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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.
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【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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Objective:To discuss the treatment and prognosis of children with torsion of inguinal cryptorchidism.Methods:Clinical data of 15 cases of inguinal cryptorchidism with testicular torsion admitted to Beijing Children's Hospital from October 2015 to February 2019 were retrospectively analyzed. The average age of onset was 5.1 years (4 months-17 years). The clinical manifestations included inguinal swelling and pain in 13 cases, abdominal pain in 1 case and abdominal pain with vomiting in 1 case. The average duration of symptoms (up to the time of surgery) was 45.9 (5-170) h. Physical examination showed scrotal voided on affected side, groin swelling with tenderness. Lesions were found in 12 cases on the left and 3 cases on the right. Groin color Doppler ultrasound examination showed testis enlargement, uneven echo, decrease or disappearance of blood flow signal, suspected testicular torsion. Clinical diagnosis was inguinal cryptorchidism testicular torsion. Inguinal canal testicular exploration under general anesthesia. During the operation, the testicle was dark and twisted with an average torsion of 600°(180°-1 080°). Testicular activity was observed after exposure and reduction and torsion. After reduction, testicular color was immediately restored in 5 cases. After cutting open the white membrane of the testicular, there was blood outflow. In 2 cases, the testis was found to be inactive during the operation, but the parents requested to retain the testis and performed orchiopexy. 8 cases underwent orchiectomy due to necrosis of testis. The mean symptom duration (up to the time of operation) of the orchiectomy group and the orchiectomy group was 24.3 (5-73) h and 64.8 (7-170) h, respectively. The average torsion degree was 514° and 675°, respectively.Results:The average operative time of 15 patients was 56.7 min (40-85 min). Intraoperative blood loss averaged 1.5 (1-2) ml. There were no complications during and after operation. Postoperative follow-up averaged 27 (8-47) months. Among the 7 patients in the orchiopexy group, 3 patients had atrophy of testis 7.3 months after operation, and the remaining 4 patients had normal testis. In the orchiectomy group, 8 cases had normal contralateral testis without torsion.Conclusions:Inguinal cryptorchidism testicular torsion is a relatively rare disease in children. Color Doppler ultrasonography and inguinal canal exploration can help diagnosis and treatment. According to the condition of testis, orchiopexy or orchiectomy can be performed. Early diagnosis of this disease is difficult, easy to lead to testicular loss or postoperative atrophy.
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Objective@#To probe the prognostic value of consolidation chemotherapy in non-favorable acute myeloid leukemia (AML) patients who were candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) with first complete remission (CR1) and negative minimal residual disease (MRD-) .@*Methods@#A retrospective analysis was conducted on 155 patients with non-favorable AML who received allo-HSCT in CR1/MRD- from January 2010 to March 2019. The survival data were compared between patients who received and those not received pre-transplant consolidation chemotherapy.@*Results@#A total of 102 patients received pre-transplant consolidation chemotherapy (consolidation group) , and 53 cases directly proceeded to allo-HSCT when CR1/MRD- was achieved (nonconsolidation group) . The median ages were 39 (18-56) years old and 38 (19-67) years old, respectively. Five-year post-transplant overall survival [ (59.3±7.5) % vs (62.2±6.9) %, P=0.919] and relapse-free survival [ (53.0±8.9) % vs (61.6±7.0) %, P=0.936] were not significantly different between the two groups (consolidation vs nonconsolidation) . There was a weak relationship between consolidation therapy and cumulative incidence of relapse [consolidation: (21.9±5.4) % vs nonconsolidation: (18.3±6.0) %, P=0.942], as well as non-relapse mortality [consolidation: (22.4±4.3) % vs nonconsolidation: (28.4±6.5) %,P=0.464]. Multivariate analysis indicated that pre-transplant consolidation and the consolidation courses (< 2 vs ≥2 courses) did not have an impact on allo-HSCT outcomes.@*Conclusion@#Allo-HSCT for candidate patients without further consolidation when CR1/MRD- was attained was feasible.
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Objective@#To summarize the clinical characteristics, treatment response and prognostic factors of rhabdomyosarcoma (RMS) in children.@*Methods@#The clinical characteristics such as age at diagnosis, primary tumor site, tumor size, pathological type, clinical stage, and risk grouping of 213 RMS patients (140 males and 73 females) treated in Hematology Oncology Center of Beijing Children′s Hospital, Capital Medical University, from May 2006 to June 2018 were analyzed retrospectively. The clinical characteristics, overall survival (OS), event free survival (EFS) and prognostic factors of children treated with the Beijing Children′s Hospital-Rhabdomyosarcoma (BCH-RMS) regimen were analyzed. Survival data were analyzed by Kaplan-Meier survival analysis, and single factor analysis was performed by Log-Rank test.@*Results@#The diagnostic age of 213 cases was 48.0 months (ranged 3.0-187.5 months), of which 136 cases (63.8%) were younger than 10 years old. The head and neck region was the most common primary site of tumor (30%, 64 cases), followed by the genitourinary tract (26.8%, 57 cases). Among pathological subtypes, embryonal RMS accounted for 71.4% (152 cases), while alveolar RMS and anaplastic RMS accounted for only 26.8% (57 cases) and 1.9% (4 cases), respectively. According to the Intergroup Rhabdomyosarcoma Study Group (IRS), IRS-Ⅲ and Ⅳ accounted for 85.0% (181 cases) of all RMS patients. In all patients, 9.4% (20 cases) patients were divided in to low-risk group, 52.1% (111 cases) patients in to intermediate -risk group, 25.8% (55 cases) patients in to high-risk group, and 12.7% (27 cases) patients in to the central nervous system invasion group, respectively. All patients with RMS received chemotherapy. The cycles of chemotherapy were 13.5 (ranged 5.0-18.0) for patients without event occurrence, while 14.2 (ranged 3.0-30.0) for patients with event occurrence. Among the 213 patients, 200 patients had surgical operation, of whom 103 patients underwent surgery before chemotherapy and 97 patients at the end of chemotherapy, 21 patients had secondary surgical resection. Radiotherapy was performed in 114 patients. The follow-up time was 23.0 months (ranged 0.5-151.0 months) . There were 98 patients with relapsed or progressed disease and 67 patients with death. The median time to progression was 10 months, of which 67 (68.4%) relapse occurred within 1 year and no recurrence occurred after follow-up for more than 5 years. The 3-year EFS and 5-year EFS were (52±4) % and (48±4) %, while the 3-year OS and 5-year OS were (65±4) % and (64±4) % by survival analysis. The 5-year OS of the low-risk, intermediate-risk, the high-risk were 100%, (74±5) %, (48±8) %, and the 2-year OS of the central nervous system invasion group was (36±11) % (χ2=33.52, P<0.01). The 5-year EFS of the low-risk, intermediate-risk, the high-risk were (93±6) %, (51±5) %, (36±7) % and the 2-year EFS of the central nervous system invasion group was (31±10) % (χ2=24.73, P<0.01) . Survival factor analysis suggested that the OS of children was correlated with age(χ2=4.16, P=0.038), tumor TNM stage (χ2=22.02, P=0.001), IRS group (χ2=4.49, P<0.01) and the risk group (χ2=33.52, P<0.01).@*Conclusions@#This study showed that the median age of newly diagnosed RMS patients was 4 years. The head and neck and the genitourinary tract were the most common primary origin of RMS. The OS was low in single-center RMS children. The median time to recurrence was 10 months, and recurrence was rare 3 years later.
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Objective To investigate the effects of astaxanthin on the proliferation and invasion of SKOV3 human ovarian cancer cells and to explore its mechanism. Methods MTT colorimetry was used to investigate the inhibition effect of astaxanthin on SKOV3 cells. Transwell assay was used to investigate the effect of astaxanthin on the invasion of SKOV3 cells. Flow cytometry was used to investigate the cell cycle of astaxanthin on SKOV3 cells. The effect of astaxanthin on cell cycle and invasion-related protein expression was investigated by Western Blot method. Results Astaxanthin had a significant inhibitory effect on cell proliferation and was concentration dependent. The invasive ability of SKOV3 cells was significantly decreased under the treatment of astaxanthin(P<0.05). Compared with control group, the proportion of SKOV3 cells in G1 phase in the astaxanthin-treated group was significantly increased. The protein expression of matrix metallo proteinase 2(MMP-2), matrix metallo proteinase 9 (MMP-9), and cyclin-dependent protein kinase 6(CDK6) and Cyclin A were significantly decreased in astaxanthin-treated SKOV3 cells compared with the control group ( all P<0 . 05 ) . Conclusions Astaxanthin can significantly inhibit the growth of SKOV3 cells and arrest the SKOV3 cell cycle in G1 phase, and can inhibit the growth and invasion of SKOV3 by regulating cell cycle and invasion-related proteins.
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Objective@#To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) .@*Methods@#In this study we retrospectively analyzed 158 Ph+ ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy.@*Results@#Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ2=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ2=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ2=7.908, P=0.005) .@*Conclusions@#Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph+ ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.
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Objective@#To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma (RMS) in children, and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms, so as to provide evidence for guiding treatment.@*Methods@#Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS, regular treatment and follow-up at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University, and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria (NCI-CTCAE version 4.0). Summary and analysis indicators included primary and metastatic site, size, international RMS clinical stage (TNM-UICC), Intergroup Rhabdomyosarcoma Study(IRS) Clinical Grouping Classification, risk grouping, pathological type, changes in major organ functions, as well as processes of surgery, chemotherapy and radiotherapy, and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used for χ2 test.@*Results@#A total of 32 children were enrolled, and 20 cases were male and 12 cases were female, their median age was 50 months (15-120 months). The primary tumor of 9 cases were sited in the chest, abdomen and basin, 8 cases in the head and neck (non-meningeal), 7 cases in bladder prostate, 3 cases in limbs, 2 cases in the meningeal area, 1 case in urogenital tract (non-bladder prostate), 2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰ stage, 5 cases were TNM-Ⅱ stage, 10 cases TNM -Ⅲ stage, 12 cases were TNM-Ⅳ stage, 21 cases were IRS-Ⅲ, 11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk (MR), 10 cases were high-risk (HR). Twenty-two cases were detected UGT1A1*6 gene, 18 cases in GG type, 13 cases in GA type, and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children, 14 cases of CT type and 13 cases of TT type; 29 cases were detected GSTP1 gene, 7 cases of GA type and 2 cases of GG type, 19 cases of AA type, 1 case of AG type; 30 cases were detected CYP3A5 gene, 2 cases of GA type, 13 cases of GG type, AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC (Vincristine, Doxorubicin, and Cyclophosphamide) as the basis for chemotherapy.From 2017, VAC and VI regimen (Vincristine, Irinotecan) were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy, among them, 5 cases underwent twice operation.Local radiotherapy was performed on the 12th week of chemotherapy, and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia, with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases, grade 3 was 3 cases.Four patients with grade 1 diarrhea, 3 patients with grade 2, 5 patients with grade 3, 3 patients with grade 4.There was significant diffe-rence between the severity of diarrhea and UGT1A1*6 genotype polymorphism(P<0.05).@*Conclusions@#Chemothe-rapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type, the dose of chemotherapy should be reduced, and the toxicity of chemotherapy drugs should be monitored dynamically.
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Objective@#To explore the clinical and prognostic values of TP53 gene mutation in patients with acute myeloid leukemia (AML) .@*Methods@#A retrospective analysis of 265 newly diagnosed AML patients with next-generation sequencing (NGS) data in the Hematology Department of Changhai Hospital from January 2010 to January 2019 was performed. Mutation analysis was carried out by targeted sequencing technology including 200 hematological malignancy related genes. The association of TP53 mutation with clinical features was analyzed.@*Results@#Alterations in TP53 were found in 20 (7.5%) patients, including 17 case (6.4%) of missense mutations, 2 cases (0.7%) of frame-shift deletion mutations and 1 case (0.4%) of splicing sites mutation. A total of 23 kinds of TP53 mutations were detected, most of them (16, 69.6%) were located in the DNA binding domain of exon 5-8, 4 in the DNA binding domain of exon 3-4, 2 in exon 10 and 1 in splice site, respectively. The median age of patients with TP53 alterations was higher than those without [52 (26-72) years old vs 45 (14-75) years old, P= 0.008]. The frequency of complex karyotypes was higher in patients with TP53 alterations than those without [45.0% (9/20) vs 6.1% (15/245) , P<0.001]. Median overall survival (OS) of patients with TP53 alterations was shorter than those without[14.1 (95%CI 6.78-21.42) months vs 31.4 (95%CI 13.20-49.59) months, P=0.029]. The OS of patients treated with "Decitabine + CAG" was superior than that of patients treated with "3 + 7" regimen [30.0 (95%CI 27.35-38.84) months vs 12.5 (95%CI 5.80-19.19) months, P=0.018]. Multivariate analysis indicated that TP53, DNMT3A and USH2A alterations, WBC ≥ 12.45×109/L had negative impacts on OS.@*Conclusion@#The frequency of TP53 mutation was 7.5% in our cohort. Most mutations were located in the DNA binding domain. TP53 alterations were strongly associated with older age, complex karyotype and shorter OS. Decitabine-based induction chemotherapy and hematopoietic stem cell transplantation may improve OS, more cases and/or multicenter randomized studies are needed for further confirmation.