OBJECTIVE Aimed at investigating whether reflux pharyngitis is an independent risk factor for the failure of type Ⅰ tympanoplasty for chronic otitis media.This is achieved by analyzing the relationship between the postoperative tympanic membrane healing in patients who underwent type Ⅰ tympanoplasty and pharyngolaryngeal reflux finding score(RFS).METHODS Patients who underwent type Ⅰ tympanoplasty in the Department of Otolaryngology Head and Neck Surgery,Nanshan People's Hospital,Shenzhen,China,from January 2023 to July 2024 were retrospectively included.All the patients received preoperative perfect nasal endoscopy,laryngoscopy,evaluation by the RFS questionnaire,preoperative otoscopy for tympanoplasty,pure tone hearing threshold,and temporal bone thin-layer CT examination.Postoperative otoscopic examination was performed to observe tympanic membrane healing and followed up for 3 months.The patients were divided into surgery success group and failure group based on the criterion of whether a complete tympanic membrane was formed by endoscopic examination within 3 months.The RFS scores of the two groups were statistically analyzed.RESULTS A total of 135 patients with an average age of 44.78 years(±12.22 years)took part in this study,with 60 males and 75 females included,and 68 left ears and 67 right ears involved.There were 120 patients in the surgery success group,and 15 patients in the failure group.Statistical analysis revealed that the RFS score of the patients in the tympanoplasty failure group was remarkably higher than that of the patients in the tympanoplasty success group.Moreover,there were significantly more cases with suspected reflux pharyngitis in the surgery failure group(P=0.007).Reflux-induced tympanic membrane lesion and reperforation mostly occurred in the central part of the tympanic membrane graft.CONCLUSION Reflux pharyngitis has been implicated with tympanoplasty failure,and thus may be a causative factor.Additionally,the RFS can be used to screen patients with chronic suppurative otitis media for suspected reflux pharyngitis.Findings from this work indicate that perioperative anti-reflux therapy,combined with dietary and lifestyle counselling for the patients who suffer from reflux pharyngitis and are about to undergo the tympanoplasty surgery may improve surgical success rate.

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Mitral valve replacement is one of the most common heart valve surgeries in China. In recent years, with the increase in degenerative valve diseases, older patients, and the progress of anti-calcification technology of biological valves, the proportion of mitral valve biological valve replacement has been increasing year by year. After the damage of traditional mitral valve biological valves, re-operation of valve replacement with thoracotomy is required. However, the adhesion between the heart and sternum, as well as the damage caused by cardiopulmonary bypass and cardiac arrest, can cause significant trauma to elderly patients and those with multiple organ dysfunction, leading to increased mortality and complication rates. In recent years, interventional valve surgery, especially transcatheter valve-in-valve surgery, has developed rapidly. This procedure can correct the damaged mitral valve function without stopping the heart, but there are still many differences between its technical process and conventional aortic valve replacement surgery. Therefore, organizing and writing multicenter expert recommendations on the technical process of transcatheter valve-in-valve surgery for damaged mitral valve biological valves is of great significance for the training and promotion of this technology.

Objectives:To evaluate the valvular and cardiac function,cardiac reverse remodeling at 6-month after transcatheter edge-to-edge repair(TEER)for patients with functional and degenerative mitral valve regurgitation,and summarize the experience of echocardiography application. Methods:The clinical data of 93 patients with moderate to severe mitral regurgitation(MR)treated with TEER and completed 6-month follow-up in Yunnan Fuwai Cardiovascular Hospital from July 2022 to February 2023 were retrospectively analyzed.Patients were divided into functional mitral regurgitation(FMR)and degenerative mitral regurgitation(DMR)groups according to MR etiology.The valve characteristic parameters,as well as valvular function,chamber volume and cardiac functional parameters before and at 6 months after operation were compared.The key points of echocardiography application were summarized. Results:Among all patients,71 were FMR and 22 were DMR.There were differences in valve structure between the two groups.Mitral TEER were successfully accomplished and all patients completed 6-month follow-up.The key points of echocardiography application included:valve structure analysis,atrial septal puncture location,device delivery process monitoring and image optimization during clamping process.The mitral regurgitation grade and NYHA grade were significantly improved in all patients at 6 months after TEER(P<0.05),and the mean mitral valve pressure gradient was higher than that before operation(P<0.05).Left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV)and left atrial volume index in FMR group were significantly decreased(P<0.05),while left ventricular and left atrial volume in DMR group remained unchanged(P>0.05).There were no significant changes in left ventricular ejection fraction and left ventricular global strain in both groups during the observation period(P>0.05).The changes of LVEDV and LVESV before and after operation were more significant in FMR group than those in DMR group(P<0.05). Conclusions:Mitral TEER can reduce the degree of regurgitation and improve cardiac function in the early postoperative period for moderate and severe MR patients with different etiologies.There are differences in preoperative valve structure and postoperative cardiac reverse remodeling between FMR and DMR patients.Echocardiography is an important imaging technique for the evaluation and monitoring process before,during and post mitral TEER.

This article reports a case using China's self-developed HaloStitch? system to complete a percutaneous suture-mediated patent foramen ovale closure under ultrasound guidance alone,achieving outstanding clinical outcomes.This innovative method represents a new approach to patent foramen ovale treatment and is an ideal surgical technique.

The present case report described a patient with paroxysmal atrial fibrillation who received pulsed-filed ablation guided by intracardiac echocardiography and 3-dimentional mapping system.All four pulmonary veins were isolated in the procedure,good clinical results and acute safety profile were achieved.The present case reveals the safety and feasibility of the technique for the treatment of paroxysmal atrial fibrillation.

Objective:To investigate the effects and significance of α-synuclein(α-syn)on the expression level of β-arrestin 2 in Parkinson's disease(PD)in a mouse model.Methods:Twenty-eight C57BL/6J mice with similar motor skills were randomly divided into a model group and a control group, with 14 mice in each group.A PD model was established by injecting preformed fibrils of α-syn into the striatum of the brain, and behavioral changes were monitored after 4 weeks.The expression levels of α-syn, the dopamine receptor(DR), tyrosine hydroxylase(TH), inflammatory factors, β-arrestin 2 and the nuclear transcription factor-κB(NF-κB)signaling pathway-related proteins were determined by Western blotting.The interaction between α-syn and β-arrestin 2 was detected by fluorescence resonance energy transfer(FRET), and the regulation of α-syn on β-arrestin 2 transcriptional activation was detected by the dual luciferase report assay.Results:After 4 weeks of modeling, compared with the control group, the average movement speed of mice in the model group was significantly reduced( t=9.415, P<0.001), the movement track was sparse and concentrated around the open field, and the time needed to climb the pole was significantly prolonged( t=16.412, P<0.001). Compared with the control group, the relative expression of α-synin in astrocytes in the model group increased significantly, the relative expressions of D1DR and TH decreased significantly[(1.14±0.18) vs.(0.53±0.16), (0.67±0.13) vs.(1.15±0.11), (0.46±0.05) vs.(0.81±0.06)]( t=9.810, 10.917 and 17.356, all P<0.001), the relative expression of tumor necrosis factor-α, interleukin-1β, interleukin-6 and NF-κB signaling pathway-related proteins increased significantly( t=3.583, 4.284, 5.396, 11.747, 16.375 and 18.294, all P<0.001), and the relative expression of β-arrestin 2 protein[(0.42±0.11) vs.(1.33±0.14)]in astrocytes decreased significantly( t=19.795, P<0.001). The FRET results suggested a possible direct interaction between α-syn and β-arrestin 2.The results of the dual luciferase report assay showed that the transcription activity of β-arrestin 2 was significantly increased after α-syn gene knockout. Conclusions:The α-syn may induce inflammation in astrocytes by activating the NF-κB signaling pathway and participate in the pathogenesis of PD by reducing dopamine biosynthesis and inhibiting its physiological function through negative regulation of β-arrestin 2.

Background::Total ankle replacement (TAR) is a viable option for the treatment of end-stage ankle arthritis. In China, the INBONE-II implant is the only total ankle prosthesis approved since 2016. The purpose of this study is to report a large sample of findings for the TAR with INBONE-II prosthesis.Methods::A total of 64 patients with end-stage ankle arthritis, who underwent primary TAR using INBONE-II by the same surgeon from 2016 to 2019, at a single institution were included in this retrospective, single-center study. Clinical data, radiographic findings, survival rate, and complications were recorded and assessed pre-operatively and at the most recent follow-up.Results::A total of 64 patients were available for follow-up at least 2 years after surgery; the mean follow-up duration for clinical outcomes was 37.9 months (24–59 months), and for radiographic findings was 22.8 months (12–59 months). There were significant improvements ( P < 0.01) in the American Orthopedic Foot and Ankle Society hindfoot scale, the visual analog scale for pain, and the Short Form-36. There were statistically significant differences between pre-operative and post-operative comparisons of the talar tilt angle (TT) and the tibial lateral surface angle (TLS) in the radiographic findings (TT from 4.7 ± 4.3° to 1.3 ± 1.3°, TLS from 80.4 ± 7.7° to 87.4 ± 2.3°, P < 0.01). There was no statistically significant difference in improvement of the tibial anterior surface angle ( P = 0.14). Ten complications (all low grade) were recorded according to the Glazebrook classification system. The survivorship of the prosthesis was 100% (64/64). Conclusion::Patients who underwent TAR with INBONE-II prosthesis demonstrated significant improvements in all measures of pain and function as well as in radiographic findings. High survival and a low incidence of complications were observed in this study.