Objective To summarize and analyze the efficacy and influencing factors of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia relapsing after the first allo-HSCT. Methods Clinical data of 17 patients with acute leukemia who underwent second allo-HSCT at Peking University First Hospital from January 2005 to December 2024 were retrospectively analyzed. Results Among the 17 patients, 7 achieved long-term disease-free survival after second transplantation. The median progression-free survival after successful second transplantation was 7 months (range 8 days to 69 months). The relapse fatality was 24%, and the transplant-related fatality was 35%. Conclusions Second transplantation is an effective treatment for relapsed and refractory acute leukemia, but the relapse fatality and transplant-related fatality remain high. Patient age, time of relapse after the first transplantation and disease status before second transplantation are all factors that affect the efficacy of second transplantation. Younger age, late relapse and complete remission of disease before second transplantation are all beneficial for long-term disease-free survival after second transplantation.

ObjectiveTo systematically assess the public health governance capacity in Zhejiang Province, to conduct an in-depth analysis of its strengths and weaknesses, so as to provide scientific basis and strategic recommendations for further enhancement. MethodsA systematic collection of policy documents, public information reports, and research literature related to public health governance capacity in Zhejiang Province from 2002 to 2023 was conducted (encompassing a total of 1 263 policy documents, 138 pieces of information reports and 631 research articles). Based on the evaluation criteria suitable for public health systems previously developed by the research team, the basic status and magnitude of change in public health governance capacity in Zhejiang Province was evaluated. Additionally, normative gap analyses were employed to identify the strengths and weaknesses. ResultsZhejiang Province ranked 4th nationwide in terms of public health governance capacity with a score of 733.4 points (1 000.0-point maximum). The province has effectively implemented the principle of health first (scoring 698.5 points in the assessment of health-first strategy implementation) and attached sufficient importance to health-related goals (scoring 658.2 points in the scientific rationality of goal setting). However, the implementation of inter-departmental coordination and incentive mechanisms only scored 178.7 points, the feasibility of management and monitoring mechanisms scored even lower at only 144.0 points, and the coverage of incentive mechanisms scored 286.0 points. ConclusionZhejiang Province has effectively implemented its health first strategy and attached great importance to health targets, but still needs to strengthen cross-departmental coordination mechanisms and health-oriented incentives.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective:To investigate and assess the situation of popularization and promotion of domestically innovative medical devices in Liaoning Province,so as to provide a basis for promoting the allocation policy of domestically innovation medical devices.Methods:Self-made questionnaire and on-site filling survey were conducted to implement investigation and analysis for the allocation situation of newly medical equipment of 188 medical institutions in 9 demonstration regions of the Project on Regional Application and Demonstration of Innovative Medical Equipment in Liaoning Province from 2015 to 2020.The allocation data of medical equipment between before(from 2015 to 2017)and after the demonstration projects were implemented(from 2018 to 2020)were compared.The occupancy rate of domestically medical devices(referred as"occupancy ratio of domestic device")was used as an evaluation indicator to assess the status of equipment allocation and application before and after the projects of application and demonstration were implemented in the region of innovative equipment for diagnosis and treatment.Results:In the 9 demonstrational regions of Liaoning province,the number of newly added domestic medical devices during the period from 2018 to 2020 increased from 1,608 units between 2015 and 2017 to 1,703 units.The occupancy ratio of newly added domestic devices increased from 72.7%to 84.9%.The occupancy ratio of domestic devices of newly added key equipment increased from 63.0%to 83.4%,and the growth rate reached 20.4%.In different districts and different grades of medical institution,the increase and application of domestically medical devices appeared difference.Conclusion:The occupancy rate of newly added domestically medical devices in 9 demonstration regions in Liaoning province has generally increased.However,there are still imbalances between different regions and different grades of medical institutions.The manufacturers of domestically medical devices still need strengthen brand building and marketing promotion,so as to further enhance market competitiveness of domestically medical devices.

Objective:To explore the clinical characteristics and healthcare burden in patients with McCune-Albright syndrome (MAS).Methods:A cross-sectional study was conducted at the Children′s Hospital, Zhejiang University School of Medicine. Clinical and healthcare burden data were systematically collected through structured questionnaires in 164 children with MAS from February 2022 to May 2023. According to the clinical characteristics, patients were categorized into 3 groups: monosymptomatic, bisymptomatic and trisymptomatic groups. Patients were also divided into 3 groups according to the age of <7, 7-<10 and 10-18 years. Comparative analyses of clinical characteristics and healthcare burden were conducted across age, sex, and symptom categories.Results:The cohort comprised 59 males (36.0%) and 105 females (64.0%) with an age of 4.6 (2.0, 7.4) years. Age stratification revealed 117 cases (71.3%) aged 0-<7 years, 29 cases (17.7%) aged 7-<10 years, and 18 cases (11.0%) aged 10-<18 years. Among monosymptomatic (67 cases, 40.9%), the cohort comprised 32 females (47.8%) and 35 males (52.2%), predominantly presenting with fibrous dysplasia (57 cases, 85.1%). This subgroup showed peak prevalence in the 0-<7 years age range (29 cases (50.9%)). The bisymptomatic cohort (56 cases, 34.1%) consisted of 39 females (69.6%) and 17 males (30.4%), predominantly manifesting fibrous dysplasia with skin hyperpigmentation (25 cases, 44.6%). Peak prevalence occurred in the 0-<7 years subgroup(16 cases (64.0%)). The trisymptomatic cohort (41 cases, 25.0%) consisted of 34 females (82.9%) and 7 males (17.1%), with peak prevalence occurring in the 0-<7 years subgroup (36 cases (87.8%)). The diagnostic journey analysis revealed 94 cases (57.3%) required 1-3 referrals, and 34 cases (20.7%) necessitated >3 referrals from symptom onset to definitive diagnosis. Healthcare expenditure analysis revealed 69 families (42.1%) incurred direct medical costs of 10 000-100 000 CNY, with 11 families (6.7%) exceeding >100 000 CNY. Direct non-medical costs reached of 10 000-100 000 CNY for 62 families (37.8%) and >100 000 CNY for 4 families (2.4%). Productivity loss affected 58 families (35.4%) at 10 000-100 000 CNY and 8 families (4.9%) above 100 000 CNY during the study period.Conclusion:MAS requires increased attention to skeletal manifestations, especially in children aged 0-<7 years. Moreover, the significant financial burden on families necessitates a society-wide support system.

Purpose To investigate the presence,proportion,clinical significance and origin of tumor cells with a macrophage phenotype in tumor tissues of patients with diffuse large B-cell lymphoma(DLBCL),and to explore wheth-er CD68 positive tumor cells can be induced in DLBCL cell lines in vitro.Methods The presence of CD68+CD163+CD20+PAX5-cells in the samples of DLBCL patients was first qualitatively detected by multiplex immunofluorescence staining,and then the proportion of CD79a+B lymphocytes,CD68+macrophages,and CD68+CD79a+double-positive cells were quantified.Patients were grouped according to the proportion of double-positive cells,and the differences in prognosis and clinicopathological features of DLBCL patients between subgroups were investigated.For cases with posi-tive BCL6 gene locus breaks,co-localization of CD68 with BCL6 gene breakapart was performed using combined immu-nofluorescence and immunological in situ hybridization to ascertain the tumor nature of B cell with a macrophage pheno-type.DLBCL cell lines(OCI-LY3,SU-DHL2)were treated with phorbol myristate acetate(PMA),and changes in the proteins levels of CD68 and PAX5 proteins were detected by flow cytometry.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA levels of PAX5,an important transcription factor for B cell differentiation and develop-ment,and macrophage-related genes(CD68,ARG1,CD163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ).In ad-dition,PMA-treated DLBCL cell lines(OCI-LY3,SU-DHL2)were co-incubated with pH-sensitive fluorescent dye pHrodo to detect the phagocytosis ability of PMA-treated DLBCL cells.Results The percentage of CD68+B lympho-cytes in 50 patients with DLBCL varied from 0 to 9.3％,and the overall survival(OS)ranged from 0.008 2 to 4.2 years.Patients with the low CD68+B lymphocytes group exhibited a significantly lower OS compared to those in the high CD68+B lymphocytes group(P=0.039).There was a significant difference in the molecular typing of DLBCL patients(P=0.009 5)between different subgroups for the proportion of CD68+B lymphocytes.CD68+B lymphocytes were derived from tumor cells in DLBCL patients.The proportion of CD68+cells and CD68+PAX5-cells significantly increased in DLBCL after treatment with PMA(P＜0.05).The other macrophage markers CD68,ARG1,CD 163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ,and the important B-cell transcription factor PAX5 were significantly different from the control group in terms of relative mRNA expression(P＜0.05).Cellular phagocytosis was enhanced after PMA treatment of DLBCL cells.Conclusion Diffuse large B-cell lymphoma tumor tissue contains a certain per-centage of CD68+neoplastic B lymphocytes.The proportion of CD68+B lymphocytes is correlated with patient progno-sis and molecular typing.DLBCL cell lines can be induced to differentiate into CD68+tumor cells in vitro.

Objective To investigate the role and mechanism of ferroptosis in cochlear hair cell injury induced by exposure to ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate(GenX).Methods Mouse cochlear hair cell line HEI-OC1 was assigned to control,GenX,ferrostatin-1(Fer-1),and GenX+Fer-1 groups.CCK-8 assay was used to assess the cytotoxicity of GenX and the rescue effect of Fer-1 co-treatment.Western blotting and qRT-PCR were employed to measure the protein and transcriptional expression of ferroptosis markers,cochlear function indicators,blood labyrinth barrier markers,and ferroptosis-related pathway.FerroOrange,Bodipy(C11),mitochondrial membrane potential assay kit(JC-1),and adenosine triphosphate(ATP)assay were applied to detect Fe2? accumulation,lipid peroxidation,mitochondrial membrane dysfunction,and cellular ATP levels,respectively.Results Exposure to 200 μmol/L GenX for 12 h significantly reduced the viability of HEI-OC1 cells(P<0.01),down-regulated the protein levels of glutathione peroxidase 4(Gpx4),solute carrier family 7 member 11(Slc7a11),and ferroptosis suppressor protein 1(Fsp1)(P<0.05),whereas up-regulated acyl-coa synthetase long-chain family member 4(Acsl4)(P<0.01),and decreased the expression of cochlear hair-cell function genes and blood labyrinth barrier genes(P<0.05).These changes were accompanied with Fe2+accumulation,elevated lipid peroxidation,mitochondrial membrane damage,and reduced ATP production(P<0.001).Addition of Fer-1 restored cell viability(P<0.05),restored the expression of ferroptosis related proteins(P<0.05),and improved the expression of several hair-cell function and blood labyrinth barrier genes(P<0.05).In parallel,the GenX+Fer-1 group exhibited reduced Fe2? accumulation,lower lipid peroxidation,attenuated mitochondrial membrane damage,and increased ATP level(P<0.001).Conclusion GenX induces iron-metabolism dysregulation and lipid peroxidation,and then leads to differentiation impairment of cochlear hair cells and barrier functions via the ferroptotic System Xc?-Gpx4-Fsp1 axis.

ObjectiveThe utilization of assisted reproductive technology to rescue genetically modified mouse strains with reproductive disorders provides a reference for improving techniques to preserve valuable experimental mouse strains. MethodsIn vitro fertilization-embryo transfer (IVF-ET) technology was performed on 28 strains of infertile male mice aged 9-18 months. Several indicators such as sperm density and sperm motility in infertile male mice were assessed to select the most viable sperm for IVF-ET experiments. Fertility rate, abnormal egg rate, and birth rate were recorded after the birth of the pups. An optimized ovarian transplantation procedure was applied to 12 strains of infertile female mice aged 8-18 months. 6-week-old female mice with the same genetic background were selected as recipients. One intact ovary was removed from each recipient mouse, and the contralateral oviduct was ligated. An ovary from a donor mouse was isolated and transplanted orthotopically into the side where the ovary had been removed in the recipient mouse. Twenty-one days post-surgery, recipient mice were co-housed with 8-week-old wild type male mice of the same genetic background for breeding. Data such as the pregnancy rate and live birth rate of the recipients were recorded after the birth of the pups. ResultsIVF-ET successfully rescued 28 mouse strains, with the oldest male mice being 18 months old. The success rate of the first round of IVF-ET experiments was 89.29% (25/28). The average fertility rate of IVF in infertile male mice was (51.01±14.97)%, the abnormal egg rate was (9.03±5.28)%, and the birth rate of offspring mice was (18.60±7.03)%. 39 out of 40 ovarian transplant recipient mice survived, with a pregnancy rate of 33.33% (13/39) for ovarian transplant recipients, and a live birth rate of 17.95% (7/39). Four mouse strains were successfully rescued using optimized ovarian transplantation technology, with the oldest female mice being 18 months old. 8 strains were not rescued as they failed to produce offspring that survived to sexual maturity. ConclusionIVF-ET is an effective approach for rescuing mice with reproductive disorders caused by different reasons, especially for those beyond the optimal breeding age. Ovarian transplantation technology can also be used as an alternative for aged female mice. But its success rate is relatively lower than that of IVF-ET, and carries a higher experimental risk.

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Purpose To investigate the presence,proportion,clinical significance and origin of tumor cells with a macrophage phenotype in tumor tissues of patients with diffuse large B-cell lymphoma(DLBCL),and to explore wheth-er CD68 positive tumor cells can be induced in DLBCL cell lines in vitro.Methods The presence of CD68+CD163+CD20+PAX5-cells in the samples of DLBCL patients was first qualitatively detected by multiplex immunofluorescence staining,and then the proportion of CD79a+B lymphocytes,CD68+macrophages,and CD68+CD79a+double-positive cells were quantified.Patients were grouped according to the proportion of double-positive cells,and the differences in prognosis and clinicopathological features of DLBCL patients between subgroups were investigated.For cases with posi-tive BCL6 gene locus breaks,co-localization of CD68 with BCL6 gene breakapart was performed using combined immu-nofluorescence and immunological in situ hybridization to ascertain the tumor nature of B cell with a macrophage pheno-type.DLBCL cell lines(OCI-LY3,SU-DHL2)were treated with phorbol myristate acetate(PMA),and changes in the proteins levels of CD68 and PAX5 proteins were detected by flow cytometry.Quantitative real-time PCR(qRT-PCR)was used to detect mRNA levels of PAX5,an important transcription factor for B cell differentiation and develop-ment,and macrophage-related genes(CD68,ARG1,CD163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ).In ad-dition,PMA-treated DLBCL cell lines(OCI-LY3,SU-DHL2)were co-incubated with pH-sensitive fluorescent dye pHrodo to detect the phagocytosis ability of PMA-treated DLBCL cells.Results The percentage of CD68+B lympho-cytes in 50 patients with DLBCL varied from 0 to 9.3％,and the overall survival(OS)ranged from 0.008 2 to 4.2 years.Patients with the low CD68+B lymphocytes group exhibited a significantly lower OS compared to those in the high CD68+B lymphocytes group(P=0.039).There was a significant difference in the molecular typing of DLBCL patients(P=0.009 5)between different subgroups for the proportion of CD68+B lymphocytes.CD68+B lymphocytes were derived from tumor cells in DLBCL patients.The proportion of CD68+cells and CD68+PAX5-cells significantly increased in DLBCL after treatment with PMA(P＜0.05).The other macrophage markers CD68,ARG1,CD 163,CD206,Dectin-1,PU.1,C/EBPα,C/EBPβ,and the important B-cell transcription factor PAX5 were significantly different from the control group in terms of relative mRNA expression(P＜0.05).Cellular phagocytosis was enhanced after PMA treatment of DLBCL cells.Conclusion Diffuse large B-cell lymphoma tumor tissue contains a certain per-centage of CD68+neoplastic B lymphocytes.The proportion of CD68+B lymphocytes is correlated with patient progno-sis and molecular typing.DLBCL cell lines can be induced to differentiate into CD68+tumor cells in vitro.