Objective:To investigate alterations in the glymphatic system of spinocerebellar ataxia type 3 (SCA3) patients based on quantitative MRI, and its association with genetic information and motor dysfunction.Methods:The study was a cross-sectional study. This prospective study recruited 39 confirmed SCA3 patients (SCA3 group) and 40 matched healthy controls (HC group) who were seen at the Southwest Hospital of Army Medical University from May 2017 to June 2023. All subjects underwent cranial MRI scanning. Clinical assessments were conducted on all participants using the scale for the assessment and rating of ataxia (SARA) and the international cooperative ataxia rating scale (ICARS). The automatic segmentation and volume measurement of the choroid plexus based on Freesurfer 6.0; the perivascular interstitial space (PVS) was automatically segmented based on the deep-learning model VB-Net, and the volume of the PVS in each brain region was quantified after manual correction. Independent samples t-test and Mann-Whitney U-test were used to analyze the changes in the class lymphatic system in the SCA3 group and the HC group. Pearson partial correlation analysis was used to explore the relationship between CAG repeats, the glymphatic system, and motor dysfunction. Results:The standardized choroid plexus volume in the SCA3 group was (1.24±0.36)×10 3 mm 3, and that in the HC group was (0.96±0.34)×10 3 mm 3, with a statistically significant difference ( t=4.01, P<0.001). PVS volumes in the frontal lobe, temporal lobe, parietal lobe, basal ganglia, cerebellum, thalamus, and brainstem regions in the SCA3 group were significantly higher than those of HC group ( P<0.05). Partial correlation analysis revealed that CAG repeats in SCA3 group were positively correlated with SARA, ICARS, and basal ganglia PVS volumes ( r=0.65, 0.58, 0.29; P=0.001, 0.001, 0.042). Cerebellar and temporal lobe PVS volumes were positively correlated with SARA ( r=0.59, 0.47; P=0.001, 0.003), and positively correlated with ICARS scores ( r=0.61, 0.40; P=0.001, 0.011). Choroid plexus volume was positively correlated with cerebellar and basal ganglia PVS volumes ( r=0.41, 0.31; P=0.009, 0.043). Conclusions:The glymphatic system of SCA3 patients have significant alteration and have association with CAG repeats and motor dysfunction.

OBJECTIVE To study the relationship between frequency specific free-field tone burst cortical auditory evoked potentials(CAEP)and aided behavioral audiometry to provide rapid,reliable insights for predicting hearing intervention efficiency in hard to cooperate cochlear implant patients.METHODS The study comprised of 22 cochlear implant pediatric patients(22 ears)free-field tone burst CAEP P1 response thresholds,free-field behavioral thresholds determined within the group across frequencies 0.5,1,2 and 4 kHz were collected for correlation analysis.RESULTS The free-field tone burst CAEP P1 response thresholds and free-field behavioral audiometric thresholds in cochlear implant pediatric patients for testing frequencies 0.5,1,2,4 kHz were compared and r correlation coefficients found were 0.567,0.670,0.637 and 0.762 across the frequencies respectively(P<0.01).The mean difference between free-field CAEP P1 response threshold and free-field behavioral thresholds for cochlear implant patients differ by 5-8 dB with statistical significance.CONCLUSION Free-field tone burst CAEP can be used for cochlear implant programming validation in patients that fail to cooperate in behavioral testing,thus is applicable in cochlear implant programming clinical practice.

Purpose: Myofibroblastic cancer-associated fibroblasts (myCAFs) are important components of the tumor microenvironment closely associated with tumor stromal remodeling and immunosuppression. This study aimed to explore myCAFs marker gene biomarkers for clinical diagnosis and therapy for patients with bladder cancer (BC). Materials and Methods: BC single-cell RNA sequencing (scRNA-seq) data were obtained from the National Center for Biotechnology Information Sequence Read Archive. Transcriptome and clinical data were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Subsequently, univariate Cox and LASSO (Least Absolute Shrinkage and Selection Operator regression) regression analyses were performed to construct a prognostic signature. Immune cell activity was estimated using single-sample gene set enrichment analysis whilst the TIDE (tumor immune dysfunction and exclusion) method was employed to assess patient response to immunotherapy. The chemotherapy response of patients with BC was evaluated using genomics of drug sensitivity in cancer. Furthermore, Immunohistochemistry was used to verify the correlation between MAP1B expression and immunotherapy efficacy. The scRNA-seq data were analyzed to identify myCAFs marker genes. Results: Combined with bulk RNA-sequencing data, we constructed a two-gene (COL6A1 and MAP1B) risk signature. In patients with BC, the signature demonstrated outstanding prognostic value, immune infiltration, and immunotherapy response. This signature served as a crucial guide for the selection of anti-tumor chemotherapy medications. Additionally, immunohistochemistry confirmed that MAP1B expression was significantly correlated with immunotherapy efficacy. Conclusions Our findings revealed a typical prognostic signature based on myCAF marker genes, which offers patients with BC a novel treatment target alongside theoretical justification.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

To analyze the endoscopic ultrasonography (EUS) and histopathological features of esophageal epithelial malignant tumors misdiagnosed as esophageal submucosal tumors (SMT), data of patients diagnosed as having esophageal SMT preoperatively but confirmed as esophageal epithelial malignant tumor by pathology after operation in Nanjing Drum Tower Hospital from January 2012 to December 2020 were retrospectively analyzed, and the clinical data including age, gender, size and location of the lesion, origin and echo of the lesion under EUS, endoscopic treatment and postoperative pathology were recorded. Among the 11 patients, there were 9 males and 2 females, aged (65.5±6.2) years. The length diameter of 9 lesions was ≤2 cm, and 8 lesions were located in the middle thoracic esophagus. Among the 11 patients, 10 underwent EUS before operation. The lesions originated from submucosa in 6 cases, muscularis propria in 2 cases and muscularis mucosa in 2 cases. The echo of the lesions was hypoechoic in 9 cases and isoechoic in only 1 case. Of the 11 patients, 3 underwent endoscopic mucosal resection, 6 underwent endoscopic submucosal dissection, and 2 underwent submucosal tunneling endoscopic resection. The histopathological types included 3 cases of moderately to poorly differentiated squamous cell carcinoma, 3 cases of basaloid squamous cell carcinoma, 2 cases of adenoid cystic carcinoma (including 1 case of adenoid cystic carcinoma colliding with squamous cell carcinoma), 2 cases of adenocarcinoma, and 1 case of esophageal sarcomatoid carcinoma with basaloid squamous cell carcinoma. Endoscopic manifestations of submucosal eminence in esophageal epithelial malignant tumors are extremely rare. EUS is helpful for differential diagnosis, and diagnostic treatment can make a definite diagnosis.

Objective:To explore the curative effect of surgical treatment for Crohn′s disease (CD), to investigate the timing of surgical intervention and the choice of surgical methods.Methods:From January 1, 2016 to August 31, 2020, at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, the clinical data of 123 patients with CD and receiving surgical treatment were retrospectively analyzed, which included the type of lesion, the location of lesion, clinical manifestation, surgical method, preoperative inflammatory and nutritional indicators, postoperative recovery of digestive tract function, and the development and treatment of postoperative complications. CD was diagnosed according to Consensus opinion on diagnosis and treatment of inflammatory bowel disease ( Beijing 2018). Patient was classitied according to the Montreal Classification. Postoperative complications were graded according to the Clavien-Dindo Criteria. Mann-Whitney U test was used for statistical analysis. Results:Among 123 patients, according to the Montreal classification, two cases (1.6%) were diagnosed at ≤16 years old (type A1), 66 cases (53.7%) were diagnosed at 17 to 40 years old (type A2), and 55 cases (44.7%) were diagnosed at >40 years old (type A3). The lesions were 52 cases (42.3%) of terminal ileum (L1) type, 20 cases (16.3%) of colon (L2) type, and 51 cases (41.5%) of ileocolon (L3) type. Four cases (3.2%) were non-stenosis and non-penetrating (B1) type, 87 cases (70.7%) were stenosis (B2) type, and 32 cases (26.0%) were penetrating (B3) type. Eighteen patients (14.6%) underwent emergency surgery due to complete intestinal obstruction (10 cases), gastrointestinal perforation (five cases), gastrointestinal bleeding (two cases), and rectovesical fistula complicated with septic shock (one case). One hundred and five patients (85.4%) received selective surgery due to poor conservative treatment effects. 51 cases (41.5%) underwent traditional open surgery and 72 cases (58.5%) underwent laparoscopic surgery. Nineteen patients (15.4%) received temporary or permanent ostomy. The preoperative C reactive protein level of patients with emergency surgery was higher than that of patients undergoing selective surgery ((39.23±24.13) mg/L vs. (11.48±2.68) mg/L), while the levels of plasma albumin (ALB) and pre-ALB were lower than those of patients receiving selective surgery ((29.90±10.60) g/L vs. (38.38±8.30) g/L, (146.00±125.49) mg/L vs. (209.06±61.19) mg/L), and the differences were statistically significant ( Z=9.603, 8.754 and 7.111, all P<0.01). During the follow-up, a total of 23 cases (18.7%) developed postoperative complications, including one case of postoperative intra-abdominal hemorrhage and underwent re-operation (Clavien-Dindo grade Ⅲ complication); four cases of anastomotic leakage after operation; six cases of postoperative paralytic ileus; 11 cases of surgical site infection, all of which were Clavien-Dindo grade Ⅱ complications, and one case of deep venous thrombosis of lower extremity. No patient with severe intraoperative complication was observed, and no patients died during the operation or hospitalization. The postoperative exhaust time of patients was (3.2±1.4) d, the time of open fluid diet was (5.8±0.8) d, the length of hospital stay was (18.0±14.1) d, and the length of postoperative hospital stay was (11.2±8.8) d. Conclusions:The concept of multidisciplinary collaboration should be emphasized in the treatment of CD. Surgical treatment can effectively control the complications and improve the quality of life of patients, but the timing of operation and the choice of surgical methods should be decided prudently after perioperative treatment, multi-disciplinary participated and regulation of the internal environment. The standardized and targeted treatments for the surgical difficulties of inflammatory bowel disease should be conducted.

AIM: To explore the efficacy of torasemide combined with levocarnitine in the treatment of chronic heart failure (CHF). METHODS: From July 2018 to July 2020, 75 patients with CHF were recruited and randomly assigned into the control group (37 cases) and the study group (38 cases) according to the random number table method. The control and study groups were treated with levocarnitine and the combination of levocarnitine and torasemide, respectively. The clinical efficacy of the two groups was evaluated. The ventricular remodeling indexes and 6-minute walk test (6MWT) distance were compared between the two groups before and after treatment. The serum levels of serum galectin-3 (Gal-3), interleukin-33 (IL-33), hypersensitive C-reactive protein (hs-CRP), and the plasma concentrations of N terminal pro B type natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) were determined. RESULTS: (1) After treatment, the total clinical effective rate of the study group (92.11%) was higher than that of the control group (72.97%) (P<0.05). (2) The diastolic interventricular septal thickness (IVST) and diastolic left ventricular posterior wall thickness (LVPWT) were decreased following the treatment in both groups (P<0.05), whereas the treatment led to the increases of the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF) in both groups (P<0.05). Compared with those in the control group, IVST and LVPWT in the study group were lower (P<0.05), and LVMI and LVEF were higher (P<0.05). (3) The levels of serum Gal-3, IL-33 and hs-CRP in the two groups were decreased after treatment (P<0.05); compared with those in the control group, the levels of serum Gal-3, IL-33 and hs-CRP were reduced to a greater extent in the study group (P<0.05). (4) Compared with that before treatment, 6MWT distance in both groups increased after treatment (P<0.05); the improvement in the study group was more significant relative to those in the control group (P<0.05). (5) Compared with before treatment, the expression levels of plasma NT-proBNP and BNP in the two groups were decreased after treatment (P<0.05); the reduction of plasma NT-proBNP and BNP levels in the study group was greater than the control group (P<0.05). CONCLUSION: Torasemide combined with levocarnitine is more effective than levocarnitine monotherapy in the treatment of CHF and can significantly improve ventricular remodeling index and motor function, reduce serum inflammation, and enhance cardiac function with definite curative effect.

Purpose: The purpose of the current study was to explore the functions and potential mechanism of miR-451a in breast cancer (BC). Methods: Quantitative reverse transcription real-time polymerase chain reaction was used to analyze the expression of miR-451a in human normal mammary cells (MCF-10A) and BC cells. Colony formation assay, terminal-deoxynucleoitidyl transferase mediated nick end labeling assay and transwell assays were conducted to validate the effect of miR-451a on proliferation, apoptosis, migration and invasion of BC cells, respectively. RNA pull-down, RNA immunoprecipitation and luciferase reporter assays were applied to investigate the upstream and downstream mechanisms of miR-451a in BC cells. Results: MiR-451a was expressed at a low level in BC cells. Overexpression of miR-451a repressed BC cells proliferation, migration and invasion. Moreover, long non-coding RNA AC092127.1 acted as a sponge of miR-451a to enhance the expression level of AE binding protein 2 (AEBP2) that was demonstrated to be the target gene of miR-451a in BC cells. Finally, rescue experiments validated that miR-451a and AEBP2 involved in AC092127.1-mediated BC cell growth, migration and invasion. Conclusion In a word, AC092127.1/miR-451a/AEBP2 axis contributes to BC cell growth, migration and invasion. Our results may help to find novel potential targets for BC treatment.

Objective:To investigate the safety and efficacy of endoscopic treatment for sporadic non-ampullary descending duodenal adenoma, and to analyze high-risk endoscopic features of malignant adenoma.Methods:Data of 54 patients diagnosed as having non-ampullary descending duodenal adenoma in Nanjing Drum Tower Hospital from November 2012 to September 2019 were retrospectively studied. The patients were divided into two groups, the high-grade intraepithelial neoplasia/adenocarcinoma (HGIN/AC) group and the low-grade intraepithelial neoplasia (LGIN) group according to pathological grade. Clinical features including gender, age, size and color of lesions, therapeutic methods, complications and postoperative follow-up results were analyzed.Results:A total of 54 patients were divided into the HGIN/AC group ( n=12) and the LGIN group ( n=42). There were significant differences in size or color of lesions between the two groups (both P<0.05). All 54 patients received endoscopic treatment. Biopsy, endoscopic mucosal resection and endoscopic submucosal dissection were performed on 8, 32 and 14 cases, respectively. A small perforation was found and clipped during operation without any complications. There were 2 cases of delayed hemorrhage, and the bleeding stopped under endoscopic treatment. The mean follow-up time was 2-58 months with no recurrence. Conclusion:Endoscopic treatment is safe and effective for non-ampullary descending duodenal adenoma. Lesions of size larger than 10 mm and those with a red surface have higher malignant tendency.

Objective: This paper studies the nutritional and vision health status of Tibetan migrant students and the differences between the local students in Lanzhou and them to provide a theoretical basis for nutrition intervention and vision protection for students. Methods: Cluster sampling method was used to select 2 434 students migrating from Gannan Tibetan Autonomous Prefecture to a boarding middle school, and 3 291 students from three middle schools in Qilihe District of Lanzhou from September to December 2020. All the students were administered physical and visual examination. Proportion of nutritional status, poor eyesight and myopia by gender and age groups between Tibetan migrant students and local students were analyzed. Results: The detection rate of overweight and obesity in Tibetan migrant boys(2.8%,5.7%) and girls(11.0%,8.3%) was lower than that of local students of the same sex(5.6%,8.3%;24.9%,20.9%) ( χ 2=12.17,7.21, P <0.05; χ 2=81.33,91.34, P <0.05); The detection rate of malnutrition in Tibetan migrant boys(9.9%) was higher than that in local boys(7.2%) ( χ 2=6.65, P <0.05). The detection rate of poor vision in Tibetan migrant boys was lower than that in local boys ( χ 2=3.93, P <0.05). The detection rate of myopia was significantly lower than that of local students ( χ 2=975.82, P <0.01). The detection rate of abnormal color vision in Tibetan migrant boys was higher than that in local boys ( χ 2=8.38, P <0.05). The detection rate of abnormal color vision in Tibetan migrant girls was lower than that in local girls ( χ 2=8.08, P <0.05). The detection rate of mild and moderate visual impairment was lower among Tibetan migrant boys than local boys ( χ 2=3.88, 8.32, P <0.05); the detection rate of mild, moderate and severe myopia was lower than local boys ( χ 2= 13.72 ,55.96, 338.50, P <0.05). The detection rate of mild, moderate and severe myopia was lower among Tibetan migrant girls than local girls ( χ 2=7.62, 37.79,424.00, P <0.05). Conclusion Tibetan migrant students was lower than that of local students. More attention should be paid to nutrition intake of Tibetan boys to prevent malnutrition. The detection rate of myopia in Tibetan migrant students is low,but the detection rate of severe poor vision among Tibetan students in the junior high school group is higher than that of local students, and attention should be paid to the visual health of Tibetan students in junior high school.