Objective:To investigate the damage of visual function in the early stage of diabetes mellitus and the response characteristics of primary visual cortex neurons in diabetic mice.Methods:Twenty 7-week-old SPF grade male C57BL/6J mice were randomly divided into diabetes group and normal control group by the random number table method, with 10 mice in each group.The diabetes model in diabetes group was established by the intraperitoneal injection of streptozotocin.Fasting blood glucose concentration and body mass of mice were measured before and 1, 2 and 3 weeks after modeling, and intraperitoneal glucose tolerance test was performed 4 weeks after modeling to evaluate the establishment of diabetes model.At 4 weeks after modeling, the electroretinogram (ERG) responses of mice were recorded at dark adaptation luminances of 0.01 and 3.0 cd·s/m 2, and the ERG response to light adaptation luminance of 3.0 cd·s/m 2 was recorded 10 minutes after light adaptation to evaluate the retinal function of mice.The fundus of mice was examined with an ultra-wide field laser scanning ophthalmoscope.The visual function of mice was evaluated via the cutoff frequency of grating discrimination detected by visual water maze.The spatial frequency tuning curves of primary visual cortex (V1) neurons were detected by in vivo electrophysiology technique and the maximum firing intensity, self-firing intensity, optimal spatial frequency, cutoff frequency and bandwidth of neurons were calculated to evaluate the neuronal function of mice.The research scheme was approved by the Experimental Animal Ethics Committee of Anhui Medical University (No.LLSC20230419). Results:The diabetic model was successfully established in 10 mice in the diabetes group.At 4 weeks after modeling, compared with the normal control group, the b-wave amplitudes of mice at a dark adaptation luminance of 0.01 cd·s/m 2, the a- and b-wave amplitudes of mice at a dark adaptation luminance of 3.0 cd·s/m 2 and the b-wave amplitudes of mice at a light adaptation luminance of 3.0 cd·s/m 2 after 10 minutes of light adaptation showed a downward trend in diabetes group, but the differences were not statistically significant (all at P>0.05).Ultra-wide field laser scanning ophthalmoscopy showed no obvious vascular changes in the retina of diabetic mice.The results of visual water maze detection showed that the cutoff frequency of diabetes group was (0.45±0.06)c/d, which was significantly lower than (0.58±0.05)c/d of normal control group ( t=5.10, P<0.05). In vivo electrophysiological results showed that the maximum firing intensity of neurons in V1 region in diabetes group 4.29(2.60, 8.33)spikes/second, which was significantly lower than 7.10(4.34, 11.6)spikes/second in normal control group( Z=-4.29, P<0.05).The optimal spatial frequency, cutoff spatial frequency and bandwidth were 0.03(0.02, 0.05), 0.07(0.05, 0.12) and 0.14(0.07, 0.22)c/d in diabetes group, which were significantly lower than 0.41(0.03, 0.05) and 0.10(0.07, 0.14), 0.14(0.10, 0.26)c/d of normal control group, and the differences were statistically significant ( Z=-3.22, -3.19, -2.19; all at P<0.05). Conclusions:The abnormal visual function may occur in the early stage of diabetes before the appearance of retinal vasculopathy, which is related to the damage of neurons in the V1 region.

Objective:To investigate the efficacy and safety of kidney sparing treatment based on Thulium laser ablation and systematic therapy in localized high-risk upper urinary tract urothelial carcinoma (UTUC).Methods:The data of 10 patients with UTUC who received combined treatment based on Thulium laser and systematic treatment from January 2020 to December 2021 in West China Hospital were retrospectively analysed. There were 5 males and 5 females with a median age of 76 (range 52 to 87)years old. Three cases were renal pelvis tumor and 7 cases were ureter tumor including 5 cases in lower ureter and 2 cases in upper and middle ureter. Five cases were with positive urine cytology and 6 cases were with hydronephrosis. One case was muscular invasion UTUC confirmed by biopsy(cT 2+), 7 cases were high-grade invasive urothelial carcinoma (cT 1+), and 2 cases were high-grade papillary urothelial carcinoma (cT a). Among 10 cases, 5 patients refused radical nephroureterectomy(RUN), among whom 3 patients were too old or in poor general condition to tolerate RNU. One case had a solitary kidney and 1 case had bilateral tumours. Patients were treated with Thulium laser tumor ablation under ureteroscopy combined with systemic therapy. The perioperative systemic treatment included platinum-based chemotherapy±immunotherapy, RC48+ immunotherapy, and immunotherapy alone. The postoperative treatment was immunotherapy maintenance±local radiotherapy. Strict follow-up was conducted after the completion of treatment. Results:Nine patients received systemic therapy before ablation. Four cycles of platinum-based chemotherapy (cisplatin in 2 cases, carboplatin in 1 case) were used in 3 cases, and platinum-based chemotherapy + immunotherapy (6 cycles of cisplatin + toripalimab in 1 case, 4 cycles of cisplatin + toripalimab in 1 case, 4 cycles of carboplatin+ trelizumab in 1 case) was used in 3 cases, four cycle of RC48 + immunotherapy (toripalimab or trelizumab) were used in 2 cases, and four cycles of immunotherapy (toripalimab) were used in 1 case. The operations of 10 cases were successfully completed without serious complications during the perioperative period and the laser working time (42.4 ± 15.2) min. Of the 10 cases, 4 achieved complete ablation at the first ablation, and 6 patients had incomplete ablation. Among them, 2 patients achieved clinical complete remission after 1-2 cycles of systemic therapy, and 4 patients achieved complete ablation after Thulium laser ablation again.All the 10 patients were treated with immunotherapy for 1 year, and 2 of them received additional adjuvant radiotherapy. The patients were followed-up for median 40 months(range 26 to 53 months). Recurrence occurred in 5 cases, of which 3 cases underwent salvage nephroureterectomy and 2 cases underwent Thulium laser ablation under ureteroscopy again. Five patients had no tumor recurrence. None of the 10 patients had distant metastasis. At the last follow-up, 1 patient died of complications and 6 patients kept the affected kidney alive. Perioperative complications including macroscopic hematuria (8 cases), fever (3 cases), the long-term complications of ureter stenosis (4 cases).Conclusions:For localized high-risk UTUC, local Thulium laser ablation combined with systemic therapy can achieve good tumor control while preserving the affected kidney in selected patients, and its potential application value should be further evaluated.

We present a summary of important research in the field of urothelial carcinoma presented at the 2023 European Society for Medical Oncology (ESMO) conference. A total of 53 studies related to urothelial carcinoma were reported, including 6 late-breaking abstract, 7 oral presentations, and 40 poster presentations. Several new treatment options were reported in the non-muscle invasive bladder cancer (NMIBC) field, providing more choices for bacillus Calmette-Guerin (BCG) failing patients. For perioperative systemic treatment of muscle-invasive bladder cancer (MIBC), studies further explored various adaptation of neoadjuvant therapy strategies. For metastatic urothelial carcinoma (mUC), the data on CheckMate-901 and EV-302 studies provided thoughts on first-line treatment options. These studies provide important guidance for clinical practice in the field of urothelial carcinoma.

The Chapter "Radical prostatectomy" has been completely update in the 2020 EAU prostate cancer guideline. Recommendation level of "No surgical approach has shown superiority in terms of functional or oncological results" and "Nerve-sparing surgery is not recommended when there is a risk of ipsilateral extracapsular extension" has been adjusted to "weak" . Various surgical techniques could further improve functional outcomes when performed appropriately based on the updated guideline.