Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Objective:To discuss the effect of DEAD-box RNA helicase 39A(DDX39A)gene silencing on the proliferation,migration and invasion of the esophageal cancer TE-1 cells,and to clarify its possible mechanism.Methods:For bioinformatics analysis,GSE63941,GSE77861,GSE20347,and GSE16153 chip data were downloaded from the GEO database.The esophagel cancer-related data were selected from the TCGA Database.R software was used to analyze the differentially expressed genes.STRING Database was used to construct the protein-protein interaction(PPI)network.Identification of key genes of high relevance was achieved using the MCODE plugin in Cytoscape.The expression of key genes in normal esophageal tissue and esophageal cancer tissue were analyzed with the GEPIA 2 database.Kaplan-Meier Plotter was used to perform survived analysis and plotting for the screened key genes.Cytological experiments were carried out on esophageal cancer TE-1 cells,and small interfering RNA(siRNA)technology was used to silence the expression of DDX39A gene.The TE-1 cells in the logarithmic growth phase were selected and divided into blank(MOCK)group,negative control(si-NC)group,and silencing(si-DDX39A)group.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the expression levels of DDX39A mRNA and protein in the TE-1 cells in various groups;CCK-8 assay was conducted to detect the proliferation activity of cells in various groups,and the cell scratch assay was used to measure the migration rate of cells in various groups;Transwell chamber assay was used to detect the number of invasion cells in various groups;Western blotting method was used to detect the expression levels of β-catenin,glycogen synthase kinase-3β(GSK3β),phosphorylated glycogen synthase kinase-3β(p-GSK3β),c-MYC,Cyclin D1 and nuclear β-catenin proteins in the cells in various groups.Results:Analyses using TCGA database combined with the GEO Database yielded a total of 56 differentially expressed genes.MCODE plugin in Cytoscape software identified 41 key genes of high relevance;DDX39A was screened by analyzing 41 genes through the GEPIA 2 and Kaplan-Meier plotter Databases.The results of RT-qPCR and Western blotting methods showed that compared with si-NC group,the expression levels of DDX39A mRNA and protein in the cells in si-DDX39A group were decreased(P＜0.05).The CCK-8 results showed that the proliferation activity of the cells in si-DDX39A group was lower than that in si-NC group(P＜0.05).The cell scratch assay results showed that the cell migration rate in si-DDX39A group after 24 h was lower than that in si-NC group(P＜0.05).The results of Transwell chamber assay showed that the number of invasion cells in si-DDX39A group was lower than that in si-NC group(P＜0.05).Compared with si-NC group,the expression levels of β-catenin,p-GSK3β,c-MYC,Cyclin D1,and nuclear β-catenin in the TE-1 cells in si-DDX39A-1 group and si-DDX39A-3 group were decreased(P＜0.01),but the expression levels of GSK3β protein had no significant differences(P＞0.05).Conclusion:Silencing of DDX39A gene could inhibit the proliferation,migration and invasion of TE-1 cells,and the mechanism may be related to the regulation of Wnt/β-catenin signaling pathway.

BACKGROUND:Acellular cartilage extracellular matrix is effective in the treatment of osteoarthritis,but its efficacy is limited when applied alone.Oxymatrine alleviates interleukin-1β-induced chondrocyte apoptosis and extracellular matrix degradation.OBJECTIVE:To observe the effect of different doses of oxymatrine combined with acellular cartilage extracellular matrix injection in knee cavity on osteoarthritis in rats.METHODS:The femoral cartilage of SD rats was obtained.The acellular cartilage extracellular matrix was prepared by physical,chemical and enzyme methods.Fifty SD rats were selected and divided into sham operation group,osteoarthritis group,simple material group,low-dose drug group,and high-dose drug group by random number table method,with 10 rats in each group.The latter four groups were treated with modified Hulth method to establish the rat model of osteoarthritis.After successful modeling,acellular cartilage extracellular matrix homogenate was injected into the knee cavity of rats in the simple material group.Acellular cartilage extracellular matrix homogenate containing 50,100 μg oxymatrine was injected into the knee cavity of rats in the low-dose drug group and the high-dose drug group,respectively.Samples were taken 4 weeks after injection for relevant detection.RESULTS AND CONCLUSION:(1) Compared with the sham operation group,the concentrations of interleukin 1β,tumor necrosis factor ɑ,and malondialdehyde in the joint effusion were increased (P<0.05),and the concentration of superoxide dismutase in the joint effusion was decreased (P<0.05) in the osteoarthritis group.Compared with osteoarthritis group,the levels of interleukin 1β,tumor necrosis factor ɑ,and malondialdehyde in joint effusion were decreased (P<0.05),while the level of superoxide dismutase was increased (P<0.05) in the low-dose drug group and high-dose drug group,and the changes were more significant in high-dose drug group.(2) TUNEL staining showed that compared with sham operation group,apoptotic chondrocytes increased in osteoarthritis group.Compared with the osteoarthritis group,the apoptotic chondrocytes decreased in the simple material group,the low-dose drug group,and the high-dose drug group,and the decrease was more significant in the high-dose drug group.(3) Hematoxylin-eosin staining and immunohistochemical staining showed that the knee cartilage was seriously degraded,the expression of type Ⅱ collagen was decreased (P<0.05),and the expression of matrix metalloproteinase-9 was increased (P<0.05) in the osteoarthritis group.Compared with the osteoarthritis group,the knee cartilage degeneration of rats in the simple material group,the low-dose drug group,and the high-dose drug group was significantly improved;the expression of type Ⅱ collagen was increased (P<0.05) and the expression of matrix metalloproteinase 9 was decreased (P<0.05),and the improvement was most significant in the high-dose drug group.(4) Western blot assay showed that compared with sham operation group,the expression of Nrf2,HO-1,and Bcl-2 protein in cartilage tissue decreased (P<0.05);expression levels of Cleaved-caspase-3,Cleaved-caspase-9,and Bax were increased (P<0.05) in the osteoarthritis group.Compared with the osteoarthritis group,the protein expression levels of Nrf2,HO-1,and Bcl-2 were increased (P<0.05),and the protein expressions of Cleaved-caspase-3,Cleaved-caspase-9,and Bax were decreased (P<0.05) in the low-dose and high-dose drug groups.The improvement was more significant in the high-dose drug group.(5) In conclusion,intracavicular injection of acellular cartilage extracellular matrix and oxymatrine can promote the synthesis of extracellular matrix,inhibit inflammation and oxidative stress,and suppress chondrocyte apoptosis,and play a therapeutic role in osteoarthritis,which may be related to the activation of Nrf2/HO-1 pathway.

BACKGROUND:Acellular cartilage extracellular matrix is effective in the treatment of osteoarthritis,but its efficacy is limited when applied alone.Oxymatrine alleviates interleukin-1β-induced chondrocyte apoptosis and extracellular matrix degradation.OBJECTIVE:To observe the effect of different doses of oxymatrine combined with acellular cartilage extracellular matrix injection in knee cavity on osteoarthritis in rats.METHODS:The femoral cartilage of SD rats was obtained.The acellular cartilage extracellular matrix was prepared by physical,chemical and enzyme methods.Fifty SD rats were selected and divided into sham operation group,osteoarthritis group,simple material group,low-dose drug group,and high-dose drug group by random number table method,with 10 rats in each group.The latter four groups were treated with modified Hulth method to establish the rat model of osteoarthritis.After successful modeling,acellular cartilage extracellular matrix homogenate was injected into the knee cavity of rats in the simple material group.Acellular cartilage extracellular matrix homogenate containing 50,100 μg oxymatrine was injected into the knee cavity of rats in the low-dose drug group and the high-dose drug group,respectively.Samples were taken 4 weeks after injection for relevant detection.RESULTS AND CONCLUSION:(1) Compared with the sham operation group,the concentrations of interleukin 1β,tumor necrosis factor ɑ,and malondialdehyde in the joint effusion were increased (P<0.05),and the concentration of superoxide dismutase in the joint effusion was decreased (P<0.05) in the osteoarthritis group.Compared with osteoarthritis group,the levels of interleukin 1β,tumor necrosis factor ɑ,and malondialdehyde in joint effusion were decreased (P<0.05),while the level of superoxide dismutase was increased (P<0.05) in the low-dose drug group and high-dose drug group,and the changes were more significant in high-dose drug group.(2) TUNEL staining showed that compared with sham operation group,apoptotic chondrocytes increased in osteoarthritis group.Compared with the osteoarthritis group,the apoptotic chondrocytes decreased in the simple material group,the low-dose drug group,and the high-dose drug group,and the decrease was more significant in the high-dose drug group.(3) Hematoxylin-eosin staining and immunohistochemical staining showed that the knee cartilage was seriously degraded,the expression of type Ⅱ collagen was decreased (P<0.05),and the expression of matrix metalloproteinase-9 was increased (P<0.05) in the osteoarthritis group.Compared with the osteoarthritis group,the knee cartilage degeneration of rats in the simple material group,the low-dose drug group,and the high-dose drug group was significantly improved;the expression of type Ⅱ collagen was increased (P<0.05) and the expression of matrix metalloproteinase 9 was decreased (P<0.05),and the improvement was most significant in the high-dose drug group.(4) Western blot assay showed that compared with sham operation group,the expression of Nrf2,HO-1,and Bcl-2 protein in cartilage tissue decreased (P<0.05);expression levels of Cleaved-caspase-3,Cleaved-caspase-9,and Bax were increased (P<0.05) in the osteoarthritis group.Compared with the osteoarthritis group,the protein expression levels of Nrf2,HO-1,and Bcl-2 were increased (P<0.05),and the protein expressions of Cleaved-caspase-3,Cleaved-caspase-9,and Bax were decreased (P<0.05) in the low-dose and high-dose drug groups.The improvement was more significant in the high-dose drug group.(5) In conclusion,intracavicular injection of acellular cartilage extracellular matrix and oxymatrine can promote the synthesis of extracellular matrix,inhibit inflammation and oxidative stress,and suppress chondrocyte apoptosis,and play a therapeutic role in osteoarthritis,which may be related to the activation of Nrf2/HO-1 pathway.

Objective:To summarize the clinical characteristics and key points of diagnosis and treatment in children with TCF3::HLF fusion gene-positive acute lymphoblastic leukemia (ALL).Methods:A case series study was conducted. Clinical data of 8 children diagnosed with TCF3::HLF positive ALL at the Hematology Center of Beijing Children′s Hospital, Capital Medical University and the Hematology Oncology Department of Henan Children′s Hospital between January 2019 and January 2024 were collected. Descriptive analysis was performed on their clinical features, laboratory findings, treatment regimens and prognosis.Results:The cohort included 8 children (3 males and 5 females) with the age of 5.5 (3.5, 7.0) years. Bone pain was the primary clinical manifestation in 4 cases, with multi-site skeletal involvement in 4 cases, hypercalcemia in 5 cases, and coagulation abnormalities in 6 cases. Immunophenotyping revealed common B-cell lineage with myeloid markers in 7 cases and common B-cell phenotype in 1 case. All 8 children were positive for the TCF3::HLF fusion gene. Regarding treatment, 1 case abandoned therapy after diagnosis, while the remaining 7 cases received chemotherapy following the Chinese Children′s Leukemia Group-ALL2018 high-risk protocol. Only 1 case achieved minimal residual disease (MRD) negativity by day 33 of induction therapy. Among the 3 cases with MRD negativity before consolidation therapy, 1 case achieved it via conventional chemotherapy, while 2 cases required additional agents (venetoclax or blinatumomab). One case failed to achieve MRD negativity after consolidation therapy and later discontinued treatment (survival periods: 7months).Of the 4 cases who achieved MRD negativity after consolidation, 2 cases received conventional chemotherapy and 2 cases achieved negativity following chimeric antigen receptor T-cell therapy (CART). All 4 cases underwent hematopoietic stem cell transplantation (HSCT). Two cases in the CART combined with HSCT group survived as of the last follow-up (survival periods: 22 and 13 months). In the conventional chemotherapy combined HSCT group, 1 case relapsed and died (survival: 38 months), and 1 case died from transplant complications (survival: 11 months). The other 2 cases achieved MRD negativity before consolidation therapy but did not receive regular subsequent chemotherapy. After MRD recurrence, they underwent CART therapy without HSCT and remained alive at the last follow-up (survival periods: 49 and 12 months).Conclusions:Children with TCF3::HLF positive ALL often present with bone destruction accompanied by hypercalcemia and coagulopathy at initial diagnosis. This subtype of ALL shows poor response to conventional chemotherapy regimens, characterized by low early remission rates and high relapse risk even after HSCT. Better therapeutic outcomes have been observed with small molecule targeted drugs, immunotherapy and CART therapy.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

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.

Objective:To compare the efficacy and safety of Castor single-branch stent and in vitro fenestration stent in treating thoracic aortic diseases with insufficient landing zone.Methods:The clinical data of patients with thoracic aortic diseases treated with Castor single-branch stent or in vitro fenestrated stent between December 2017 and June 2021 in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. A total of 184 patients were included, 99 patients were treated with Castor branch stent, and 85 patients with in vitro fenestration stent. All patients′ general clinical data, surgical data, perioperative and follow-up clinical and imaging data, and postoperative complications were collected. The χ2 test was used to compare the incidence of complications between the two groups, and the Kaplan-Meier method was used to plot the survival rate without adverse events between the two groups. Results:Stent placement was successful in all patients, and the success rate of the technique was 100%. Other branches were reconstructed in 2 patients in the Castor group and double fenestrated stent were reconstructed in 12 patients in the fenestrated group. The mean operation time of the Castor group was significantly shorter than that of the fenestrated group, the number of patients who received local anesthesia was significantly lower than that of the fenestrated group, and the endoleak rate during follow-up was significantly lower than that of the fenestrated group ( P<0.05). There was no significant difference in the postoperative hospital stay, the incidence rate of perioperative complications, mortality, the incidence rate of neurological complications, new dissection or aneurysm rate, branch stent stenosis rate, second surgical intervention rate, and false lumen thrombosis between the two groups ( P>0.05). The adverse event-free survival rate of the Castor group was slightly higher than that of the fenestrated group, but its difference was not statistically significant ( P>0.05). Conclusion:Castor branch stent and in vitro fenestration stent have good short-term and mid-term efficacy in the treatment of aortic diseases with insufficient landing zone, which are safe and effective options for reconstruction of LSA and other branch arteries.

【Objective】 To analyze the associations between different types of video screen time and psychological behaviors of preschool children, in order to provide evidence for promoting the development of children′s mental health. 【Methods】 From February to March 2023, a total of 1 361 parents of children aged 3 - 6 years from 6 kindergartens of Lanzhou were surveyed by cluster sampling method.Parents were surveyed to obtain information about the video use, and the children′s Strengths and Difficulties questionnaire (parent version) was used to assess children′s psychological and behavioral problems. 【Results】 The rate of daily screen time exceeding standard was 36.96% (503/1 361).The screen time was mainly spent in watching TV cartoons, followed by educational APP.The detection rate of abnormal total difficulty score was 11.61% (158/1 361), and the abnormalities of peer communication (32.26%) and prosocial behavior (12.34%) were the most prominent.After adjusting for related factors by multiple Logistic regression analysis, total screen time≥2h/d (OR=1.802) was found to be a risk factor for abnormal total difficulty score; watching TV cartoons≥2h/d was a risk factor for abnormal total difficulty score (OR=2.409) and peer communication (OR=2.222); playing games≥1h/d was a risk factor for abnormal total difficulty score, emotional symptoms, conduct problems, hyperactive behavior, and abnormalities of peer communication, the differences were all statistically significant (P<0.05).However, educational APP screen time<1h/d was a protective factor for abnormal total difficulty score(OR=0.615) and prosocial behavior (OR=0.549), but educational APP screen time≥2h/d was a risk factor for conduct problems (OR=2.302), the differences were all statistically significant (P<0.05). 【Conclusions】 The screen time of preschool children in Lanzhou cannot be ignored, and there is a significant correlation between overuse and children′s psychological and behavioral problems.Parents and schools should attach importance to the parent-child and peer interaction of preschool children and strengthen the intervention of preschool children′s video behavior.

OBJECTIVE To compare the efficacy， safety and economy of tacrolimus （TAC）， cyclosporin A （CsA）， cyclophosphamide （CTX） and rituximab （RTX） in the treatment of membranous nephropathy （MN）. METHODS Retrieved from Pubmed， the Cochrane Library， Wanfang data， CNKI and health technology assessment （HTA） official website， HTA reports， systematic reviews/meta-analysis and pharmacoeconomic studies about TAC， CsA， CTX and RTX combined with glucocorticoid in the treatment of MN were collected during the inception and Mar. 2022. After data extraction and quality evaluation， descriptive analysis was performed on the results of the included studies. RESULTS A total of 15 articles were included， involving 13 systematic reviews/meta-analysis and 2 pharmacoeconomic studies. In terms of efficacy， TAC and CsA showed significant advantages in increasing the response rate， and could improve the levels of urine protein， serum albumin， serum creatinine and serum total cholesterol. In terms of safety， the incidence of adverse reaction induced by TAC， CsA and RTX was low and the symptoms were mild. In terms of economics， CTX cost lower but caused severe adverse reaction； TAC cost higher but showed higher remission rate and good safety. CONCLUSIONS TAC combined with glucocorticoid may be the recommended scheme for MN.