Objective:To evaluate the clinical efficacy and safety of Blinatumomab on the treatment of refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R BCP-ALL) in children.Methods:Clinical data of children with R/R BCP-ALL treated with Blinatumomab in the Department of Hematology, Children′s Hospital of Soochow University, from August 2021 to June 2022 were retrospectively analyzed.Children were divided into<45 kg group and ≥45 kg group according to their weight at admission.They were treated with different dosages of Blinatumomab, and bone marrow remission was assessed at about 15 days.Clinical indicators and adverse events during the treatment period were recorded.The rank sum test of two independent samples were used to compare the differences between groups.The Fisher′ s test was used for comparing categorical variables. Results:Among the 16 children with R/R BCP-ALL, 12 cases (75%) achieved complete response (CR) and minimal residual lesion (MRD) turned negative at about 14 days.Among them, 5 out of 9 children with bone marrow primitive naive cell ratio≥0.5 achieved CR, and 7/7 children with bone marrow primitive naive cell ratio<0.5 achieved CR.The peak value of interleukin-6 (IL-6) in children with CR was significantly higher than those without CR ( Z=2.50, P=0.012). Twelve cases achieved CR on bone marrow assessment around day 15, and 3 cases who did not achieve CR remained in remission on day 28, with an efficacy prediction accuracy of 93.8%(15/16). Adverse events included fever, neutropenia, hypokalemia, abnormal liver function, hypocalcemia, edema, rash, hypertension, myocardial damage, abdominal pain, hypotension, and cytokine release syndrome, which were all grade 1.Neurotoxicity and death were not reported. Conclusions:The remission rate of R/R BCP-ALL in children treated with Blinatumomab was high, especially in patients with a low tumor load.The toxicity and adverse events of Blinatumomab treatment are minor and controllable.Day 15 is the optimal time point to evaluate the efficacy of Blinatumomab on children with R/R BCP-ALL, and a higher IL-6 peak can be served as a predictor of its efficacy.

Objective:This work aims to explore the application value of cervical exfoliated cell DNA (Cysteine dioxygenase type 1, CDO1 and CUGBP Elav-like family member 4, CELF4) methylation in the detection of endometrial cancer in women of childbearing age. Methods:From November 2021 to October 2022, a prospective study was conducted on a total number of 517 reproductive-age women with abnormal uterine bleeding who had surgical indications for hysteroscopy at the Xiangya Third Hospital of Central South University. The cervical exfoliated cells were collected for cytology, HPV (human papillomavirus) and gene methylation detection before operation. Clinical information of patients, level of tumor-related biomarkers, and endometrial thickness of transvaginal ultrasound (TVS) were also collected. Single factor regression method was used to analyze the high-risk factors of endometrial cancer. Receiver operating characteristic curve analysis was used to obtain the area under the curve(AUC), focusing on the screening efficacy of gene methylation test for endometrial cancer in women of childbearing age.Results:The age, body mass index (BMI)≥25 kg/m 2, endometrial thickness≥11 mm, CDO1 m ΔCt≤8.4, CELF4 m ΔCt≤8.8, and double gene methylation were associated with endometrial cancer in women of childbearing age, 1.16(1.08-1.25), 4.33(1.89-10.31), 9.49(3.88-26.69), 69.62(25.70-224.36), 23.64(9.66-63.99), 87.39(24.83-555.05), all P<0.05. The AUC was 0.90 (95% CI 0.83-0.97) of CDO1 m/ CELF4 m in diagnosing endometrial carcinoma was higher than others factors, with sensitivity and specificity of 91.7% (95% CI 80.6%-100%) and 88.8% (95% CI 86.0%-91.6%). TVS combined with DNA methylation detection further improved the sensitivity to 95.8% (95% CI 87.8%-100%), but could not improve the specificity 68.0% (95% CI 63.8%-72.1%). Conclusions:For women of childbearing age with abnormal uterine bleeding or abnormal vaginal discharge, the accuracy of cervical cytology DNA methyl detection of endometrial cancer is better than other non-invasive clinical programs. DNA methylation combined with TVS can improve the sensitivity of detection.

Background and Objectives: Although human-induced pluripotent stem cells (hiPSC) can be efficiently differentiated into cardiomyocytes (CMs), the heterogeneity of the hiPSC-CMs hampers their applications in research and regenerative medicine. Retinoic acid (RA)-mediated signaling pathway has been proved indispensable in cardiac development and differentiation of hiPSC toward atrial CMs. This study was aimed to test whether RA signaling pathway can be manipulated to direct the differentiation into sinoatrial node (SAN) CMs. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, RA signaling pathway was manipulated during the differentiation of hiPSC-CMs on day 5 post-differentiation, a crucial time point equivalent to the transition from cardiac mesoderm to cardiac progenitor cells in cardiac development. The resultant CMs were characterized at mRNA, protein and electrophysiology levels by a combination of qPCR, immunofluorescence, flow cytometry, and whole-cell patch clamp. The results showed that activation of the RA signaling pathway biased the differentiation of atrial CMs, whereas inhibition of the signaling pathway biased the differentiation of sinoatrial node-like cells (SANLCs). Conclusions Our study not only provides a novel and simple strategy to enrich SANLCs but also improves our under-standing of the importance of RA signaling in the differentiation of hiPSC-CMs.

Objective:To explore the predictive value of preoperative prognostic nutritional index(PNI) and systemic immune-inflammation index(SII) for local tumor stage in bladder cancer after radical cystectomy(RC).Methods:This study is a retrospective study, collecting information on 195 patients with bladder cancer who underwent RC at the Second Hospital of Tianjin Medical University from April 2011 to October 2019. Extract the patient’s preoperative laboratory examination and calculate the PNI and SII. The calculation formula was PNI=albumin (g/L)+ 5×total lymphocyte count (10 9/L); SII=platelets×neutrophils/lymphocytes . Univariate and multivariate Cox regression analysis were used to analyze whether PNI and SII can be used as predictors of muscular invasive bladder cancer(MIBC) and non-muscular invasive bladder cancer(NMIBC). Continuous variables were expressed as mean±standard deviation ( Mean± SD), and t-test was used for comparison between groups; Chi-square test was used for comparison of categorical variables between groups. Generate receiver operating characteristic curve (ROC), calculate area under the curve (AUC) to judge the predictive ability of PNI and SII scoring indicators. The larger of AUC, the stronger the predictive ability. Univariate and multivariate Cox regression analysis were used to calculate the corresponding odds ratio ( OR) and 95% CI. Results:All patients were males, with a mean age of (67.94±8.97) years. Mean serum albumin was (42.13±4.28) g/L, mean PNI was 51.29±6.09 and mean SII was 661.67±506.22. Univariate Cox regression analysis showed that both PNI and SII had statistical significance for the incidence of MIBC; multivariate Cox regression analysis showed that PNI and SII could not be used as the diagnosis of MIBC and NMIBC. PNI was an independent risk factor for predicting tumor stage (pT<3a and pT≥3a).Conclusion:The low preoperative PNI can be used as an independent factor for predicting poor pathological stage (pT≥3a).

Objective: : To explore the correlation between the polymorphism of histone deacetylase 9 gene (rs1060499865, rs723296, rs957960) and ischemic stroke (IS) in Chinese Han population in Dali region. Methods: : This study included 155 IS patients and 128 healthy physical examinees. TaqMan-polymerase chain reaction technology and multivariate logistic regression were performed. Results: : In the case group, there was no polymorphism of rs1060499865 observed in the two groups; whereas on the rs723296 locus the frequencies of C allele and TC genotype were significantly higher than that in the control group, alleles C and T were associated with a 2.158-fold increase in IS risk, and genotypes TC and TT were associated with a 2.269-fold increase in IS risk. The locus rs957960 exhibited no significant difference between the two groups. Conclusion : An association between rs723296 and the risk of IS was found in the Chinese Han population in Dali region. No significant association was found between rs1060499865, rs957960 and IS in the Chinese Han population in Dali region.

Background and Objectives: Manipulating different signaling pathways via small molecules could efficiently inducecardiomyocytes from human induced pluripotent stem cells (hiPSC). However, the effect of transcription factors on the hiPSC-directed cardiomyocytes differentiation remains unclear. Transcription factor, p53 has been demonstrated indispensable for the early embryonic development and mesendodermal differentiation of embryonic stem cells (ESC).We tested the hypothesis that p53 promotes cardiomyocytes differentiation from human hiPSC. Methods: and Results: Using the well-characterized GiWi protocol that cardiomyocytes are generated from hiPSC via temporal modulation of Wnt signaling pathway by small molecules, we demonstrated that forced expression of p53 in hiPSC remarkably improved the differentiation efficiency of cardiomyocytes from hiPSC, whereas knockdown endogenous p53 decreased the yield of cardiomyocytes. This p53-mediated increased cardiomyocyte differentiation was mediated through WNT3, as evidenced by that overexpression of p53 upregulated the expression of WNT3, and knockdown of p53 decreased the WNT3 expression. Mechanistic analysis showed that the increased cardiomyocyte differentiation partially depended on the amplified mesendodermal specification resulted from p53-mediated activation of WNT3-mediated Wnt signaling. Consistently, endogenous WNT3 knockdown significantly ameliorated mesendodermal specification and subsequent cardiomyocyte differentiation. Conclusions These results provide a novel insight into the potential effect of p53 on the development and differentiation of cardiomyocyte during embryogenesis.

Objective:To evaluate the effect of gonadotropin-releasing hormone antagonist (GnRH-A) protocol on in vitro fertilization-embryo transfer (IVF-ET) in patients with diminished ovarian reserve (DOR). Methods:A retrospective cohort study was performed to analyze the clinical data of the DOR patients who received IVF-ET treatment for the first time at the Northwest Women's and Children's Hospital Reproductive Center during January 2015 to December 2016. They were divided into a GnRH-A protocol group and an gonadotropin-releasing hormone agonist (GnRH-a) short protocol group according to different ovulation induction protocols. The general conditions, clinical and laboratory indicators, and pregnancy outcomes of the two groups were compared.Results:There was no statistically significant difference in live birth rate, clinical pregnancy rate and implantation rate between the two groups ( P>0.05). The dosage of gonadotropin (Gn) used in GnRH-A protocol group [(3 082.04±1 004.40) IU] was less than that in GnRH-a short protocol group [(3 510.05±1 119.09) IU], P<0.001], the duration of Gn used [(9.66±2.13) d] was shorter than that in GnRH-a short protocol group [(10.63±2.27) d, P<0.001], the number of eggs (4.54±2.97) was less than that in GnRH-a short protocol group (5.54±3.54, P<0.001). Conclusion:DOR patients using GnRH-A protocol for hyperovulation therapy have similar outcomes to GnRH-a short protocol pregnancy, with less Gn used dosage and shorter Gn used duration. Therefore, the GnRH-A protocol is also one of the suitable ovulation induction for DOR patients.

Objective:To evaluate the effect of gonadotropin-releasing hormone antagonist (GnRH-A) protocol on in vitro fertilization-embryo transfer (IVF-ET) in patients with diminished ovarian reserve (DOR). Methods:A retrospective cohort study was performed to analyze the clinical data of the DOR patients who received IVF-ET treatment for the first time at the Northwest Women's and Children's Hospital Reproductive Center during January 2015 to December 2016. They were divided into a GnRH-A protocol group and an gonadotropin-releasing hormone agonist (GnRH-a) short protocol group according to different ovulation induction protocols. The general conditions, clinical and laboratory indicators, and pregnancy outcomes of the two groups were compared.Results:There was no statistically significant difference in live birth rate, clinical pregnancy rate and implantation rate between the two groups ( P>0.05). The dosage of gonadotropin (Gn) used in GnRH-A protocol group [(3 082.04±1 004.40) IU] was less than that in GnRH-a short protocol group [(3 510.05±1 119.09) IU], P<0.001], the duration of Gn used [(9.66±2.13) d] was shorter than that in GnRH-a short protocol group [(10.63±2.27) d, P<0.001], the number of eggs (4.54±2.97) was less than that in GnRH-a short protocol group (5.54±3.54, P<0.001). Conclusion:DOR patients using GnRH-A protocol for hyperovulation therapy have similar outcomes to GnRH-a short protocol pregnancy, with less Gn used dosage and shorter Gn used duration. Therefore, the GnRH-A protocol is also one of the suitable ovulation induction for DOR patients.

Objective To investigate the clinical features, diagnosis, treatment and prognosis of myelodysplastic syndromes (MDS) with mature plasmacytoid dendritic cells (PDC) proliferation. Methods The clinical data of one case of MDS with excess blasts (EB)﹣1 with mature PDC proliferation in Air Force Medical Center was retrospectively analyzed, and the literature was reviewed. Results The patient′s physical examination revealed anemia and thrombocytopenia. Bone marrow smears showed 0.064 of myeloblasts and 0.152 of dendritic cells. Immunophenotyping showed two groups of abnormal proliferation cells, namely, myeloblasts and mature PDC. Decitabine treatment was given, and the red blood cells and platelets were infused intermittently. The condition of patient was basically stable. Conclusions MDS with mature PDC proliferation is extremely rare. No special clinical manifestations are found, and the diagnosis is based on bone marrow cytology and immunophenotyping. There is no standard regimen for treatment of MDS with mature PDC proliferation, and the prognosis depends on the progression of MDS.

Objective To improve the diagnostic accuracy of pediatric mesenchymal hamartoma of liver(M HL)by analyzing and summarizing the CT findings.Methods Five pediatric patients with M HL confirmed by postoperative pathology were enrolled,all patients underwent contrast-enhanced CT before operation.Results All lesions were located in the right lobe of liver.The tumor size ranged from 98 mm to 139 mm(mean size was 122 mm)in diameter.Four cases showed cystic and solid mixed masses,and one solid masses.After contrast administration,the substantial part of the mass and its septa showed enhancement while no enhancement was observed in the cystic part.No calcification was observed in the tumor.Conclusion M HL has some special CT characters.Most of M HL can be diagnosed combined with clinical practice as well as CT.