Objective:To compare the preoperative presentation, intraoperative findings, and postoperative outcomes between middle ear cholesteatoma with tympanosclerosis （MECwTS） and middle ear cholesteatoma without tympanosclerosis （MECw/oTS）, thereby investigating the clinical characteristics of MECwTS. Methods:A retrospective analysis was conducted on the clinical data of 120 patients with middle ear cholesteatoma. Patients were divided into two groups based on the presence or absence of concomitant tympanosclerosis: the MECwTS group （n=49） and the MECw/oTS group （n=71）. All patients underwent preoperative evaluations including temporal bone CT, otoscopic examination, pure-tone audiometry, tympanometry, and assessment using the Zurich Chronic Middle Ear Inventory （ZCMEI-21） quality of life scale. All patients underwent canal wall down mastoidectomy with tympanoplasty. Concurrent ossicular chain reconstruction was performed: partial ossicular replacement prosthesis （PORP） in 83 cases and total ossicular replacement prosthesis （TORP） in 37 cases. Intraoperative disease severity was assessed using the Cholesteatoma Comprehensive Score Scale （CCSS）. Postoperative follow-up lasted at least one year and included pure-tone audiometry, otoscopic examination, and the ZCMEI-21 scale administered at ≥1 year post-surgery. Preoperative and postoperative air-bone gap （ABG） and ZCMEI-21 scores were compared between the MECwTS and MECw/oTS groups. Additionally, surgical efficacy was defined as a postoperative ABG ≤20 dB; the hearing improvement efficacy of PORP versus TORP was compared based on this criterion. Results: ①Preoperative ABG showed no significant difference between the MECw/oTS and MECwTS groups（P>0.05）. Postoperative ABG was （18.65±10.21） dB in the MECw/oTS group versus （22.55±9.53） dB in the MECwTS group, demonstrating a statistically significant intergroup difference （P<0.05）. ②Intraoperative CCSS scores were significantly higher in the MECwTS group （8.04±2.18） compared to the MECw/oTS group （5.93±1.44） （P<0.05）. ③Preoperative ZCMEI-21 scores showed no significant difference between groups （P>0.05）. Postoperative ZCMEI-21 scores were （22.24±8.11） in the MECw/oTS group versus （27.02±7.21） in the MECwTS group, indicating a statistically significant difference （P<0.05）. ④Postoperative ABG ≤20 dB was achieved in 54 patients （65.06%, 54/83） in the PORP group and 16 patients （43.24%, 16/37） in the TORP group. This difference in efficacy rates was statistically significant （P<0.05）. The overall efficacy rate for ossiculoplasty was 58.33% （70/120）. Conclusion: Patients with MECwTS exhibit more severe middle ear and mastoid pathology compared to those with MECw/oTS, resulting in poorer postoperative hearing levels and quality of life outcomes. Both PORP and TORP implantation can improve postoperative hearing to some extent; however, PORP appears to offer superior hearing improvement efficacy compared to TORP.
Humans ; Cholesteatoma, Middle Ear/complications* ; Retrospective Studies ; Tympanoplasty ; Myringosclerosis/surgery* ; Female ; Male ; Adult ; Middle Aged ; Ossicular Replacement ; Ossicular Prosthesis ; Young Adult ; Ear, Middle ; Treatment Outcome ; Mastoidectomy ; Audiometry, Pure-Tone ; Adolescent ; Quality of Life

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Objective:To analyze the failure patterns and survival after stereotactic body radiotherapy (SBRT) in patients with T 1-2N 0M 0 non-small cell lung carcinoma (NSCLC). Methods:Clinical data of early-stage NSCLC patients who received SBRT at Zhejiang Cancer Hospital from January 2012 to September 2018 were retrospectively analyzed. The primary observed endpoint was the pattern of disease progression, which was divided into intra-field recurrence, regional lymph node recurrence and distant metastasis. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier method. Univariate analysis was conducted by log-rank test, and multivariate analysis was performed by Cox's model.Results:A total of 147 patients with 156 lesions were included. The median follow-up time was 44.0 months (16.5-95.5 months). A total of 57 patients (38.8%) progressed: 14 patients (24.5%) had recurrence with the 1-, 3-, and 5-year local recurrence rates of 2.0%, 10.9%, and 14.3%, respectively; 36 patients (63.2%) had Distant metastasis with the 1-, 3- and 5-year distant metastasis rates of 12.2%, 22.4% and 28.6%, respectively; and 7 patients (12.3%) had recurrence complicated with distant metastasis. The 3-, 5- and 7-year OS rates were 80.5%, 64.2% and 49.9% for all patients, respectively. The median OS was 78.4 months. The 3-, 5- and 7-year PFS rates were 64.8%,49.5% and 41.5%, with a median PFS of 57.9 months (95% CI: 42.3-73.5 months). Univariate and multivariate analyses showed that biologically equivalent dose and age were the factors affecting the efficacy of SBRT (both P<0.05). Conclusion:Distant metastasis is the main failure pattern in patients with T 1-2N 0M 0 NSCLC after SBRT. High-risk population should be selected for further systematic treatment to improve the efficacy.

We report a case of a female teenage with monogenic diabetes mellitus caused by glucokinase regulator (GCKR) gene mutation who presented with diabetic ketosis and misdiagnosed as type 1 diabetes. The patient was treated with insulin for 3 years since diagnosis. The islet function was well preserved, but polycystic ovary syndrome was developed. Whole-exome gene sequencing revealed a GCKR gene c. 69delG heterozygous mutation. After molecular diagnosis, the insulin dosage was gradually reduced to full cessation, and only metformin sustained-release tablets were taken to control blood glucose. It is necessary to regular evaluate islet function of patient with type 1 diabetes, and genetic test is of significance for accurate diagnosis and treatment.

Objective This study aimed to investigate the mechanism of artesunate-induced cardiotoxicity by using network toxicology and serum untargeted metabolomics.Methods The key targets and signaling pathways of artesunate-induced cardiotoxicity were expored by network toxicology technique.The toxic effect of artesunate on Healthy C57BL/6J mice was evaluated according to the pathological morphology of the heart and the levels of serum biochemical indexes included LDH and CKMB.Serum untargeted metabolomics analysis was combined with multivariate statistical analysis to search the key endogenous metabolites of artesunate cardiotoxic injury and related metabolic pathways.Results 64 targets including AKT1,EGFR,CASP3,VEGFA and 165 signaling pathways including Apoptosis,PI3K-Akt,FoxO were screened out by network toxicology,.Serum metabolomics analysis identified the serum metabolites affected by artesunate-induced cardiotoxicity included lysophosphatidylcholine,lysophosphatidylethanolamine,indoleacetaldehyde,etc.The results of metabolic pathways enrichment analysis were glycerophosphatidylcholine metabolism and tryptophan metabolism.Conclusion Artesunate 600 mg·kg-1 can induce cardiotoxicity in C57BL/6J mice after 1-week administration,and the mechanism is related to glycerophosphatidylcholine metabolism disorder and tryptophan metabolism disorder.This study provides a reference for the early prediction and evaluation of artesunate induced drug-induced cardiotoxicity.

Micropenis is an objective diagnosis based on accurate measurement of the length of the penis. Micropenis can be caused by many factors, including the structure of the hypothalamic-pituitary-gonadal axis or hormone defects. Therefore, examination of the endocrine system is extremely important for the diagnosis of the etiology. Once the diagnosis is confirmed, a multidisciplinary team of endocrinologists, geneticists, pediatricians, pediatric surgeons, and urologists are required to jointly develop individualized treatment plans. This article reviews the etiology, diagnosis and treatment of micropenis, aiming to raise awareness and concern about micropenis.

Hepatic hydrothorax (HH) is a challenging complication of liver cirrhosis associated with portal hypertension, and its pathogenesis and therapeutic measures remain unknown. This article summarizes and reviews the advances and challenges in the research on the pathogenesis, clinical manifestations, diagnosis, and treatment of HH and proposes a multidisciplinary treatment strategy, including reducing the production of ascites, preventing effusion from entering the thoracic cavity, removing pleural effusion, occluding the pleural cavity, and performing liver transplantation, so as to provide a reference for more clinicians.

The impairment of islets β cell by autoimmune response is an important cause of type 1 diabetes mellitus (T1DM). Some monogenic autoimmune syndromes could induce T1DM in difference chance, which are important disease models to deeply understand autoimmunity and T1DM. This article reviews the diagnosis, treatment and genetic detection of eight known single gene autoimmune syndromes associated with T1DM, arming to expand the diagnosis and treatment of T1DM.

One case of 46, XY partial gonadal dysgenesis due to a congenital defect of DEAH-box RNA helicase 37(DHX37) was reported. The clinical and genetic data of a boy who was admitted to the Department of Endocrinology and Metabolism, the First Affiliated Hospital of Henan University of Science and Technology due to ambiguous external genitalia in September 2020 were collected and analyzed. This 3-month-old male patient showed a micropenis, bilateral cryptorchidism, 46, XY karyotype, a decrease in testosterone, anti-Müllerian hormone, inhibin B, an increase in follicle stimulating hormone. Testis biopsy indicated gonadal dysgenesis. The proband harbored a de novo heterozygous mutation in the DHX37 gene c. 923G>A(p.Arg308Gln). DHX37 variants need to be considered for 46, XY gonadal dysgenesis.