OBJECTIVES: To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer. METHODS: PBK expression levels were investigated in 33 cancer types based on data from TCGA, GEO and CPTAC databases. RT-PCR and Western blotting were employed to examine PBK expression in clinical pancreatic cancer specimens and cell lines. The diagnostic and prognostic value of PBK in pancreatic cancer was evaluated using survival analysis, Cox regression analysis, ROC curve analysis, and clinical correlation studies. Gene enrichment and immune correlation analyses were conducted to explore the potential role of PBK in tumor microenvironment, and its correlation with drug sensitivity was investigated using GDSC and CTRP datasets. In pancreatic cancer BXPC-3 cells, the effects of lentivirus-mediated PBK knockdown on cell proliferation, migration, and invasion were examined using CCK-8, colony formation, and Transwell assays. The interaction between PBK and non-SMC condensin II complex subunit G2 (NCAPG2) was analyzed using co-immunoprecipitation and Western blotting. RESULTS: PBK was overexpressed in multiple cancer types, including pancreatic cancer. A high PBK expression was associated with a poor prognosis of the patients and correlated with immune infiltration and alterations in the tumor microenvironment. Elevated PBK expression was positively correlated with the sensitivity to MEK inhibitors (Trametinib) and EGFR inhibitors (Afatinib) but negatively with the sensitivity to Bcl-2 inhibitors (TW37) and niclosamide. In BXPC-3 cells, PBK knockdown significantly suppressed NCAPG2 expression and inhibited cell proliferation, migration, and invasion. Co-immunoprecipitation confirmed a direct binding between PBK and NCAPG2. CONCLUSIONS PBK is a key regulator of pancreatic cancer and interacts with NCAPG2 to promote tumor progression, suggesting its value as a potential biomarker and therapeutic target for pancreatic cancer.
Humans ; Pancreatic Neoplasms/genetics* ; Prognosis ; Biomarkers, Tumor/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Adenocarcinoma/metabolism* ; Tumor Microenvironment ; Cell Movement ; Mitogen-Activated Protein Kinase Kinases

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Objective:To evaluate the mid-term complication rates of the Hui-Jing one-stage procedure (lingual mucosa combined with longitudinal preputial island flap onlay urethroplasty + tubularized incised plate glansplasty)versus the classic Bracka staged surgery for children with severe hypospadias.Methods:A retrospective analysis was conducted on clinical data of 75 children with proximal hypospadias who were treated at the Seventh Medical Center of PLA General Hospital from March 2017 to June 2022. Of these patients, 31 cases (15 cases penoscrotal type and 16 cases perineal type) were underwent the Bracka two-stage surgery with a median age of 38 months (24.0, 44.5) and 44 cases underwent the Hui-Jing one-stage procedure (23 cases penoscrotal type and 21 perineal type) with a median age of 40.5 months (20.75, 90.5). The length of urethral plate defect after correction of penile curvature was (4.30±0.84)cm in the Bracka group and (4.56±0.79)cm in the Hui-Jing group, which also showed no significant difference.There was no statistically significant difference of the median age and the position of preoperative urethral opening between the two groups( P=0.47, P=0.74). The first stage of Bracka repair consists of orthoplasty and urethral bed substitution with free preputial graft. After 6 months, the urethral plate created from free graft was tabularized to form neourethra; Hui-Jing procedure group used the free lingual mucosal as urethral plate substitution, then we conducted longitudinal preputial island flap Onlay and Snodgrass phalloplasty. The incidence of postoperative urethral fistula, urethral stricture and urethral diverticulum was compared between the two groups of cases and the difference in efficacy between the two procedures was assessed. Results:Among the 75 patients included in the study, there was no statistically significant difference in age or location of urethral meatus between the Bracka and Hui-Jing groups. In Bracka group, 9 cases of urethral stricture (29.0%), 6 case of urethral fistula (19.4%), and 2 cases of urethral diverticulum (6.5%) occurred after surgery, while 12 cases of urethral fistula (27.3%) and 3 case of urethral fistula (6.8%) occurred in the Hui-Jing group. No urethral stricture occurred in Hui-Jing group. There was no statistically significant difference in overall incidence of complications between the two groups [17/31(54.8%) vs.15/44(34.1%), P=0.12]. The incidence of urethral fistula and urethral diverticulum show no significant differences between two groups(19.4% vs 27.3, P=0.61, 6.5% vs. 6.8%, P=0.13). The number of operation in Bracka group was (2.68±1.03) and the hospitalization cost was (12 984.63±3 808.15) Yuan, while the number of operation in Hui-Jing group was (1.36±0.53) and the hospitalization cost was (8 490.54±3 136.84) Yuan. Conclusions:The Hui-Jing one-stage procedure can be used for the surgical treatment of children with severe hypospadias. There is no urethral stricture happened in Hui-Jing group, while the general complication incidence and incidence of urethral fistula and diverticulum show no differences.

Objective:To discuss the efficacy of robotic-assisted laparoscopic hemi-nephrectomy for the treatment of complete duplex kidney.Methods:We retrospectively reviewed the clinical data of the 20 patients who had robotic-assisted laparoscopic hemi-nephrectomy surgery from March 2017 to November 2019. Four of these patients were male, while the others were female.The average age of these patients was 28.6 months, ranged from 1-2 months.The duplex kidneys were on the upper pole, 9 on the left side, and l1 on the right side. All the patients had a history of gradual exacerbations of hydronephrosis before surgery. The most commonly seen symptoms were lumbar/abdominal pain(2 cases), dysuresia(1 case) and leakage of urine(1 case). Twelve patients had a history of repeated urinary tract infections. One patient expressed the cystic mass of the urethra protruded from the external orifice. Preoperative diagnosis was confirmed by magnetic resonance urinary water imaging (MRU), diuretic renal dynamic imaging(ECT), intravenous pyelography(IVP), and voiding cystoureterography(VCUG). Two cases were of ectopic urete, 4 of ureterocele and 4 of vesieoureteral reflux(VUR). All the patients underwent hemi-nephrectomy for the treatment of complete duplex kidney. Then we observed the intraoperative and postoperative complications and follow-ups.Results:A11 the cases performed by robotic-assisted laparoscopic surgery transperitoneally were completed successfully.There was no significant complication during the surgery with quick recovery after the surgery.The mean operative time was 109.5min(range 82-150 min). The mean estimated blood loss was about 9 ml (range 5-22 ml). Routinely placing a peripelvic catheter drainage was recommended. The mean hospital stay was 5.9 days(range 4-8 days). One patient was lost to follow-up.Mean follow-up was 13.6 months (range 3 -30 months). The results of the re-examination of ECT did not indicate loss or atrophy of lower renal function 3 months after operation. Primary symptoms improved.Conclusions:Robotic-assisted laparoscopic hemi-nephrectomy for hydronephrosis with duplex kidney could be minimal invasive and effective, and has achieved similar results with cosmetic scar .

Objective:To evaluate the safety and feasibility of robotic-assisted laparoscopic resection of bladder rhabdomyosarcoma.Methods:A retrospective study was performed in 4 children underwent robotic-assisted surgery for bladder rhabdomyosarcoma from July 2018 to September 2019 in our hospital. The perioperative information and short time outcomes were collected. All the four patients were male. The average age of these patients was 68 months (from 11 to 122 months). After cystoscopy biopsy was conducted, preoperative chemotherapy was carried out. Preoperative radiotherapy was also added depends on the tumor response, then robotic-assisted surgery was performed. Radical cystectomy and orthotopic neobladder reconstruction with bilateral ureter reimplanataion were carried out for the bladder was widely occupied case. Bladder preserving surgery was performed for the other three localized cases.Results:All of the four operations have been conducted successfully without conservation to open surgery. The mean operative time was 189(104-316) min while the mean estimated blood loss was 32.5(20-50) ml. The mean tumor diameter was 4.48(2.7-6.0)cm. According to the pathological results, all of the four cases were diagnosed as embryonal rhabdomyosarcoma. One case had positive margin while other three cases had negative margins. No complication more than Clavien-Dindo grade Ⅲ was observed. The mean length of hospital stay was 18(14-24)days and the mean follow-up time was 14.7(7-21) months. Postoperative chemotherapy was carried out according to the protocol of IRS low risk group for all cases (VAC, eight cycles). Postoperative radiotherapy was conducted for the case with positive margin. No recurrence was recorded during the follow-up period.Conclusions:Robotic-assisted laparoscopic technique for the treatment of bladder rhabdomyosarcoma in children is safe and feasible.

Objective To investigate the feasibility and safety of robotic-assisted laparoscopic pyeloplasty (RALP) in infant ureteropelvic junction obstruction.Methods Of 31 infants who underwent RALP between March 2017 and August 2017 were reviewed,including 25 boys and 6 girls.22 infants were found that the hydronephrosis was in the left kidney and 9 in the right kidney.The average age of the infants was (3.5 ± 0.7) months,ranged from 8 days to 6 months,including 7 infants less than 2 months.The average weight of the infants was (6.7 ± 1.2) kg,with a minimum weight of 3.3 kg.The diagnosis and outcomes of ureteropelvic junction obstruction (UPJO) were reviewed on clinical and imaging data.The ultrasound showed that the mean anteroposterior diameter of hydronephrotic kidney was (4.01 ±0.56)cm.The split renal function was (37.1 ± 3.2) ％ in infants who were more than 2 months.Patients with proximal defect were positioned in the lateral flank position with 50°-70° inclination and as close as possible to the edge of operating table.The trocars of robotic lens and No.1 robotic arm were placed on the middle of the umbilicus and the Pfannenstiel line respectively,and the trocar of No.2 robotic arm was placed on the supraumbilical symmetry point of the trocar No.1 robotic arm,and the auxiliary trocar was placed on the Pfannenstiel line outside the 3-4 cm of healthy side of the trocar of No.1 robotic arm.During operation,the ureteropelvic junction was dissected and tailored.Then the ureter was open longitudinally at the posterior lateral side and was anastomosed at the lowest part the renal pelvis.We assessed preoperative clinical data and outcomes,and analyzed the transition experience.Data are expressed as medians for continuous variables.Results All operations were successful with no serious intraoperative complication and traditional laparoscopic or open surgical conversion.The average operative time was 108 min,the average intraoperative blood loss was 9.5 ml.The average drain removal was 1.2 days,the average start oral of feeding was 3.2 hours days and the average postoperative hospital stay was 6.2 days.Postoperative pathological results showed smooth muscle hyperplasia,hypertrophy and fibrous tissue in the urothelium,accompanied by chronic inflammation of urothelial mucosa.Patients with Clavien Ⅰ and Ⅱ complications 22.6％ (7/31) postoperatively were managed conservatively.Among them,there were 1 cases of flank pain,1 cases of hematuria,2 cases of urinary leakage,and 3 cases of urinary tract infection.Patients' symptoms disappeared by conservative treatment.No patient suffered Clavien Ⅲ and Ⅳ complication postoperatively.The renal pelvis anteroposterior diameter was 1.58 cm at three months postoperatively,which was significantly smaller than that of peroperation (P ＜ 0.05).A diuretic T1/2 showed the improvement of split renal function without urinary obstruction in all patients at three months postoperatively.The postoperative split renal function was (39.2 ± 3.5) ％,which was slightly higher than that of preoperation (P ＞ 0.05).Conclusions Severe hydronephrosis in neonates can be acted as an indication for exploratory surgery when the surgeon's ability,anesthesia,monitoring and management conditions are available.Robotic-assisted laparoscopic pyeloplasty is a safe and feasible option for the treatment of UPJO in infant with less trauma,rapid recovery and good cosmetic result.We suggest that RALP is potentially a recommended feasible treatment option for infant with UPJO.

Objective: To evaluate the clinical efficacy of robot-assisted laparoscopic ureteral reimplantation (RAUR) for primary obstructive megaureter (POM) in children. Methods: Twenty-one patients who underwent RAUR for POM in Bayi Children’s Hospital between 2017 April and 2018 April were retrospectively analyzed. The study population consisted of 15 boys and 6 girls aged between 2 months and 11 years. Ten patients had left POMs, 9 had right POMs and two had bilateral POMs. All patients were preoperatively diagnosed with a POM based on urinary system ultrasonography, magnetic resonance urography, and diuretic renal dynamic imaging. Our main technique key steps include: Under general anesthesia, the patients were placed in a Trendelenburg position approximately 40 degrees from the horizon. An 8.5-mm camera port was placed at the level of the umbilicus. Followed by two 5-mm robotic Trocars placed under direct vision 6 cm to the camera port separately, a 5-mm assistant port was placed on the right upper abdominal quadrants which was located 3 cm from the camera and robotic port. The ureter was identified at the pelvic brim. The peritoneum covering the ureter was incised and the ureter was mobilized to the level of the vesico-ureteric junction. The bladder was filled with 60 ml saline and a 5 cm length and 1.5 cm wide submucosal detrusor tunnel was created. The ureter was transected at the bladder mucosa and the narrowed ureteral segment was discarded. The ureteroneocystostomy was performed using 6-0 absorbable suture. Dissecting the perivesical fascia appropriately and using down-top suturing approach, use of an apical stay stitch, and incorporation of the ureteral adventitia during detrusorraphy. Postoperative complications were analysed using the Clavien-Dindo classification. Success was defined as symptomatic relief, decreased hydronephrosis on ultrasound and no evidence of vesicoureteral reflux on voiding cystourethrography. Results: All surgeries were successfully completed without conversion and no intra-operative complication was encountered. The mean operative time was 117.6±18.1(89-165)min, the mean estimated blood loss was 11.9±4.3(5-25)ml, the abdominal drainage tubes were removed after a mean of 4.9±1.1(3-8)days, and the mean postoperative hospital stay was 6.3±1.3(4-10) days. Postoperative complications (Clavien Ⅰ-Ⅱ) occurred in 9.5% (two patients had recurrent urinary tract infections postoperatively) children, no grade Ⅲ-Ⅳ complication was observed. The pre-operative symptoms in all patients disappeared. One patient had grade Ⅱ VUR on VCUG, who were followed conservatively. Ultrasound at postoperative follow-up showed that the hydronephrosis was disappeared in 20 ureters and significantly decreased in 3 ureters. The success rate was 95.7% at a mean follow-up of 16.3±4.0(10-23)months. Conclusion RAUR is a safe and feasible option for the treatment of POM in children with higher success rate and lower complication rate.

Objective: To explore urinary NAG, Cr, MA, α1-MG andβ2-MG as the early renal damage index in children hydronephrosis. Methods: The clinical data of 206 patients in the Bayi Children′s Hospital Affiliated to the Seventh Medical Center of Chinese PLA General Hospital from May 2018 to January 2019 were analyzed retrospectively. Among them, 152 children with hydronephrosis were set as observation group, 54 children without hydronephrosis were set as control group. In the observation group, the age ranged from 1 month to 18 years old, and the median age was 2 years old. There were 123 cases of hydronephrosis caused by ureteropelvic junction obstruction (UPJO) and 29 cases of posterior urethral valve complicated with hydronephrosis. In the control group, the age ranged from 1 month to 15 years old, with a median age of 5 years. There were 18 hypospadias cases, 15 occult penis cases and 21 phimosis. All children with hydronephrosis underwent nuclear medicine renal dynamic imaging. Urine specimens were tested for urinary NAG, Cr, MA, α1-MG, and β2-MG. According to renal dynamic results, the observed components were the renal function injury group and the normal renal function group. The above indicators analyzed to judge the clinical value to find the early renal damage. Results: The expression levels of urinary NAG, MA, α1-MG and β2-MG in the observation group were higher than those in the control group, and the difference was statistically significant. The expression of urinary Cr and the abnormal rate were no significant difference between any two groups(P=0.647, P=0.572). The expression levels of urinary NAG, MA, α1-MG and β2-MG were not significantly different between the normal renal hydronephrosis group and the renal function impairment group (P=0.365, P=0.448, P=0.379, P=0.338). The abnormal expression rate of Urine MA and β2-MG was not statistically significant in the patients with normal renal hydronephrosis and the renal function impairment group (P=0.436, P=0.478). MA got the highest sensitivity of (58.8%), and NAG had the highest specificity of 89.3% to detect early renal demage. Four indexes combined analysis, sensitivity, negative predictive rate, diagnostic coincidence rate improved obviously. Joint analysis of posterior urethral valves combined with hydronephrosis, the abnormal rate was 89.7%(26/29). The renal dysfunction of the posterior urethral valve showed that the renal dynamics dysfunction rate was only 37.9%(11/29). Conclusions The combined analysis of urinary NAG, MA, α1-MG and β2-MG can accurately predict early renal injury. The index of early renal loss may be the early evidence to judge whether the posterior urethral valve is complicated with upper urinary tract function injury.

Objective To summarize the experience of patient positing,port placements setting and robot cart docking in pediatric robot-assisted laparoscopic upper urinary tract operations.Methods From March 2017 to December 2017,140 robot-assisted laparoscopic upper urinary tract procedures were performed in our institution,including 110 cases of pyeloplasty,15 upper pole heminephroureterectomy,12 simple nephrectomy and 3 adrenalectomy.There were 103 males and 37 females with a range age from 1 month to 18 years.The assistant surgeon was adjacent to the instrument nurse,and patients were placed in a supine position with 60°-80° inclination and keep the legs low to the body.Room setup and patient positioning were similar to the traditional laparoscopic surgery.Semi-hidden incision technique was used in 140 patients:the camera port was placed umbilicus,two additional arm ports (one 5 mm and one 8 mm) were placed under direct vision,the 8 mm arm port was placed on the line of a Pfannenstiel incision and the 5 mm arm port was placed below the Xiphoid along the midline.Finally,a 3 or 5 mm assistant port was placed approximately 3 cm lateral to the inferior arm port,the line of a Pfannenstiel incision.Results The average time was (11.5 ± 3.2) min (10.5-16.5 min) from skin incision to robot cart docking completed.All surgeries were successfully completed without open conversion.One patient required an additional assist port for severe adhesion after the previously open surgery,there was no injury to other viscera.Average operative time was (146.9 ± 48.7)min (78-259 min) and average post-operative hospitalization time was (5.7 ± 1.4) d(4-10 d),respectively.There was no visual scar on abdominal 6 weeks postoperatively,and all parents made comments about their satisfaction with the cosmetic appearance.All operations got complete success at a mean follow up of 6 (1-9) months.Conclusions A good room setup,patient positioning and the semi-hidden incision technique port placements are maintaining the safety of the patient,avoiding compression injuries,allowing maximum mobility of the robotic arms,and facilitating a smooth and efficient surgery,and improving post-operative recovery.