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*

Objective:To investigate the expressions of cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE)and their effects on the malignant biological behaviours of breast cancer cells,and to elucidate their mechanisms.Methods:The breast cancer tissue and paracancerous normal tissue from 15 cases of patients were selected,and RT-qPCR and Western blotting methods were used to detect the mRNA and protein expression levels of CBS and CSE in breast cancer tissue,paracancerous normal tissue,MCF-7 cells,and MDA-MB-231 cells.The MCF-7 cells were divided into siNC group(transfected with siNC)and siCBS group(transfected with siCBS),and the MDA-MB-231 cells were divided into ovNC group(transfected with CSE over-expression empty plasmid)and ovCSE group(transfected with CSE over-expression plasmid).CCK8 assay was used to detect the proliferation activities of breast cancer cells in various groups,Transwell assay was used to detect the numbers of migration and invasion cells in various groups,and Western blotting method was used to detect the protein expression levels of E-cadherin,N-cadherin and Vimentin proteins in the breast cancer cells in various groups.Results:Compared with paracancerous normal tissue,the expression levels of CBS and CSE mRNA and proteins in breast cancer tissue were increased(P＜0.05 or P＜0.01).Compared with MDA-MB-231 cells,the CBS mRNA expression level in the MCF-7 cells was increased(P＜0.05);compared with MCF-7 cells,the expression level of CSE protein in the MDA-MB-231 cells was decreased(P＜0.05).Compared with siNC group,the proliferation activity,the numbers of migration and invasion cells,the expression levels of N-cadherin and Vimentin proteins in the MCF-7 cells in siCBS group were significantly decreased(P＜0.05),and the expression level of E-cadherin protein was increased(P＜0.05).Compared with ovNC group,the proliferation activity,the numbers of migratoin and invasion cells,and the expression levels of N-cadherin and Vimentin proteins in the MDA-MB-231 cells in ovCSE group were increased(P＜0.05),while the expression level of E-cadherin protein was significantly decreased(P＜0.05).Conclusion:The expressions of CBS and CSE are upregulated in breast cancer tissue,and high levels of CBS and CSE promote proliferation,migration,invasion and epithelial-mesenchymal transition(EMT)of breast cancer cells.

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ

Objective: To develop the Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary Schools Students, and to determine its reliability and validity, in order to provide a basis for developing targeted strategies to promote family-school-community cooperation in the area of nutritional education. Methods: Based on overlapping spheres of influence theory, the initial scale was developed through a qualitative and literature review, discussion with Delphi experts and a pilot survey from July 2022 to July 2023. From July to September 2023, a total of 125 primary school parents, 118 primary school teachers and 113 community personnel were selected from six cities in Jiangsu Province by convenient sampling methods, who were investigated to test the reliability and validity of the scale and to develop a formal scale. Results: The final Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School students consisted of 3 dimensions and 19 items. The exploratory analysis extracted three metric factors, with a contribution ratio of 69.07% to the accumulated variance. The mean scale component effectiveness was 0.94, and the coefficient of association between the respective dimensions and the scale ranged from 0.80 to 0.91.The overall Cronbach α coefficient for the scale was 0.95, the folded half reliability was 0.87, and the retest reliability was 0.98. Conclusion The Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School Students has good reliability and validity, and can be used to measure the degree of the family-school-community cooperation dilemma regarding nutritional education in primary school students.

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.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective:To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods:The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results:In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions:Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

The lymphatic system, as well as pathological changes of the lymphatic system, underlies the progress of an array of diseases and conditions, including cancer, inflammation and autoimmune disorders, infectious diseases and metabolic syndrome. A variety of biological targets in the lymphatic system can be employed to modulate these high-burden diseases, and the pharmacokinetics and drug delivery strategies in the context of lymphatics are of critical importance to optimise drug exposure to lymphatic-related targets. As such, research and drug development in this field has gained increasing attention in recent years. This article aims to provide an overview of pharmaceutical research with a focus on the lymphatic system and therapeutic targets within the lymphatics, followed by lymphatic drug delivery approaches, which may be of interest for researchers in academia, pharmaceutical industry and regulatory sciences.