Objective To study the efficacy and safety of sedation in gastroscopy with a combined use of rimifentani and propofol compared to a control,non-sedative group.Methods 120 cases in sedative group were given intravenous rimifentani and propofol.Patients'feeling and discomfort,operator's satisfaction and operative duration were compared with the controI group(n=120,without sedation).The changes of blood pressure,heat rate and blood oxygen saturation were recorded and analysed.Results 118 patients(98.3%)in sedative group and 0 patient(0)in control group did not complain any discomfort and pain duing gastroscopy(P＜0.01).The incidence of cough,restlessness,nausea and vomiting,and guttural discomfort in sedative group(1.7%,3.3%,1.7%,and 0,respectively)was lower as compared with the control group(9.2%,26.7%,48.3%and 100%,respectively,P＜0.01).The blood pressure in sedative group was decreased duing the procedure and recovered after the procedure.Conclusion With intravenous use of rimifentani and propofol,gastroscopy can be performed effectively and safely.

Objective To assess the therapeutic effect and quality of life (QOL) of patients with anastomotic stenosis after bougienage of esophagus following resection of esophagus with esophageal and of cardiac carcinoma.Methods A total of 135 patients suffering from anastomotie stenosis after resection operations were divided into a treatment group and a control group at random. All patients were given an esophageal dilator under gastroseope. In treatment group, deglutition training was given additionally, twice daily, 10 to 20 trials in each session. Therapeutic effect was evaluated according to patients' food intake and gastroscopy results of diameter of stenosis before treatment and 2,4,8 weeks after treatment. QOL was evaluated with Chinese version of SF-36 instrument. Results The food intake of all the patients improved. There was no difference of diameter of stenosis in degree Ⅰ stenosis patients be-tween two groups (P > 0.05 ) ; but the differences were statistically significant in degree Ⅱ and Ⅲ stenosis patients (P < 0.05). In treatment group, the degree and duration of improvement were more obvious. QOL of patients with degree Ⅱ and Ⅲ stenosis in both groups improved significantly after treatment ( P < 0.05 ), but compared with con-trol group the improvement was significantly greater in treatment group (P < 0.05). Conclusion The therapeutic effect of bougienage of esophagus can be strengthened with deglutition training. This combinative therapy is safe and effective.

ObjectiveTo evaluate the safety and efficacy of submucosa dilation assisted laser resection of bladder tumor for the treatment of solitary non-muscle invasive bladder cancer. MethodsA total of 12 patients with solitary non-muscle invasive bladder tumor were treated with the procedure of submucosa dilation assisted laser resection under total intravenous anesthesia or epidural anesthesia.lntravesical instillation chemotherapy was performed according to CUA 2007 guidelines.Patients were followed up for 4 - 36 months after the operation. ResultsThe diameter range of the tumors was 0.5 - 2.3 cm with the clinical stage Ta - T1 and low pathology grade.Submucosa dilation assisted laser resection of bladder tumor was successfully performed on all patients.The average operation time was 25 min (range,20 -45 min ),and the catheter time was 3 d ( range,1 -4 d).The mean volume of bleeding was less than 5 ml,no patient required blood transfusion.No complications such as obturator nerve reflex,bladder perforation and over-hydration occurred.No recurrence occurred during the follow-up. ConclusionsSubmucosa dilation assisted laser resection of bladder tumor could be an effective,safe,and excellent alternative procedure for the treatment of solitary non-muscle invasive bladder cancer,with few complications and a low recurrence rate.More studies and long-term follow-up should be warranted to ultimately evaluate this procedure.

Objective To innovate and improve the feasibility of flexible ultrasonic cystoscopy (FUCS) in the diagnosis and treatment for urinary tract diseases in vivo by using female pigs as animal model.Methods Endobronchial ultrasonography was took as a substitute for FUCS and the operating skills and experience of FUCS in vivo by using female pigs as animal model were summarized,in order to testify the efficacy and safety of needle biopsy guided by FUCS.Results FUCS could simultaneously display the endoscopic images and ultrasonic images.Ninety ml was suitable in pig bladder for FUCS when the layers of bladder wall were clear.The mucosa,submucosa,muscularis and serosa layers were legible,which contributed to the needle positioning biopsy.Doppler ultrasound mode could distinguish the vessels,which could guide the puncture and avoid accidental injury of blood vessels and surrounding organs.Pathological results of positioning biopsy were consistent with FUCS evaluation for the three major layers of bladder wall.Conclusion Studies in vivo show that application of FUCS in the diagnosis and treatment for bladder disease is feasible,and further improvement of the FUCS equipment and clinical practice should be made.

Objective To perform an exploratory investigation on confocal laser endomicroscopy (CLE) in the diagnosis of malignant bladder tumour.Methods From June 10 to July 11,2017,6 male bladder cancer patients underwent white light cystoscopy (WLC) + CLE examination,aging 64-86 years (median 72 years).All patients received TURBT on suspected lesions.WLC and CLE imaging results were recorded and validated by pathologic specimens.Results Lesions confirmed by histopathology were 3 low grade non-invasive papillary urothelial carcinomas,1 high grade non-invasive papillary urothelial carcinoma,1 low grade invasive urothelial carcinoma,1 high grade invasive urothelial carcinoma,1 carcinoma in situ (CIS),1 high grade dysplasia,1 cystitis glandularis,1 chronic inflammation,and 1 scar tissue.For CLE images in the normal urothelium,three layers of cells with different presentation were observed,namely,the superficial umbrella cells,the intermediate cells smaller in size and uniformly shaped,and the capillary network in the lamina propria.For non-invasive urothelial carcinoma,tumour cells appeared as papillary lesions growing from fibrovascular cores,with low grade cells appearing monomorphic and more cohesively arranged,and high grade cells relatively pleomorphic,more disorganised and with tortuous blood vessels in the fibrovascular core.For invasive urothelial carcinoma,tumour cells invaded the lamina propria,with uniform appearances,poor cohesion and indistinct cellular borders,and high grade ones were more pleomorphic.CIS and inflammation both appeared as erythematous patch-like flat lesions under WLC and sometimes difficult to differentiate.Under CLE,the former appeared as dysplastic and disorganised cells with indistinct cellular borders,with intact lamina propria,and inflammatory cells were discovered as infiltrative clusters in the lamina propria that were uniformly shaped and loosely connected.Dysplasia appeared somewhat similar compared with CIS under WLC,but with lower cellular irregularity as confirmed with pathology.Cellular appearance and structure in scar tissue was similar to that in the normal urothelium,but superficial umbrella cells were more likely absent,with thinner cell layers,and inflammatory infiltration was sometimes discovered in the lamina propria.Conclusions CLE provides real-time cellular imaging of the urothelium,and shows promising potential for clinical diagnosis,especially in differentiating fiat urothelial lesions.Large prospective studies are required for further validation.

Objective:To explore the effect of different HER2 expression levels and gene amplification on the efficacy of immunotherapy in metastatic urothelial carcinoma (UC).Methods:The clinical data of 77 patients with metastatic UC who received immunotherapy from June 2017 to April 2021 after failure to the previous chemotherapy were analyzed retrospectively, including 49 males and 28 females with the median age of 62 years. The primary tumors located in bladder in 28 cases (36.4%), renal pelvis in 25 cases (32.5%) and ureter in 24 cases (31.2%). The common metastatic sites included: lymph nodes (n = 45, 58.4%), lung (n = 40, 51.9%), bone (n = 20, 26.0%) and liver (n = 16, 20.8%). 27 patients with bladder UC received surgery on the primary tumors including radical cystectomy (n = 18), partial cystectomy (n = 4) and transurethral resection (n = 5). 43 patients with renal pelvis or ureteral UC received surgery on the primary tumors including radical nephroureterectomy (n = 38), local resection (n = 3) and palliative resection (n = 2). Postoperative intravesical chemotherapy was performed in 15 cases, adjuvant radiotherapy was performed in 6 cases. 3 patients who emerged postoperative bladder recurrence received local radiotherapy. 7 patients received radiotherapy and 1 case received microwave ablation to their metastatic sites. All patients had received first-line chemotherapy and 30 patients (40.0%) had received at least second-line treatment including 70 cases (90.9%) with platinum containing chemotherapy. All 77 patients received anti-PD-1 treatment. 38 patients received sequential regimen after failed to the anti-PD-1 therapy, including antibody-drug conjugate (n = 17), chemotherapy (n = 18) and chemotherapy combined with anti-angiogenesis drugs (n = 12). Immunohistochemical (IHC) staining was used to detect the expression level of HER2 protein in the tumor tissues (74 cases from primary tumors and 3 cases from metastatic tumors) obtained from the initial diagnosis. For patients with HER2 IHC (+ + ), the copy number (CN) of HER2 gene was detected by next-generation sequencing (NGS). HER2 copy number amplification [CN (+ )] was defined as CN ≥ 4, and HER2 copy number non-amplification [CN(-)] was defined as CN < 4. HER2 IHC (0) was defined as HER2 negative, IHC (+ ) or IHC (+ + ) / CN (-)was defined as HER2 low expression, while IHC (+ + ) / CN(+ ) and IHC (+ + + ) were defined as HER2 high expression. Chi-square test or Fisher exact test were used to evaluate the correlation between HER2 expression and objective response rate (ORR) after anti-PD-1 treatment. Kaplan-Meier method and log-rank test were used to compare the differences of median progression free survival (PFS) and overall survival (OS) under different HER2 expression status.Results:All the 77 patients received a median of 11 (range: 2 - 45) doses of anti-PD-1 treatment with a median duration of treatment of 6.4 (range: 1.5 - 47.8) months and the ORR was 33.8% (26/77). The median follow-up time was 30.9 months. The overall median PFS time was 5.8 (95% CI: 3.0 - 8.6) months and the median OS time was 23.6 (95% CI: 8.5 - 38.7) months. HER2 IHC tests were performed in 77 patients. HER2 IHC levels of (0), (+ ), (+ + ) and (+ + + ) were found in 33 (42.9%), 19 (24.7%), 20 (26.0%) and 5 (6.5%) patients, respectively. HER2 copy number was detected in 20 patients with IHC (+ + ), while 1 CN(+ ) and 19 CN(-) were found. The ORR of HER2 negative, low expression and high expression patients were 42.4% (14/33) vs. 31.6% (12/38) vs. 0 (0/6) ( P = 0.08), respectively. The median PFS of the three groups were 11.0 months, 3.7 months and 1.8 months, respectively, with significant differences in overall and pairwise comparison( P=0.001). The median OS of patients with HER2 negative and low expression after anti-PD-1 treatment were 23.6 months and 22.7 months, respectively, while the median OS of patients with HER2 high expression had not been reached, with no significant difference in the overall comparison ( P=0.623). Conclusions:For patients with metastatic UC received anti-PD-1 treatment, the PFS of patients with high HER2 expression was significantly worse than that of patients with low or negative HER2 expression. HER2 expression may have potential value in predicting the efficacy of immunotherapy for metastatic UC who failed the previous chemotherapy, which needs further research.

OBJECTIVE：To investigate the risk factors for the recurrence of ischemic stroke after secondary prevention ，and to observe the effect of glutathione on 4-HNE. METHODS ：Totally 97 patients with ischemic stroke relapse within one year were treated from Oct. 2017 to Oct. 2019 in 3 hospitals as the Second Affiliated Hospital of Shandong First Medical University due to cerebral thrombosis or cerebral embolism as observation group ，and 97 non-recurrence patients in the same period were paired as control group. The patients in the observation group were randomly divided into conventional treatment group （49 cases）and drug intervention group （48 cases）. The patients in conventional treatment group received routine treatment such as cerebral blood flow recanalization， improving circulation ， controlling blood pressure ， maintaining blood glucose ， treating hyperlipidemia and arrhythmia during hospitalization. Drug intervention group was additionally given Glutathione for injection 1.8 g intragastrically ， once a day ，on the basis of conventional treatment group. 4-HNE concentrations in plasma were determined at admission and 14 days after treatment ，the genetic type of ALDH2 and type of TAST were determined at admission. Multiple liner regression was used to analyze the factors associated with 4-HNE increasing ； conditional Logistic analysis was used to identify independent risk factors resulting to ischem ic stroke recurrence after secondary prevention. RESULTS ：The plasma concentration of 4-HNE at admission and the percentage of arte ry atherosclerosis patients in observation group were significantly higher than control group（P＜0.05）. The distribution of each ALDH2 genotype in 2 groups complied with Hardy-Weinberg genetic equilibrium （P＞ 0.05）. The proportion of patients carrying ALDH2*2 allele in observation group （50.50％）was significantly higher than control group（36.08％）（P＜0.05）. ALDH2*2 allele [ B＝2.33，95％CI（1.35，5.50），P＝0.03] and artery atherosclerosis [ B＝1.90，95％CI （1.29，3.74），P＝0.04] were significantly associated with the elevation of plasma concentration of 4-HNE；artery atherosclerosis [OR＝ 2.93，95％CI（1.84，4.67），P＜0.01]，stroke family history [OR ＝1.50，95％CI（1.18，1.90），P＝0.04]，elevated plasma concentration of 4-HNE [OR ＝1.34，95％CI（1.11，1.62），P＝0.04] were regarded as independent risk factors associating with ischemic stroke recurrence after secondary prevention. After intervention ，plasma concentration of 4-HNE in drug intervention group and conventional treatment group was significantly lower than before intervention （P＜0.05）；there was no statistical significance between 2 groups（P＞0.05）. CONCLUSIONS ：Stroke family history ，artery atherosclerosis and the elevation plasma concentration of 4-HNE are independent risk factors associating with ischemic stroke recurrence after secondary prevention. Although drug intervention can reduce the elevated plasma concentration of 4-HNE，the effect of additional use of glutathione is not more significant than that of conventional treatment.