Background::Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods::In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results::Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy ( P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10 9/L (range 18-219) among patients who received rhTPO and 73 × 10 9/L (range 42-197) among those who received GCSF alone ( P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10 9/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10 9/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups ( P=0.362 and P=0.067, respectively). Conclusions::Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration::This trial has been registered in Clinicaltrials.gov as NCT03014102.

Background::Chemotherapy plus granulocyte colony-stimulating factor (GCSF) regimen is one of the available approaches to mobilize peripheral blood progenitor cells (PBPCs). It causes thrombocytopenia and delays leukapheresis. This study aimed to evaluate the role of recombinant human thrombopoietin (rhTPO) before mobilization chemotherapy in facilitating leukapheresis in patients with lymphoma.Methods::In this randomized open-label phase 2 trial, patients were randomly assigned in a 1:2 ratio to receive mobilization with rhTPO plus GCSF in combination with chemotherapy (the rhTPO plus GCSF arm) or GCSF alone in combination with chemotherapy (the GCSF alone arm). The recovery of neutrophils and platelets and the amount of platelet transfusion were monitored.Results::Thirty patients were enrolled in this study between March 2016 and August 2018. Patients in the rhTPO plus GCSF arm (n = 10) had similar platelet nadir after mobilization chemotherapy ( P=0.878) and similar amount of platelet transfusion (median 0 vs. 1 unit, P=0.735) when compared with the GCSF alone arm (n = 20). On the day of leukapheresis, the median platelet count was 86 × 10 9/L (range 18-219) among patients who received rhTPO and 73 × 10 9/L (range 42-197) among those who received GCSF alone ( P=0.982). After the use of rhTPO, the incidence of platelet count <75 × 10 9/L on the day of leukapheresis did not decrease significantly (30.0% vs. 50.0%, P=0.297). Platelet recovery after PBPC transfusion was more rapid in the rhTPO plus GCSF arm (median 8.0 days [95% confidence interval 2.9-13.1] to platelets ≥50 × 10 9/L vs. 11.0 days [95% confidence interval 8.6-13.4], P=0.011). The estimated total cost of the mobilization and reconstitution phases per patient was similar between the two treatmtent groups ( P=0.362 and P=0.067, respectively). Conclusions::Our findings indicate that there was no significant clinical benefit of rhTPO use in facilitating mobilization of progenitor cells, but it may promote platelet recovery in the reconstitution phase after high-dose therapy.Trial registration::This trial has been registered in Clinicaltrials.gov as NCT03014102.

Objective To explore the choice of handling methods for bilateral internal ring during the transumbilical single-site laparoscopic orchiopexy for cryptorchidism with bilateral processus vaginalis unclosed in children,and evaluate the clinical effect.Methods Retrospective analysis was conducted for the clinical data of 102 children with cryptorchidism and bilateral processus vaginalis unclosed who were hospitalized at Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2011 to January 2016.They were divided into the observation group (55 cases) and the control group(47 cases).In the observation group,the internal rings of the affected side were destroyed and stitched with a needle between the edge of arcuate of musculus trasversus abdominis and fascia trans versalis of posterior peritoneum.If the diameter of opposite internal ring was less than 0.5 cm,only a circle was destroyed.Otherwise,a circle was destroyed and sutured with a needle.In the control group,the processing methods for orchiopexy and affected side internal ring were same as the observation group.Purse string suture was done for opposite internal rings of all cases in the control group.The parameters of operative duration,intraoperative blood loss,postoperative hospital stay,postoperative complications were compared between 2 groups.Results All operations were successful in both groups,spermatic cords were reserved and testicles were in scrotum of all cases.Operative duration was significantly shorter in the observation group than that in the control group [(42.02 ± 3.21) min vs.(48.43 ± 4.18) min,t =-8.739,P ＜ 0.01].The differences in intraoperative blood loss,postoperative hospital stay and postoperative complications between 2 groups were not statistically significant[(4.38 ± 1.42) mL vs.(4.80 ± 1.37) mL,t =-1.533,P ＞0.05;(2.87 ±0.64) dvs.(2.98 ±0.61) d,t =-0.853,P ＞0.05;1.8％ (1/55 cases) vs.2.1％(1/47 cases),x2 =0.013,P ＞ 0.05].During a mean follow-up of 30(12-72) months,there was no case of testicular ascent or atrophy,or hernia,or hydrocele.Conclusions The transumbilical single-site 3-port laparoscopic orchiopexy for cryptorchidism has stable efficacy.The improved method for bilateral internal ring is simple and has satisfactory effect,which is worthy of clinical promotion.

Objective To evaluate the clinical effect of treatment for high intra-abdominal cryptorchidism of children with transumbilical single-site and multichannel laparoscopic single stage Fowler-Stephens (F-S) orchiopexy.Methods The case records of the intra-abdominal cryptorchidism of children who had undergone transumbilical single-site laparoscopic single stage F-S orchiopexy were reviewed retrospectively in Children's Hospital Affiliated to Capital Institute of Pediatrics between January 2011 and January 2017,were assigned as the observation group,whose age ranged from 1 to 8 years and average age was 18 months,with 22 unilateral and 8 bilateral,38 testis in total.A total of 31 children with intra-abdominal cryptorchidism who had undergone laparoscopic two stage F-S orchiopexy were assigned as the control group,whose age was from 11 months to 9 years and average age was 20 months,with 23 unilateral and 8 bilateral,39 testis in total.Postoperative follow-ups were conducted with the evaluation index included the testical position,with or without atrophy.The procedure effect and postoperative complications were observed,and the difference between two operation methods was evaluated.Results Operations in all cases were successful in both groups without intraoperative complication.A total of 38 testis were operated with single stage F-S orchiopexy in the observation group,and 39 testis were operated with two stage F-S orchiopexy in the control group.Postoperative complications included scrotum wound infection one case and scrotum hematoma in one case in the observation group,and abdominal wall emphysema in one case,intestinal obstruction in one case as well as umbilicus infection 1 case in control group.Follow-ups ranged from 6 months to 6 years,median 24 months.All testicals were within the scrotum,and each group had 1 case of testical atrophy.The difference of postoperative complication and effect between two groups had no statistical significance(x2 =0.184,0.107,all P ＞ 0.05).Conclusions Outcomes between single stage and two stage F-S orchiopexy are similar.The transumbilical single-site laparoscopic F-S orchiopexy not only has the satisfactory effect,but also saves some patients from reoperation and secondary anaesthesia,but doctors must be aware of the indications and contraindications of this procedure should be brought to attention.

Objective To explore treatment scheme and surgery for hypospadias with small glans.Methods Between January 2014 and January 2017,40 cases of hypospadias with small glans were enrolled in the study including 13 cases with penile hypospadias and 27 cases with penoscrotal hypospadias.The boys's average age was 1.5 years,aged from 1 to 5 years old.The boys whoes glans width less than 10 mm received the treatment of topical testosterone propionate smeared on penis once a day for 1 or 2 months.The patients received operation when their glans width reached 10 mm to 14 mm.Among of 27 cases of severe penile recurvation patients,17 cases received staging operation,one-stage was correction of penile recurvation and two-stage was Tubularized incised plate with pull-through procedure,10 cases received adopted modified Duplay combined with Duckett operation,then overturn split-skin graft for incision in the urethra located in glans penis.Among of 13 cases with mild and moderate recurvation,after penile correction,3 cases received Tubularized incised plate urethroplasty and 10 cases received Onlay island flap urethroplasty.All of the patients received modified plastic surgery for glans.Results All of patients were followed-up,from 3 months to 3 years.The surgical success rate was 70％ (28/40).12 cases got operative complications,including urinary fistula 6 cases and glans dehiscence 1 case,who were cured by reoperation,external orifice stricture 1 case and urethral stricture 4 cases who were healed by Urethra dilatation.All patients acquired good appearance glans and satisfied void stream.Conclusions Topical use testosterone propionate for hypospadias with small glans helps the growth of penis.Individualized diagnosis and treatment plan should be made for the particular case of hypospadias with small glans.The modified plastic surgery of glans is suitable for hypospadias with small glans,which could improve surgery success rate and reduce the postoperative complication.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.

Objective The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair ( MMR) function on the tumorigenesis of colorectal cancer. Methods The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 ( hRad9) gene in these samples were detected by reverse transcriptase?polymerase chain reaction ( RT?PCR) and sequencing. The plasmid of pFLAG?hRad9 ( L101M ) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9?deleted mouse cells ( mRad9-/- cells) . The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. Results Mutation from Leu to Met at the residue 101 ( L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9-/-+L101M cells ( mRad9?deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0± 5. 6)%, which was significantly lower than that in the mRad9-/-+ hRad9 cells [ mRad9?deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N?nitroso?N?methylurea (MNU) treatment, the survival rate of mRad9-/-+L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9-/-+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post?translational modification in mRad9-/- cells also led to a reduced MMR activity. Conclusion Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.

Objective To assess the feasibility and efficacy of renal pelvis drainage and ureteral stent of laparoscopic pyeloplasty in treatment of ureteropelvic junction obstruction.Methods Eighteen patients(14 boys and 4girls) with ureteropelvic junction obstruction,the average patient age was 66 months (range 3-182 months),who underwent transabdominal laparoscopic Anderson-Hynes pyeloplasty in Capital Institute of Pediatrics from Aug.2011 to Oct.2012 were selected.The ureteral stent and renal pelvis drainage were installed during the performance of surgery.They were removed in 7 days and 9 days after operation respectively.Results Eighteen cases successfully underwent laparoscopic pyeloplasty,without conversion to open surgery.The mean operating time was 102.8 minutes (ranging between 90 and 150 minutes).Two cases had complications on postoperative day 3,one patients ureteral stent was inadver-tentely pulled out,another was removed because of blood clots.No patient had postoperative urinary leakage or anastomotic stenosis.Postoperative follow-up time was 6 months.The hydronephrosis vanished in 13 patients,reduced obvious ly in 5 patients as revealed by ultrasound examination.Conclusions Intraoperatively,renal pelvis drainage and ureteral stent for postoperative drainage is effective,and it is worthy of application in a large scale.Patients can avoid further anesthesia for removing stents and the complications of long-term indwelling stent tubes,and have an improved quality of life.

The Rad1 gene is evolutionarily conserved from yeast to human. The fission yeast Schizosaccharomyces pombe Rad1 ortholog promotes cell survival against DNA damage and is required for G(2)/M checkpoint activation. In this study, mouse embryonic stem (ES) cells with a targeted deletion of Mrad1, the mouse ortholog of this gene, were created to evaluate its function in mammalian cells. Mrad1 (-/-) ES cells were highly sensitive to ultraviolet-light (UV light), hydroxyurea (HU) and gamma rays, and were defective in G(2)/M as well as S/M checkpoints. These data indicate that Mrad1 is required for repairing DNA lesions induced by UV-light, HU and gamma rays, and for mediating G(2)/M and S/M checkpoint controls. We further demonstrated that Mrad1 plays an important role in homologous recombination repair (HRR) in ES cells, but a minor HRR role in differentiated mouse cells.
Animals ; Cell Division ; Cell Proliferation ; DNA Damage ; DNA Repair ; Embryonic Stem Cells ; metabolism ; Exonucleases ; genetics ; metabolism ; physiology ; G2 Phase ; Gamma Rays ; Gene Deletion ; Hydroxyurea ; pharmacology ; Mice ; Ultraviolet Rays

Objective To establish a stable and repeatable experimental partial bladder outlet obstruction(p-BOO)rat model and to figure out the impaction of p-BOO on detrusor biomechanical properties.Methods P-BOO animal model was established by partialligation of the bladder neck of male Wistar rats,a urethra stricture by laying a trochar outside of bladder neck.The rats were divided into sham-operation group,P-BOO 6 weeks group(P-B006W)and P～BOO 12 weeks group(PBOO12W)by time.Cystomety was performed in P-BOO6W and the rats were divided into detrusor instability group(DI)and destrusor stability group(DS)on the basis of destrusor stability.The active contraction of detrusor muscle stripes to Carbachol was recorded with tensile foree transducer.The compliance and maximum volume of bladder,bladder leak point pressure were examined by filling cystometry.Results The bladders of P-BOO animal model demonstrated typical post obstruction alterations after P-BOO.The maximum volume increased significantly in DI group(10.8±3.0)ml,DS group(10.3±1.9)ml and P-B0012W group(9.5±2.3)ml as compared with that in sham-operation group(2.1±0.3)ml(P＜0.05).The bladder leak point pressures were significantly higher in DI group(39.4±7.1)cm H2O,DS group(35.9±6.2)cmH2O and P-B0012W group(48.6±9.5)cm H2O as compared with that in sham-operation group(16.2±2.1)cm H2O(P＜0.05).The bladder compliances were significantly higher in 13I group(0.27±0.08)ml/cm H2O,DS group(0.29±0.05)ml/cm H2O and P-BOO12W group(0.21±0.05)ml/cm H2O as compared with that in sham-operationgroup(0.13±0.03)ml/cm H20(P＜0.05).The detrusor contractile force of DI group was significantly lower than that in the sham-operation group and DS group(P＜0.05).No definite contraction wave was detected in the detrusor muscle of P-BOO12W group(amplitude＜0.05g).Conclusions There are 2 different types of the detrusor contraction after P-BOO:DI group with impaired contraction and conversely DS group with compensatory contraction.The contractility of detrusor muscle will be damaged and even irreversible contractile function incapacitation will occur if the obstruction is not removed.The effect of bladder stability tO bladder compliance is inconspicuous and there is close correlation between bladder compliance and bladder capacity.