Refractory inner ear disease refers to a spectrum of inner ear diseases that fail to achieve good therapeutic effects even after standardized treatment recommended by existing clinical practice guidelines. This disease spectrum is characterized by diverse etiological factors, high phenotypic heterogeneity, unclear subtype characteristics, unknown pathogenic mechanisms, and variable prognosis, making it difficult to define precisely. Refractory inner ear disease accounts for a significant proportion of the total population with inner ear diseases and has not been systematically summarized, refined, and deeply studied to date. This article, for the first time, clearly proposes the concept, definition, and scope of refractory inner ear disease, and elaborates on the current research status, challenges, and coping strategies for refractory inner ear disease. With the development and progress of science and technology, we believe that in the future we will witness more innovative technologies and new drugs applied to the treatment of refractory inner ear disease, bringing hope of cure to patients.
Humans ; Labyrinth Diseases/therapy*

Objective:To study the clinical efficacy of percutaneous transhepatic cholangial drainage (PTCD) and primary closure of common bile duct after laparoscopic common bile duct exploration (LCBDE) in treatment of choledocholithiasis complicated with moderate and severe cholangitis.Methods:The clinical data of 127 patients with choledocholithiasis complicated with acute cholangitis admitted to Yantai Affiliated Hospital of Binzhou Medical University from January 2021 to August 2023 were retrospectively analyzed. Finally, 45 patients were enrolled, including 20 males and 25 females, aged (71.3±8.2) years. All 45 patients were treated with sequential PTCD and primary closure of common bile duct after LCBDE. The interval from PTCD to primary closure, white blood cell count, total bilirubin, alanine transaminase before and after PTCD, operation time of primary closure, intraoperative blood loss, postoperative retention time of abdominal drainage tube, postoperative hospitalization time, postoperative complications (bile leakage, bleeding, etc.) were analyzed.Results:The serum total bilirubin, alanine transaminase and white blood cell count of 45 patients were (143.2±32.1) μmol/L, (173.6±23.4) U/L, (16.3±2.9)×10 9/L at admission, and (100.5±21.4) μmol/L, (103.5±12.7) U/L, (8.6±1.7) ×10 9/L after PTCD, respectively. The interval between PTCD and primary closure of common bile duct after LCBDE was (4.3±1.1) d, the operative time of primary closure was (123.4±20.5) min, the amount of intraoperative blood loss was (32.6±8.7) ml. The postoperative hospitalization time was (6.8±1.6) d, and the postoperative retention time of abdominal drainage tube was (4.5±1.3) d, and postoperative complications occurred in 7 cases (15.6%), including biliary leakage in 4 cases (8.9%), subxiphoid incision infection in 1 case (2.2%), and effusion in gallbladder fossa with infection in 2 cases (4.4%). Conclusion:The sequential application of PTCD and primary closure of common bile duct after LCBDE in treatment of choledocholithiasis complicated with moderate and severe cholangitis is a safe, effective and minimally invasive method, and primary closure of common bile duct after LCBDE is safe and reliable within 1 week after PTCD.

AIM: To evaluate the combining ability of prostate-specific membrane antigen (PSMA) targeted radioactive drug

Objective:To evaluate the feasibility and efficacy of 68Ga-PSMA PET/CT-guided targeted prostate biopsy for the diagnosis of clinically significant prostate cancer(csPCa). Methods:This retrospective analysis allocated 89 patients with elevated PSA levels between 4.0-20.0 ng/ml to PET group(n=48) or TRUS group(n=41) between September 2017 and June 2019. Patients with PSMA-avid lesions (SUV max≥8.0) underwent PET-TB via a single-puncture percutaneous transgluteal approach (n=19), while patients with negative PSMA-PET underwent systematic TRUS-GB (n=29). Patients in the TRUS group who did not get 68Ga-PSMA PET/CT examination underwent TRUS-GB directly (n=41). The mean age, prostate volume, PSA value of PET group and TURS group were (71.2±9.1) years vs. (68.0±12.0) years, (62.9±29.1)ml vs. (65.4±38.9)ml , 8.8(6.6, 13.6) ng/ml vs. 9.8(7.1, 13.1)ng/ml, respectively (all P>0.05). The diagnostic efficacy and difference of PCa and csPCa between the two groups were compared. PET-TB adopts a new mode of percutaneous gluteus approach and carries out precise image fusion of PSMA-PET/CT and pelvic CT in the same machine and in the same position (prone position). Under the direct guidance of CT, the biopsy is performed with only one precise puncture. Results:PCa and csPCa were detected in 27/89(30.3%)and 20/89(22.5%)in all patients. PET group detected significantly more cases of PCa and csPCa than those of TRUS group [PCa: 41.7%(20/48) vs. 17.1%(7/41), χ2=6.328; csPCa: 33.3%(16/48) vs. 9.8%(4/41), χ2=7.055, P<0.01]. Of 19 patients with PSMA-PET positive, PET-TB detected 16 cases of PCa(84.2%) by a single needle puncture, and the proportions of cancer tissues were ≥80% in 2, 50%-79% in 8, and <50% in 6 cases. Among these, Gleason score was underestimated by biopsy histopathology in 2 patients. Of 3 patients with PET-TB negative, 1 case of low-risk PCa(Gleason 3+ 3) was detected by complementary TRUS-GB. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 68Ga-PSMA PET/CT(SUV max≥8.0) for the diagnosis of csPCa were 73.9%(14/19), 93.1%(27/29), 87.5%(14/16), 81.3%(26/32)and 85.4%(41/48), respectively. For PET-TB, only one patient had slight symptoms of haematuria after the puncture, no cases of hematochezia, hemospermia, urinary retention or pelvic infection were observed. Conclusions:68Ga-PSMA PET/CT is a feasible novel puncture technique that may serve as a triage tool for prostate biopsy, and PET-TB may improve the detection rate of csPCa compared with TURS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.

Objective To investigate the safety and efficacy of 177Lu-prostate specific membrane antigen (PSMA)-617 in the treatment of metastatic castration-resistant prostate cancer (mCRPC).Methods From August 2017 to September 2018,11 patients(average age 70.6 years) with mCRPC who underwent 177Lu-PSMA-617 therapy in Nanjing First Hospital were studied.All patients underwent 68Ga-PSMA-11 PET/CT before therapy to assess the tumor radioactive uptake.Blood routine examination and renal function test results were documented before and after therapy to assess the safety.The efficacy was reflected by the changes of prostate specific antigen (PSA) levels and maximum standardized uptake value (SUVmax) on 68Ga-PSMA-11 PET/CT imaging.Paired t test and Wilcoxon's sign rank test were used to analyze the data.Results No acute side effects were observed after therapy of 177Lu-PSMA-617.There were no statistically significant differences after therapy in WBC counts,RBC counts,and PLT,as well as Hb levels (t values:-0.28-1.11,all P＞ 0.05).No kidney toxicity was found.The PSA level after 177Lu-PSMA-617 therapy was significantly lower than that before therapy (80.70 (14.29,1 538.00) μg/L vs 604.60 (88.41,3 980.00) μg/L;u =59,P =0.023).Of the 11 patients,only 2 had elevated PSA levels and disease progression,while the other 9 patients had varying decreases,of which 2/11 decreased by ＞30％ and 7/11 decreased by ＞50％.After therapy,SUVmax of metastatic lesions and metastatic lymph nodes were decreased in 9 and 2 patients respectively.Conclusions 177Lu-PSMA-617 has a good therapeutic value for mCRPC.It is safe and has no obvious side effects.

Objective To summarize the characteristics of BI-RADS 4a breast diseases under ultrasonic examination referring to patients' clinical data and pathological reports.Methods 82 patients who were firstlydiagnosed and treated in the Affiliated Hospital of Jiangnan University were included.The ultrasonograms were retrospectively reviewed along with the correlated pathological and clinical findings.Results 48 (58.5％) cases were benign,among which fibroadenoma was the most common.34 cases (41.4％) were malignant,among which invasive ductal carcinoma was the most common.68 of the 82 cases were neoplastic disease (82.9％),6 (9.8％)were inflammatory disease,and 8(7.3％) were adenosis.Conclusions The patients who are graded BI-RADS 4a by ultrasonic examination may have completely different diseases.Beyond the most common benign diseases,few of them are malignancies with atypical,even ambiguous sonographic features.Therefore,in clinical practice,sonologists should set appropriate parameters of ultrasonic devices appropriately,and evaluate the sonographic features carefully,in order to make the correct grading and diagnosis.While for clinicians,it is necessary to learn to read the ultrasonographic features along with patients' manifestations,and finally reduce the misdiagosis and missed diagnosis of such diseases.

Objective: To study the expression and significance of Notch1-Jagged1 in nasal mucosa of allergic rhinitis (AR) mouse model in various stages and in the serum of AR patients. Methods: Thirty-six mice were divided into 3 groups: control group, basal sensitization group (OVA) and OVA/AR group, with 12 mice in each group. Allergic symptom in each group were scored after AR model establishment. HE staining method was used to observe the nasal mucosa eosinophils infiltration. ELISA was used to detect the serum level of total IgE. Flow cytometry was used to detect the change of Treg cells in each group. Western blot was used to detect the expression of Notch1 and Jagged1 in nasal mucosa. Flow cytometric bead array (CBA) was used to detect the level of Th1/Th2/Th17 cytokines in splenic lymphocytes. The serum was obtained from 50 patients with AR and 30 control volunteers in Department of Otorhinolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University from June to October 2017. ELISA was used to detect the expression of Notch1 and Jagged1. Results: Compared with the control group, the allergy symptom, the number of nasal mucosal eosinophils and the level of total IgE were not significantly different in basal sensitization group, but increased significantly in OVA/AR group (6.11±0.78 vs 0.67±0.50, 77.67±5.61 vs 10.33±0.82, (106.80±11.91) pg/ml vs (82.45±19.80) pg/ml, t value was 19.471, 34.848, 2.542, respectively, all P<0.05). Compared with the control group, the ratio of Treg cell increased in basal sensitization group but decreased in OVA/AR group ((10.29±0.47)% vs (9.28±0.16)%, (8.49±0.15)% vs (9.28±0.16)%, t value was 5.838, 4.540, respectively, all P<0.01). Compared with control group, the expression of Notch1 increased significantly both in basal sensitization group and OVA/AR group (1.04±0.05 vs 0.71±0.05, 1.83±0.10 vs 0.71±0.05, t value was 9.293, 31.363, respectively, all P<0.01); and the expression of Jagged1 only increased significantly in OVA/AR group (0.41±0.04 vs 0.21±0.01, t=13.472, P<0.01). It was found that Notch1 was positively correlated with the level of IL-6, IL-10 by Pearson test (r value was 0.98, 0.87, respectively, all P<0.01). Compared with control volunteers, the expression of Notch1 and Jagged1 increased significantly in AR group patients ((1 135.0±254.9) pg/ml vs (436.0±139.3) pg/ml, (1 200.2±401.0) pg/ml vs (559.9±124.2) pg/ml, t value was 13.99, 11.94, respectively, all P<0.01). Conclusions The expression of Notch1 receptor and ligand increased significantly in the pathogenesis of AR. Notch1-Jagged1 may promote the occurrence and development of AR by up-regulating the expression of IL-6 and IL-10.

Objective To explore the long-term outcomes of endoscopic submucosal dissection (ESD) of gastric GISTs.Methods Data of 25 patients with gastric stromal tumors,who underwent ESD,were reviewed in terms of clinical characteristics,histopathologic results,complications and long-term outcomes.Results Twenty-five patients underwent one-time complete removal of lesion, with a average tumor size of 3.0 cm (range,0.6 to 7.6 cm).The average time of operation was 65 minutes (range,15 to 154 minutes).one case was observed with intraoperative hemor-rhage of 200 mL blood,which was successfully managed by hemostatic forceps.Perforation with incidence rate of 16%occurred in 4 cases and was closed well with clips.Mucosal mechanical laceration of esophagus occurred in 1 case when the big tumor was taken out.The average length of hospi-talization was 7.3 days (range,4 to 21 days).A follow-up for 30 months (range,13 to 54 months) showed no tumor recurrence or metastasis. Conclusion ESD is an effective and safe endoscopic procedure to remove gastric GISTs for long-term outcomes in patients with no metastasis.

BACKGROUND:Periprosthetic infection after artificial joint replacement is a disastrous complication for a patient. Currently, during treating for the periprosthetic infection, most of patients need two-stage revision, which bring about enormous physical and psychological pain for patients, and a heavy burden for the families and society. To make matters worse, the effect is not very perfect, and some of these cases require multi-stage revision, even amputation. OBJECTIVE:To investigate the therapeutic effect of vacuum sealing drainage combined with iodophor douche for the infection after artificial joint replacement. METHODS:Nine cases (six knees and three hips) of infection after artificial joint replacement were col ected, with an average age of 63.4 years. Infection occurred at 7 days-14 months, and a median time of 1 month after replacement. Al patients suffered from purulent or purulent blood secretion. Fistula formed in two cases and incision and drainage sites were not healed in one case. According to the bacterial culture results, above symptoms were accorded with clinical diagnosis of prosthesis infection. The prosthesis was remained for debridement. Vacuum sealing drainage was performed. Iodophor douche (30-50 mL) was conducted every day. The drainage tube at proximal end was occluded for 30 minutes, and then vacuum sealing drainage was performed. Al patients were regularly fol owed up to assess the therapeutic effects of vacuum sealing drainage combined with prosthesis infection after replacement. RESULTS AND CONCLUSION:(1) Except that one case was stil in treatment, one case was dead, and one case of tumor prosthesis was failure and final y amputated, the remaining six patients were healed. (2) The time of vacuum sealing drainage and iodophor douche was 10 to 84 days, with the median time of 57 days. No adverse reactions or complications occurred. Al healed patients were fol owed up for 12-60 months, without recurrence. (3) These results indicated that vacuum sealing drainage combined with iodophor douche retained the prosthesis to the greatest degree, is simple, safe, and effective for the infection after artificial joint replacement, needs a low cost, and is a kind of therapy for prosthesis infection after artificial joint replacement.

Objective To evaluate the distribution of fetal abnormal chromosome karyotype in mid-pregnancy and analyse the possible misdiagnosis risks of molecular techniques in clinical prenatal diagnosis.Methods Fetal karyotype ( fetal cell collected from amniotic fluid ) in Prenatal Diagnosis Center of Zhejiang Province between 2001 and 2010 were retrospectively analyzed on distribution according to 7 different referral indication:positive screening for trisomy 21, trisomy 18, advanced maternal age , abnormal history of pregnancies , abnormal family history , fetal structural abnormalities and others.The combination of trisomy 21, trisomy 18 and trisomy 13 ( T21/18/13 Group) and the aneuploidies of chromosome 21, 18, 13, X, Y (21/18/13/X/Y Group) were further analyzed based on the current molecular target detection range.Results There were 462 cases out of 12 481 with chromosomal abnormality (3.60%, 462/12 841), with 215 cases of high risk (detection rate 1.67%, 215/12 841) and 247 cases of low risk (detection rate 1.92%, 247/12 841).Under different indications , the detection rate on abnormal chromosome of high risk (high-risk CA) is different,“abnormal fetal ultrasound” is the highest(27.27%,24/88).Among the high-risk CA, T21/18/13 Group accounted for 72.56%(156/215), while the 21/18/13/X/Y Group accounted for 94.88%(204/215).For the 7 regular indications , the high-risk CA distribute different;Except the T21/18/13 Group and 21/18/13/X/Y Group, the rates of other abnormal chromosome karyotype in the high risk CA were 0.28%( 2/719 )-12.5%( 11/88 ) and 0.06%( 4/6 915 )-1.14%( 1/88 ) according to different indication, respectively.Conclusions The distribution of abnormal karyotype were different under different referral indication;the detection power and possible misdiagnosis risks were varied under different indication for each molecular technique.It was suggested that doctors should select suitable molecular technique according to different clinical indications and each molecular method has its own limitations .