[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

The effectiveness of transport in a toy car for reducing preoperative anxiety in preschool children: a randomised controlled prospective trial.

BACKGROUND: This study was designed to determine whether transport of a paediatric inpatient in a children's ride-on toy car has an effect on perioperative levels of anxiety compared with transport on a hospital gurney with or without oral midazolam premedication. METHODS: In this prospective study, 108 children aged 2-5 yr with congenital heart disease and undergoing first surgical correction were randomly allocated to one of three groups: Group C (transport in a children's ride-on car), Group G (transport on a gurney without premedication), or Group M (transport on a gurney and received premedication of oral midazolam 0.5 mg kg-1). The modified Yale Preoperative Anxiety Scale-Short Form and parent-recorded anxiety VAS were applied to evaluate anxiety in the following time points: pre-anaesthesia visit (the day before surgery), upon getting in the ride-on car or on the gurney in the ward, upon arriving in the preoperative holding area, at the moment of leaving from the holding area to the operating room (OR) (coincided with separation from parents), at the time after entering the OR, and at the time just before anaesthesia induction. RESULTS: Children in Group C exhibited significantly lower levels of anxiety from the time they got into the ride-on car until the time they entered the OR, compared with the other two groups (P<0.001). The subjects in Group C had similarly low anxiety levels to those in the Group M at the time before induction (P=0.914). CONCLUSIONS: Transport in a ride-on toy car can relieve preoperative anxiety in preschool children undergoing surgery to a comparable degree as midazolam. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-17012791.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Occurrence and development of diabetic nephropathy caused by CD63 by inhibiting Wnt-ß-catenin signaling pathway.

OBJECTIVE: This study aimed to investigate the occurrence and development of diabetic nephropathy caused by CD63 by inhibiting Wnt-ß-catenin signaling pathway. PATIENTS AND METHODS: Renal tissues and normal renal tissues distant from renal lesions of patients with diabetic nephropathy treated in The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University from January 2018 to November 2018 were selected. Human renal tubular epithelial cell HKC was purchased. CD63-siRNA group, NC group, blank group, CD63-mimics, CD63-mimics+si-Wnt4, and CD63-inhibitor+sh-Wnt4 were transfected into renal tubular epithelial cell HKC; mRNA expression in the cells was detected by qRT-PCR, and the protein expression in the cells was detected by WB. CCK8 and flow cytometry were used to detect cell proliferation and apoptosis. RESULTS: CD63, Wnt4, ß-catenin, and p-GSK-3ß were highly expressed in diabetic nephropathy. Cell experiments showed that inhibiting CD63 and Wnt-ß-catenin signaling pathway could promote cell proliferation and reduce cell apoptosis, and the protein expressions of Wnt4, ß-catenin, p-GSK-3ß, and Bcl-2 were significantly reduced. Rescue experiments showed that after the co-transfection of CD63-mimics+si-Wnt4 and CD63-inhibitor+sh-Wnt4 into EC109 and EC9706, the cell proliferation and apoptosis rates were not different from those of the NC group without transfection sequence. CONCLUSIONS: CD36 can mediate cell apoptosis by inhibiting the expression of the related proteins in nodal Wnt/ß-catenin signaling pathway, and is expected to become a potential therapeutic target for clinical treatment of patients with diabetic nephropathy.

NiS2 nanoparticles anchored on open carbon nanohelmets as an advanced anode for lithium-ion batteries.

Low intrinsic conductivity and large volume expansion seriously restrict the efficient lithium storage performance of metal sulfides. Here, we fabricate a hybrid material of NiS2 nanoparticles/carbon nanohelmets (NiS2/CNHs) to address the above issues. As an anode material in lithium-ion batteries, NiS2/CNHs exhibit excellent cycling stability (490 mA h g-1 after 3000 cycles at 5 A g-1) and rate properties (412 mA h g-1 at 10 A g-1), outperforming other NiS x -based anode materials. These remarkable performances originate from the three-dimensional helmet-like integrated architecture of NiS2/CNHs, which reduces the electrode resistance due to the tight combination between NiS2 and CNHs, provides efficient diffusion paths for the electrolyte and Li+ owing to the amorphous nanoporous carbon structure, and significantly mitigates the aggregation and buffers the large volumetric expansion of NiS2 nanoparticles upon long-term cycling thanks to the open three-dimensional architecture and well-dispersed NiS2 nanoparticles on it.

[Clinical characteristics and gene expression profiles in children with ETV6-RUNX1 acute lymphoblastic leukemia].

Objective: To evaluate the heterogeneity in pediatric ETV6-RUNX1 acute lymphoblastic leukemia (ALL) by gene expression profile and to study clinical characteristics in different clusters. Methods: An improved advanced fragment analysis (iAFA) technique was developed to detect 57 marker genes in 264 pediatric ALL patients treated in Beijing Children's Hospital from August 2016 to June 2019. The 56 ALL patients with ETV6-RUNX1 positive were evaluated by clinical characteristics in gene expression profile, immunophenotype and early response of chemotherapy in different clusters. Results: The 56 ETV6-RUNX1-positive patients were clustered into 2 groups of E/R-1 (45, 80.4%) and E/R-2 (11, 19.6%) . Spearman coefficient was 0.788 and 0.901 in E/R-2 and E/R-1, respectively. The median of initial platelet counts was 104 (27-644) and 50 (8-390) (P<0.01) in E/R-2 and E/R-1, respectively. The median of proportion of initial bone marrow immature cells was 0.830 (0.270-0.975) and 0.935 (0.445-0.990) (P<0.05) in E/R-2 and E/R-1, respectively. The most specific immunophenotype at initial diagnosis, CD22(+)CD34(+)CD20(-)CD117(-)CD56(-), mainly gathered in E/R-2 (P<0.001) . Patients negative of minimal residual disease detected by flow cytometry (MRD-FCM) at day 33 were 5 (55.6%) and 32 (88.9%) in E/R-2 and E/R-1, respectively. There was no significant difference in the original analysis (P=0.064) but difference in sensitivity analysis (P=0.035) . Nevertheless, patients negative of MRD detected by polymerase chain reaction (MRD-PCR) at day 33 were 7 (77.8%) and 36 (100%) in E/R-2 and E/R-1, respectively, with significant difference (P=0.047) . Conclusion: Gene expression profile shows heterogeneous in ETV6-RUNX1 ALL, and the E/R-2 profile indicates that these patients may have a less tendency to thrombocytopenia at the initial diagnosis but have poorer response to induction chemotherapy and may influence further outcome.

Exploring factors shaping population genetic structure of the freshwater fish Sinocyclocheilus grahami (Teleostei, Cyprinidae).

Phylogeographical analyses on Sinocyclocheilus grahami samples from seven localities within the Lake Dianchi Basin in China were conducted to explore the main factors shaping population structure within this species. Phylogenetic and network analyses revealed two major clades in 24 mtDNA haplotypes. One clade included three haplotypes exclusively from samples of the lower basin and another clade encompassed other haplotypes from samples of the upper basin. The estimated divergence time between the two clades predated the river capture event connecting the lower and upper lake basin and thus supported geographical isolation as the main factor shaping genetic divergence between these two clades. Furthermore, analysis of molecular variance and pair-wise Phi(ST) distances revealed significant genetic differentiation within the upper basin. Mantel tests clearly supported patterns of differentiation arose purely as a result of isolation by distance. These results further highlight the importance of geographical isolation in shaping differentiation within this species.

[The application of cineMRI in evaluation of upper airway obstruction levels in complicated pediatric OSAS].

Objective:The aim of this study is to explore the role of cineMRI in the localization of upper airway obstruction in complicated pediatric OSAS. Method:Eleven persistent OSAS and 11 complex OSAS patients underwent cineMRI. Each patient was imaged midline sagittal and axial magnetic resonance cine image. The obtained sagittal and axial images were displayed in cine format, creating a real time "movie" of airway motion, to make a personalized treatment for each child. Polysomnography was performed to evaluate the effectiveness of cineMRI directed treatment for pediatric OSAS. Result:cineMRI could effectively define the upper airway obstruction level. There was a significant improvement in AHI (P=0.019) and saturation nadir (P<0.01). Conclusion:cineMRI is an effective method for assessing the level of airway obstruction on persistent or complex pediatric OSAS.

[The incidence and risk factors of catheter-related-thrombosis during induction chemotherapy in acute lymphocytic leukemia children].

Objective: To investigate the current status of catheter-related-thrombosis (CRT) and the risk factors of Chinese acute lymphocytic leukemia (ALL) children with peripherally inserted central catheter (PICC) . Methods: The clinical data of the 116 inpatients preliminarily diagnosed ALL in the Leukemia Ward of Beijing Children's Hospital with PICC from 1(st) March 2014 to 31(st) December 2014 were collected prospectively. Results: ①Refer to the B-ultrasound on the 15(th) day after catheterization, the incidence of CRT was 28.4% (33/116 cases) , all cases were symptom-free. ②There were no statistical differences in terms of gender, age distribution, degree, immunotype between CRT and CRT-free groups. This study revealed no statistical differences of blood routine test items, coagulation function items, co-infection and catheterization vein between the two groups. While there was significant statistical difference of catheterization side, the frequency of right catheterization was higher in CRT group[75.8% (25/33) vs 55.4% (46/83) , P=0.043]. ③On the 15(th) day after catheterization, significant statistical difference of D-Dimer between the two groups was revealed[0.18 (0.05-2.45) mg/L vs 0.11 (0.01-5.34) mg/L, P=0.001], while no statistical differences of blood routine test items and other coagulation function items. Multivariate Logistic regression analysis verified catheterization on right was a risk factor of CRT. ④During the observation, there were 3 cases of catheter-related complications other than CRT, all of which were CRI, 2 of them had CRT meanwhile. ⑤The B-ultrasound on the 33(rd) day after catheterization showed that 73.1% of the cases had reduced thrombosis, 3.8% had growth thrombosis, 23.1% had no obvious change respectively. Conclusion: CRT was a common catheter related complication among ALL children during induction chemotherapy, and CRT cases with symptoms were rare. Catheterization on right was a risk factor for CRT, and regular test of D-Dimer and B ultrasound contributed to detect CRT. Most of the CRT cases had reduced thrombosis without specific management.

Correlation of growth capacity of human tumor cells in hard agarose with their in vivo proliferative capacity at specific metastatic sites.

The purpose of this study was to determine whether the degree of anchorage-independent growth of human tumor cells in increasing concentrations of agarose correlated with the capacity of the cells to produce experimental metastases in nude mice. Human melanoma, breast carcinoma, and colon carcinoma cells from parental lines and variants selected in vivo for metastasis and in vitro cloned lines were plated into medium containing 0.3%, 0.6%, 0.9%, or 1.2% of agarose. These cells were also injected into nude mice: intravenously for melanoma, into the mammary fat pad for breast carcinoma, and into the spleen for colon carcinoma. Production of tumor cell colonies in dense agarose (greater than 0.6%) correlated with production of experimental metastases in the lung (melanoma, breast carcinoma) or liver (colon carcinoma). We conclude that the degree of anchorage-independent growth of tumor cells can predict their biological behavior and metastatic potential in vivo. Thus, this technique may be useful for the isolation of metastatic cells from heterogeneous human neoplasms.

Tumorigenicity and metastasis of human breast carcinoma cell lines in nude mice.

There are few reports describing experimental models of the growth and metastasis of human breast carcinomas. This article discusses the tumorigenic and metastatic properties of two estrogen receptor-negative breast carcinomas injected into nude mice. Tumor growth in the mammary fatpad (m.f.p.) and the subcutis was compared in female nude mice. The injection of 10(5) viable cells of two human breast carcinoma cell lines (MDA-MB-231 and MDA-MB-435) gave a 100% tumor take rate in the m.f.p., whereas only 40% of the s.c. injections produced tumors and these occurred several weeks after the appearance of the m.f.p. tumors. Thus, the m.f.p. of nude mice is a favorable site for the growth of human breast carcinomas. MDA-MB-435 tumors produced distant metastases in 80% to 100% of recipients. The most common sites for metastasis were the lymph nodes and lungs, with a lower incidence of metastases in muscle (chest wall and thigh), heart, and brain. New variant cell lines were isolated from metastases in the lungs, brain, and heart. All the cell lines were tumorigenic in the m.f.p., and the lung- and heart-derived metastasis lines produced slightly more lung metastases than the original cell line. However, the brain metastasis variant produced significantly fewer lung metastases. Intravenous inoculation of the spontaneous metastasis-derived cell lines produced few lung colonies. Only cell variants isolated from experimental lung metastases showed enhanced lung colonization potential when reinjected i.v. Our results suggest that the estrogen receptor-negative MDA-MB-435 cell line injected in the m.f.p. of nude mice could be a valuable tool for analysis of the cellular and molecular basis of the metastasis of advanced breast cancer.

Malignant potential of cells isolated from lymph node or brain metastases of melanoma patients and implications for prognosis.

We studied the correlation between the formation of brain metastasis and the malignant growth potential of seven human melanoma cell lines, isolated from lymph node metastases (A375-SM, TXM-1, DM-4) or from brain metastases (TXM-13, TXM-18, TXM-34, TXM-40), and the potential of three variants of the mouse K-1735 melanoma. Growth rates in different concentrations of fetal bovine serum and colony-forming efficiency in semisolid agarose were measured, and the tumorigenicity and metastatic ability were determined in nude mice (for the human melanoma cell lines) or in C3H/HeN mice (for the K-1735 variants). The ability to form brain metastasis was tested by injection of cells into the carotid artery. A high colony-forming efficiency in agarose, especially at concentrations of agarose greater than 0.6%, corresponded with high tumor take rates, rapid tumor growth rates, and metastatic colonization of the lungs of the recipient mice. For the human melanomas, the lymph node metastasis-derived cells were more tumorigenic and metastatic than the brain metastasis-derived cells. In the K-1735 mouse melanoma, the tumorigenic and metastatic behavior of the cells after i.v. and s.c. injection corresponded with growth in agarose cultures. However, for growth in the brain after intracarotid injection, the different melanoma cell lines showed similar frequencies of tumor take, regardless of tumorigenicity in other sites of the recipient mice, although mice given injections of brain metastasis-derived cells survived longer than mice given injections of lymph node metastasis (human melanoma) or lung metastasis (K-1735 M-2)-derived cell lines. The results from the human and mouse melanoma cell lines show that the brain metastasis-derived cell lines were not more malignant than the lymph node or lung metastasis-derived cells. These data imply that the production of brain metastasis is not always the final stage of a metastatic cascade.

Genetic mapping and DNA sequence-based analysis of deleted regions on chromosome 16 involved in progression of bladder cancer from occult preneoplastic conditions to invasive disease.

Histologic and genetic mapping with 30 hypervariable markers mapped to chromosome 16 were performed on 234 DNA samples of five cystectomy specimens from patients with invasive bladder cancer. Allelic losses of individual markers were related to microscopically identified precursor conditions in the entire bladder mucosa and invasive cancer. Their significance for the development and progression of neoplasia from in situ preneoplastic conditions to invasive disease was analysed by the nearest neighbor algorithm and binomial maximum likelihood analysis. Using this approach we identified five distinct regions of allelic losses defined by their flanking markers and predicted size as follows. p13.3(D16S418-D16S406, 1.2 cM), p13.1(D16S748-D16S287, 12.9 cM), q12 1(D16S409-D16S514, 24.0 cM), q22.1 (D16S496-D16S515, 5.4 cM), and q24 (D16S507-D16S511, 5.9 cM and D16S402-D16S413, 17.4 cM). The regions mapping to p13.1 and q24 were involved in early intraurothelial phases of bladder neoplasia such as mild to moderate dysplasia. On the other hand the deleted region mapping to p13.3 was involved in progression of severe dysplasia/carcinoma in situ to invasive bladder cancer. Testing of markers that exhibited statistically significant LOH in relation to progression of neoplasia from precursor conditions to invasive cancer on 28 tumors and voided urine samples from 25 patients with bladder cancer revealed that q12.1 showed LOH in 46.4% of tumor and 32.0% of voided urine samples. The LOH of a single marker D16S541 could be detected in approximately 28% of tumors and 20% of voided urine samples of patients with bladder cancer. These data imply that the deleted region centered around marker D16S541 spanning approximately 10 cM and flanked by D16S409 and D16S415 contains a novel putative tumor suppressor gene or genes playing an important role in the development of human bladder cancer. To facilitate more precise positional mapping and identification of pathogenetically relevant genes, we analysed of human genome contig and sequence databases spanning the deleted regions. Multiple known candidate genes and several smaller gene-rich areas mapping to the target regions of chromosome 16 were identified.

Synergy between human immunodeficiency virus type 1 and Epstein-Barr virus in T lymphoblastoid cell lines.

CR2 (CD21), the EBV receptor, was detected on three of four CD4-positive cell lines by indirect fluorescent labeling, and its corresponding mRNA was found by use of the reverse transcription-based polymerase chain reaction. To determine whether CR2 on CD4-positive cells was functional, their ability to be infected by EBV was analyzed. EBV DNA, EBV nuclear antigen 2 (EBNA-2A), and EBV-encoded small RNA (EBER1) transcripts could be detected in CR2-expressing CD4-positive cells following infection by the B95.8 strain of EBV. Analysis of the terminal region showed the EBV genome remained linear following infection, and copy number decreased with time. Since CD4-positive cell lines are targets for HIV-1 infection, the effects of EBV infection on HIV-1 expression were analyzed. HIV-1 replication was upregulated when CD4-positive cells were coinfected with EBV strain B95.8 but not P3HR-1K. These results suggested that EBNA-2 is involved in upregulation of HIV-1 expression in T lymphoblastoid cell lines. To test this hypothesis an EBNA-2-expression vector was transfected into T lymphoblastoid cell lines and HIV-1 expression measured. First, trans-activation of HIV-1 long terminal repeat (LTR) by Tat was enhanced by EBNA-2 type 1 expression. trans-Activation of the HIV-1 LTR by Tat was also enhanced when CD4-positive cells were infected by EBV (strain B95.8) encoding an intact EBNA-2, but not by P3HR-1K with a deleted EBNA-2. In addition, CD4-positive cell clones stably expressing EBNA-2 supported enhanced HIV-1 replication as measured by accumulation of reverse transcriptase activity and syncytium induction. This provides direct evidence that EBV infection can enhance HIV-1 replication in T cells. Whether this in vitro phenomenon contributes to disease progression in vivo remains to be determined.

Study of dihydrofolate reductase-thymidylate synthase in Plasmodium falciparum.

The production of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) bifunctional protein of Plasmodium falciparum was measured in the wild type, pyrimethamine sensitive strain, FCR3, and in a pyrimethamine resistant mutant, FCR3-D7, which contains a DHFR-TS gene duplication that overproduces a mutant enzyme. The DHFR-TS content in both strains began to increase significantly from the early trophozoite stage through schizogony. The DHFR-TS content in either the ring or trophozoite-schizont stage parasites remained constant for at least 9 hr in the presence of protein synthesis-inhibitory levels of cycloheximide, which suggested that the measure of enzyme accumulation was a measure of enzyme synthesis. Actinomycin D treated parasites did not accumulate DHFR-TS which suggested that the DHFR-TS mRNA had a short half-life. DHFR-TS accumulated in the presence of aphidicolin inhibition of DNA synthesis which indicated that both syntheses could be uncoupled.

Gaussian neural networks for glass bottles inspection: a learning procedure.

In glass bottle inspection, the defects detection is of first importance. For online system detection, high speed and robust detection of faults are highly required. Neural networks have recently, and successfully, been applied to fault detection in many manufacturing processes. In this study, a Gaussian neural network, an extension of the RBF network, trained through a competitive algorithm, has been chosen for fault detection. Four parameters extracted from images of the bottles are used as inputs of the network. The number of Gaussian units is adjusted by an informational criterion. Experimental results show that the performance of this network are better than classical parametric and non parametric classifiers.