Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.

Objective To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. Methods GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). Results GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. Conclusion GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.

Objective To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. Methods GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). Results GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. Conclusion GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.

Objective:To investigate the efficacy and safety of semisupine-lithotomy position placement of Allium ureteral stent to treat ureteral stricture caused by pelvic tumours.Methods:The clinical data of 29 patients who received Allium ureteral stent(URS) placement for ureteral stricture in Sun Yat-sen Memorial Hospital, Sun Yat-sen University between April 2020 and March 2022 were retrospectively analyzed. There were 3 males and 26 females, with the median age of 56(54, 61) years old. All patients had a pathology confirmation of carcinoma before the treatment, including 26 patients with gynaecological tumours, two with urinary system tumours, and one with rectal carcinoma. A preoperative imaging examination confirmed the diagnosis of ureteral stricture. There were 15 patients with unilateral and 14 with bilateral stenosis, median stenosis length was 3.6(2.0, 4.9)cm. Preoperative median urine white blood cell count was 62(21, 354) U/L, median serum creatinine (SCR) was 170.0(85.5, 273.5) μmol/L, and renal pelvis separation was (32.98±6.64) mm. The median time of long-term indwelling double J (D-J)ureteral stent before surgery was 12.0 (6.5, 35.5) months. Seven patients had mild hydronephrosis, 18 had moderate hydronephrosis, and four had severe hydronephrosis. In all patients, Allium URS were placed in the way of the semisupine-lithotomy position (Galdakao-modified supine Valdivia position). Anterograde flexible ureteroscope was inserted into the percutaneous nephrostomy channel, and the retrogradel rigid ureteroscope were advanced simultaneously, looking for location of strictures. Allium URS were inserted retrogradely with transureteroscope when the two ureteroscope were connected. Perioperative conditions and postoperative follow-up for the last examination of SCR, renal pelvis width under ultrasound, and plain abdominal film (KUB). Allium URS patency and complications, hydronephrosis and renal function were evaluated.Results:A total of 61 Allium URS were successfully placed. Seven patients were placed in stages, and 18 patients were placed in series with multiple stents. The mean follow-up period was (12.1±5.8) months. At last follow-up, median SCR was 124.0(81.5, 193.0)μmol/L and renal pelvis separation was(14.96±5.18)mm, which were significantly decreased compared with preoperative(all P<0.01). There were 24 cases of hydronephrosis disappeared and 5 cases of mild hydronephrosis in the last follow-up. Postoperative follow-up, urinary tract infection occurred in 3 patients after operation, such as hematuria and fever within one week, and the symptoms were relieved after anti-infective and symptomatic treatment. One case had mild urine leakage, and 4 patients had occasional low back pain, which may be related to the activity. One case occurred stent displacement due to stent migration to the bladder after eight months, the URS was replaced and a D-J stent was inserted .The patency rate was 96.6%(28/29). Conclusions:Allium URS was placed in the semisupine-lithotomy position for treating pelvic tumour-induced ureteral stricture, with low incidence of complications, high patency and good curative effect.

Objective:To analyze the clinical characteristics of nephrogenic adenoma of the bladder.Methods:The clinical and pathological data of 8 patients with bladder nephrogenic adenoma, during the period from July 2016 to June 2019, were retrospectively analyzed. Patients’ age were 33 to 71 years old and the average age was 55, including 5 males and 3 females. The clinical manifestations were hematuria in 7 cases, urinary tract irritation in 6 cases, and no obvious symptoms in 1 case. There were 7 cases with cystitis, 3 cases with urolithiasis, 2 cases with bladder cancer, 1 case with invasive colonic mesentery fibroma, and 1 case without other complications. 5 cases had the history of urological operation. The predilection site was the lateral wall with 5cases; 5 cases were solitary; the average maximum diameter of the tumor was 0.9 cm (range 0.1-1.8 cm). Under cystoscope, papillary mass can be seen, the surface is bright red, the pedicle is not obvious, the papilla is thick and short, easy to bleed when touching; some of them are scattered and lichen like changes. All patients received transurethral resection of bladder mucosa.Results:Pathological examination shows that the bladder mucosa showed chronic inflammation, interstitial edema, granulation tissue hyperplasia, eosinophil infiltration and metaplasia of mesonephroid epithelium. All of the 8 patients were followed up by telephone for 2 to 38 months, with an average of 17.1 months. So far, neither recurrence has been detected.Conclusions:The diagnosis of nephrogenic adenoma of the bladder depends on pathological examination. It must be totally removed during operation. The recurrence and malignancy should be treated in time after operation.

A series of 2-(((5-akly/aryl-1-pyrazol-3-yl)methyl)thio)-5-alkyl-6-(cyclohexylmethyl)-pyrimidin-4(3)-ones were synthesized and their anti-HIV-1 activities were evaluated. Most of these compounds were highly active against wild-type (WT) HIV-1 strain (IIIB) with EC values in the range of 0.0038-0.4759 μmol/L. Among those compounds, had an EC value of 3.8 nmol/L and SI (selectivity index) of up to 25,468 indicating excellent activity against WT HIV-1. anti-HIV-1 activity and resistance profile studies suggested that compounds and displayed potential anti-HIV-1 activity against laboratory adapted strains and primary isolated strains including different subtypes and tropism strains (ECs range from 4.3 to 63.6 nmol/L and 18.9-219.3 nmol/L, respectively). On the other hand, it was observed that those two compounds were less effective with EC values of 2.77 and 4.87 μmol/L for HIV-1A (K103N + Y181C). The activity against reverse transcriptase (RT) was also evaluated for those compounds. Both and obtained sub-micromolar IC values showing their potential in RT inhibition. The pharmacokinetics examination in rats indicated that compound has acceptable pharmacokinetic properties and bioavailability. Preliminary structure-activity relationships and molecular modeling studies were also discussed.

Objective To compare split-cuff nipple and direct ureteroileal anastomosis during ureteroileal anastomosis.Methods Between December,2014 and March,2017,a prospective randomized study was conducted on 70 patients who underwent radical cystectomy and urinary diversion.In every patient,both ureters were randomized to be implanted using an antireflux,split-cuff nipple technique (group A) or a reflux,direct technique (group B).After pelvic lymph node dissection and radical cystectomy,a Mshape orthotopic ileal neobladder was constructed and two ureters were implanted with single-J tubes placed for 10-12 days.For split-cuff nipple technique,a 0.5 cm longitudinal incision in the ureter was made,and the ureteral wall was turned back on itself,construction a nipple.The cuff was stabilized at the corners with sutures.The ureter was then placed into the bowel with 0.5 cm nipple.The ureter was sutured to the full thickness of the bowel wall with interrupted 4-0 PDS.For direct technique,a 0.5 cm incision in the ureter was made,the full thickness of the ureter was sewn to the mucosa of the bowel.Results 70 patients were enrolled in the study,63 males and 7 females,(62.5 ± 10.4) years old.Over a median follow-up of 13.2 months,one patients had bilateral anastomosis stricture 3 months after operation,1 patient in group A had stricture 6 months after operation,2 patients in group B had stricture 6 and 12 months after operation,respectively.Six patients (8.6％) in group A found reflux compared with 21 patients (30.0％) in group B (P =0.004).The reflux pressure was (23.5 ± 9.0) cmH2O and (15.5 ± 4.9) cmH2O in group A and group B (P =0.042),respectively.The GFR of group A was (38.1 ± 7.6) ml/min compared with (38.6 ± 12.9) ml/min in group B at 12 months after operation.One patient in group A and four patients in group B had acute nephropyelitis.Four patients in group A had renal stones formation compared with 1 patients in group B.The time of anastomosis was (8.8 ± 3.5) minutes and (6.7 ± 1.5) minutes (P =0.037) for group A and group B,respectively.The patients in both groups had no urine leakage.Conclusion Compared with direct technique,split-cuff nipple technique had lower reflux rate,higher antireflux pressure and longer anastomosis time than direct technique.

Objective To observe the effect of qixiantang decoction on asthma model mice and to explore its mechanism of phosphatase gene ( PTEN)-up-regulation. Methods A total of 28 healthy female BALB/c mice were divided into 4 groups according to the random number table ( n=7 ): normal control group, model control group, qixiantang decoction group, and dexamethasone group. The mice were sensitized with ovalbumin ( OVA) for asthma model. Qixiantang decoction group was treated with drug after OVA sensitization. Hematoxylin-eosin ( H-E) staining was applied to observe the pulmonary inflammation in mice, and periodic acid Schiff ( PAS) staining was used to examine airway mucus secretion. ELISA was used to detect the concentration of serum IgE. Real-time quantitative PCR was used to examine IL-13 and IL-5 gene expression changes in lung tissues of mice. Western blotting was used to detect the expression of PTEN and SIRT1 protein in lung tissues. Results The lung tissue inflammatory infiltration and mucus secretion in model control group were higher than normal control group (P<0. 01), and that in the qixiantang decoction group. The level of serum IgE in model control group [(6. 67 ± 2. 59) pg·mL-1)] was significantly higher than normal control group [(0.27 ± 0.05) pg·mL-1, P <0.01] ,and that in the qixiantang decoction group [(3.52 ±1.44) pg·mL-1,P<0.05]. The expression of PTEN and SIRT1 in lung tissue of model control group were significantly lower than normal control group, and that of qixiantang decoction group. The expression of IL-5 and IL-13 mRNA of qixiantang decoction group was significantly lower (P<0. 05). Conclusion Qixiantang decoction could significantly ameliorate inflammation in asthmatic mice by regulate IgE、IL-5、IL-13 expression, and might up-regulate PTEN expression via SIRT1 signal.

Objective To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM).Methods This was a 26-week,randomized,open-label,parallel-group,treat-to-target trial in 560 Chinese subjects with T2DM (men/women:274/263,mean age 56 years,mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs).Subjects were randomized 2:1 to once-daily IDeg (373 subjects) or IGlar(187 subjects),both in combination with metformin.The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks.Results Mean HbA1c decreased from 8.2％ in both groups to 6.9％ in IDeg and 7.0％ in IGlar,respectively.Estimated treatment difference (ETD) of IDegIGlar in change from baseline was-0.10％ points (95％ CI-0.25-0.05).The proportion of subjects achieving HbA1c ＜ 7.0％ was 56.3％ and 49.7％ with IDeg and IGlar,respectively [estimated odds ratio of IDeg/IGlar:1.26 (95 ％ CI 0.88-1.82)].Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar,respectively [estimated rateratio of IDeg/IGlar 0.69 (95％ CI 0.46-1.03),and 0.43 (95％ CI 0.19-0.97)].No differences in other safety parameters were found between the two groups.Conclusions IDeg was non-inferior to IGlar in terms of glycaemic control,and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia.IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment.Clinical trail registration Clinicaltrials.gov,NCT01849289.

[ ABSTRACT] AIM:To explore the role of SHARPIN in regulation of Rip1 in castration-resistant prostate cancer LNCaP-AI cells.METHODS:The LNCaP-AI cells were treated with TNF-α+Z-VAD ( an inhibitor of pan-caspase) to activate necroptosis, which were compared to the cells treated with TNF-α+Z-VAD+Nec-1 ( an inhibitor of Rip1 ) .A blank group and a TNF-α-treated group were set up as controls.The cell viability in each group was measured by MTS as-say.In addition, SHARPIN was knocked down by siRNA, and the inhibitory efficiency was evaluated by RT-qPCR.The expression of Rip1 at mRNA and protein levels after knocking down SHARPIN was determined by RT-qPCR and Western blot to explore the underlying mechanism of regulatory network of necroptosis in prostate cancer.RESULTS: Compared with blank control group and TNF-α-treated group, the viability of LNCaP-AI cells treated with TNF-α+Z-VAD decreased by 28%(P<0.05).After treated with TNF-α+Z-VAD+Nec-1, the LNCaP-AI cells showed no significant difference in the viability compared with blank control and TNF-α-treated groups.Taken together, necroptosis may be an important way of cell death in LNCaP-AI cells.Besides, the expression of Rip1 at protein level was up-regulated following the inhibition of SHARPIN using siRNA, indicating that down-regulation of SHARPIN enhanced necroptosis via activating Rip1 in
LNCaP-AI cells.CONCLUSION:Necroptosis is an important way of cell death .Inhibition of oncogenic factor SHARPIN enhances necroptosis via activating Rip1 in LNCaP-AI cells.