Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective:To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP).Method:This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control.Result:All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 μg/L.Conclusions:The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

Objective:To investigate the clinical efficacy of simultaneous arthroscopic repair of anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) for treating chronic lateral ankle instability (CLAI) in conjunction with subtalar instability (STI).Methods:This is a retrospective case series study. The clinical data of 15 patients with ankle arthroscopic in the Department of Hand and Foot Surgery, the Second Affiliated Hospital of Soochow University from January 2019 to December 2022 were analyzed retrospectively. There were 11 male cases and 4 female cases, aged (28.6±1.5) years (range: 19 to 39 years). All the patients were evaluated by manual inversion stress X-ray and MRI before operation. Arthroscopically observing and then repairing the ATFL and CFL separately after further diagnostic confirmation. One year after operation, MRI was performed, and pain visual analogue score(VAS), American Orthopedic Foot and Ankle Society ankle hindfoot scale (AOFAS-AH) and Karlsson ankle functional scale(KAFS) were evaluated. Data were compared using paired sample t test. Results:The follow-up period was (23.6±2.3) months (range: 12 to 30 months). At last follow-up,the VAS decreased from 6.1±1.4 preoperatively to 1.4±1.2( t=9.482, P<0.01).The AOFAS-AH improved from 50.5±11.7 preoperatively to 94.2±6.1( t=-13.132, P<0.01), and the KAFS improved from preoperatively 44.3±10.8 to 90.8±6.4 ( t=-12.510, P<0.01). There was no complication such as recurred instability or joint stiffness. Conclusions:Arthroscopically repairing the ATFL and CFL separately can effectively restore the stability of the ankle and subtalar joint with small trauma. Patients can recover quickly after surgery. It provides a new idea for the clinical treatment of CLAI combined with STI.

Objective:To investigate the efficacy and safety of laparoscopic subtotal cystectomy with augmentation ileocystoplasty(SC-CP) and laparoscopic total cystectomy with ileal conduit (TC-IC) for refractory interstitial cystitis/bladder pain syndrome (IC/BPS).Methods:Clinical data of 39 patients diagnosed with refractory IC/BPS treated with SC-CP and TC-IC in Beijing Chaoyang Hospital of Capital Medical University from January 2008 to December 2023 were retrospectively analyzed. All patients were female, and had unsatisfactory results after more than three types of conservative + minimally invasive treatments. There were 12 patients in the SC-CP group and 27 patients in the TC-IC group. In the SC-CP group, the patients had the age of (50.8±14.4) years old, preoperative medical history of (4.7±2.5) years, daytime voiding frequency of 25.0 (18.5, 45.0) times/day, nocturia frequency of 12.5 (10.0, 15.0) times/night, functional bladder capacity of 40.0(18.5, 47.5) ml, and anesthetized bladder capacity of 150.0 (150.0, 195.0) ml. The patients in TC-IC group had the age of (60.3±8.0) years old, preoperative medical history of (6.5±3.6) years, daytime voiding frequency of 30.0 (20.0, 40.0) times/day, nocturia frequency of 10.0 (8.0, 15.0) times/night, functional bladder capacity of 50.0(30.0, 60.0) ml, and anesthetized bladder capacity of 200.0 (150.0, 330.0) ml. SC-CP was performed to resect the bladder wall beyond the trigone and bladder neck, and bladder enlargement was performed by using an ileal segment anastomosed to the remaining bladder. TC-IC was performed to resect the entire bladder, and a segment of free ileum with a mesentery was taken, which was closed proximally and then anastomosed to the ureters on both sides, and a cutaneous ureterostomy was performed at the distal end. The patients in the two groups were followed up after the operation, and the intraoperative conditions and postoperative complications were recorded. The visual analogue scale (VAS) score, quality of life (QOL) score, O′Leary-Sant score, pelvic pain and urgency/ frequency patient symptom scale (PUF) score were recorded before and after the operation, and the differences were compared to evaluate the improvement of symptoms.Results:In the SC-CP group, the operation time was 240.0 (202.8, 293.8) min, the intraoperative hemorrhage was 50.0 (27.5, 50.0) ml, and the postoperative hospital stay was 12.0 (7.3, 16.5) days. In the TC-IC group, the operation time was 300.0 (240.0, 329.0) min, the intraoperative hemorrhage was 100.0 (50.0, 100.0) ml, and the postoperative hospital stay was 10.0 (8.0, 12.0) days. The median follow-up time of 39 patients was 31.0(10.0, 70.0) months, and the follow-up time of SC-CP group and TC-IC group was 11.0 (4.0, 22.0) and 56.0 (13.0, 75.0) months, respectively. Compared with preoperative data of SC-CP group, the postoperative VAS score [10.0 (10.0, 17.5) points vs. 90.0 (90.0, 98.8) points], the QOL score [1.0 (1.0, 2.0) points vs. 6.0 (6.0, 6.0) points], the O′Leary-Sant score [10.0 (8.5, 13.5) points vs. 35.0 (33.3, 35.8) points], and the PUF score [11.0 (7.3, 12.8) points vs. 29.5 (28.3, 32.0) points] of SC-CP group were all significantly reduced ( P < 0.05). Compared with preoperative data of TC-IC group, the postoperative VAS score [0 vs. 95.0 (90.0, 96.0) points], the QOL score [2.0 (1.0, 3.0) points vs. 6.0 (6.0, 6.0) points], the O′Leary-Sant score [1.0 (1.0, 2.0) points vs. 35.0 (35.0, 36.0) points] and the PUF score [3.0 (3.0, 4.0) points vs. 32.0 (29.0, 32.0) points] of TC-IC group were all significantly reduced ( P< 0.05). Two patients in the SC-CP group required postoperative clean intermittent catheterization, and one patient underwent TC-IC for residual bladder pain. Three patients in the TC-IC group had postoperative bowel obstruction relieved by conservative treatment, and two patients had postoperative wound infection cured by dressing change. Conclusions:Both SC-CP and TC-IC have better efficacy in patients with refractory IC/BPS. Although TC-IC has more potent relief of pain symptoms, SC-CP is closer to the normal human urination habit, eliminating the need to carry an ostomy bag, which is especially suitable for young patients with recalcitrant IC/BPS.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Objective To study the relationship between peripheral blood Toll like receptor 4(TLR4),interleukin-1β(IL-1β)and neutrophil-to-lymphocyte ratio(NLR)and the progression and prognosis of acute pancreatitis(AP).Methods A total of 250 patients with AP were divided into the mild group(121 cases),the moderately severe group(89 cases)and the severe group(40 cases)according to the disease severity.Patients were divided into the poor prognosis group(33 cases)and the good prognosis group(217 cases)based on the prognosis after 5 days of treatment.Peripheral blood levels of TLR4,IL-1β and NLR were compared at different time points,different conditions and different prognosis in patients.The correlation of peripheral blood levels of TLR4,IL-1β and NLR,Ranson score and amylase were analyzed by Pearson correlation analysis.The value of each indicator in the diagnosis of severe AP was analyzed using ROC curve,and multivariate Logistic regression analysis was conducted to identify the prognostic risk factors.Results TLR4,IL-1β and NLR levels in AP patients were higher 24 h after admission than 48 h and 72 h after admission(P＜0.05).Peripheral blood TLR4 and IL-1β levels in AP patients at 24 h after admission increased with the condition became worse.NLR level was higher in the severe group than that in the moderately group or the mild group(P＜0.05).Peripheral blood TLR4,IL-1β and NLR levels in AP patients 24 h after admission were positively correlated with Ranson score at 48 h after admission and amylase level at 24 h after admission(P＜0.05).The area under ROC curve,sensitivity and specificity of the combination of TLR4,IL-1β and NLR at 24 h after admission for predicting severe AP were 0.895,84.53%and 81.69%.Peripheral blood TLR4,IL-1β and NLR levels 24 h after admission were higher in the poor prognosis group than those in the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that elevated TLR4,IL-1β and NLR at 24 h after admission were independent risk factors for poor prognosis of patients with AP(P＜0.05).Conclusion Peripheral blood TLR4,IL-1β and NLR in patients with AP are closely related to disease progression and prognosis.Therefore,they can be taken as important monitoring indicators.

Objective To investigate the effects of remazolam on melatonin secretion,sleep rhythm and postoperative delirium(POD)in elderly patients undergoing spinal surgery.Methods A total of 160 elderly patients,76 males and 84 females,aged 65-80 years,BMI 18.5-24.0 kg/m2,ASA physical status Ⅱ or Ⅲ,from November 2023 to January 2024 undergoing spinal surgery(lumbar interbody fusion,posterior approach)under general anesthesia were selected.The patients were divided into two groups by random number table method:the remazolam group(group R)and the propofol group(group P),80 pa-tients in each group.Group R was given remazolam 0.3 mg/kg for anesthesia induction,and then continued to pump remazolam 0.3-0.8 mg·kg-1·h-1 for anesthesia maintenance.Group P was given propofol 2.0 mg/kg for anesthesia induction,and then continued to pump propofol 4-6 mg·kg-1·h-1 for anesthesia maintenance.The levels of melatonin and cortisol were recorded at 04:00 a.m.on the day of surgery,1 day,2 and 3 days after surgery.Pittsburgh sleep quality index(PSQI)and VAS pain scores at rest were recorded 1 day before surgery,1 day and 2 days after surgery and before discharge.The occurrence of POD and post-operative sleep disorder(POSD)were recorded.The duration of extubation,PACU stay time,total analgesia pump compressions,effective analgesia pump compressions,number of remedial analgesia cases,intraoperative hypotension,postoperative nausea and vomiting,dizziness,respiratory depression and other adverse events were recorded.Results Compared with group P,the extubation time and PACU residence time in group R were significantly shortened(P＜0.05),the level of melatonin was significantly increased while the level of cortisol was significantly decreased at 4:00 a.m.,and the PSQI was significantly decreased 1 day after surgery(P＜0.05),the incidence of POD,POSD,and intraoperative hypotension were signifi-cantly decreased(P＜0.05).There were no significant differences in extubation time,total and effective times of analgesic pump,rate of remedial analgesia,intraoperative hypotension,postoperative nausea,vom-iting,dizziness and respiratory depression between the two groups.Conclusion Remazolam has little effect on the secretion rhythm of melatonin and cortisol and the sleep rhythm after spinal surgery in elderly pa-tients,and the recovery is faster,which can reduce the incidence of POD and alleviate the sleep disorder af-ter spinal surgery.

Objective:To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP).Method:This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control.Result:All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 μg/L.Conclusions:The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.