Effect of knockdown of PRDX6 on adaptive expression of bile acid transporter in HepG2 cells induced by rifampicin / 安徽医科大学学报

Objective @#To investigate the role of knockdown of peroxiredoxin-6 ( PRDX6) in injury and adaptive expression of bile acid transporter in human hepatoellular carcinomas ( HepG2 ) cells induced by rifampicin (RFP) . @*Methods @#Cells in logarithmic growth phase were uniformly inoculated in six-well plates , and HepG2 cells were transiently transfected with specific PRDX6-siRNA and control-siRNA to construct the knockdown group and control group . After 24 h of induction with 100 μmol/L RFP , Western blot and qRT-PCR were performed to detect the protein and gene expression levels of PRDX6 , multidrug resistance protein 1 (MDR1) , multidrug resist- ance-associated proteins 2 , 3 and 4 (MRP2 , MRP3 and MRP4) , and Na + /taurine taurocholate cotransporter pro- tein (NTCP) . Annexin V-FITC/PI double staining assay was used to detect the apoptosis rate of cells in each group ; CCK-8 assay was used to detect the changes of cell proliferation in each group; The relative contents of ala- nine aminotransferase ( ALT) , aspartate aminotransferase ( AST) , total bilirubin ( TBIL) , indirect bilirubin (IBIL) and total bile acid (TBA) in the supernatant of cell culture medium of each group were detected by kits .@*Results @#RFP increased the protein and gene expression levels of MRP2 , MRP3 , MRP4 , MDR1 , NTCP and PRDX6 in HepG2 cells (P < 0. 05) , while the protein and gene expression levels of MRP2 , MRP3 , MRP4 , MDR1 and NTCP decreased to different degrees after PRDX6 knockdown (P < 0. 05) . In addition , PRDX6 knockdown re- sulted in increased apoptosis rate of HepG2 cells (P < 0. 05) , decreased cell proliferation ability (P < 0. 05) , and increased levels of cell injury markers (ALT , AST , TBIL , DBIL , TBA) in cell culture supernatants (P < 0. 05) . @*Conclusion @#RFP increased the protein and gene expression of bile acid transporter and PRDX6 to increase in HepG2 cells . However , following knockdown of PRDX6 and treatment with RFP , the protein and gene expression levels of the bile acid transporter decreased and cell injury was aggravated , suggesting that PRDX6 played a protec- tive role in RFP-induced adaptive response in HepG2 cells .

Islet β cell dedifferentiation in pathogenesis of type 2 diabetes / 中国病理生理杂志

Insulin secretion by islet β cells is a fundamental component in glucose homeostasis.Chronic meta-bolic stress causes β cell dysfunction as manifested by reduced cell mass and impaired insulin secretion,which contributes to the pathogenesis of type 2 diabetes(T2D).In the last decade,it has been putatively accepted that β cell dedifferentia-tion is a key pathological mechanism for β cell failure.β cell dedifferentiation is referred as the progressive process that β cells lose their identity and dedifferentiate into non-functional endocrine progenitor-like cells.Typically,aldehyde dehy-drogenase 1 family member A3(ALDH1A3)is a marker of β cell dedifferentiation.Chronic hyperglycemia can lead to de-differentiation of mature β cells,the mechanism of which involves oxidative stress and some key factors.β cell dedifferen-tiation is reversible,therefore,to intervene this process may represent a promising approach to the restoration of β cell function.In this review,we update the recent progress in the pathophysiology of β cell dedifferentiation to provide new strategy for the prevention and treatment of T2D.

Allele frequency polymorphism of Duffy, Kidd, Diego blood group system: a study in Dongxiang ethnic group in Gansu Province / 中国输血杂志

【Objective】 To investigate the allele frequencies polymorphic distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu Province. 【Methods】 Blood samples of 100 unrelated blood donors were randomly selected from Dongxiang ethnic group in Gansu from January to December 2017. Allelic typing of Duffy, Kidd and Diego blood groups was performed by fluorescence PCR. 【Results】 The allele frequencies of Duffy, Kidd, and Diego blood group systems of Dongxiang ethnic group were 0.835 for Fy*01, 0.165 for Fy*02, 0.570 for Jk*01, 0.430 for Jk*02, 0.020 for DI*01, 0.980 for DI*02, respectively. No Fy(a-b-), Jk(a-b-), Di(a+b-) rare phenotypes were found. The antigen incompatibility rates of Fya/Fyb, Jka/Jkb, Dia/Dib of Duffy, Kidd, and Diego blood group systems were 23.76%, 37.01% and 3.84%, respectively. 【Conclusion】 The allele frequencies distribution of Duffy, Kidd and Diego blood group systems in Dongxiang ethnic group in Gansu were polymorphic and has unique ethnic distribution characteristics.

Evaluation of efficacy and safety of Sintilimab+Bevacizumab combined with PP regime in patients with advanced non-squamous non-small cell lung cancer / 中国药师

Objective To investigate the clinical efficacy and safety of the combination PP(Pemetrexed+Cisplatin)regimen of sindilizumab(Sintilimab)+bevacizumab(Bevacizumab)in advanced non-squamous non-small cell lung cancer(NSCLC)with disease progression after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors.Methods Patients with advanced non-squamous NSCLC with disease progression after receiving EGFR tyrosine kinase inhibitor treatment from January 2019 to January 2022 were retrospectively selected from The Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine.According to the different treatment modalities,patients were divided into the pemetrexed+cisplatin treatment group(Chemotherapy)group and the pemetrexed+cisplatin+si ndilizumab+bevacizumab treatment(Sintilimab+Bevacizumab)group.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and disease control rate(DCR)were compared between the two groups and the occurrence of adverse reactions was assessed.Results A total of 107 patients were enrolled in the study,53 in the Sintilimab+Bevacizumab group and 54 in the Chemotherapy group.The median PFS and median OS were significantly higher in the Sintilimab+Bevacizumab group than in the Chemotherapy group(P＜0.05).The median PFS and median OS in the Sintilimab+Bevacizumab group were significantly higher than in the Chemotherapy group.Bevacizumab group had no statistically significant difference in ORR with Chemotherapy group(P＞0.05),while DCR was significantly higher than Chemotherapy group(P＜0.05).The main adverse reactions were similar in both groups with the most common adverse events being anemia and neutrophils decrease.Conclusion Sintilimab+Bevacizumab combined with PP regimen treatment improved DCR and prolonged PFS and OS in patients with advanced non-squamous NSCLC whose disease progressed after EGFR tyrosine kinase inhibitor treatment.

Effects of knockdown of MANF on adaptive expression of bile acid transporter in HepG2 cells induced by rifampicin / 安徽医科大学学报

Objective @#To investigate the effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the adaptive expression of bile acid transporter in human hepatoellular carcinomas (HepG2) induced by rifampicin (RFP) ．@*Methods@#The control group cell line (Y07) and the knockdown group cell line (Y25) were constructed by lentiviral stable transfection technology．The Y07 and Y25 cells were treated with RFP of 200 μmol / L for 48 h， and qRT-PCR and Western blot were used to detect the protein and gene expression levels of MANF，bile salt export pump ( BSEP) ，multidrug resistance-related proteins 2 /3 /4 ( MRP2 ，MRP3 ，MRP4) ，multidrug resistance protein 1 (MDR1) ，organic solute transporter a / β ( OSTα/ β) ，organic anion transporter ( OATP2B1) ．The protein and gene expression levels of proliferating cell nuclear antigen ( PCNA) ，proliferating cell marker Ki67 were used to evaluate the proliferation of cells in each group changes in levels．Changes in the protein and gene expression levels of C / EBP homologous protein( CHOP) and cysteinyl aspartate specific proteinase-3 ( Caspase-3) were used to evaluate the apoptosis of cells in each group．The relative contents of alanine aminotransferase(ALT) ，aspartate aminotransferase(AST) ，alkaline phosphatase ( ALP) ，total bilirubin ( TBIL) ，indirect bilirubin ( IBIL) and total bile acid(TBA) in the supernatant of cell culture medium of each group were detected by kits. @*Results@#RFP could induce the protein and gene expression of MANF，BSEP ，MRP2 ，MRP3 ，MRP4 ，MDR1 ，OSTα , OSTβ , OATP2B1 in HepG2 cells (P ＜0. 05 ) ，while the protein and gene expression levels of BSEP ，MRP2 ，MRP3， MRP4，MDR1，OSTα、OSTβ、OATP2B1 decreased after MANF knockdown(P＜0. 05) ．Moreover，under the action of RFP，the protein expression of PCNA and Ki67 in the knockdown group was still higher．The protein and gene levels of CHOP and Caspase-3 significantly increased after MANF knockdown(P＜0. 05) ．The levels of the hepatic cell injury markers in the cell supernatant increased significantly(P＜0. 05) ．@*Conclusion @#RFP can induce the expression of bile acid transporter such as BSEP，MRP2，MRP3，MRP4，MDR1，OSTα , OSTβ and OATP2B1 to increase in HepG2 cells(P＜0. 05) ，but the expression of bile acid transporter of HepG2 after MANF knockdown will significantly decrease under the induction of rifampicin(P＜0. 05) ，and cell indury is aggravated，indicating that MANF plays a protective role in RFP-induced adaptive responses by regulating the bile acid transporter.

Clinical observation of ticagrelor combined with Compound xueshuantong capsule in the treatment of unstable angina pectoris / 中国药房

OBJECTIVE To observe the efficacy and safety of ticagrelor combined with Compound xueshuantong capsules in the treatment of unstable angina pectoris. METHODS Totally 120 patients with unstable angina pectoris with deficiency of Qi and Yin combined admitted to Sanmenxia Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were randomly divided into clopidogrel group （group A）， ticagrelor group （group B） and combined medication group （group C）， with 40 patients in each group. In addition to conventional treatment， group A was given clopidogrel orally； group B was given ticagrelor orally； group C was given ticagrelor and Compound xueshuantong capsule orally. After 12 weeks of treatment， the clinical efficacy， frequency of angina attacks， coagulation function indicators， cardiac function indicators， traditional Chinese medicine syndrome efficacy， and the incidence of adverse cardiovascular events and bleeding incidence were evaluated in the 3 groups. RESULTS The total effective rates of group A， group B and group C were 77.5%， 85.0% and 90.0%， respectively. The incidence of adverse cardiovascular events and bleeding events were 7.5%， 7.5% and 5.0% in the respective groups， with no statistically significant difference （P＞0.05）. The frequency of angina attacks， duration of angina attacks and duration of dyspnea were significantly reduced or shortened in all 3 groups after treatment compared to before treatment （P＜0.05）. The frequency of angina attacks in group C was significantly lower than that in groups A and B after treatment （P＜0.05）. The levels of fibrinogen （FBG） and D-dimer in all 3 groups were significantly lower after treatment compared to before treatment （P＜0.05）； group A had significantly higher levels of FBG and D-dimer compared to group B and C （P＜0.05）. The left ventricular end-diastolic diameter and left ventricular end-systolic diameter in all three groups were significantly shorter after treatment， and the left ventricular ejection fraction was significantly higher compared to before treatment （P＜0.05）， but there were no statistically significant differences among those groups （P＞0.05）. The total effective rates of traditional Chinese medicine syndrome efficacy in groups A， B and C were 67.5%， 80.0% and 87.5%， respectively， with group C being significantly higher than group A （P＜0.05）. CONCLUSIONS In addition to conventional treatment， ticagrelor combined with Compound xueguantong capsules can more significantly reduce the frequency of angina attacks in patients with unstable angina pectoris， reduce the levels of FBG and D- dimer， improve traditional Chinese medicine syndrome efficacy， and do not increase the risk of bleeding.

Experience in the treatment of urethral injuries due to old pelvic fractures in girls / 中华泌尿外科杂志

Objective:To discuss the treatment methods for old pelvic fractures and urethral injuries in young girls.Methods:We retrospectively analyzed the clinical data of 10 girls, mean age of(8.5±4.3)years with old pelvic fractures and urethral injuries treated with different surgical methods in our hospital from April 2015 to April 2023. 7 cases were complicated with urethrovaginal fistula, 1 case was complicated with vesicovaginal fistula; 5 patients had distal urethral atresia or stenosis; 5 cases complicated with vaginal stenosis or partial atresia. One case underwent repair of urethrovaginal fistula via transpertoineal approach, two cases underwent urethral anastomosis (end to end anastomosis) via transpubic approach, one case underwent repair of urethrovaginal fistula and bladder neck urethral anastomosis via transpubic approach, four cases underwent urethroplasty repair of urethrovaginal fistula and bladder neck reconstruction surgery, one underwent urethroplasty and bladder neck reconstruction surgery via transpubic approach, one underwent augmented enterocystoplasty and continent urinary diversion by using the appendix. Observe the urination condition after operation (Urinary incontinence is defined as the use of more than 1 piece of urine pad per day, good urination is defined as the use of ≤ 1 piece of urine pad per day, and dysuria is defined as the complaint of laborious urination, and the maximum urine flow rate is less than 10 ml/s).Results:All surgeries were successfully completed without complications such as wound infection or tissue necrosis.The postoperative follow-up time was (52.0±26.2) months. 2 cases achieved good continence and no dysuria.Postoperative complications occurred in 7 cases, of which 2 cases had dysuria due to urethral stricture and improved after urethral dilatation; 5 cases of urethrovaginal fistula recurred, of which 3 cases had undergone rerepair surgery, and 2 of them achieved good urinary control without dysuria. One case with enterocystoplasty and contiunent urinary diversion recovered well after surgery.Conclusions:The management of old pelvic fractures and urethral injuries in girls is complicated, with a high rate of postoperative complications. It is necessary to choose appropriate treatment methods based on age, severity of the lesion, and urethral and vaginal conditions.

Elevated phosphorylated ubiquitin level elicits neuro-degeneration by aggregating the decline of ubiquitin-dependent proteasomal degradation / 中国药理学与毒理学杂志

OBJECTIVE To determine the roles of phosphorylated ubiquitin(pUb)on ubiquitin-dependent proteasomal(UPS)degradation activity,and the roles of pUb on neurodegeneration.METHODS We use PTEN induced kinase 1(PINK1)to phosphorylate ubiquitin.The Ub/S65A cannot be phosphorylated by PINK1,and was used to antagonize the roles of pUb.The Ub/S65E was used to mimic the roles of pUb.The roles of pUb on UPS degradation activity were determined by immunoflu-orescence,Western blot and TIRF microscope at cellular and protein level.The roles of pUb on neurodegeneration were determined by behavior tests,immunofluorescence,Golgi staining,TEM,Western blot and proteomics sacle in mouse.RESULTS The level of soluble PINK1(sPINK1)and pUb increased in the neurons of aged mouse brain,and in the cells upon the administration of MG132,a proteasome inhibitor.The elevation of sPINK1 and pUb was accompanied by protein aggregation upon aging or the proteasomal inhibition.The pink1 knockout alleviated proteasomal inhibition induced protein aggregation and association of ubiquitinated proteins with proteasome.The over-expression of sPINK1 increased pUb level in hippocampal neuron,which chronically induced protein aggregation,mitochondrial damage and damage the structure of neuronal spines.Such neuronal injury lead to cognitive impairment of mice.The roles of sPINK1 was reversed by co-expression with Ub/S65A,and was mimic by over-expression with Ub/S65E.CONCLUSION The phosphorylation of ubiquitin aggravates UPS degrada-tion,and accelerates neuronal degeneration upon the decline of proteasomal degradation in aging and age-related neuronal diseases.

Failed pyeloplasty in children: our experience and clinical characteristics / 中华泌尿外科杂志

Objective:To summarize the clinical characteristics、diagnosis and treatment experience of children with reobstruction after pyeloplasty.Methods:A retrospective analysis was conducted on patients admitted to the Department of Urology, Beijing Children's Hospital from January 2015 to April 2022. Due to the unrelieved hydronephroplasty after the primary pyeloplasty, the anterior and posterior diameter of the pelvis was larger than that before the primary operation. Intravenous pyelography and diuretic renal radionuclide scanning confirmed the diagnosis of ureteropelvic reobstruction. Or underwent reoperation after undergoing puncture angiography for reobstruction. Fifty-four children were included in the study, 47 males (87.03%) and 7 females (12.96%), with a median age of 51.67(21.30, 117.24)month, and, 38 cases (70.37%) on the left side and 16 cases (29.63%) on the right side. The primary operation was open pyeloplasty (POP) in 20 cases and laparoscopic pyeloplasty (PLP) in 34 cases. 45 patients underwent primary operation in our hospital, and 9 patients were referred from other hospitals after primary operation. The interval between reoperation and initial operation was 7.25(6.15, 15.40)month. There were 28 cases with clinical symptoms before operation, and 26 cases without symptoms but reobstruction on imaging. 21 cases presented with recurrent abdominal pain, nausea and vomiting, and 7 cases presented with recurrent fever and urinary tract infection. All 54 patients underwent re-pyeloplasty after definite diagnosis of re-obstruction. In order to further study the feasibility of RLP, patients in the two groups were divided into RLP and ROP groups according to different surgical procedures. In the RLP group, there were 8 males (72.72%) and 3 females (27.28%). The median age was 82.21(49.83, 114.05) months, and obstruction was located on the left side in 8 cases (72.72%) and the right side in 3 cases (27.28%). There were 3 cases (27.28%) with POP and 8 cases (72.72%) with PLP. The time between the second operation and the primary operation was 12.83 (6.34, 16.86) months. APD before operation was 5.18 (4.25, 6.14) cm. There were 43 cases in the ROP group, including 38 males (88.37%) and 5 females (12.63%). The median age was 52.32 (26.62, 77.35) months; Obstruction was located on the left side in 31 cases (72.09%) and the right side in 12 cases (27.91%). The primary operation was performed in 19 cases (44.19%) with POP and 24 cases (55.81%) with PLP. The time between the second operation and the primary operation was 10.02 (8.03, 15.51) months. Preoperative APD was 5.42 (5.14, 5.90) cm. The causes of obstruction were found in the second operation: there were 28 causes (51.85%) of scar hyperplastic anastomotic stenosis, 7 cases (12.96%) of residual ectopic vascular compression, 8 cases (14.81%) of high ureteral anastomosis, 7 cases (12.96%) of ureteral adhesion distortion, and 4 cases (7.41%) of other causes (1 case of medical glue shell compression, 1 case of luminal polypoid hyperplasia, and 2 cases of complete luminal occlusion). Operation time, postoperative complications, APD, APD improvement rate (PI-APD), renal parenchyma thickness (PT), anteroposterior pelvis diameter/renal parenchyma thickness (APD/PT) at 3 and 6 months after operation were compared between RLP and ROP groups.Results:In this study, 54 patients were followed up with an average follow-up time of (34.41±20.20)month. APD of 3 months after pyeloplasty was 3.29(3.03, 3.52) cm, which was statistically significant compared with 5.45(5.13, 5.77)cm before pyeloplasty ( P=0.02). APD/PT changed from preoperative 21.71(21.08, 31.77)to 5.40(4.79, 6.79)3 months after surgery, and the difference was statistically significant ( P=0.03). The APD improvement rate was 37%(33%, 42%) 3 months after surgery and 49%(44%, 54%) 6 months after surgery. Among the 54 patients, 3 had lumbago and fever after clamping the nephrostomy tube, and 3(5.55%) had sinus angiography indicating that obstruction still existed and required reoperation. Therefore, the success rate of repyeloplasty in this group was 94.45%. Comparing RLP group and ROP group, operation time in RLP group was longer than that in ROP group [169.13(113.45, 210.66)]min vs. 106.83(103.14, 155.32)min, P=0.02]. The length of hospitalization in RLP group was shorter than that in ROP group [7.45(5.62, 9.28)d vs.11.64(10.45, 15.66)d, P=0.03], and the difference was statistically significant. The improvement rate of APD 3 months after surgery was compared between the two groups [30.48%(19.81%, 41.16%) vs.39.96%(35.16%, 47.76%), P=0.15], and the improvement rate of APD 6 months after surgery was compared between the two groups [48.00%(27.19%, 48.81%) vs.52.27%(46.95%, 56.76%), P=0.05], there was no significant difference in the success rate of operation between the two groups (90.90% vs. 95.34%, P=0.63). Conclusions:The common cause of reobstruction after pyeloplasty is cicatricial adhesion stenosis. The operation is challenging, but repyeloplasty can effectively relieve the obstruction and the overall success rate is 94.45%. RLP is a safe and effective surgical method for the treatment of reobstruction, which can achieve comparable surgical results with ROP.

Effects of individualized treatment of contralateral patent processus vaginalis during laparoscopic high ligation of processus vaginalis / 现代泌尿外科杂志

【Objective】 To explore the rational management of contralateral patent processus vaginalis (CPPV) in laparoscopic high ligation of processus vaginalis. 【Methods】 A total of 300 children with unilateral oblique inguinal hernia/hydrocele who received laparoscopic high ligation of processus vaginalis in Baoding Children’s Hospital during Jun.2018 and Jun.2022 were selected and divided into two groups by random number table method, with 150 in either group. In the control group, 53 cases of CPPV were found intraoperatively, which were treated simultaneously. In the study group, 58 cases of CPPV were detected, among which 11 met the indications of high ligation and received simultaneous surgical treatment. The incidence of recurrence was compared between the two groups. 【Results】 After 1 year of follow-up, the recurrence rate was 8.62% in the study group and 1.88% in the control group (P>0.05). The detection rate of CPPV was 23.02% in children with unilateral inguinal hernia, significantly lower than that in children with unilateral hydrocele (49.07%, P<0.001). The detection rate of CPPV was 42.71% in children with left patent processus vaginalis and 32.95% in children with right patent processus vaginalis (P=0.19). The detection rate of CPPV was 62.93% in the age group of 1-2 years, significantly higher than that in other age groups (P<0.001). 【Conclusion】 The incidence of CPPV conversion into oblique inguinal hernia or hydrocele is low. Only children who meet the indications can be treated at the same time during surgery.

Diagnosis and treatment of nephroblastoma with WAGR syndrome / 中华泌尿外科杂志

Objective:To discuss the diagnosis and treatment 0f WAGR syndrome.Methods:The clinical data of 10 cases of WAGR syndrome children admitted to our hospital from January 2008 to November 2019 were respectively analyzed including the clinical features, diagnosis, and surgical treatments. There were 6 males and 4 females, aged from 13 to 36 months, with an average of 23.6 months. 9 cases were diagnosed as iris absence due to ocular abnormalities in infancy, and 1 case was diagnosed as iris absence due to ocular abnormalities by physical examination because of renal mass. There were 2 boys with cryptorchidism, and 2 boys with hypospadias, 1 of which did not received operation because of mild hypospadias, and another undergoing surgery. There were no abnormality of genitourinary system in the remaining 5 cases. There were 7 cases of unilateral nephroblastoma, with 1 case at the left and 6 cases at the right, and there were 3 cases of bilateral nephroblastoma. Abdominal doppler ultrasound and enhanced abdominal CT were performed for all patients. Abdominal doppler ultrasound indicated solid mass in renal parenchyma or non-uniform echo zone. Abdominal enhanced CT indicated renal tumor with diameter of 1.8 cm-12.7 cm and locally non-uniform enhanced echo. Among the 7 cases of unilateral nephroblastoma, 4 underwent nephrectomy, 1 underwent tumor enucleation, and 2 underwent tumor enucleation for unilateral tumor complicated with nephrogenic rests. There were 3 cases of bilateral nephroblastoma, 2 cases undergoing unilateral tumor enucleation firstly and contralateral tumor enucleation following chemotherapy. One case underwent unilateral tumor nephrectomy followed by contralateral tumor enucleation. One case of unilateral nephrogenic rests did not undergo renal tumor surgery. Preoperative chemotherapy was performed in 7 patients, including 3 bilateral nephroblastoma, 1 unilateral nephroblastoma combined with contralateral nephroblastoma, and 3 unilateral tumors larger enough to pass the midline. The chemotherapy regimen was VCR+ ACTD in 5 cases, VCR+ ACTD+ CTX+ DOX/CDDP+ VP16 and VCR+ CTX+ DOX in another 2 cases respectively.Results:All 10 cases were diagnosed as nephroblastoma. There were 3 patients without preoperative chemotherapy which belongs to COG stageⅠ(1 case) and STAGEⅢ(2 cases); Preoperative chemotherapy was performed in 2 patients with SIOP stage Ⅱ, 2 patients with SIOP stage Ⅲ, and 3 patients with SIOP stageⅤ. Nine children received regular chemotherapy after surgery, among which 1 child in stage Ⅰ received DD4A chemotherapy regimens, 2 children in stage Ⅱ received DD4A and EE4A regimen respectively, and 3 of the 4 children in stage Ⅲ received regular chemotherapy after surgery, including EE4A(1 case)and DD4A(2 cases). EE4A(1 case)and DD4A(2 cases) chemotherapy were performed in 3 patients with stage Ⅴ according to their unilateral tumor stage. Ten cases were followed up, with 9 of the 10 cases having no tumor recurrence or metastasis, and death in 1 case. At present, abdominal doppler ultrasound of 1 child with nephrogenic rests showed no obvious progress. The renal function of 9 children was not significantly abnormal during the regular follow-up. The results of intelligence screening showed that 6 of the 10 patients were significantly behind their peers, and 4 had no obvious abnormality compared with their peers. Gene tests were performed 3 times after surgery, and the results showed the deletion of 11p13 and adjacent distal genes.Conclusions:WAGR syndrome is rare in clinical practice, and renal ultrasound should be monitored after diagnosis to detect renal tumors in early stage. For bilateral cases, renal function should be preserved as long as possible in order to reduce the probability of renal failure. Long-term follow-up of nephroblastoma with this syndrome is particularly important.

Correlation between the mean platelet volume and testicular viability in children with testicular torsion / 中华实用儿科临床杂志

Objective:To investigate the correlation between hematological parameters and testicular viability, and to identify potential indicators of intraoperative testicular viability or postoperative testicular atrophy.Methods:Clinical data of 173 children with testicular torsion treated by emergency operation in the Department of Urology, Beijing Children′s Hospital, Capital Medical University from January 2006 to January 2020 were retrospectively analyzed.According to the surgical methods, 90 and 83 cases were included in the orchiectomy group and orchiopexy group, respectively.The duration of onset, spermatic cord torsion degree and hematological parameters of the 2 groups were compared by the independent-samples t test, χ2 test and Mann- Whitney U test.Risk factors for testicular resection were analyzed by multivariate Logistic regression.In addition, 30 children in the orchiopexy group were followed up for bilateral scrotal ultrasound at 6 months postoperatively.They were sub-grouped into testicular atrophy group (13 cases, 43.3%) and non-atrophy group (17 cases). Differences between 2 subgroups were compared by the independent-samples t test and Mann- Whitney U test.Receiver operating characteristic (ROC) curves were plotted to analyze the prognostic potentials of indexes with significant differences in children with the duration of onset of >6-<51 h. Results:Duration of onset (9.3 h vs.51.0 h)( Z=-8.293, P<0.001), spermatic cord torsion degree (360.0° vs. 540.0°)( Z=-5.267, P<0.001), mean platelet volume (MPV) (9.8 fL vs.10.1 fL)( Z=-2.018, P=0.044) and age (147.5 months vs. 143.0 months)( Z=-2.165, P=0.030) were significantly different between the orchiopexy group and the orchiectomy group.The multivariate Logistic regression analysis suggested that the duration of onset ( OR=1.033, P<0.001), spermatic cord torsion degree ( OR=1.004, P<0.001) and MPV ( OR=1.662, P=0.044) were positively correlated with testicular resection.For patients with the duration of onset of >6-<51 h, the area under the curve (AUC) of duration of onset, spermatic cord torsion degree and MPV was 0.753, 0.755 and 0.629, respectively.MPV was significantly different in the postoperative testicular atrophy group and the non-atrophy group [(10.2±0.5) fL vs.(9.8±0.5) fL]( t=2.426, P=0.022). The ROC curve analysis showed that the cut-off value of MPV for predicting testicular atrophy was 9.9 fL, and its sensitivity and specificity were 83.3% and 70.6%, respectively, the AUC was 0.752. Conclusions:The duration of onset, spermatic cord torsion degree and MPV can be used as predictors of intraoperative testicular viability, which are helpful for clinicians to predict and judge the testicular necrosis caused by testicular torsion before operation.In addition, 43.3% of children with testicular torsion eventually developed testicular atrophy after orchiopexy, and only MPV may be used as a predictor of postoperative testicular atrophy.

Effect of cellular immunotherapy combined with chemotherapy on apoptosis-related genes and immune function in patients with non-small cell lung cancer / 中国基层医药

Objective:To investigate the effect of immunotherapy with dendritic cells and cytokine-induced killer cells combined with chemotherapy on apoptosis-related genes and immune function in patients with middle- and advanced-stage non-small cell lung cancer.Methods:A total of 100 patients with middle- and advanced-stage non-small cell lung cancer who received treatment in Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, China from February 2018 to May 2019 were included in this study. They were randomly divided into control and observation groups ( n = 50/group). The two groups were given chemotherapy with pemetrexed and cisplatin. The observation group was given immunotherapy with dendritic cells and cytokine-induced killer cells based on chemotherapy with pemetrexed and cisplatin. Changes in apoptosis-related genes [primary autosomal recessive microcephaly gene (MCPH1), ataxia-telangiectasia mutated (ATM), ataxia telangiectasia mutated and Rad3 related (ATR), transcription factor 21 (TCF21)] and immune function were monitored. Clinical efficacy of immunotherapy with dendritic cells and cytokine-induced killer cells combined with chemotherapy with pemetrexed and cisplatin in the treatment middle-and advanced-stage non-small cell lung cancer was assessed. Results:After treatment, expression of MCPH1, ATM, ATR and TCF21 in the observation group was 301.11 ± 41.12, 239.98 ± 30.15, 270.01 ± 36.01, 270.01 ± 34.02, respectively, which was significantly higher than that in the control group [101.32 ± 15.32, 103.00 ± 13.97, 101.12 ± 14.90, 100.20 ± 14.99, t = 32.194, 29.149, 30.644, 32.299, all P < 0.001]. The proportion of the number of Th1-positive cells in the number of CD +4 T cells in the observation group was significantly higher than that in the control group [(29.00 ± 3.41)% vs. (22.61 ± 3.22)%, t = 9.634, P < 0.001]. The proportion of the number of Th17-,Th2 and CD +4CD +25Treg-positive cells in the number of CD +4 T cells in the observation group were (0.89 ± 0.10)%, (12.01 ± 1.36)%, (11.02 ± 1.92)%, respectively, which were significantly lower than those in the control group [(1.70 ± 0.20)%, (17.61 ± 2.20)%, (18.70 ± 2.40%)%, t = 25.614, 15.310, 17.670, all P < 0.001]. Total effective rate in the observation group was significantly higher than that in the control group [52.0% (26/50) vs. 30.0% (15/50), χ2 = 5.002, P < 0.05]. Conclusion:Immunotherapy with dendritic cells and cytokine-induced killer cells combined with chemotherapy with pemetrexed and cisplatin can induce apoptosis and regulate immune function. The combined therapy exhibits better clinical efficacy in the treatment of non-small cell lung than chemotherapy alone.

Effect of surgical treatment of solitary kidney with ureteropelvic junction obstruction / 中华实用儿科临床杂志

Objective:To investigate the effect of timing of surgical treatment on renal function of children with solitary kidney and ureteropelvic junction obstruction (UPJO).Methods:The clinical data of patients with solitary kidney and UPJO admitted to Beijing Children′s Hospital, Capital Medical University and Shunyi Women′s and Children′s Hospital of Beijing Children′s Hospital from January 2006 to January 2018 were retrospectively analyzed.A total of 23 cases were enrolled, including 16 males and 7 females.The age of first visit ranged from 1 day to 15 years and 8 months (average: 2 years and 2 months). All the patients were conservatively treated for an average of 2 years and 9 months.SPSS 20.0 software was used for data analysis.Results:All patients received Anderson-Hynes pyeloplasty(A-H operation), and the age at operation ranged from 10 months to 16 years and 4 months, with an average of 4 years and 11 months.There were only 2 cases under 1 year old (10 months old and 11 months old, respectively). The double J stent was retained for 2 months after operation, and intravenous pyelography(IVP) was reexamined at 3 months after operation.The results showed that hydronephrosis either had no obvious change or was alleviated in different degrees.In 3 cases, IVP remained undetected for 40 minutes before operation.After operation, IVP was detected at 10-20 minutes.The follow-up period ranged from 1 year and 1 month to 10 years, with an average of 3 years and 9 months.Urinary ultrasound showed that the degree of pyeloplasty was less severe than that before operation.Conclusions:Close follow-up visits and conservative treatment of solitary kidney with UPJO are safe after 6 months.The first choice of operation is pyeloplasty.

Impact of caudal regional anesthesia on complications after hypospadias repair with tubularised incised plate urethroplasty / 中华实用儿科临床杂志

Objective:To assess the impact of caudal regional anesthesia on complications after hypospadias repair with tubularised incised plate urethroplasty (TIP).Methods:A total of 125 cases with hypospadias undergoing TIP surgery from June 2017 to June 2019 at Beijing Children′s Hospital, Capital Medical University, were reviewed, aged 12-75 months, American Society of Anesthesiologists Ⅰ orⅡ grade.Totally, 86 cases had distal and 39 cases suffered from proximal hypospadias.Caudal anesthetics were used in 42 cases (caudal anesthesia group) and general anesthetics were used in 83 cases (general anesthesia group). All cases were repaired by TIP procedure.The children with urethral fistula and urethral stricture were followed up for 6 months, and multivariate statistical analyses were performed.Results:There were 11 cases of urethral fistula after hypospadias surgery, with 8 cases (9.64%)in the general anesthesia group and 3 cases (7.14%) in the caudal anesthesia group.There were no significant differences between the 2 groups ( χ2=0.223, P=0.636), and 12 cases of urethral stricture, with 8 cases(9.64%) in the general anesthesia group and 4 cases(9.52%) in the caudal anesthesia group.There were no significant differences between the 2 groups ( χ2=0.001, P=0.984). Based on multivariable Logistic regression, urethral fistula was associated with proximal hypospadias ( OR=0.036, 95% CI: 0.003-0.511, P=0.014), and the width of glans( OR=0.469, 95% CI: 0.220-0.998, P=0.049). Urethral stricture was correlated with proximal hypospadias( OR=0.004, 95% CI: 0.000-0.146, P=0.002), the width of urethral plate( OR=0.004, 95% CI: 0.000-0.422, P=0.020), and the duration of catheter( OR=72.976, 95% CI: 1.802-2 594.790, P=0.023). Conclusion:Caudal regional anesthesia appears to have no impacts on urethral fistula and stricture after hypospadias repair.

Efficacy observation of recombinant human granulocyte macrophage stimulating factor combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To observe the clinical efficacy and safety of recombinant human granulocyte macrophage stimulating factor (rhGM-CSF) combined with R-CHOP regimen in treatment of diffuse large B-cell lymphoma (DLBCL).Methods:The clinical data of 39 patients with newly diagnosed DLBCL treated with rhGM-CSF combined with R-CHOP regimen, and 39 patients with newly diagnosed DLBCL treated with R-CHOP regimen in Naval Medical University (Changhai Hospital) from February 2017 to November 2019 were retrospectively analyzed. The total response rate (ORR), remission rate (CR) rate, overall survival (OS), progression-free survival (PFS) and adverse reactions of both groups were compared.Results:In rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group, ORR was 87.2% (34/39) and 82.1% (32/39), respectively, and the difference was statistically significant ( χ2 = 0.394, P = 0.53); CR rate was 71.8% (28/39) and 56.4% (22/39), respectively, and the difference was statistically significant ( χ2 = 2.006, P = 0.157). Until the last follow up on September 19, 2020, 32 patients survived and 7 patients died in rhGM-CSF combined with R-CHOP regimen group, of which 1 case died of bowel cancer, and the primary disease was still in CR. In the R-CHOP regimen group, 32 survived and 7 died. The 2-year OS rates of the two groups were 82.5% and 73.9%, respectively ( χ2 = 0.038, P = 0.845); the 2-year PFS rates of the two groups were 67.1% and 55.2%, respectively ( χ2 = 0.457, P = 0.499). Subgroup analysis results showed that there were no statistically significant differences in CR rates among germinal center B-cell (GCB) and non-GCB subgroups, Lugano stage Ⅰ-Ⅱ and Lugano stage Ⅲ-Ⅳ subgroups, aged <60 years and aged ≥60 years subgroups in rhGM-CSF combined with R-CHOP regimen group and R-CHOP regimen group (all P > 0.05). The major adverse reactions included bone marrow suppression and its inducible infections. There were no significant differences in the incidence of grade 3-4 hematological adverse reactions and infections between the two groups (all P > 0.05). All patients safely went through bone marrow suppression after support treatments without treatment-related deaths. Conclusions:rhGM-CSF combined with R-CHOP regimen is safe and effective in treatment of newly diagnosed DLBCL.

Gardenoside alleviates diabetic cardiomyopathy via inhibiting VPO1/ERK1/2 signaling pathway to improve myocardial apoptosis in rats / 中国临床药理学与治疗学

AIM: To investigate the effect of geniposide (GE) on diabetic cardiomyopathy and its mechanism. METHODS: Twenty-four adult male SD rats were randomly divided into three groups: Control group (n=8), DCM group (n=8) and DCM+ GE group (n=8). The diabetic cardiomyopathy model was established by high fat diet combined with streptozotocin (STZ), and H9C2 injury model was induced by hypochlorite (HOCl). After 12 weeks of intervention, the histopathological changes of heart were observed by HE and Masson staining, the level of cardiomyocyte apoptosis was detected by TUNEL staining, and the expression levels of VPO1/ERK1/2 signal pathway and apoptosis-related proteins were detected by immunohistochemistry and Western blot. The changes of ERK1/2, p-ERK1/2, Bcl-2 and Bax protein expression in cardiomyocytes were detected by Western blot after HOCl stimulation. After administration of ERK1/2 inhibitor U0126, the protein expression levels of ERK1/2, p-ERK1/2, Bcl-2 and Bax were detected again by Western blot assay. RESULTS: Compared with the control group, the arrangement of myocardial fibers was disordered and the content of myocardial collagen was significantly increased in DCM group by HE and Masson staining, while the myocardial injury was significantly improved in DCM+GE group (P<0.05). Compared with the control group, the apoptotic rates of cardiomyocytes and the ratio of Bax/Bcl-2 in DCM group were remarkably increased, while the myocardial apoptosis in DCM+GE group was significantly improved (P<0.05). The results of immunohistochemistry and Western blot showed that the expression of VPO1 and p-ERK1/2 was increased in DCM group, while the expression level of VPO1 and p-ERK1/2 was inhibited in DCM+GE group (P<0.05). When H9C2 cells were stimulated with HOCl, the expression of p-ERK1/2 and the ratio of Bax/Bcl-2 were both increased as compared with the control group, while the expression level of p-ERK1/2 and the ratio of Bax/Bcl-2 were decreased after the addition of ERK1/2 inhibitor U0126 (P<0.05). CONCLUSION: Geniposide alleviates the diabete-induced myocardial injury by suppressing cardiomyocyte apoptosis via inhibiting VPO1/ERK1/2 signal pathway.

Expression of miR-1182 in ovarian cancer and its effect on tumor cell proliferation and metastasis / 国际生物医学工程杂志

Objective:To investigate the expression of miR-1182 in ovarian cancer tissues and its effect on tumor cell proliferation and metastasis.Methods:Reverse transcription polymerase chain amplification (RT-PCR) technology was used to detect the expression level of miR-1182 in normal ovarian tissue, ovarian cancer and corresponding adjacent tissues. The human ovarian cancer cell line SKOV-3 was transfected with miR-1182 mimics virus, and the expression levels of miR-1182 and hTERT protein were detected by RT-PCR and Western Blot respectively. The thiazolyl method was used to detect the proliferation and invasion of the transfected SKOV-3 cells.Results:The expression level of miR-1182 in ovarian cancer tissue was significantly lower than that in normal ovarian tissue and adjacent tissues (all P<0.05). Regarding the expression level of miR-1182, the difference between patients with different tumor stages and degree of tissue differentiation was statistically significant (all P<0.05), but the difference between patient age and tumor type was not statistically significant (all P>0.05). Compared with the blank virus group and the control group, the miR-1182 expression level of the transfected group was significantly increased (all P<0.05), while the expression of hTERT protein was significantly decreased (all P<0.05). The proliferation and migration ability of SKOV-3 cells in the transfected group was significantly inhibited at 24, 48, and 72 h after transfection (all P<0.05). Conclusions:The expression of miR-1182 is low in ovarian cancer tissues. Overexpression of miR-1182 can inhibit the proliferation and invasion of ovarian cancer, and the mechanism may be related to the targeted regulation of hTERT expression to achieve regulation.

Research progress of miRNA in ovarian cancer / 国际生物医学工程杂志

Ovarian cancer is one of the most common gynecological malignancies leading to female deaths, and its early diagnosis and prevention are very complicated. Therefore, biomarkers for this disease prediction and prognosis are urgently needed for early diagnosis and individualized treatment. miRNAs are short-chain, highly conserved non-coding RNA molecules that mainly degrade or inhibit target genes at the post-transcriptional level to regulate cell growth, proliferation, differentiation, metabolism, and apoptosis. Existing studies have confirmed that miRNAs can be used as potential biomarkers for clinical diagnosis and treatment of cancer. Moreover, tumor-related miRNAs play an important role in the occurrence, invasion and metastasis of ovarian cancer by regulating the expression of multiple oncogenes and tumor suppressor genes. In this paper, the roles of miRNAs as biomarkers for early prevention or detection of ovarian cancer, prognostic diagnosis and treatment targets were reviewed, and the future clinical application of miRNA in patients with ovarian cancer was proposed.

A summary of single center diagnosis and treatment experience of extracranial malignant germ cell tumor in children / 中华实用儿科临床杂志

Objective:To summarize the clinical features, therapeutic effects and prognostic factors of children with extracranial malignant germ cell tumor (MGCT), and further to improve the recognition of this disease.Methods:The clinical information and therapeutic effects of children patients diagnosed with MGCT and treated in Hematology-Oncology Center in Beijing Children′s Hospital, Capital Medical University from January 2008 to December 2018 were analyzed retrospectively, and the risk factors affecting the prognosis were discussed.Results:A total of 35 patients were collected in this study, including 19 girls and 16 boys, with a median age of 71 months.Forty-two point four percent (14/33 cases) of them were <3 year-old, and 39.3% (13/33 cases) of them were >6 year-old.The primary tumors were located at the gonad in 9 cases (6 cases in the ovary and 3 cases in the testis), and extragonadal sites in 26 cases (8 cases in the pelvic cavity, 8 cases in the mediastinum, and 10 cases in the sacrococcygeal region). Five cases were in stage Ⅱ, 16 cases in stage Ⅲ, and 14 cases in stage Ⅳ.Eleven cases were at intermediate risk, and 24 cases were at high risk.All children were followed up for (25.43±4.82) months, and given standard treatment of surgery plus chemotherapy.The 2-year overall survival (OS) rate and event-free survival (EFS) rate were 87.4% and 67.1%, respectively.The 2-year OS rate and EFS rate in patients at stage Ⅱ and Ⅲ (93.8% and 80.4%, respectively) were significantly higher than those at stage Ⅳ (66.7% and 45.1%, respectively) ( χ2=0.649, 0.739; P=0.021, 0.037). The 2-year EFS rate in patients with and without distant metastasis at the early stage of the disease was 43.8% and 86.9%, respectively, and the differences were significant ( χ2=0.694, P=0.028). The complete remission (CR) rates of intermediate-risk and high-risk children with tumor completely resected at the early stage of the disease were 100.0% (8/8 cases) and 71.4% (5/7 cases), respectively.The CR rate of patients who received 2-4 cycles of chemotherapy and had complete tumor resection after diagnosis by puncture was 72.7% (8/11 cases), and 40.0% (2/5 cases) of the children with incomplete resection got tumor progression.For eight patients with events, their alpha-fetoprotein (AFP) levels decreased slowly at the early stage of the disease and increased significantly as the disease progressed. Conclusions:The onset-age of MGCT is mainly <3 year-old and >6 year-old.The stan-dard treatment that combines surgery and chemotherapy can achieve a good overall prognosis.Incomplete surgical resection and a slow decline of AFP during treatment contribute to adverse prognosis.The outcomes of patients with tumor progression can be improved by increasing chemotherapy courses, secondary surgery and autologous stem cell transplantation.