[摘 要] 目的：探究连翘苷（PHN）调节高迁移率族蛋白B1（HMGB1）/晚期糖基化终产物受体（RAGE）信号通路对胶质瘤U251细胞增殖、侵袭及上皮间质转化（EMT）的影响。方法：将人胶质瘤U251细胞分为PHN-0组（0 µmol/L PHN处理）、PHN低、中和高剂量组（PHN-50、PHN-100、PHN-200组，分别用50、100和200 µmol/L PHN处理）、PHN + pcDNA-NC组（转染pcDNA-NC质粒后200 µmol/L PHN处理）和PHN + HMGB1组（转染过表达HMGB1质粒后200 µmol/L PHN处理）。CCK-8法和克隆形成实验检测各组细胞的增殖能力，流式细胞术检测各组细胞的凋亡水平，Transwell实验检测各组细胞的迁移和侵袭能力，ELISA检测各组细胞分泌IL-8水平，免疫荧光法检测各组细胞中神经钙黏素（N-cadherin）和上皮钙黏素（E-cadherin）阳性率，WB法检测各组细胞中Toll样受体4（TLR4）、核因子-κB（NF-κB）、HMGB1、RAGE、N-cadherin、E-cadherin、细胞周期蛋白D1（cyclin D1）、细胞周期蛋白依赖性激酶2（CDK2）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（BAX）蛋白的表达水平。结果：与PHN-0组相比，PHN-50、PHN-100、PHN-200组U251细胞增殖活力、克隆形成数、迁移和侵袭数、IL-8分泌水平、N-cadherin阳性率及其蛋白表达、TLR4、NF-κB、HMGB1、RAGE、cyclin D1、CDK2蛋白表达均显著降低（均P < 0.05），细胞凋亡率、E-cadherin阳性率及其蛋白表达、BAX/Bcl-2比值均显著升高（均P < 0.05）；同时过表达HMGB1则可逆转PHN对U251细胞增殖、迁移、侵袭及EMT的抑制作用和对凋亡的促进作用（均P < 0.05）。结论：PHN通过HMGB1/RAGE信号通路抑制胶质瘤U251细胞增殖、侵袭及EMT进程。

Objective:To compare the performance and surgical outcomes of disposable digital flexible ureteroscope with a reusable fiberoptic flexible ureteroscope in treatment of upper urinary stones.Methods:A prospective, multicenter, single-blind and randomized controlled study was performed from April 2018 to December 2018. Eligible patients were randomized, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-60 years, solitary upper urinary stone or multiple stones with stone size less than 2 cm, absence of urinary tract infection (UTI) or UTI was controlled, normal liver and renal function. Exclusion criteria included: patients with congenital anomalies, calyceal diverticular stone, IP angle less than 30°, renal insufficiency. pregnancy or lactation, cardiopulmonary function abnormality and coagulation abnormalities. Patients in experimental group received ureteroscopy through a disposable digital flexible ureteroscope (PU3022A, PUSEN), while patients in control group received ureteroscopy through a reusable fiberoptic flexible ureteroscope (Flex-X2, STORZ). The primary endpoint was the high-quality rate of images during the operation. The secondary endpoints included success rate of fragmentation and postoperative complication rates.Results:93 patients were recruited, and 90 of them were finally complete the study (i.e., 45 patients in each group). The demographic and preoperative parameters were comparable between the two groups except the stone size in patients with solitary stone. The high-quality rate of images was significantly higher in experiment group than that in control group (100.0% vs. 15.6%, P<0.001). There were no significant differences in terms of success rate of fragmentation(68.9% vs. 71.1%, P=0.818), hemoglobin dropped (3.91 g/L vs. 3.62 g/L, P=0.880), serum creatinine changed, and postoperative complication rates(6.7% vs.6.7%, P=1.000). Conclusions:Disposable digital flexible ureteroscope achieves similar surgical outcomes to the reusable fiberoptic flexible ureteroscope with a better quality of endoscopic images.

Objective To observe the effect of hyperbaric oxygen (HBO)on neuropathic pain and detect the expression of Wnt/β-catenin signaling pathway in the mechanism of treatment. Methods A total of 30 healthy male SD rats were randomly divided into three groups (n =10):group S(sham group),group CCI(chronic sciatic nerve constrictive injury group),group HBO(HBO treat-ment for seven days group).Rats of group HBO received HBO one time per day for 7 days since the 1st day after surgery.Rats of group S and group CCI were just placed inside the chamber for approxi-mately 100 min,no HBO treatment.The mechanical withdrawal threshold (MWT)and thermal with-drawal latency (TWL)of all rats were measured on 1 d before CCI,1 d,3 d,5 d,7 d after CCI respec-tively.The animals were sacrificed after the last measurement of pain threshold,and the lumbar spinal cord specimen were taken to detect the expression of Wnt3a,β-catenin by immuno-histochemis-try and Western blot analysis.Results Compared with group S,MWT decreased significantly and TWL shortened significantly in CCT and HBO groups at 1,3,5,7 d after operation (P <0.05).Com-pared with group CCI,MWT was elevated and TWL was prolonged in group HBO at 1,3,5,7 d after operation (P <0.05).The Wnt3a,β-catenin expression increased after CCI treatment compared with group S and group HBO (P <0.05).Compared with group CCI,the expression of Wnt3a,β-catenin decreased significantly in the group HBO and group S at 7 d after operation (P <0.05).There was no significant difference between group S and group HBO.Conclusion HBO post-conditioning may relieve the neuropathic pain of rats by inhibiting the activation of spinal path of Wnt3a,β-catenin.

First aid skills are very important in the process of disaster medical rescue methods. Some first aid skills is rarely applied in clinical work at ordinary times, resulting in relevant medical personnel grasp of these skills being not enough skilled. This training method combined with the sim-ulator, has the characteristics and advantages of being close to the real, operational and repeatable. The main training program consists of 6 basic skills such as ventilation, hemostasis, bandaging, fixing, handling, basic life support. By simulating the real disaster scenario and simulation cases, we have targeted a single first aid skills training and multiple comprehensive ability training of first aid skills to trainees. To evaluate the training effect we have examined the individual skills of our trainees, with excellent performance as the goal, and in the comprehensive skills ability assessment we have paid attention to the emergency team's team cooperation ability. By the application of comprehensive simu-lation training and evaluation, the trainees can master all kinds of first aid skills in a short period of time.

Objective To evaluate the efficacy and safety of retrograde flexible ureteroscopic lithotripsy ( RFUL) with holmium:YAG laser for the treatment of renal stones with a large series.Methods The data of 466 patients who underwent RFUL with holmium:YAG laser for the treatment of kidney stones between January 2013 and December 2013 were collected.The maximum diameter of stone was 23 ±16 mm.The stone free rate, complications, retreatment rate were evaluated.Results Out of the 466 patients, the mean operative time and postoperative hospital stay were 33.5 ±18.8 min and 2.3 ±2.0 d.The stone free rate was 67.6% ( 315/466 ) after single procedure, which increased to 69.5% ( 324/466 ) via re-treatments after 3 months.The retreatment rate was 4.3%(20/466), with a total of 493 RFUL procedures performed and 1.06 times per patient.There were 67 (14.4%) cases undergoing complications.Five cases had false passage of ureter orifice causing slight ureteral wall injuries.Steinstrasse occurred in 9 cases, ureteral perforation in 3 cases and perirenal hematoma in 1 case.Overall postoperative fever rate was 10.7%(50/466) with urosepsis in 16 cases (3.4%).When the stone size was≤10, 11-20, 21-30, 31-40, and >40 mm, the stone free rates after a single procedure were 97.0% ( 65/67 ) , 84.2% ( 160/190 ) , 63.1%(70/111), 29.2%(14/48), 12.0%(6/50) (P<0.001), and the postoperative fever rates were 1.5%(1/67), 9.5%(18/190), 13.5% (15/111), 14.6% (7/48), 18.0% (9/50), respectively. The postoperative fever rates were 19.3%(27/140) and 7.1%(23/326) (P<0.001) in the patient with positive and negative preoperative urine leukocyte, and 22.0% ( 22/100 ) and 7.7% ( 28/366 ) ( P <0.001) in patients with positive and negative preoperative urine culture.Conclusions RFUL with holmium:YAG laser is a safe and effective treatment for kidney stones.The postoperative fever rate would increase and stone free rate would reduce with the increased stone size.

Objective To discuss the diagnosis and treatment of renal pelvic carcinoma associated with renal stone.Methods A total of 13 patients,aged from 49 to 73 years old and averaged 59years old.The history of renal stone was 16 years.13 patients accepted B ultrasound check and 1 was found soft tissue occupying.8 patients accepted IVU check and none was found soft tissue occupying.7 patients accepted CT scan and 4 were found soft tissue occupying.The fluorescence in situ hybridization (FISH) examination was done for 2 patients and both were positive.6 patients were found lesions at renal pelvis mucous membrane during the operation of percutaneous nephrolithotripsy,4 accepted radical operations of renal pelvic carcinoma and 2 patients accepted radical nephrectomy according to the biopsy pathology.4 were found soft tissue occupying before operation and accepted radical operation of renal pelvic carcinoma ultimately.1 patient suffered gross hematuria and renal insufficiency accepted the renal pelvic carcinoma vaporization under the ureteroscope.Results The pathology showed that 7 cases were transitional cell carcinoma,4 were transitional cell carcinoma combined squamous cell carcinoma (SCC) metaplasia and 2 were squamous cell carcinoma.6 of 8 patients' stone chemical composition were infection stone and 2 were calcic blended stone.3 patients were followed up 1 to 2 years and survival with no tumor recurrence.The tumor recurred 10 months of the patient accepted the operation of renal pelvic carcinoma vaporization and accepted vaporization again.1 patient bsuffered SCC and local lymph node metastasis.He died 13 months post-operation.Conclusions For the patient who had long history of stone,combining infection with symptoms of severe hematuria and postoperation hematuria,the possibility of renal pelvic carcinoma should be considered.CT scan and urine FISH may help for diagnosis.The biopsy should routinely perform for the doubtful mucosa lesion during the cavity stone operation.Early and timely diagnosis and operation is the key for the patients with pelvic carcinoma associated with renal stone.

Objective　To analyze the clinical indications,efficacy and safety of Chinese minimally invasive percutaneous nephrolithotomy (MPCNL) in treating upper urinary calculi based on our experience.Methods　From June 1992 to September 2010,a total of 10,452 patients (6060 males and 4392 females)with a mean age of (47.6 ± 13.7) years (7 months-93 years) received MPCNL in our center.The mean stone burden was (777.4 ± 740.3) mm2 (20 - 4 080 mm2 ).The data of stone burden,operative techniques,operating time,stone-free rate,major complication,hospital stay and stone composition were investigated.　Results　Of the 10 452 cases,11 801 procedures were performed on 10 876 (5493 left and 5383right) renal units,including 10 102 first stage procedures,1604 secondary procedures,86 third procedures and 9 fourth procedures.There were 11 830 tracts established,including 373 (3.15％ ) tracts of 14 F,7867 (66.50％) tracts of 16 F and 3590 (30.35％) tracts of 18 F.There were 1207 (10.20％),9174(77.55％) and 1449 (12.25％) punctures located in upper,middle and lower pole,respectively.956(8.79％) renal units were managed with multiple tracts,which including 2 tracts in 846 (7.78％) units,3tracts in 85 (0.78％) units,4 tracts in 18 (0.17％) units and 5 tracts in 7 (0.06％) units.Pneumatic lithotripsy was used in 8563 (72.56％) procedures,Holmium:YAG laser lithotripsy was used in 2981(25.26％)　procedures and Pneumatic lithotripsy + Holmium: YAG laser lithotripsy was used in 257(2.18％) procedures.762 (7.29％) cases needed ESWL to clean the stone after MPCNL.The average operating time was ( 101.3 ± 44.2) min ( 10 -240 min).The stone-free rate of MPCNL was 89.9％,which increased to 93％ by adjunctive ESWL.And the mean hospital stay was ( 13.2 ± 6.4) days (2 - 72 days).The major complications happened on 321 (3.07％) cases,including 294 (2.81％ ) cases of blood transfusion,12 (0.11％ ) cases of sepsis,2 (0.02％) cases of renal abscess,9 (0.09％) cases of pleura injury,2 (0.02％) cases of colon injury and 2 (0.02％) cases of death.53 (0.51％) cases needed selective renal arterial embolization to achieve hemostasis.The main stone compositions were analyzed in 4345 cases.Calcium oxalate,calcium phosphate,magnesium ammonium phosphate,uric acid,ammonium urate,carbapatite and cystin were 91.74％,90.33％,14.91％,17.77％,4.83％,8.47％ and 0.51％,respectively. Conclusions　MPCNL is an effective and safe treatment option for all kinds of upper urinary calculi in patients at all ages with a high stone free rate and low major complication rate.

Objective To review the safety and efficacy of upper-pole access percutaneous nephrolithotomy (PCNL). Methods From May 2008 to May 2010,237 cases ( 135 males and 102 females with mean age of 42 yrs) of renal or proximal ureteral calculi treated with upper-pole access PCNL were reviewed.The indications included calculus larger than 1.5 cm or impacted proximal ureteral calculi in 94 cases,calculus≥2 cm or impacted renal pelvic calculi in 26 cases,staghorn or multiple calculi in 68 cases,complex lower calyx calculi in 13 cases,upper calyx calculi not amenable to ESWL or URS in 12 cases,calculi within upper calyx diverticulum in 3 cases,combined UPJ obstruction or upper ureteral stenosis in 8 cases,morbidly obese patients in 3 cases,calculi within horseshoe kidneys in 6 cases,calculi within transplanted kidneys or ureters in 4 cases.Of the 237 cases,175 tracts (73.8％) were above the 12th rib,46were above the 11th rib,12 were below the 12th rib,4 were in the lower abdomen for renal transplant patients. Results The overall stone clearance rate with upper-pole access PCNL monotherapy was 74.3％.Additional punctures were required in 55 cases and combined ESWL in 6 cases.Total stone clearance rate at 3 months after operation was 88.2％.16 patients (6.8％) had a pleural injury.Thoracentesis was required in 8 patients,closed thoracic drainage in 5 patients,conservative treatment in 3 patients.After nephrostomy tube removed,pleural irritation symptom appeared in 12 cases (5.1％) who required symptomatic treatment.No patient had injury to the lung or other viscera.Significant bleeding requiring blood transfusion was olserved in 5 patients,while selective renal arterial embolization was required in 2 cases. Conclusions Upper-pole access offers optimal visibility,convenience for the movement of rigid nephroscope and high stone-free rate.It should be attempted in selected cages of upper ureteral calculi and complex renal calculi.

Objective To evaluate the efficacy and safety of bladder hydrodistention for the treatment of ketamine-associated bladder dysfunction.Methods Six patients were required to withdraw the ketamine and treated with bladder hydrodistention therapy and sodium hyaluronate irrigation,and medicine to pretect liver and kidney was also used.Results The biopsies of 6 cases demonstrated the cystitis through biopsy.Lower urinary tract symptoms such as urgency,thamuria and odynuria were significantly relieved after bladder installation within 30 days.The O'Leary-Sant ICSI scores and the ICPI scores reduced to 3.5 ± 1.6,2.8 ± 1.5 respectively.The functional bladder capacities increased to an anverage of (180 ± 28)ml,.2-3 times of nocturia,Qmax (14.4 ± 4.3) ml/s.All cases were followed up for 4 to 18 months.Symptoms disappeared or were significantly relieved in all patients.Conclusion Contracture of bladder might be the main presentation of ketamine-associated bladder dysfunction.Intravesical hydrodistention therapy and sodium hyaluronate irrigation could be the safe and effective therapy in the treatment of katamine-associated dysfunction.

Objective To compare ureteroscopic hthotomy (URL)and minimally invasive percuta-neous nephrolithotomy (MPCNL) for the management of upper-ureteral calculi ≥ 1.5 cm. Methods Fifty-eight patients with upper-ureteral calculi ≥ 1.5 cm were selected in randomized for URL group (35patients)or MPCNL group (23 patients). Ultrasonography and intravenous X-ray were performed for all pa-tients before surgery. Results In the URL group, 13 cases (37.1%)were rendered stone-free, 8 stones mi-grated upward to the pelvis of kidney. In these cases,a double- J stent was inserted, and ESWL was per-formed,7 cases had ureteral distortion, 3 cases had ureteral stricture, 4 cases had bad field of vision, MPCNL or open operation was performed in these eases. The mean operative time was 38 minutes (range 25-48 min-utes). In the MPCNL group,21 eases (91.3%)were rendered stone-free. In the other 2 patients,ESWL was performed because the stone fragments migrated upward to the pelvis of kidney. The mean operative time was 34 minutes (range 20-58 minutes). Conclusion Compared with URL,MPCNL is a safe and effective procedure for treating upper-ureteral calculi ≥ 1.5 cm.