The application of large multimodal models （LMMs） in the medical field has significantly enhanced efficiency， yet it is also accompanied by ethical and safety risks. In terms of medical quality assurance， LMMs face risks such as poor data quality， over-reliance， and skill degradation. Regarding patient safety， there are risks of information misunderstanding and privacy infringement. With respect to responsibility and accountability， there are risks of vague clinical responsibility boundaries and incomplete legal frameworks. As for sustainable medical development， there is a lack of governance and evaluation systems and insufficient monitoring of environmental impacts and climate change. To address these challenges， this paper proposed a series of ethical governance countermeasures. In terms of medical quality assurance， it was necessary to improve the quality of training data， optimize data protection strategies， strengthen cross-departmental collaboration and supervision， enhance the professionalism of data annotation， and establish ethical review mechanisms. Regarding patient safety， it was crucial to improve public digital literacy， establish transparent data processing mechanisms， promote public participation in ethical governance， increase the transparency and interpretability of output results， and encourage empirical research in the academic community. With respect to responsibility and accountability， it was essential to establish a clear framework for responsibility allocation， strengthen the distinction between clinical and AI responsibilities， reinforce legal regulations and policy support， and develop a qualification certification system for users. As for sustainable medical development， it was essential to establish a systematic governance evaluation system， promote social experiments and third-party monitoring， predict the human resource needs of medical development， monitor and warn about the impacts of climate change on health， and enhance cooperation and communication among stakeholders. In summary， the application of LMMs in the medical field requires comprehensive consideration of factors such as ethics， safety， responsibility， and sustainable development. Through multi-party co-governance and systematic governance， it ensures that medical quality and patients’ rights and interests are safeguarded while advancing technology.

To compare the clinical efficacy of intralesional corticosteroid injection combined with topical corticosteroids versus topical corticosteroids alone in patients with idiopathic granulomatous mastitis (IGM).

Objective:To improve the understanding of acute lymphoblastic leukemia (ALL) secondary to Burkitt lymphoma (BL) in children.Methods:The clinical data of a child with ALL secondary to BL who was admitted to Children's Hospital Affiliated to Zhengzhou University in June 2024 were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a boy with the age of 8 years and 8 months. He presented with a neck mass at the age of 4 years and 6 months, and pathological examination revealed a diagnosis of BL with clinical stage Ⅲ. The patient was given regular chemotherapy according to the Chinese Children's Lymphoma Group non-Hodgkin lymphoma mature B-cell 2017 protocol-B2 regimen. PET-CT showed recurrence of lymphoma in 6 months after the suspension of treatment. The patient was given with placement of 125I particles, oral etoposide and dexamethasone, and traditional Chinese medicine. The patient was admitted to hospital at the age of 8 years and 8 months with fever and skin hemorrhagic spots, bone marrow morphology, immunology, cytogenetics and molecular biology typing indicated a diagnosis of B-ALL with TCF3::PBX1 fusion gene. The patient received induction chemotherapy according to the Chinese Children's Leukemia Group-ALL 2018 protocol. A review of bone marrow cytology achieved complete remission on the 33rd day of chemotherapy, and minimal residual disease detected by flow cytometry indicated less than 0.01%. TCF3::PBX1 fusion gene was negative. Conclusions:ALL secondary to BL in children is rare, and the ALL treatment regimens are effective.

Objective:To improve the understanding of pediatric acute promyelocytic leukemia with TTMV::RARA fusion gene positive caused by torque teno mini virus (TTMV).Methods:A retrospective analysis was conducted on the clinical data of a patient with relapsed TTMV::RARA fusion gene-positive acute promyelocytic leukemia who was admitted to Children's Hospital Affiliated to Zhengzhou University in July 2024, and literature review was conducted.Results:The patient was a girl with the age of 5 years and 7 months. She presented with joint pain and fever. Combined with bone marrow cell morphology and whole transcriptome sequencing, she was diagnosed with TTMV::RARA fusion gene-positive acute promyelocytic leukemia. After induction therapy with regimens such as retinoic acid +daunorubicin+cytarabine and retinoic acid+venetoclax+homoharringtonine, the joint pain was relieved, but the primary disease did not improve. Subsequently, there was no regular treatment. One year later, the disease recurred and was complicated with severe infection. Her condition improved following anti-infection and induction therapy.Conclusions:TTMV::RARA fusion gene-positive pediatric acute promyelocytic leukemia is a special type of acute promyelocytic leukemia caused by the insertion of viral sequences from TTMV infection. It is rare in clinical practice and difficult to treat, and the overall prognosis may be poor.

Objective:To explore the treatment of the patients with severe phenotype of mucopolysaccharidosis (MPS) type ⅣA by analysing the clinical feature and diagnosis.Methods:Two pediatric patients diagnosed as MPS ⅣA in severe form were enrolled in Children′s Hospital Affiliated to Zhengzhou University from August 2021 to April 2022.Two children from 2 pedigrees with the main manifestations of short stature and bone deformities were retrospectively included.The clinical manifestations, biochemical indexes, and bone imaging findings were retrospectively analyzed.Peripheral blood leukocytes were collected and subjected to the N-acetylgalactosamine-6-sulfatase (GALNS) assay and genetic sequencing.Gene analysis of amniotic fluid cells at the 18 th week of the second pregnancy of the mother of case 2 was performed for prenatal diagnosis.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed in both patients and to explore the treatment of patients with MPS ⅣA. Results:Both cases presented clinical manifestations of short stature, joint laxity, pectus carinatum, and genu valgus.X-ray examination revealed the decreased bone mineral density, ulnar deviation of the radial epiphysis, kyphosis and scoliosis.The respiratory and skeletal systems were affected in both patients, and the optic nerve was suspiciously affected. GALNS gene analysis showed that there were 2 missense mutations of c. 1019G>A (p.G340D) and c. 706C>G (p.H236D) in case 1, and 2 missense mutations of c. 425A>G (p.H142R) and c. 463G>A (p.G155R) were detected in case 2.Mutations in both cases were inherited from their fathers and mothers, which were all newly discovered that have not been reported.Only the c. 463G>A mutation was detected in the amniotic fluid cells of the mother of case 2.It is confirmed that case 2 was the carrier of MPS ⅣA, whose gene mutation was from the mother, and case 2 did not suffer the same disease as the proband.Both cases were treated with allo-HSCT with full donor chimerism and no severe transplant complications were reported.Their GALNS activity was within the normal range, and the scores of activities of daily living were higher than those before transplantation. Conclusions:The MPS ⅣA patients with severe phenotype is a rare autosomal recessive disease caused by GALNS mutations that is difficult to diagnose and poor prognosis.Early detection, diagnosis, and effective treatment contribute to improve the long-term quality of life.The allo-HSCT is an effective therapeutic strategy for MPS ⅣA.

Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.

Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.

Objective:To investigate the clinical characteristics of children with high-risk acute lymphoblastic leukemia (ALL) receiving lasting remission after severe infection.Methods:The data of 3 children with high-risk ALL who were treated in Children's Hospital Affiliated of Zhengzhou University in 2014, 2015 and 2017 were analyzed retrospectively. The clinical and laboratory characteristics of all patients were also analyzed, and the relevant literatures were reviewed.Results:All 3 children were clinically classified as high-risk ALL with severe infection. A variety of anti-infective drugs and blood products were used in the treatment, and all achieved lasting remission.Conclusions:Children with high-risk ALL after severe infection can acquire lasting remission, which may be related with the production of infection stimulating inflammatory factors and cytokines to activate certain immune pathways, or various kinds of antibiotics, blood products participating in the immune regulation to make the body regain the immune surveillance function of the tumor cells.

Objective:To investigate the clinical characteristics and gene mutations of subcutaneous panniculitis-like T-cell lymphoma (SPTCL) secondary to familial hemophagocytic syndrome (FHL).Methods:The clinical features, disease evolution, gene mutation and genetic characteristics of 1 SPTCL patient secondary to FHL in Henan Children's Hospital in June 2012 were analyzed retrospectively, and the related literatures were reviewed.Results:The UNC13D of FHL patient was homozygous mutation accompanied by STXBP2 heterozygous mutation, while that of his parents and elder brother was heterozygous mutation. After regular chemotherapy with HLH-2004 regimen, the disease relapsed 4 years later, and secondary SPTCL developed after 1 year of remission with the second chemotherapy. After giving SMILE regimen chemotherapy, allogeneic hematopoietic stem cell transplantation was performed, and now the patient had disease-free survival.Conclusions:The detection of related genes in children with hemophagocytic syndrome should be improved in time to confirm the diagnosis of primary disease. FHL can follow SPTCL, and chemotherapy combined with allogeneic hematopoietic stem cell transplantation can be the only method to cure this disease.

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.