Objective To identify the key immune-related genes and potential drug targets of Krabbe disease by using neural stem cells(NSCs)derived from induced pluripotent stem cells(iPSCs)generated from patients with Krabbe disease.Methods 1)The transcriptome data of GLD-NSCs(GSE212512)was analyzed using GEO2R and Sangerbox;2)Differential expression genes(DEGs)related to immunity were identified through various methods;3)Functional enrichment and pathway analysis were performed using DAVID;4)The protein-protein interaction network was constructed and analyzed using STRING and Cytoscape;5)Key immune-related genes were deter-mined through topological analysis;6)Potential therapeutic drugs were screened using DGIdb and drug MAP data-bases;7)Molecular docking was performed using CB-DOCK2.Results 1)Sixty-one immune-related DEGs were identified in patient NSCs,with GDNF,EGF,KDR,FGF10,and MET being identified as key immune-related genes;2)Drug candidates with high binding affinity to these genes were identified,including gentamicin for GDNF,cetuximab for EGF,tivozanib for KDR,and capmatinib for MET.Conclusions The predictions suggest cetuximab,gentamicin,tivozanib,and capmatinib exhibit high binding affinity with EGF,GDNF,KDR,and MET,respectively,indicating their potential application value in GLD targeted therapy.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

Objective:To study the feasibility of detecting vertical semicircular canal function and to analyze the three-dimensional(3D)characteristics and normal reference value in healthy young people.Methods:This was a cross-sectional study conducted from January to June 2024. A three-axis rotating chair was used to perform vertical sinusoidal rotation on 52 healthy young adults (26 males and 26 females, aged 18-40 years) in the left anterior-right posterior (LARP) and right anterior-left posterior (RALP) semicircular canal planes. For each plane, nystagmus was induced with six combinations of different angles and velocity front and back rotation angles of ±30°,±60°,±90°, and velocities of 40°/s and 80°/s, the slow phase velocity (SPV) and their symmetry of 3D nystagmus were analyzed. SPSS 20.0 was used to compare the statistical differences in these two parameters across different stimulation protocols.Results:There were no spontaneous nystagmus in the 52 subjects, and all tests were finished. Except the combinations of (±30°-40°/s), three components of nystagmus were induced stably in the rest of the stimulations. The SPVs of vertical components were no statistically insignificant ( P>0.05), and some horizontal or torsion components were statistically significant ( P<0.05). The 95% reference range of the symmetry was≤25% in the vertical and≤30% in the torsional component of the nystagmus except for (±30°-80°/s), the symmetry was 32.2% and 49.2% respectively. The trend changes of the three components were consistent, among which the vertical and torsional components induced by (±60°-80°/s) and (±90°-80°/s) were the best, the SPV value of the vertical components was higher in the latter group than the former apart from the front RALP, while no significant difference was found in the torsional components ( P>0.05). Conclusion:The (±90°-80°/s) combination is the optimal method to detect the function of vertical semicircular canal in 3D chair test. When observing torsional component, the combining scheme of (±60°-80°/s) and (±90°-80°/s) is better. Considering tolerance, the (±60°-80°/s) combination is recommended.

Objective:To analyze the characteristics of pulse-step-sine (PSS) test in healthy people of different ages and to discuss its clinical value.Methods:From July 10, 2018 to December 9, 2020, a total of 78 healthy volunteers, including 40 males and 38 females, were enrolled and divided into youth group, middle age group and old age group. The I Portal NOTC rotational-chair system (NKI) was applied for PSS detection to analyze the clinical characteristics of gain, phase, asymmetry, and slope of step and sinusoidal components. Statistical analysis was performed using SPSS17.0 software.Results:In the same age group, there were no statistically significant differences in left and right step gain, slope gain and sine gain (All P values were greater than 0.05). Pairwise comparison between different age groups showed that there was no significant difference in the corresponding parameters between the youth group and the middle age group. Compared with young group, the old age group had a significantly lower step gain value in their left side ( P<0.01) but not in the right side ( P>0.05).The left and right slopes of the old age group were significantly lower than those of the young group and the middle group, and the differences were statistically significant (All P values<0.05). Conclusion:The PSS test can detect bilateral and unilateral horizontal semicircular canal function with good tolerance in different age groups, better than the traditional rotational chair examination to determine the well-compensated unilateral vestibular function. PSS test is a new vestibular detection method.

Objective To investigate the application value of transesophageal echocardiography(TEE) in allogeneic lung transplantation. Methods The study enrolled 37 patients receiving allogeneic lung transplantation because of end stage lung disease,including sequential bilateral lung transplantation 20 cases and unilateral lung transplantation 17 cases,the latter included 4 cases with extracorporeal membrane oxygenation (ECM O).Echocardiographic parameters before surgery,including right ventricular transverse diameter (RVTD),left ventricular transverse diameter (LVTD),right atrial transverse diameter (RATD), left atrial transverse diameter (LATD),main pulmonary artery (DMPA),left ventricular ejection fraction (LVEF),pulmonary arterial systolic pressure (SPAP),and TEE parameters during surgery,including pulmonary artery anastomosis diameters (DRPAand/or DLPA) and blood flow velocity (VRPAand/or VLPA), pulmonary vein anastomosis blood flow velocity (V RPVand/or VLPV),were measured. Results ①Preoperative transthoracic echocardiographic showed a slight increase of right heart in patients with allogeneic lung transplantation,different degrees of increase in SPAP,a normal or slightly increase of D MPA and a normal LVEF,according to the ASE guidelines. ②Compared with pre-operation,the diameters of left and right pulmonary artery decreased ( P < 0.001) and the blood flow velocity of arteries and veins increased ( P <0.001). ③Patients with ECMO support had a higher SPAP before operation ( P <0.05) and a lower LVEF ( P <0.05),but within a normal range.The blood flow velocity of pulmonary artery and vein had no difference between two groups ( P > 0.05). Conclusions During allogeneic lung transplantation,TEE plays an important role in the monitor of pulmonary arteriovenous anastomosis. It could remind the surgeon whether anastomosis is narrow timely,and determine the patient′s hemodynamic status and cardiac load to guide the surgical process.

Objective: To investigate the influence of inhibiting expression of polyamine-modulated factor (PMF-1) on the antitumor effect of glucocorticoid dexamethasone (DEX) in human cervical cancer Caski cells. Methods: siRNAs which target human PMF-1 gene were designed and synthesized, and their effect on the expression of PMF-1 in Caski cells was evaluated by Western blotting. The PMF-1 down-regulated and control Caski cells were treated with DEX, and then the affect of PMF-1 down regulation on the sensitivity of the tumor cells to DEX was analyzed. MTT method was used to detect cell proliferation, flow cytometry was used to analyze cell cycle, Western blotting method was used to evaluate expression level of glucocorticoids receptor (GR), and HPLC was used to analyze intracellular polyamine content. Results: The transient transfection of Caski cells with siRNAwhich targets PMF-1 gene can significantly reduce the expression level of PMF-1 protein. Compared with the control cells, treating PMF-1 down-regulated Caski cells with DEX can more effectively inhibit cell proliferation（P<0.01), up regulate GR expression, arrest cell cycle at G2 stage（P<0.01), and also significantly reduce intracellular polyamine level（P<0.01). Conclusion：Inhibiting PMF-1 expression can enhance antitumor pharmacological activity of DEX against human cervical cancer cells, and the underlying mechanism may be related with enhanced cell cycle inhibition and decreased intracellular polyamine level.

Objective: To evaluate the feasibility of combining simultaneous triple semicircular canal plugging (TSCP) and cochlear implantation (CI) to treat vertigo and hearing loss in advanced Meniere's disease(MD) patients, so as to provide an alternative surgical procedure for treating this disorder. Methods: Data from seven patients, who were referred to our hospital and diagnosed with unilateral MD strictly meeting the criteria issued by Chinese Academy of Otolaryngology-Head and Neck Surgery Committee (2006), from Jan. 2015 to Jan. 2016, were retrospectively analyzed in this work. Seven patients, in whom the standardized conservative treatment had been given for at least one year and frequent vertigo still occurred, underwent simultaneous TSCP and CI under general anesthesia via mastoid approach. Postoperative follow-up time was more than six months. Vertigo control and auditory function were measured. Pure tone audiometry, speech perception scores, caloric test, head impulse test (HIT), and vestibular evoked myogenic potential (VEMP) were performed for evaluation of audiological and vestibular functions. Results: All patients had bilateral severe sensorineural hearing loss preoperatively. One side hearing loss was due to MD and another side was due to reasons including sudden sensorineural hearing loss, mumps and other unknown reason. The total control rate of vertigo in seven MD patients was 100.0% in the six-month follow-up, with complete control rate of 85.7% (6/7) and substantial control rate of 14.3% (1/7). Improved hearing threshold and speech perception scores were observed in all study participants. Postoperative average aided hearing threshold was 32.5 dBHL, the average monosyllabic word score was 42.6% and speech perception scores of sentences tested in quiet was 52.3%. Tinnitus improved in five cases, and no significant change in two patients. Post-operatively, all patients suffered from temporary vertigo and balance disorders. Vertigo was disappeared in all patients within 3-5 days, while, an average recovery time of balance disorders was 19.7 days. Six months after treatment, loss of semicircular canal function by caloric test was found in the operation side of all patients and no change in cVEMP or oVEMP test was noted. All patients had no facial paralysis, cerebrospinal fluid leakage, and other complications. Conclusions A combined approach of TSCP and CI which could control vertigo effectively and improve hearing loss and tinnitus represents an effective and safe therapy for some advanced MD patients.

Objective To investigate the prognostic factors relevant to acute low-tone sensorineural hearing loss (ALHL).Methods 196 adult ALHL patients,including 82 males and 114 females with mean age of (43.1 ± 14.3)years old were included.All patients received the same therapy and were evaluated the curative effect.To evaluate the impact factors on the prognosis of hearing,inclusive of age,gender,time delay before the first visit,degree of deafness,vestibular function,electrocochleogram,and the serum levels of thyroxines by SPSS 18.0 software.Results Of those 196 patients with ALHL,124 (63.3％) were recovery,5(2.6％) were excellent better,42(21.4％) were better,and 25 (12.8％) were poor,with a total effective rate of 87.2％.Among 15 (12.1％) who recurred the hearing loss,2 developed into Meniere's disease during the follow-up.The mean age of patients with poor hearing effect was significantly older than that of other patients (P ＜ 0.05).No relativity was found between gender and hearing curative effect.There existed a statistical difference in total effective rate among subjects with different histories (P ＜ 0.05).In addition,the recovery rate was significantly different between groups,i.e.,the course of disease was less than 14 days,between 14 days and 6 months,and between 6 months and 2 years (P ＜0.05).There was no statistical significance in total effective rate among different degrees of deafness (P ＞ 0.05).However,in term of the recovery rate,the difference was statistical significance (P ＜ 0.05).The recovery rate in patients with mild hearing loss was higher than that in middle or heavy hearing loss (both P ＜ 0.05).Among patients with mild deafness,the recovery rate in patients whose history was less than 3 months was significantly higher than that more than 3 months (P ＜ 0.05).For moderate deafness patients,the recovery rate in patients whose history was less than 7 days was significantly higher than that more than 1 month (P ＜ 0.05).There were statistical differences in hearing effect of 130 (66.3％) patients with abnormal vestibular function in comparison to that with normal vestibular function (x2 =15.1,P ＜ 0.05).There were 17(8.7％) patients with abnormal electrocochleogram combined with abnormal vestibular function,and the hearing effects were all poor.There were 45 (23.0％) patients with abnormal thyroxine levels in serum,which was significant higher than that in health adults of 5.9％ (x2 =7.26,P ＜ 0.01).There was no significant difference in hearing prognosis between patients with abnormal and normal thyroxine levels (x2 =2.51,P ＞ 0.05).Conclusions With respect to ALHL,the hearing effect is associated significantly with the history.The severity of hearing loss is negative prognostic factor for hearing recovery.Age,vestibular function,and electrocochleogram might predict hearing recovery.Gender and thyroxine levels couldn't predict the hearing prognosis,although there is a high incidence rate in patients with ALHL.

Objective To discuss the correlation between right ventricular function and systolic pulmonary artery pressure (PASP ) in patients with chronic thromboembolic pulmonary hypertension (CTEPH)and explore the change of right ventricular function under different degree of PASP.Methods One hundred and thirty-seven CTEPH patients were divided into four groups by PASP:Group Ⅰ (50 mmHg≤PASP<70 mmHg),20 cases;Group Ⅱ (70 mmHg≤PASP<90 mmHg),35 cases;Group Ⅲ,55 cases (90 mmHg ≤ PASP < 1 10 mmHg);Group Ⅳ (PASP ≥ 1 10 mmHg),27 cases.Echocardiographic parameters include:PASP,tricuspid regurgitation area (ATR ),left ventricular transverse diameter (LVTD), right ventricular transverse diameter (RVTD),inner diameter of main pulmonary artery (DMPA ),inner diameter of left arterial branch (DLPA ),inner diameter of right pulmonary arterial branch (DRPA ).Right ventricular function parameters include:tissue Doppler-derived tricuspid lateral annular systolic velocity (s'),tricuspid annular plane systolic excursion (TAPSE),RV index of myocardial performance (RIMP)and right ventricular fractional area change (FAC).Results There were significant differences in RVTD, TAPSE,FAC and RIMP in CTEPH patients under different PASP(P <0.05).RV structure and function was significantly correlated with PASP in CTEPH patients.With the elevation of PASP,RV was significantly enlarged and RV function becomes worse.Conclusions Echocardiography may contribute to evaluate RV function in CTEPH patients and provide basis for clinical treatment and prognosis evaluation.

Objective To evaluate right ventricular systolic function in patients with pulmonary hypertension (PH) by real-time three-dimensional echocardiography (RT-3DE),and compared with cardiac magnetic resonance.Methods A total of 23 patients with PH who underwent MRI and echocardiography in the study.Right ventricular index of myocardial performance (RIMP),fractional area change (RVFAC),tricuspid annular plane systolic excursion (TAPSE) and tissue Doppler-derived tricuspid lateral annular systolic velocity (S') were measured by echocardiography.RV end-diastolic volume (RVEDV) and endsystolic volume (RVESV) were measured by RT-3DE and cardiac magnetic resonance and RV ejection fraction (RVEF) was calculated.Results A positive correlation was found between RVFAC and RVEF (r =0.595,P =0.003),there was a negative correlation between RIMP and RVEF (r =-0.745,P =0.000),has no correlation between TAPSE and RVEF (r =-0.029,P =0.896),a positive correlation was found between S' and RVEF (r =0.489,P =0.018).There were close correlation between RVEDV,RVESV and RVEF measured by RT-3DE and MRI (P ＜0.001,respectively);Bland-Altman analyses showed good agreement between them.Conclusions RT-3DE can noninvasive,accurate assessment right ventricular systolic function in patients with PH,and provide prognosis and treatment choice for clinical demands.