OBJECTIVE: To analyze the molecular genetic spectrum of children with acute myeloid leukemia (AML), and explore its correlation with clinical characteristics and prognosis. METHODS: The clinical and molecular genetic data of 116 children with newly diagnosed AML in Wuhan Children's Hospital from September 2015 to August 2022 were retrospectively analyzed. The Fisher's exact test was used to analyze the correlation of gene mutations with clinical features, and Kaplan-Meier curve was used to analyze the influences of gene mutations on the prognosis. RESULTS: NRAS (22%), KRAS (14.9%), and KIT (14.7%) mutations were the most common genetic abnormalities in 116 children with AML. Children with KIT, CEBPA and GATA2 mutations showed a higher median onset-age than those without mutations (all P < 0.05). Children with FLT3-ITD mutation exhibited a higher white blood cell count at initial diagnosis compared to those without mutations (P < 0.05). Children with ASXL2 mutation had lower platelet count and hemoglobin at initial diagnosis than those without mutations (both P < 0.05). KIT mutations were often co-occurred with t(8;21)(q22;q22). There was no significant relationship between gene mutation and minimal residual disease (MRD) remission rate after the first and second induction therapy (P >0.05). KIT and NRAS mutations were not associated with prognosis significantly (P >0.05). The overall survival (OS) rates of children with CEBPA and FLT3-ITD mutations were superior to those without mutations, but the differences were not statistically significant (P >0.05). The 3-year OS rate of 61 children treated by allogeneic hematopoietic stem cell transplantation was 89.8%, which was significantly higher than 55.2% of those only treated by chemotherapy (P < 0.001). CONCLUSIONS Gene mutations are common in children with AML, and next-generation sequencing can significantly improve the detection rate of gene mutations, which can guide the risk stratification therapy. In addition, FLT3-ITD and KIT mutations may no longer be poor prognostic factors.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Prognosis ; Retrospective Studies ; fms-Like Tyrosine Kinase 3/genetics* ; Child ; Proto-Oncogene Proteins c-kit/genetics* ; Male ; Female ; CCAAT-Enhancer-Binding Proteins/genetics* ; Membrane Proteins/genetics* ; Child, Preschool ; Adolescent ; GATA2 Transcription Factor/genetics* ; GTP Phosphohydrolases/genetics* ; Proto-Oncogene Proteins p21(ras)/genetics*

Lung cancer is the leading cause of cancer-related deaths worldwide, characterized by high incidence and mortality rates. The primary reasons for treatment failure in lung cancer patients are tumor invasion and drug resistance, particularly resistance to chemotherapeutic agents and epidermal growth factor receptor (EGFR) mutant targeted therapy, which considerably undermine the therapeutic outcomes for those with advanced lung cancer. Epithelial-mesenchymal transition (EMT) serves as a crucial biological process closely associated with physiological or pathological processes such as tissue embryogenesis, organogenesis, wound repair, and tumor invasion. Numerous studies have indicated that EMT, mediated through various signaling pathways, plays a pivotal role in the initiation, progression, and metastasis of lung cancer, while it is also closely associated with drug resistance in lung cancer cells. Therefore, research focusing on the molecular mechanisms and pathophysiology related to EMT can contribute to reversing drug resistance in drug treatment for lung cancer, thereby improving prognosis. This article reviews the progress in research on EMT in the invasion, metastasis, and drug resistance of lung cancer based on relevant domestic and international literature.
Humans ; Epithelial-Mesenchymal Transition/drug effects* ; Drug Resistance, Neoplasm ; Lung Neoplasms/physiopathology* ; Neoplasm Metastasis ; Neoplasm Invasiveness ; Animals ; Antineoplastic Agents/therapeutic use*

A a novel composite ZIF-8/MWCNT was synthesized by combining zeolitic imidazolate framework-8(ZIF-8)with multi-walled carbon nanotubes(MWCNT).The composite was modified on glassy carbon electrode(GCE)to obtain ZIF-8/MWCNT/GCE,which was served as an effective electrochemical sensor for detection of Pb2+ and Cd2+.Benefiting from the high electrical conductivity of MWCNT and the synergistic effect between ZIF-8 and MWCNT,ZIF-8/MWCNT showed excellent electrocatalytic activity in individual and simultaneous detection of Cd2+ and Pb2+.Under the optimized conditions,the linear ranges were 0.03?8.00 μmol/L and 0.03?6.00 μmol/L with corresponding limits of detection(S/N=3)of 0.019 and 0.035 μmol/L for individual detection of Cd2+and Pb2+,respectively.Whereas for simultaneous detection of Cd2+and Pb2+in their mixture solutions,the linear ranges were 0.03?5.00 μmol/L and 0.03?5.00 μmol/L with corresponding limits of detection(S/N=3)of 0.022 and 0.048 μmol/L,respectively.In addition,the sensor exhibited good stability,reproducibility and anti-interference ability.Moreover,the sensor showed good feasibility and accuracy for determination of Cd2+ and Pb2+ in actual river water samples with spiking recoveries of 98.1%?104.0%and 98.3%?102.2%,respectively.

Pulmonary disease is one of the major threats to human health. However, the current clinical treatment drugs for lung diseases generally have problems such as low lung delivery efficiency, fast clearance rate and obvious toxic side effects. Recently, membrane biomimetic nanocarriers have attracted more and more attention. Due to their advantages of high targeting, long cycle time, good biocompatibility and strong immune escape ability, membrane biomimetic nanocarriers have become a major research hotspot in targeted therapy of lung diseases. In this review, we discuss the main preparation methods of membrane biomimetic nanoparticles, the characteristics of membrane biomimetic nanocarriers from different cell sources and their application in the targeted therapy of lung diseases. At the same time, according to the characteristics of different membranes, the shortcomings, current technical limitations and future prospects are discussed. This review is expected to provide references for the design of membrane biomimetic nanocarriers and their potential applications in the treatment of lung diseases.

Objective To analyze the differences of clinical features of acute gout flare and postoperative infection under arthroscopy of knee gouty arthritis patients to offer guiding opinions of clinical diagnosis and treatment.Methods Between Jan-uary 2017 and December 2022,235 patients with gouty knee osteoarthritis were admitted,and underwent arthroscopic debride-ment combined with synovectomy.Among them,35 cases had fever with a temperature higher than 38 ℃ postoperatively while acute inflammatory appears under redness,swelling,heat and pain of the operated joints.There were 29 males and 6 females,with an average age of(41.48±13.90)years old.Among them 23 patients were diagnosed with acute gout attack,and recovered well after being given colchicine and prednisolone;12 patients were diagnosed with postoperative joint infection,and were cured after being given anti-infective treatments and cleaning and rinsing of the joint cavity.The two groups of patients were compared and analyzed in terms of preoperative general data,surgical conditions,hematology,joint fluid,limb function and other clinical characteristics.Results There were no significant difference in the preoperative general data between two groups.The onset of fever in the postoperative acute gout flare group occurred mostly within 48 hours,significantly earlier than that in the postoperative infection group(P=0.037).The visual analogue scale score was significantly higher in the acute gout flare group(5.32±1.38)score than in the postoperative infection group(2.45±0.68)score(P=0.000),while 14 patients with acute gout flare were accompanied by severe pain in other joints.Hematologically,indicators such as white blood cell counts and ra-tios were significantly higher in both groups.In terms of inflammatory indicators,IL-6,erythrocyte sedimentation rate,procal-citonin and other inflammatory indicators were significantly elevated in both groups,but there was no statistical difference be-tween two groups.The C-reactive protein level in the postoperative infection group(220.97±1 16.30)mg·L-1 was higher than that in the postoperative acute gout attack group(120.67±82.45)mg·L-1(P=0.006).Blood uric acid(316.55±112.84)μmol·L-1 was higher in the acute postoperative gout flare group than in the postoperative infection group(159.14±126.92)μmol·L-1(P=0.001).In the joint fluid examination of the postoperative infection group,the glucose metabolism indicator was signifi-cantly lower than that of the acute gout flare group,and five of them had positive bacterial cultures Conclusion The symptoms of acute gout flare could be mistaken as postoperative infection due to their similarity,therefore requires careful differentiation.Differential diagnosis should be based on a combination of clinical signs,hematology and joint fluid findings,and targeted treatment should be given to avoid serious complications.

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 study the mechanism of icariin inhibiting the proliferation of human PCa PC-3 cells based on cell metabolomics technology.Methods:We determined the proliferation activity of human PC-3 cells by methyl thiazolyl tetrazolium(MTT)assay,and compared the proliferation of the PC-3 cells among the control,5-fluorouracil and icariin intervention groups.Using the Bligh Dyer method,we extracted endogenous metabolites from the cells,analyzed the metabolic profile by ultra-high pressure liquid chromatography tandem quadrupole time-of-flight mass spectrometry,identified the differential metabolites by principal component anal-ysis and orthogonal partial least-squares discrimination analysis,and enriched the metabolic pathways based on the MetaboAnalyst data-base.Results:Icariin significantly inhibited the proliferation of human PCa PC-3 cells.A total of 89 differential metabolites were i-dentified,mainly including amino acids,phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine,and lysophosphati-dylethanolamine,all with the tendency to return to the normal level after icariin intervention.Icariin significantly downregulated the metabolic levels of the glycerophospholipid metabolites phosphatidylcholine,phosphatidylethanolamine,lysophosphatidylcholine and ly-sophosphatidylethanolamine,and upregulated those of amino acid metabolites tryptophan,leucine,and proline in the PC-3 cells.Conclusion:Icariin inhibits the proliferation of human PCa PC-3 cells,which may be closely related to its regulatory effect on lipid metabolism(glycerophospholipid metabolism)and amino acid metabolism.

Conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins leads to the accumulation of 5hmC in the central nervous system; however, the role of 5hmC in the postnatal brain and how its levels and target genes are regulated by TETs remain elusive. We have generated mice that lack all three Tet genes specifically in postnatal excitatory neurons. These mice exhibit significantly reduced 5hmC levels, altered dendritic spine morphology within brain regions crucial for cognition, and substantially impaired spatial and associative memories. Transcriptome profiling combined with epigenetic mapping reveals that a subset of genes, which display changes in both 5hmC/5mC levels and expression patterns, are involved in synapse-related functions. Our findings provide insight into the role of postnatally accumulated 5hmC in the mouse brain and underscore the impact of 5hmC modification on the expression of genes essential for synapse development and function.
Animals ; Brain/growth & development* ; 5-Methylcytosine/metabolism* ; Mice ; Synapses/genetics* ; Proto-Oncogene Proteins/metabolism* ; DNA-Binding Proteins/metabolism* ; Dioxygenases/metabolism* ; Cognition/physiology* ; Gene Expression ; Mixed Function Oxygenases/metabolism* ; Epigenesis, Genetic ; Mice, Knockout ; Mice, Inbred C57BL

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

Humans ; Adult ; Mucormycosis ; Leukemia, Myeloid, Acute/complications* ; Acute Disease ; Antifungal Agents