[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Objective:This study aimed to compare the detection efficacy of transrectal ultrasound-guided transrectal cognitive fusion targeted+ systematic prostate biopsy and transperineal cognitive fusion targeted + systematic biopsy in patients with suspected prostate cancer (PCa). In addition, the relative clinical characteristics of PCa were evaluated.Methods:A total of 385 patients with suspected prostate cancer in the affiliated hospital of Qingdao University from May 2019 to November 2019 were retrospectively analyzed. All patients met the prostate biopsy criterion, who underwent transrectal(n=275)and transperineal(n=110)prostate biopsy respectively. There were no significant differences of mean age [(70.7±7.3)years vs.(69.2±8.4) years], PSA [(55.12±116.96)ng/ml vs. (63.41±315.34)ng/ml], prostate volume [(55.96±35.26)ml vs. (64.35±55.99)ml] between two groups. According to preoperative prostate magnetic resonance imaging combined with intraoperative ultrasound, 2-4 needles targeted puncture of suspected lesion were performed, followed by 12 needle systematic prostate biopsy. The detection rate of prostate cancer between two biopsy ways were compared. The related factors of PCa including age, prostate volume and PSA level were collected for univariable and multivariable logistic analysis. The cancer detection rate was compared and logistic regression was used to assess the impact of patient characteristics on PCa detection.Results:For all patients, the detection rate with cancer between transrectal group and transperineal group were 121/275(40.0%) and 67/110(60.9%), respectively. The transperineal group detected a higher rate of PCa ( P=0.003)and more clinically significant prostate cancers (csPCa) (54.6% vs.36.7%, P=0.001) than that of the transrectal group, there were significant differences between two groups ( P<0.05). Univariate and multivariate logistic regression analysis revealed that PSA( OR=1.025, P=0.001) and prostate volume( OR=0.984, P=0.001)were two independent factors for the detection rate of prostate cancer between two biopsy ways( P<0.05). The effect of age on the detection rate of PCa in the transperieal group was significantly lower than that of the transrectal group( OR=0.037, P=0.238 vs. OR=0.053, P=0.002). Conclusion:The transperieal biopsy could find more PCa than the transrectal biopsy. PSA level and prostate volume could affect the detection rate of cancer between two prostate biopsy ways.

Objectives:To investigate the diagnostic value of whole blood quantitative PCR for DNA load of Epstein-Barr virus (EBV) in post-transplant lymphoproliferative disease (PTLD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A total of 694 patients with hematologic diseases who underwent allo-HSCT at the Hematology Department of Peking University First Hospital from April 2004 to April 2019 were included, and their data were retrospectively analyzed.Results:①Among the 694 cases, 29 cases (22 males and 7 females, with a median age of 22 (1-52) years) developed PTLD after allo-HSCT with a cumulative incidence of 4.2% and a median onset time of 2.1 (0.8-20.6) months. ② Univariate analysis showed that age<30 years, diagnosis with aplastic anemia, human leukocyte antigen (HLA) mismatch, use of antithymocyte globulin (ATG) in preconditioning regimens, and EBV reactivation were the risk factors for the occurrence of PTLD. Multivariate analysis showed that EBV reactivation was an independent risk factor for the occurrence of PTLD. ③Further analysis of EBV reactivation cases showed that the peak value of EBV-DNA load was significantly higher in the PTLD group than that in the non-PTLD group ( P<0.001) and the incidence of PTLD increased with the increase of EBV-DNA load. Receiver operating characteristic (ROC) curve analysis indicated that PTLD was more likely to be diagnosed when the EBV-DNA load was >1.19×10 6 copies/ml (sensitivity 0.800 and specificity 0.768) . ④All patients with PTLD received rituximab-based treatment, with an overall response rate of 86.2% and an overall survival rate of 54.3%. Conclusion:The PTLD occurrence after allo-HSCT is highly correlated with EBV reactivation, and the higher the EBV-DNA load, the greater the risk of PTLD occurrence. The dynamic monitoring of EBV-DNA load plays an important role in predicting PTLD occurrence.

Objective:To study the influence of G protein-coupled estrogen receptor 1 (GPER1) specific agonist G1 and antagonist G2 in epilepsy susceptibility of temporal lobe epileptic rats.Methods:Sixty rats were randomly divided into control group, G1 treatment group and G15 treatment group ( n=20). Rats in the latter two groups were intraperitoneally injected with GPER1 agonist G1 (10 μg) or antagonist G15 (40 μg) for a consecutive 12 d. Lithium chloride pilocarpine epilepsy models were prepared in the 3 groups. The behavior manifestations of these rats were observed within 1 h of intraperitoneal injection of pilocarpine; Racine grading was used to evaluate the severity of epileptic seizures every 5 min; the latency of epileptic seizures (Racine grading IV) and epileptic seizure grading at different time points in the 3 groups were compared. The EEG monitoring was performed to these rats, and EEG data were recorded from 10 min before pilocarpine injection to 2 h after pilocarpine injection; EEG time-frequency was analyzed by Fast-Fourier transform (FFT); distribution of brain electrical energy and changes of θ and α wave energy during 20 min of epileptic status were compared among the 3 groups. Results:(1) As compared with that in the control group and G1 treatment group, the latency of epileptic seizures in the G15 treatment group was significantly shortened ( P<0.05); 15 and 20 min after pilocarpine injection, the epileptic seizure grading of rats in G1 treatment group was statistically lower than that in control group ( P<0.05); 15-35 min after pilocarpine injection, the epileptic seizure grading of rats in G15 treatment group was significantly higher than that in control group ( P<0.05). (2) As compared with those in the control group, rats in the G1 treatment group had smaller brain wave amplitude, while the rats in the G15 treatment group had earlier seizure time, larger brain wave amplitude and higher frequency. There were no obvious changes in the amount of brain electrical energy between the G1 treatment group and control group; while the amount of brain electrical energy in the G15 treatment group 2 h after pilocarpine injection was higher than that in the control group. As compared with those in the control group and G1 treatment group, the θ and α wave energy values of rats in the G15 treatment group were significantly increased within 20 min of epileptic status ( P<0.05). Conclusion:Activation level of GPER1 might be associated with susceptibility to epileptic seizures, and specific inhibition of GPER1 activation can enhance the susceptibility to epilepsy and increase the energy values of specific frequency bands during epilepsy.

Objective Promote the management and service of scientific research platforms and make sure their supporting role in hospital.Methods The demand of service object and service evaluation of scientific research platforms were obtained in Peking University People's Hospital,and the demand-oriented service mode for scientific research platforms was established and applied.Results With the implementation of this mode in hospital,the service strategies of scientific research platforms were optimized continuously,the awareness rate and service satisfaction were promoted in some extent.Conclusions This mode based on demand survey can promote the management and service of scientific research platforms in some extent and the better support and service can be provided for the sustainable development of scientific research in hospital.

Purpose To explore the relationship between epicardial adipose tissue (EAT) volume and ascending aortic stiffness by CT,so as to early evaluate the lesions of ascending aortic by measuring EAT.Materials and Methods 169 patients with suspected coronary artery disease who underwent coronary CT angiography and coronary angiography in First Affiliated Hospital of Jinzhou Medical University from January 2016 to September 2016 were enrolled.According to the presence of coronary atherosclerosis or not,the patients were divided into research group (109 cases) and control group (60 cases).The research group were further divided into slight,mild,moderate and severe group according to the Gensini score of coronary atherosclerosis.The recorded threshold of EAT volume was 107.2 cm3.The patients with EAT volume higher than 107.2 cm3 belonged to the exposure group,and the rest belonged to the non exposure group.The EAT volume and ascending aortic stiffness were measured,and the relationship between them was assessed.The relationship between EAT volume and coronary atherosclerosis was also analyzed.Results In the control group,there was no correlation between EAT volume and ascending aortic stiffness (r =-0.156,P＞0.05).However,there were negative correlations between EAT volume and ascending aortic stiffness in slight,mild,moderate and severe group (r=-0.378,-0.340,-0.514 and-0.459,P＜0.05).The EAT volumewas an independent risk factor of ascending aortic stiffness (β=-0.009,t=-2.653,P＜0.05).The incidence of CAD in the exposure group was 9.318 times of that in the non exposure group.Conclusion There is obvious correlation between EAT volume and ascending aortic stiffness in patients with CAD.The evaluation of EAT volume can provide an effective reference for the early prediction of ascending aortic lesions in patients with CAD.

Objective To explore the value of iDose4 iterative reconstruction for coronary CT angiography (CCTA).Methods Totally 124 coronary heart disease patients underwent iDose4 iterative reconstruction and filtered back projection (FBP) reconstruction,of whom,56 ones with BMI not less than 20 kg/m2 were put into No.1 iteration group using 135 kV tube voltage and 68 ones with BMI less than 20 kg/m2 were into No.2 iteration group using 110 kV tube voltage.FBP reconstruction was executed with 110 kV tube voltage.Comparison analyses were carried out on signal noise ratio (SNR),contrast to noise ratio (CNR) and image quality.Results There were significant differences between the values of SNR,radiation dose and image quality in No.1 iteration group and FBP group (P＜0.05).Statistical differences were also found between the values of CNR and radiation dose in No.2 iteration group and FBP group,while there were no obvious differences between the values of SNR and image quality in the above two groups (P＜0.05).Conclusion Low-voltage iDose reconstruction gains advantages in radiation dose and image quality during 64-slice CCTA,and thus is worthy promoting clinically.

Objective To investigate the correlation between normal ascending aortic elasticity and the left ventricular function by 256 slice iCT.Methods 105 subjects who underwent CTA and echocardiography inspection and diagnosed with normal coronary artery and without ascending aortic atherosclerosis were collected.Subjects were divided into three groups according to age and two groups according to gender respectively.Left ventricular function parameter values on CT were measured, including ESV,EDV,SV,EF,CO and MM.The aortic elasticity on CT and echocardiography was measured and calculated respectively on cross-sectional area at 15 mm above aortic valve.The relationship between ascending aortic elasticity and the left ventricular function was evaluated.Results Bland-Altman plot revealed that there was a good conformity between CT and echocardiography in measurement the value of ascending aortic elasticity(ICC=0.988,P<0.05).In different grougs of age,normal ascending aortic elasticity was positively correlated with EDV,ESV,SV,EF and negatively correlated with MM.There was no correlation with the CO.There was a negative relationship between aortic elasticity and age(r=-0.546,P<0.05)

OBJECTIVETo provide guidance for the high-dose methotrexate (HD-MTX) treatment of pediatric acute lymphoblastic leukemia (ALL), and to understand the impact of SLCO1B1c.521T>C (rs4149056) variant on methotrexate (MTX) pharmacokinetics and clinical outcome in children with ALL.

METHODEighty-two children with ALL in Division of Hematology of Wuhan Children's Hospital from January 2008 to February 2013 were enrolled. All patients were genotyped for rs4149056 single nucleotide polymorphism (SNP) into wild-type group (TT genotype) and variant group (TC/CC genotype). According to the ALL-BFM 2000 protocol, all patients received intravenous infusion of MTX every ten days at 3 to 5 g/m(2). Leucovorin rescue was performed after 36 hours of the MTX administration and its dose was adjusted according to the MTX plasma concentration at 48 hours. The concentrations of MTX and its metabolite at 24, 48 and 72 h were determined by high performance liquid chromatography with solid phase extraction. Population pharmacokinetic parameters were estimated by the NLME software. The pharmacokinetics, toxicity and leucovorin rescue was compared. The relapse rate within 5 years and event-free survival were followed up.

RESULTEighty-two pediatric patients were classified into two groups: variant group including 20 TC genotype carriers and one CC genotype carrier, wild-type group included 61 patients with TT genotype. Compared with wild-type group, plasma concentration of MTX at 48 and 72 h increased significantly [48 h: (1.00±1.41) vs.(0.34±0.17) µmol/L, t=2.131, P=0.046; 72 h: (0.31±0.26) vs.(0.08±0.04) µmol/L; t=3.995, P=0.001]. Area under the concentration time curve (AUC48-∝) of MTX significantly increased in variant group [(23.18±19.91) vs.(5.66±2.01) h·µmol/L] (t=4.025, P=0.001). Time above the MTX safety threshold (TC>0.1 µmol/L) increased significantly in variant group [(95.3±22.0) vs.(67.1±7.5) h, t=5.880, P<0.001]. Rescue dosage of leucovorin in variant group was higher than that in wild-type group [(312.7±287.8) vs.(140.6±27.5) mg/m2, t=2.614, P=0.017]. The children carrying rs4149056 C allele suffered from a higher frequency of serious adverse effect [gastrointestinal toxicity: 33% (7/21) vs. 5% (3/61);hepatic toxicity: 24% (5/21) vs. 2% (1/61)]. The difference was statistically significant (χ2=9.275, 8.289, all P<0.05). Hospital stay of variant group was significantly longer than that of wild-type [(4.95±1.43) vs. (4.05±0.22) d, t=2.881, P=0.009]. The relapse rate within 5 years of variant group and wild-type group were 9% (2/21) and 13% (8/61), respectively. There were no significant differences in the event-free survival between the two groups (χ2=0.001, P=0.971).

CONCLUSIONThe SLCO1B1 c.521T>C variant was an important determinant of MTX pharmacokinetics. An appropriate leucovorin dose raise in variant group was beneficial to reducing the serious toxicity and did not affect the long-term clinical outcome.

Alleles ; Antineoplastic Combined Chemotherapy Protocols ; Asparaginase ; Child ; Daunorubicin ; Disease-Free Survival ; Genotype ; Humans ; Leucovorin ; administration & dosage ; Methotrexate ; administration & dosage ; pharmacokinetics ; Organic Anion Transporters ; genetics ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Prednisone ; Solute Carrier Organic Anion Transporter Family Member 1b1 ; Treatment Outcome ; Vincristine