Objective:To evaluate the role of neuronal nitric oxide synthase (nNOS)-nitric oxide synthase 1 adaptor protein (NOS1AP) coupling in remifentanil-induced hyperalgesia in rats.Methods:Forty clean-grade healthy adult male Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), nNOS-NOS1AP inhibitor ZLc002 group (group C+ Z) and remifentanil + ZLc002 group (group R+ Z). Normal saline was intravenously infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C group. Remifentanil was intravenously infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R group. ZLc002 10 mg/kg was intraperitoneally injected for 3 consecutive days, and then normal saline 0.1 ml·kg -1·min -1 and remifentanil 1.0 μg·kg -1·min -1 were intravenously infused for 60 min in C+ Z group and R+ Z group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before intravenous infusion and 6, 24 and 48 h after intravenous infusion (T 0-3). All the rats were sacrificed after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of nNOS, NOS1AP and Dexamethasone-induced Ras-related protein 1 (Dexras1) protein and mRNA using the real-time polymerase chain reaction. Nitrosylated proteins were extracted by biotin conversion for determination of the expression of nNOS, NOS1AP and total and nitrosylated Dexras1 (by Western blot) and co-expression of nNOS-NOS1AP (by co-immunoprecipitation). The content of NO in the spinal cord was measured. Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3, the expression of nNOS and NOS1AP protein and mRNA was up-regulated, the co-expression of nNOS-NOS1AP and NO production were increased, and the expression of nitrosylated Dexras1 was up-regulated in group R ( P<0.05), and no significant change was found in each aforementioned parameter in group C+ Z ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, the co-expression of nNOS-NOS1AP and NO production were decreased, the expression of nitrosylated Dexras1 was down-regulated ( P<0.05), and no significant change was found in the expression of nNOS and NOS1AP protein and mRNA in group R+ Z ( P>0.05). There were no significant differences in total Dexras1 protein and mRNA expression among the four groups ( P>0.05). Conclusions:The mechanism by which remifentanil induces hyperalgesia may be related to up-regulating the expression of nNOS and NOS1AP in the spinal cord, promoting interaction between nNOS and NOS1AP and mediating NO generation and Dexras1 nitrosylation modification in rats.

Objective:To investigate the clinical and pathological characteristics and prognosis of upper tract urothelial carcinoma (UTUC) with concurrent other histological variants.Methods:The clinical data of 566 UTUC patients admitted to Peking University People's Hospital from January 2007 to April 2021 were retrospectively analyzed. Among them, 289 were males and 277 were females, with an average age of (67.3±10.0)years old. Among the patients, 97 had a history of smoking, 29 had undergone kidney transplantation, 120 had diabetes, 76 had coronary heart disease, 146 had hyperlipidemia, 271 had hypertension, and 50 had a history of chronic kidney disease. Among the UTUC cases, 366 had concurrent hydronephrosis, 55 had concurrent bladder cancer, and 43 had a history of previous bladder cancer. The distribution included 210 cases of renal pelvis carcinoma, 5 cases of carcinoma at the renal pelvis-ureter junction, 226 cases of ureteral carcinoma, and 125 cases of multifocal tumors. Patients were classified into the pure UTUC group and the UTUC with concurrent other histological variants group based on postoperative pathology, and their clinical and pathological features were compared. Logistic regression analysis was used to explore risk factors for the occurrence of histological variations in UTUC. The log-rank test was employed to compare the overall survival (OS) and cancer-specific survival (CSS) between the two groups, while Cox regression analysis was performed to investigate prognostic factors.Results:Among the 566 cases, 511 were pure UTUC and 55 were UTUC with concurrent other histological variants. Among the latter, 30 cases had squamous differentiation, 6 had glandular differentiation, 5 had mucinous differentiation, 5 had sarcomatoid carcinoma, 2 had micropapillary carcinoma, 2 had neuroendocrine carcinoma, 1 had giant cell carcinoma, and 4 had other mixed histological variations. The proportion of patients with a history of kidney transplantation was higher in the UTUC with concurrent histological variants group than that in the pure UTUC group [14.5% (8/55) vs. 4.1% (21/511)], with statistically significant difference ( P=0.003). In the UTUC with concurrent histological variants group, the proportion of postoperative high-grade tumors [98.2% (54/55) vs. 80.2% (410/511)], muscle-invasive tumors [89.1% (49/55) vs. 68.1% (348/511)], lymph node metastasis tumors [10.9% (6/55) vs. 2.3% (12/511)], and maximum tumor diameter [(3.60±2.64) cm vs. (2.96±1.98) cm] were higher than those in the pure UTUC group ( P<0.05). Multivariate logistic regression analysis showed that a history of kidney transplantation ( OR=4.991, 95% CI 1.749-13.615, P=0.002) was an independent predictive factor for the occurrence of histological variants. Follow-up was conducted for 1 to 174 months, with a median follow-up time of 32.8 months. UTUC with concurrent histological variants was significantly associated with worse OS and CSS ( P<0.05). Multivariate Cox regression analysis indicated that histological variants were an independent risk factor for OS ( HR=1.860, 95% CI 1.228-2.816, P=0.003) and CSS ( HR=2.146, 95% CI 1.349-3.412, P=0.001). Conclusions:UTUC with concurrent other histological variants exhibited higher postoperative tumor grade and stage compared to pure UTUC, and UTUC with concurrent other histological variants was an independent risk factor for worse prognosis.

Objective:To assess the association between warm ischemia time (WIT) and renal function in patients undergoing laparoscopic partial nephrectomy.Methods:A total of 344 patients treated with laparoscopic partial nephrectomy in Peking University People’s Hospital were included. There were 240 males (69.8%) and 104 females (30.2%) with a median age of 57 (23-89) years.The median BMI was 25.6 (16.7-36.0) kg/m 2.213 cases (61.9%) were associated with hypertension.There were 66 (19.2%) patients with diabetes mellitus. There were 92 cases (26.7%) with smoking history. The median preoperative creatinine was 73 (32-170) μmol/L. The median preoperative estimated glomerular filtration rate (eGFR) was 95 (33-142) ml/(min·1.73m 2). The maximum diameter of the tumor was 2.5 (7-9) cm.314 (91.3%) patients with renal cancer stage T 1. All patients underwent warm ischemia during the operation. The patients were divided into three groups for analysis. Restricted cubic spline regression analysis was used to assess the association between WIT as a continuous variable and percentage change of eGFR. Analysis of covariance was used to compare postoperative eGFR among the three groups, and to adjust for preoperative eGFR and tumor diameter. Results:There were statistically significant differences in the percentage change of postoperative eGFR ( P=0.009) and tumor diameter ( P<0.001) among the three groups. Restricted cubic spline regression analysis showed that with the prolongation of WIT, the percentage change of postoperative eGFR gradually decreased, and the curve began to stabilize after 30 minutes (R 2=0.044, P=0.015). The results of covariance analysis showed that after adjusting for baseline preoperative eGFR and tumor size, the effect of WIT on postoperative eGFR was significantly different among the three groups ( F=3.864, P=0.022). The postoperative eGFR in the WIT<20 min group was significantly higher than that in 20 min≤WIT<30 min group( P=0.009) and WIT≥30 min group( P=0.017). There was no significant difference in postoperative eGFR between the two groups with longer WIT( P=0.806). Conclusions:In partial nephrectomy, patients with WIT less than 20 minutes had higher postoperative eGFR levels than those with WIT greater than 20 minutes. However, when WIT exceeded 20 minutes, prolonged ischemia time did not lead to further decline in renal function.

Objective:To investigate the correlation of intratumoral fibrosis with the prognosis of clear cell renal cell carcinoma (ccRCC).Methods:The correlation of the transcriptional expression of the primary collagen with the prognosis in ccRCC was evaluated using the Cancer Genome Atlas (TCGA) database, including 530 ccRCC patients with complete information. Of them, 344 cases were male, 186 cases were female. The age of 264 cases was ≤ 60 years, and the age of 266 cases was > 60 years. The pathology grade of 241 patients was G 1-2 grade, and the pathology of 281 cases were G 3-4 grade, 8 cases were undetermined grade. There were 322 cases with AJCC stage Ⅰ-Ⅱ and 205 cases with AJCC stage Ⅲ-Ⅳ, and 3 cases with undetermined stage. There were 420 cases in M 0 and 78 cases in M 1, and 32 cases without distant metastases information. Furthermore, the paraffin sections of 158 non-cystic ccRCC patients confirmed by pathology from November 2005 to November 2017 were further used to evaluate the level of collagen of ccRCC and the status of the pseudocapsule by the Masson staining, Sirius red staining and multicolor immunofluorescence staining of collagen Ⅰ and collagen Ⅲ. Of them, 112 cases were male, 46 cases were female. There were 100 cases with age ≤ 60 years, and 58 cases with age > 60 years. The pathology grade of 111 cases were G 1-2, and the pathology grade of 47 cases were G 3-4. There were 144 cases with AJCC stage Ⅰ-Ⅱ, 14 cases with AJCC stage Ⅲ-Ⅳ. Kaplan-Meier survival curve were used to analyze the relationship between tumor collagen parameters and the overall survival prognosis of patients with ccRCC. Results:The transcriptome results of the TCGA database indicated that the expression level of COL1A1 in ccRCC tissues was significantly higher than that in adjacent normal tissues ( P<0.001). The high expression of collagen suggested a worse overall survival prognosis ( HR=1.165, P=0.002). In addition, the high ratio of COL1A1/COL3A1 indicated a worse overall survival prognosis ( HR=1.901, P<0.001) compared with the low ratio. We further confirmed that the abundance of collagen in tumor was significantly increased compared with the normal adjacent tissues by the Masson staining [41.0 (14.0-75.0) vs.15.0 (3.0-57.0), P<0.001] and the Sirius red staining [42.5 (10.0-90.0) vs.10.0 (2.5-60.0), P<0.001] on 30 ccRCC tissues and adjacent normal tissues. Based on the Masson staining, we found that high collagen abundance in tumor tissue was associated with more G 3-4 grade of tumor compared with low collagen abundance (38.5% vs.21.3%, OR=2.316, 95% CI 1.146-4.681, P=0.023). Kaplan-Meier survival curve showed that higher collagen abundance was associated with a worse overall survival prognosis in ccRCC ( HR=2.630, P=0.007). However, incomplete fibrous pseudocapsule was associated with a worse overall survival prognosis ( HR=11.140, P<0.001). Conclusions:In ccRCC, intratumoral collagen fiber level was overexpressed. High intratumoral collagen level and incomplete fibrous pseudocapsule may indicate a poor overall survival prognosis.

Objective:To investigate the effect of short single reverse-α fixation of nasobiliary tube after endoscopic nasobiliary drainage.Methods:From January 2019 to October 2019, the patients who performed with endoscopic nasolbiliary drainage in Tongji University Affiliated Shanghai East Hospital were randomly divided into experimental group (short single reverse-α fixation, 155 cases) and control group (routine reverse-α fixation, 137 cases). The incidences of the fixation time, prolapse rate, nursing time, scores of nasal comfort and bile flow rate of nasobiliary duct were evaluated between the two groups.Results:The average time of nasobiliary duct fixation was (18.31±1.67) s, the prolapse rate was 5.2% (8/155) and the time of nursing was (35.03±2.68) s, which were lower than those of the control group (46.50±5.50) s, 13.9% (19/137) and (72.07±7.63) s. The difference was statistically significant ( t or χ 2 values were 60.795, 6.570, 56.629, P<0.01 or 0.05). The comfort score of the experimental group was (4.61±1.06) points, the bile flow rate was (241.52±53.95) ml/days, which were higher than (5.76±0.76) points and (174.09±47.55) ml/days of the control group, the difference was statistically significant ( t values were 10.448, 11.265, P<0.01). Conclusions:Shortening the length of nasobiliary duct combined with single reaction "α" method has the advantages of simper operation and nursing, low prolapse rate, high comfort and good drainage effect. It is worthy of clinical application.

Norepinephrine (NE) can raise blood pressure and speed up heart rate. However, because its effect of raising heart rate is less than that of reflex reduction of heart rate caused by the increase of blood pressure, NE causes more heart rate decrease in patients. A case of tachyarrhythmia caused by low dose NE was admitted to department of intensive care unit (ICU) of Shijiazhuang Third Hospital. The heart rate of the patient increased with the elevation of NE application dose. A variety of antiarrhythmic drugs was invalid. The related examination was prescribed to eliminate the cause of arrhythmia caused by the disorder of electrolysis and thyroid function, and found that heart rate decreased as the dose of NE tapered. After NE was stopped, the patient recovered sinus rhythm. During one month of follow-up, the patient's heart rhythm was normal. Therefore, the occurrence of tachyarrhythmia is related to NE.

Objective:To observe the efficacy and safety of mechanical thrombectomy with retrievable stent in patients with acute basilar artery occlusion (ABAO).Methods:Twenty-five patients with ABAO admitted to our hospital from December 2016 to October 2019 were chosen in our study. In patients who were eligible for intravenous thrombolysis and had onset within 4.5 h, mechanical thrombectomy with Solitaire AB stent was performed besides intravenous thrombolysis. In patients who had contraindications for intravenous thrombolysis or had onset within 4.5-24 h, mechanical thrombectomy with Solitaire AB stent or mechanical thrombectomy with Solitaire AB stent combined with balloon dilatation and stenting were performed. The prognoses of the patients were determined by modified Rankin scale (mRS) 90 d after surgery. The clinical data and efficacy of the patients were analyzed retrospectively, and the differences in clinical data and prognoses between patients with cardiogenic embolization and those with large artery atherosclerosis were compared.Results:Twenty-four patients had successful recanalization, and one failed. Follow-up for 90 d showed that 11 patients had good prognosis, 8 had poor prognosis, and 6 died. In patients with cardiogenic embolization, the occlusion sites were located in the upper segment of the basilar artery ( n=4) and the middle segment of the basilar artery ( n=10); in patients with large-artery atherosclerosis, occlusion sites were located in the middle segment of the basilar artery ( n=6) and the under segment of the basilar artery ( n=5); the distribution of basilar artery occlusion sites between patients with cardiogenic embolization and those with large artery atherosclerosis was statistically different ( P<0.05). The mRS scores 90 d after surgery showed no significant differences ( P>0.05). Conclusion:Mechanical thrombectomy with retrievable stent is safe and feasible for patients with ABAO, and the occlusion sites of the basilar artery in ABAO may indicate the etiology of occlusion.

OBJECTIVE:To investigate the effects of NOS1AP rs12742393 A/C gene polymorphism on lipid-regulating re-sponse of rosuvastatin calcium. METHODS:Two hundred and tuirty six patients with coronary heart disease(CHD)were selected from cardiology department of our hospital during Jan. 2014-Jun. 2015,and then given rosuvastatin calcium and other symptomatic treatment for 12 weeks. Polymorphism of NOS1AP rs12742393 A/C was detected by PCR-RFLP. The levels of TG,TC,HDL-C and LDL-C were detected by photoelectric colorimetry before treatment and 4,12 weeks after treatment. The serum relationship of genotype with the level of blood lipid was analyzed. RESULTS:Among 236 CHD patients,there were 131 cases of AA genotype (55.5%),98 cases of AC genotype(41.5%) and 7 cases of CC genotype(3.0%);genotype and allele frequencies met the Har-dy-Weinberg balance(P>0.05). There were 132 patients with normal blood lipid and 104 patients with hypercholesterolemia;there was statistical significance in genotype and allele frequencies (P<0.05). Among 104 CHD patients with hypercholesterolemia be-fore treatment,there was no statistical significance in the levels of TG,TC,LDL-C and HDL-C between AA genotype and AC+CC genotype(P>0.05). 4th and 12th week after treatment,the levels of TG,TC and LDL-C in different genotypes were all de-creased significantly;4th week after treatment,the level of LDL-C in AC+CC genotype was significantly lower than AA genotype, and the change compared to before treatment was significantly more than AA genotype,with statistical significance (P<0.05). There was no statistical significance in the level of HDL-C among different genotypes compared to before treatment;there was no statistical significance in the levels of TG,TC and HDL-C 4th,12th week after treatment and their changes compared to before treatment between AA genotype and AC+CC genotype;there was no statistical significance in the level of LDL-C 12th week after treatment and their changes between AA genotype and AC+CC genotype(P>0.05). CONCLUSIONS:NOS1AP rs12742393 A/C gene polymorphism is associated with CHD complicated with hypercholesterolemia;the C allele of NOS1AP rs12742393 may strengthen the response of CHD patients with hy-percholesterolemia to rosuvastatin calcium through influencing the level of LDL-C.

Objective To investigate the epidemiology of chronic kidney disease (CKD) in patients with hypertension and diabetes mellitus in Kunming urban area.Methods A multistage cluster randomized sampling method was used to collect 400 randomly selected patients (community managed hypertension and diabetes mellitus) in community service centers in the 4 main urban districts of Kunming,Yunnan province.The subjects were screened for CKD by questionnaires,physical examinations,and microalbuminuria tests.Results A total of 343 people were surveyed.The prevalence of albuminuria,proteinuria by routine urinalysis,decreased glomerular filtration rate,and CKD prevalence were respectively 37.3％,12.2％,5.0％ and 39.1％.A total of 134 patients with CKD (134/343) were screened.Logistic regression analysis showed male (OR=2.312,95％CI 1.325-4.037,P=0.003),hyperuricemia (OR=1.751,95％ CI 1.109-2.765,P=0.016) and obesity (OR=2.150,95％ CI 1.115-4.146,P=0.022) were related to CKD.Conclusions The prevalences of CKD and albuminuria are 39.1％ and 37.3％ in patients with chronic diseases (hypertension and diabetes) in the main urban community of Kunming,Yunnan.Hyperuricemia,male and obesity are independent risk factors for CKD.