BACKGROUND:Previous studies have confirmed that drug-containing serum with low concentration of assemble flavone of rhizome drynaria (AFDR) promotes osteogentic differentiation of ciliary neurotrophic factor (CNTF)-modified myoblasts, but the underlying mechanism remains unclear.
OBJECTIVE:To observe the influence of mitogen-activated protein kinase (MAPK) inhibitor in the process of AFDR promoting the osteogentic differentiation of myoblasts.
METHODS:Transfected-CNTF myoblasts were preprocessed prior to osteogentic induction. Changes of alkaline phosphatase specific activities were detected in blank serum, AFDR drug serum and p38 pathway inhibitor SB203580 groups. mRNA and protein expression levels of core binding factor a1 and alkaline phosphatase were detected by real-time PCR and western blot, respectively.
RESULTS AND CONCLUSION:Real-time PCR showed that the mRNA expression levels of core binding factor a1 and alkaline phosphatase in the AFDR group were the highest;while p38 inhibitor SB203580 significantly downregulated the above levels. Western blot findings showed that a significant reduction in the protein expression levels of core binding factor a1 and alkaline phosphatase after p38 inhibitor SB203580 addition. These results suggest that p38 pathway inhibitor can downregulate osteogenesis-related gene and protein expressions, and thus AFDR promoting the osteogentic differentiation of CNTF-modified myoblasts probably through activating p38 MAPK signaling pathway.

Objective To explore the safety and efficacy of fusion imaging technique and traditional ultrasound guidance in percutaneous nephrolithotomy,and to compare the difference of two methods for PCNL.Methods Patients with renal calculus,who underwent percutaneous nephrolithotomy from January 2016 to August 2016,were enrolled in the study.The patients were randomly divided into two groups by SAS software.The control group was treated with traditional ultrasound guided puncture technique (Ultrasound group).Experimental group was treated with fusion imaging method (CT-US group).Preoperative patient CT image data was uploaded to the image fusion ultrasound machine for data synchronization.Both groups used the same way to establish a standard channel (F24).Lithoclast system from EMS was used to remove stones.Intraoperative parameters (time to define the target calyx,access establishment time,operative duration) and postoperative perioperative data (estimated blood loss,stone-free rate,severe complications) were compared between the two groups.Results 65 cases of patients were enrolled into the study.There was no significant difference in age (P =0.72),body mass index (P =0.78),stone size (P =0.53) and so on.Compared with the control group,the time duration to define the target calyx in CT-US group is significantly decreased in experiment group(50.4 ± 18.1) s vs.(82.1 ± 37.7) s,(P =0.02).The time to establish the access and fulfill the procedure shows no significant difference between the two groups,respectvely(P =0.45,0.61).Also,significant differences can be found in the hemoglobin loss during and after the surgery(1.1 ± 0.5) g/L vs.(1.4 ± 0.4) g/L (P =0.04).The difference in severe complications (Clavien Ⅲ and above),stone-free rate (P =0.60) and transfusion rate (P =1.00) was not significant.Conclusions Our primary study shows CT-altrasound image fusion guide PCNL is a safe and reliable technology.The time duration to define the target calyx was decreased compared with traditional US guidance method.The target calyx chosen was more accurate,with lower blood loss during the perioperative period.

Objective:To summarize the preliminary clinical experience of utilizing ureteral balloon dilation catheter in the treatment of "difficult ureter" during ureteroscopic lithotripsy, and to discuss the efficacy and safety of the technique.Methods:Clinical data of 28 patients (30 sides) with upper urinary tract calculi admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University from April 2021 to July 2022 were retrospectively analyzed. There were 23 males (82.1%) and 5 females (17.9%), with age of (51.5±13.6) years. Among the 30 sides, 20 (66.7%) on the left and 10(33.3%) were on the right. Calculi were either located in the renal pelvis or calyxes in 7 sides (23.3%), upper ureter in 17 sides (56.7%), and lower ureter in 6 sides (20.0%). The maximum diameter of the stones was (9.4±4.2)mm, and 23 sides (76.7%) were combined with hydronephrosis before surgery. When "difficult ureter" was encountered during the procedure, that is, it was difficult to insert ureteroscope or ureteral access sheath (UAS) due to small ureteral lumen, balloon catheter was used for dilation in the first stage, in which the balloon diameter was 4 mm on 22 sides and 5mm on 8 sides. The instrument was retrogradely inserted through the working channel of F8 semi-rigid ureteroscope, and the small site of the ureteral lumen was dilated under direct endoscopic view. After a single dilation, the balloon catheter was withdrawn, and the effect of dilation was evaluated by semi-rigid ureteroscopy to determine whether to proceed with the following procedures. The intraoperative data were recorded, including surgical method, stage of "difficult ureter" occurred, site of the small part of the ureter, related data of utilizing ureteral dilatation balloon catheter, grade of ureteral injury after dilatation (according to the 0-4 grading classification of endoscopic ureteral injuries), total operation time, balloon catheter-related adverse events, stone-free rate, and time of removing ureteral stents.Results:Among the 30 sides, 29 (96.7%) had difficulty in the stage of ureteroscope insertion, and 1(3.3%) had difficulty in the stage of UAS insertion. A total of 37 small sites of ureter were involved, including 18 in the intramural segment, 10 in the lower part, 2 in the middle part, and 7 in the upper part. Each site was dilated once with a median time of 3 (0.5, 5.0) minutes and a median maximum balloon pressure of 1 215.9(1 215.9, 1 443.9)kPa[12.0(12.0, 14.3)atm]. There were 28 sites of grade Ⅰ injury, 8 sites of grade Ⅱinjury, and 1 site of grade Ⅲinjury. The total duration of unilateral procedure was (73.4±30.3) min. Ureteroscope or UAS insertion was successful in 28 sides(93.3%) after balloon dilation, and failed in 2 sides(6.7%), both of which were in the stage of inserting ureteroscope and ureteral stent was indwelled for the second-stage procedures. On the first day after surgery, the hemoglobin level was (134.1±12.9)g/L, which was significantly different from the preoperative parameters ( P<0.01), and serum creatinine level was (86.7±23.2)μmol/L, which showed no significant difference from the preoperative one ( P=0.263). The primary stone-free rate was 92.9% (26/28), and the total postoperative complication rate was 13.3% (4/30), including 3 of grade Ⅰ (lateral lower abdominal pain requiring additional analgesic drugs) and 1 of grade Ⅱ (postoperative hematuria requiring intravenous hemostatic drugs). Follow-up was conducted for 3 months. All of the 28 successful sides had their ureteral stents removed before the last follow-up, and the time of removal was (36.9±11.5) days. No hydronephrosis was found in the ipsilateral kidney by ultrasound 3 months after operation. Conclusions:Balloon dilation technique showed good efficacy and safety in the treatment of "difficult ureter" during ureteroscopic lithotripsy.

Lactylation is a novel lactate-dependent post-translational modification that can alter the structure and function of proteins by covalently coupling lactoyl groups to lysine residues.Therefore,gene expression is regulated and lactylation participates in cellular metabolic and growth processes.Recent studies have shown that lactylation in tumor tissues can affect tumor occurrence and development by regu-lating intracellular signal transduction,gene expression,and protein function.This review summarizes the discovery process of lactylation and recent research progress in tumors,providing novel insights into their prevention and treatment.

Objective:To retrospectively summarize disease characteristics and the clinical experience of minimally invasive endoscopy in the treatment of upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease.Methods:Three patients with bilateral ureteropelvic encrusted inflammatory disease admitted to our hospital from March 2018 to July 2021 were involved. Case 1, male, 45 years old, admitted due to bilateral hydronephrosis for 5 months. The preoperative diagnosis were bilateral ureteropelvic stones (encrustation), right ureteral atresia, left ureteral stenosis, and systemic vasculitis. Left double J tube insertion and right nephrostomy were performed in another hospital. We conducted antegrade percutaneous nephroscopy combined with retrograde ureteroscopy surgery and assisted balloon dilation to treat bilateral lesions stage by stage. Case 2, Male, 12 years old, admitted due to bilateral abdominal pain for 6 weeks. The preoperative diagnosis were bilateral ureteral stones, bilateral hydronephrosis, and dermatomyositis. After the failure of double J tube insertion in another hospital, double nephrostomy was performed instead. We performed left percutaneous nephroscopy and right percutaneous nephroscopy combined with ureteroscopy for the treatment of bilateral lesions. Case 3, female, 32 years old, was admitted because of pain in the left lower back and abdomen for over 6 months. The preoperative diagnosis were bilateral ureteral stones, bilateral ureteral stenosis, and dermatomyositis. She underwent three times of ESWL and once URS before. We performed ureteroscopic surgery for bilateral lesions. During the surgery, various degrees of crusting in the renal pelvis or ureter were observed in all 3 cases, and the lesions were removed using pneumatic lithotripsy combined with forceps or baskets. After surgery, oral antibiotics were continuously used for 1-3 months. The efficacy and prognosis were evaluated based on the follow-up of urine, imaging, and endoscopic examinations at 3, 6, and 12 months after surgery.Results:All 3 surgeries were successfully completed. At 3, 6, and 12 months after surgery, follow-up CT showed no crusting in the left ureter, and endoscopy showed good mucosal wound healing and unobstructed lumen in case 1. There were still some crusting lesions and lumen stenosis in the right renal pelvis, and the right ureter reconstruction surgery was ultimately performed. There were no crusting on both sides and the urinary tract was unobstructed after 3, 6, and 12 months of follow-up in case 2 and case 3. Postoperative pathological examination showed chronic inflammation of urothelial mucosal tissue, small pieces of proliferative fibrous tissue with peripheral calcification. Calcification layer composition analysis showed magnesium ammonium phosphate and carbonate apatite. No related complications occurred in case 2 and case 3.Conclusions:Urothelial crusted inflammatory disease is rare clinically, and the diagnosis and treatment strategies are rarely reported domestically and internationally. Preoperative imaging examination, intraoperative findings and postoperative pathology or calcification composition analysis are of instruction for the diagnosis and treatment of this disease. Minimally invasive endoscopy treatment for upper urinary tract obstruction caused by ureteropelvic encrusted inflammatory disease has a good effect. Long-term efficacy and other adjuvant treatment need long-term follow-up and clinical practice.

Objective:To discuss the clinical experience and efficacy of minimally invasive anterograde multiple endoscopic treatment of upper urinary tract stones in allograft kidney.Methods:We retrospectively analyzed 14 patients with upper urinary tract stones in allograft kidney admitted to our hospital from June 2018 to August 2020. 8 cases were female and 6 cases were male, with an average age of 47.3±11.1 years. 3 patients had hyperuricemia and four had hypertension and diabetes. The history of renal transplantation was over ten years in 3 cases, three to five years in 4 cases, two years in 3 cases, 1 year in 3 cases, and 4 months in 1 case. 3 patients had a history of RIRS, and the operation was terminated due to severe ureteral tortuosity resulting in failure of sheathing or ureteroscopy. Ureteral stent was performed in 2 cases due to stone obstruction and hydronephrosis. Serum creatinine was normal in 7 patients before operation, and serum creatinine was 91-139μmol/L in 4 patients in the compensatory stage of chronic renal insufficiency. The serum creatinine was 292, 544 and 708μmol/L respectively in 3 patients in the decompensated stage of chronic renal insufficiency or renal failure stage. The preoperative average hemoglobin was 117.5g/L. 3 cases were partial staghorn calculi, 4 cases were single caliceal or renal pelvis calculi, 2 cases were renal pelvis or caliceal calculi with upper ureteral calculi, and 5 cases were renal pelvis or renal caliceal calculi with multiple calculi. Stone size were 1 case of single upper caliceal stone of 0.7cm, 3 cases of lower caliceal stones of 1.5, 1.6 and 2.0cm, 1 case of renal pelvic stone of 1.5cm, 2 cases of middle and upper caliceal stones of 2.8 and 3.1cm, 2 cases of middle and lower caliceal stones of 1.5 and 3.2cm, respectively. 3 cases of middle upper caliceal and renal pelvic stones were 2.2, 2.5 and 2.6cm. 2 cases of renal pelvis with upper ureteral stones were 1.3 and 1.7cm, 0.7 and 0.5cm respectively. Preoperative routine urine examination showed that 9 cases had urinary tract infection, among which 5 cases had positive urine culture. Surgery was performed after therapeutic improvement with sensitive antibiotics. According to the size and distribution of stone, the combination of single access or multi-access PCNL in different diameters was adopted, supplemented by FURS. Surgical methods selection and performance: 2 cases performed in single S-PCNL with stone size were 2.2cm and 2.6cm, 2 cases performed in single M-PCNL with stone size were 1.5cm and 1.5cm, 1 case performed in Needle-perc with stone size was 0.7cm, 2 cases performed in S-PCNL combined M-PCNL with stone size were 2.8cm and 3.1cm, 3 cases performed in S-PCNL combined Needle-perc with stone size were 2.0cm, 2.5cm and 3.2cm, 2 cases performed in M-PCNL combined Needle-perc with stone size were 1.5cm and 1.6cm, 2 cases performed in S-PCNL combined anterograde FURS with stones size were 1.3cm and 1.7cm in allograft kidney and ureter stone were 0.7cm and 0.5cm, a total of 7 kinds of way, and postoperative stone free rate, laboratory indexes (serum creatinine, blood hemoglobin), surgical complications, postoperative hospital stay were analyzed.Results:All 14 patients (mean age was 47.3±11.1 years) were successfully operated. Postoperative examination revealed 1 case had 0.6cm residual stone and it was cleared at the second stage anterograde FURS through the original access. The mean operative time and postoperative hospital stay were 68.2±21.6min and 6.2±1.3 days. Compared with preoperative serum creatinine changes, 2 cases showed slight increase (mean 12.6±0.3μmol/L), 3 cases showed significant decrease (mean 329.6±216.6μmol/L), and the other 9 cases showed no significant change (range<10μmol/L), among which 5 cases showed an increase (mean 5.4±0.7 μmol/L) and 4 cases showed a decrease (mean 3.7±0.4 μmol/L). The mean decrease of hemoglobin was 9.3±4.1g/L. Two patients had fever and their body temperature returned to normal after anti-inflammatory treatment. No blood transfusion, abdominal organ injury or urogenic sepsis occurred.Conclusions:Invasive anterograde multiple endoscopic treatment of upper urinary tract stones in allograft kidney is a single or combined operation using single-channel PCNL, multi-channel PCNL of different sizes and diameters and anterograde FURS according to individual differences, which can effectively reduce renal function injury is safe, efficient and feasible.

Objective:To retrospectively analyze and summarize the clinical experience and therapeutic effect of anterograde Needle-perc combined with RIRS, namely N+ R (Needle perc + RIRS) technique in the treatment of complex calyceal diverticular stone.Methods:Retrospective analysis of 23 cases of complex renal caliceal diverticulum stones admitted to our hospital from January 2020 to December 2022. The complex factors mainly include the invisible cervical orifice of diverticulum, large stone volume, and special anatomical location, which makes single RIRS or PCNL treatment difficult or unsuccessful. There were 14 males and 9 females with an average age of (42.3±6.1) years. Three cases were upper calyceal diverticular stone, average size was (0.9±0.2)cm. Nine patients had diverticular stone in the middle posterior calyx, and the average size was (1.2±0.3)cm. The average size of four diverticular stone was (1.8±0.2)cm in the anterior middle calyx. Seven patients had diverticular stone with an average size of (1.3±0.1)cm in lower calyx. Among them, 12 patients underwent RIRS which were difficult or stone undiscovered, and 3 patients underwent PCNL and the operation was terminated due to failure of channel establishment. In our center, oblique supine lithotomy position (male) or prone split-leg position (female) was adopted, and the combined treatment of Needle-perc and RIRS was performed. Needle-perc puncture was completed under the guidance of full ultrasound. During the operation, methylene blue reagent or mutual guidance of two endoscopes was used to find the diverticulum neck and expand the outlet with holmium laser incision. Depending on the size and location of the stones, a single Needle-perc laser lithotripsy combined with stone removal in flexible ureteroscope was used, or dual lasers were be used simultaneously for stone removal under double endoscopes. The first stage stone free rate, operation time, hemoglobin decrease, complications, postoperative hospital stay and other conditions were analyzed.Results:All the 23 operations were completed successfully. The stone free rate within 48 hours and one month after surgery was 78.2% and 100.0% respectively. The average operation time was (61.5±12.2)min. The mean postoperative hospital stay was (2.8±0.6) days. The mean decrease of hemoglobin was (3.6±0.4)g/L. Three patients had fever and one patient had renal subcapsular effusion. After anti-inflammatory and symptomatic treatment, the patient was discharged. There was no incidence of Clavien-Dindo≥Ⅱcomplications such as blood transfusion, abdominal organ injury or urosepsis.Conclusions:Treatment of complex renal caliceal diverticulum stones using N+ R technique of anterograde needle-perc combined with RIRS can effectively improve the success rate of first-stage surgery. Overall, it is safe, efficient and feasible with the advantages of high stone free rate, lower damage, and few postoperative complications.