessels.Conclusion:The most common symptom recurring to patients with prior CABG was chest pain. Graft status in symptomatic patients with prior CABG was worse than we expected. Patients received repeated revascularization mostly by PCI and PCI was mainly performed in native vessels.

Objective:To explore the perioperative effect of coronary artery bypass grafting(CABG) or CABG+ mitral valve repair(MVP) in patients with coronary heart disease(CAD) and moderate ischemic mitral regurgitation(IMR).Methods:The clinical data and perioperative complications of 210 patients with CAD and moderate IMR, who underwent CABG from January 2018 to December 2019, were included into this study, with 155 males and mean age of(62.3±8.5) years old. According to the operation mode, patients were divided into CABG group(138 cases) and CABG+ MVP group(72 cases).Results:There were no significant differences in age, gender, comorbidities(diabetes, hypertension, hyperlipidemia, peripheral vascular disease, cerebrovascular events, previous history of myocardial infarction and PCI), LVEF and of coronary artery lesions between the two groups(all P>0.05). Sequential anastomosis was the main method, and most patients underwent internal mammary artery graft in both groups, there was no significant difference between the two groups( P>0.05). CABG group was higher than CABG+ MVP group in all-cause death, heart failure, cerebrovascular events, secondary thoracotomy, CRRT and IABP support events, but there were no significant differences between the two groups( P>0.05). Echocardiographic reexamination showed that the indexes of cardiac function in CABG+ MVP group were higher than those in CABG group, but there was no significant difference between the two groups( P>0.05). The mean area of mitral regurgitation in CABG + MVP group was 1.3 cm 2, significantly lower than that in CABG group(2.5 cm 2), P<0.05. Conclusion:CABG+ MVP has low perioperative risk in patients with CAD and moderate IMR, and the area of mitral regurgitation is lower.

Objective:To analyze the administration of rabies immunoglobulin (RIG) in populations who had rabies virus exposure, and to investigate the safety of RIG and related factors affecting its administration.Methods:This cross-sectional study included the rabies virus exposed victims who were treated at the sixth medical center of the People’s Liberation Army (PLA) General Hospital from April to November 2019. The clinical characteristics of the patients who accepted RIG injection and those who refused RIG were analyzed and compared, and the determinant factors of the RIG injection were studied by stepwise multiple logistic regression analysis.Results:There were 1 395 cases of category III exposure, of whom 662 (47%) were males, 733 (52.5%) were females. The median age was 29 (9-49) years. Among them, 1 049 cases were injected with RIG, while 346 were not injected with RIG. Side effects associated with RIG injection included pain (97.6%), dizziness (7.0%), nausea (6.5%), chest tightness (2.1%), and syncope (0.3%). Stepwise multiple logistic regression analysis showed that adults ( OR=17.14, 95% CI: 9.69-30.32), middle-aged and elderly ( OR=12.92, 95% CI: 6.83-24.43), and those whose injury was caused by cats ( OR=3.18, 95% CI: 2.09-4.84), scratches ( OR=7.66, 95% CI: 4.27-13.75), those with minor injuries ( OR=21.75, 95% CI: 11.70-40.42) more likely to choose not to inject RIG. Conclusions:It is safe and effective to inject RIG for patients with grade III exposure to rabies virus. Exposed persons who are not injured by dogs, slightly injured and elderly people tend not to inject RIG.

Objective To analyze clinicopathological characteristics and the potential risk-related factors of female breast hyperplasia in different age groups.Method From Jan 2015 to Dec 2016,patients diagnosed with breast hyperplasia in 12 hospitals were evaluated.All patients completed the self-designed questionnaires on women'health,including basic demographic information,clinic examination information,radiologic information and pathologic results.The patients were divided into a young group (＜ 45 years old) and an elderly group (from 45 to 75 years old).Results There were 3 684 cases of breast hyperplasia,including 2 291 cases in young group and 1 393 cases in elder group,respectively Clinically breast pain type were most commonly observed in both young and older groups (50.3％ vs.42.7％,P ＜ 0.001).While pathological research based on biopsy showed that breast adenopathy were the most common changes in both groups (67.9％ vs.61.7％,P ＜0.001).More breast cancer cases were identified in elder group than that in young group,especially in clinically lump type patients (9.4％ vs.4.2％,P ＜ 0.001).Compared with elder group,patients in young group have different distribution characteristics regarding to fertility factors,lifestyle factors and psychology scale including anxiety and depression.Conclusion Distributions of clinicopathological characteristics and risk factors of female breast hyperplasia differ across different age groups.