Objective: To analyze the etiological surveillance results of influenza-like illness (ILI) cases in Jiangsu Province, and investigate the distribution characteristics of different influenza virus types, so as to provide the evidence for improving influenza prevention and control measures. Methods: Influenza laboratory testing data for sentinel surveillance of ILI cases in Jiangsu Province from 2019 to 2024 were collected through the China Influenza Surveillance Information System. The positive detection rate of influenza virus was calculated, and descriptive analysis was performed to characterize the distribution of different influenza virus types. Using the farthest neighbor linkage method, influenza virus positive detection rates clustering was analyzed by year and week. Clusters were defined based on inter-cluster distance, and the intensity of the positive detection rate was visualized through color gradients in the clustering heatmap. Results: From 2019 to 2024, a total of 183 878 ILI specimens were collected in Jiangsu Province. Among them, 20 059 specimens tested positive for influenza virus, corresponding to an overall positive detection rate of 10.91%, and an average annual positive detection rate of 10.89%. The primary circulating influenza virus types were influenza A H3N2 subtype, accounting for 40.92%, followed by influenza B Victoria linage at 34.00%, and influenza A H1N1 subtype at 24.80%. Influenza B Yamagata linage was not detected throughout the five-year period. Influenza A H3N2 subtype predominated during two distinct periods: from January to March 2019, and from June 2022 to December 2023. Influenz B Victoria linage was the dominant type from April 2019 to May 2022 and again from January to April 2024. Influenza A H1N1 subtype emerged as the primary type from May to December 2024. Year-based clustering analysis grouped the annual positive detection rates from 2019 to 2024 into three clusters. The closest cluster distance was observed between 2019 and 2024. The highest annual positive detection rate occurred in 2023. Both influenza A H3N2 and H1N1 subtype each formed a single cluster, with their peak positive detection rates also recorded in 2023. Influenza B Victoria lineage was separated into two clusters, with its highest positive detection rate occurring in 2020. Week-based clustering analysis revealed that influenza virus detection was concentrated in weeks 47 to 52 and weeks 1 to 15. More specifically, the positive detection rates for influenza A H3N2 subtype peaked during weeks 30 to 34 and weeks 42 to 52; for influenza A H1N1 subtype, during weeks 9 to 15 and weeks 51 to 52; and for influenza B Victoria lineage, during weeks 1 to 11 and weeks 50 to 52. Conclusions From 2019 to 2024, the average annual positive detection rate of influenza virus in Jiangsu Province remained relatively low. Influenza activity characterized by the alternating circulation of influenza A H1N1 subtype, influenza A H3N2 subtype, and influenza B Victoria linage. It is necessary to maintain the surveillance sensitivity for the influenza B Yamagata lineage.

The construction of a training system for visiting physicians in the department of rare diseases in China is an important measure to improve the overall diagnosis and treatment capacity for rare diseases and address the critical challenge of insufficient knowledge and skills among clinicians in practice. This article systematically describes the visiting physician training system established by the Department of Rare Diseases at Peking Union Medical College Hospital. It summarizes the training objectives and positioning, design logic, and learning modules of the system, aiming to provide a reference for the construction of the specialized talent team for rare diseases in China.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

BACKGROUND:Rheumatoid arthritis is widely prevalent worldwide,with its high incidence and universality that considerably affects patients' quality of life.Previous studies have focused on a few immune cells or cytokines,whereas this study comprehensively provides a more complete view of the immune mechanisms in rheumatoid arthritis.OBJECTIVE:To explore the causal relationship between 731 immune cell phenotypes and rheumatoid arthritis using the Mendelian randomization method,thereby providing evidence of causality.METHODS:The 731 immune cell phenotypes used in this study were sourced from the GWAScatalog database,jointly developed by the National Human Genome Research Institute(NHGRI)and the European Bioinformatics Institute(EBI).The rheumatoid arthritis data were from the Finngen database,developed by the Finnish Institute for Molecular Medicine(FIMM).The inverse variance weighting method was employed as the primary analytical approach.Additionally,multiple analytical methods,including MR-Egger,weighted mode,simple mode,and weighted median,were concurrently utilized to complement the final results.Sensitivity analyses(Cochran's Q test,MR-Egger regression,and MR-presso analysis)were also conducted to verify the stability and feasibility of the data.RESULTS AND CONCLUSION:(1)After excluding results through heterogeneity testing,the inverse variance weighting analysis indicated that 10 absolute cell counts,15 median fluorescence intensities of surface antigen levels,1 morphological characteristic,and 9 relative cell counts had a causal relationship with the occurrence of rheumatoid arthritis.(2)According to cell classification,this study found that seven types of B cells,seven types of classical dendritic cells,six types of mature T cells,four types of monocytes,three types of myeloid cells,three types of TBNK cells(lymphocyte subset T cells,B cells and natural killer cells),and five types of Tregs had a causal association with the occurrence of rheumatoid arthritis.(3)Through comprehensive bidirectional two-sample MR analysis,we demonstrated the complex causal relationships between multiple immune phenotypes and rheumatoid arthritis,highlighting the intricate interaction patterns between the immune system and rheumatoid arthritis.These results provide new biomarkers for the early screening and diagnosis of rheumatoid arthritis in China,and help to improve the diagnostic accuracy and sensitivity.

Immunoglobulin G4-related disease (IgG4-RD) is a rare systemic immune-mediated disorder characterized by infiltration of IgG4-positive plasma cells and multiorgan fibrosis. Among them, cases with multiple pancreatic cystic lesions as the prominent manifestation are relatively rare, and they are easily misdiagnosed as pancreatic tumors or pancreatitis in clinical practice. Herein, we report one patient with IgG4-RD admitted to Peking Union Medical College Hospital. The patient initially presented with multiple pancreatic cystic lesions and aneurysmal dilatation of the abdominal aorta, accompanied by markedly elevated serum IgG4 levels. Combined with pathological findings from submandibular gland biopsy, the diagnosis of IgG4-RD was ultimately established. After treatment with a regimen of glucocorticoids combined with cyclophosphamide, the patient′s condition improved. Meanwhile, we performed a literature review of cases with IgG4-RD-related pancreatic cystic lesions, aiming to improve clinicians′ understanding of this rare disease phenotype.

ObjectiveTo explore the anti-eczema efficacy and mechanism of Mongolian medicine Cymbaria dahurica n-butanol extract. MethodsThe compounds of C. dahurica n-butanol extract were obtained by ultra-performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Exactive MS） analysis and literature mining. GEO chip analysis and network pharmacology were employed to predict potential targets and pathways for the anti-eczema effect. Seventy-five mice were randomized into a normal group （10 mice） and a modeling group （65 mice）. The model was induced by 1% dinitrochlorobenzene （DNCB） for 3 days. The modeled mice were grouped as follows： Positive drug （hydrocortisone butyrate cream， 250 mg·kg^-1·d^-1） and low-， medium-， and high-dose （95.94， 191.88， and 383.76 mg·kg^-1·d^-1， respectively） C. dahurica n-butanol extract， with 13 mice in each group. From day 5 of the experiment， 0.5% DNCB was applied， once every other day， until day 22. At the same time， drugs were applied daily from day 5. The appearance damage of back skin of mice in each group was analyzed. The pathological changes of the back skin of mice in each group were observed by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The levels of inflammatory factors ［histamine （HIS）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TFN-α）］， thymic stromal lymphopoietin （TSLP）， and immunoglobulin E （IgE） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. Metabolomics analysis was performed for the mouse skin. The HaCaT cell model of eczema was induced with TNF-α/interferon-γ （IFN-γ）. The secretion levels of IL-6， IL-8， thymus and activation-regulated chemokine （TARC/CCL17）， macrophage-derived chemokine （MDC）， and TSLP in the cell supernatant from each group were measured by ELISA， while the protein levels of phosphorylated （p）-Janus kinase 2 （JAK2）， JAK2， p-signal transducer and activator of transcription 3 （STAT3）， and STAT3 were assessed by Western blot. ResultsThrough UPLC-Q-Exactive MS and literature review， a total of 125 compounds of C. dahurica n-butanol extract were obtained. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis showed that the anti-eczema mechanism of C. dahurica n-butanol extract may be related to the Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway. The results of animal experiments showed that compared with the normal group， the modeling group exhibited redness， swelling， exudation， erosion， and scab formation on the back skin surface， and thickened dermis and epidermis with inflammatory cell infiltration. Compared with the modeling group， the positive drug and C. dahurica n-butanol alleviated the skin lesions （including redness， swelling， exudation， roughness， and keratosis and scab formation on the back）， reduced the thickness of dermis and epidermis， mitigated inflammatory cell infiltration， and restored the skin tissue structure. Compared with the normal group， the modeling group showed elevated levels of HIS， IL-4， IL-6， IL-8， TNF-α， TSLP， and IgE （P<0.05， P<0.01）， which were reversed in the positive drug group and C. dahurica n-butanol extract groups （P<0.05， P<0.01）. The results of metabolomics analysis showed that 12 differential metabolites might be the key substances for mitigating metabolic disorders of the skin and were closely related to the JAK/STAT signaling pathway. The cell experiement showed that compared with the normal group， the model group exhibited upregulated expression levels of IL-6， IL-8， MDC， TARC， TSLP， p-JAK2， p-STAT3， p-JAK2/JAK2， and p-STAT3/STAT3 in HaCaT cells （P<0.05， P<0.01）. Compared with the model group， C. dahurica n-butanol extract and dexamethasone downregulated the expression levles of these molecules （P<0.05， P<0.01）. ConclusionC. dahurica n-butanol extract may play an anti-eczema role by inhibiting the JAK2/STAT3 signaling pathway， reducing the inflammatory response， and correcting the metabolic disorder.

Objective To investigate the effect of ATP synthase inhibitory factor 1 (ATPIF1) on the antitumor activity of chimeric antigen receptor (CAR)-NK92 cells. Methods HER2-targeted CAR-NK92 cells with ATPIF1 overexpression or knockdown were constructed. CAR-positive expression rate was detected by flow cytometry. Cell proliferation capacity was measured using CCK-8 assay. Glycolytic capacity was analyzed by Seahorse metabolic analyzer. Mitochondrial membrane potential levels were detected using JC-1 probe. Target cell lysis rate was evaluated by firefly luciferase reporter assay. Expression levels of CD107a, natural-killer group 2 member D (NKG2D), granzyme B (GzmB), perforin, and interleukin 2 (IL-2) were detected via flow cytometry. Quantitative real-time PCR was used to measure the expression of interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), tumor necrosis factor α (TNF-α), ATPIF1, and hexokinase 1 (HK1). The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined. Results Successfully generated HER2-targeting control CAR-NK92 cells, as well as ATPIF1-overexpressing and ATPIF1 knockdown CAR-NK92 cells. The ATPIF1-overexpressing CAR-NK92 cells showed significantly enhanced target cell lysis rate, elevated expression levels of NKG2D and CD107a, increased secretion capacities of Granzyme B (GzmB) and IL-2, and upregulated mRNA expression levels of IFIT1 and TNF-α, while ATPIF1-knockdown cells exhibited opposite effects. ATPIF1 overexpression induced metabolic reprogramming in CAR-NK92 cells, manifested by significantly decreased mitochondrial membrane potential (δpsim), markedly upregulated HK1 mRNA expression, and enhanced basal glycolysis and glycolytic capacity. After glycolysis inhibition with 2-DG (5 μmol/L), both ATPIF1-overexpressing and knockdown CAR-NK92 cells showed no significant differences in NKG2D and CD107a expression levels compared to control cells. Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.
Humans ; Glycolysis ; Killer Cells, Natural/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Granzymes/genetics* ; Hexokinase/metabolism* ; Cell Line, Tumor ; Interleukin-2/genetics* ; Cell Proliferation ; NK Cell Lectin-Like Receptor Subfamily K/genetics* ; Membrane Potential, Mitochondrial

Objective:To identify factors influencing treatment-free remission (TFR) outcomes in children and adolescent patients with chronic myeloid leukemia (CML) after imatinib (IM) discontinuation.Methods:This multicenter retrospective study analyzed 36 children and adolescent patients with CML from eight hematology centers in China (December 1, 2016, to September 27, 2024) who discontinued IM therapy with documented post-cessation outcomes. Clinical characteristics and molecular response dynamics were assessed. Univariate analysis and multivariate Cox proportional hazards regression models were employed to assess factors associated with TFR outcomes.Results:A total of 36 patients were documented, comprising 17 males and 19 females. The median ages at CML diagnosis and IM discontinuation were 11 years ( IQR: 5,16) and 20 years ( IQR: 14,25), respectively. The median time from IM initiation to first deep molecular response (DMR) was 21 months ( IQR: 13, 38). Pre-discontinuation, patients received IM for a median duration of 96 months ( IQR: 84, 121) and maintained DMR for 74 months ( IQR: 63, 89). With a median post-discontinuation follow-up of 38 months ( IQR: 15, 68), cumulative TFR rates at 6, 12, 24, and 36 months were 74.1%, 60.7%, 60.7%, and 56.0%, respectively, generating an overall TFR rate of 58.3%. Fifteen patients lost major molecular response at a median of 5 months post-discontinuation ( IQR: 3, 11). All 15 patients resumed tyrosine kinase inhibitor therapy, comprising 13 who restarted IM and 2 who switched to dasatinib. By the last follow-up, 13 (86.7% ) patients regained DMR after a median treatment duration of 5 months ( IQR: 3, 17), and no disease progression occurred in any patient. Withdrawal syndrome occurred in 2 (5.6% ) patients. Univariate analysis revealed significantly higher TFR rates in patients with pre-discontinuation IM duration of ≥100 months vs <100 months (82.4% vs 36.8%, P=0.017) and pre-discontinuation DMR duration of ≥72 months vs <72 months (84.2% vs 29.4%, P=0.003). Multivariate Cox analysis identified pre-discontinuation DMR duration as an independent protective factor for TFR ( HR=5.419, 95% CI: 1.524–19.272, P=0.009) . Conclusion:DMR duration was identified as an independent protective factor influencing TFR outcomes in children and adolescent patients with CML after IM discontinuation. Patients who maintained DMR for ≥72 months before IM discontinuation demonstrated a significantly higher TFR rate.

Natural killer cells(NK)are important innate immune cells that do not require prior antigen exposure and can directly recognize and attack virus-infected cells and tumor cells.The activation and effector functions of NK cells are regulated by a balance of signals delivered through their surface activating receptors and inhibitory re-ceptors,which bind to ligands on target cells to achieve cytotoxicity via"induced self"and"missing self"recogni-tion models.The killing mechanisms of NK cells primarily include release of cytotoxic granules such as perforin and granzymes to induce target cell lysis,death receptor-mediated apoptosis,secretion of various cytokines,chemokines and growth factors to coordinate with other immune cells in killing tumor cells,thereby generating secondary im-mune responses and antibody-dependent cellular cytotoxicity(ADCC).

Objective To explore the influencing factors of cognitive impairment in non-dialysis patients with chronic kidney disease(CKD).Methods A total of 60 hospitalized non-dialysis patients with CKD in the Department of Nephrology of Northern Jiangsu People's Hospital Affiliated to Yangzhou University from September 2022 to September 2023 were enrolled as research objects.According to the estimated glomerular filtration rate(eGFR),they were divided into stage 1 to 2 of CKD group[eGFR ≥60 mL/(min·1.73 m2)]with 23 cases,the stage 3 of CKD group[eGFR 30～＜60 mL/(min·1.73 m2)]with 20 cases,and stage 4 to 5 of CKD group[eGFR＜30 mL/(min·1.73 m2)]with 17 cases.The Montreal Cognitive Assessment Scale(MoCA)was used to evaluate the cognitive function of the patients.Basic data and common clinical laboratory in-dicators on hospital admission were collected to analyze the differences in cognitive function levels under different renal function statuses and to explore the influencing factors of cognitive impairment.Results The incidence rates of cognitive impairment in the stage 1 to 2 of CKD group,stage 3 of CKD group,and stage 4 to 5 of CKD group were 47.8％,85.0％,and 94.1％respectively,the median MoCA scored 26,24 and 20 respectively,with statistically significant between-group differ-ences(P＜0.05).Cognitive function was significantly negatively correlated with age(r=-0.634,P＜0.001),blood urea nitrogen(BUN)(r=-0.574,P＜0.001),serum creatinine(Cr)(r=-0.417,P＜0.001),cystatin C(Cys-C)(r=-0.327,P=0.011),serum β2-microglobulin(β2-MG)(r=-0.259,P=0.046),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(r=-0.474,P＜0.001),and was significantly positively correlated with hemoglobin(HB)(r=0.401,P=0.001)and eGFR(r=0.485,P＜0.001).Multivariate Logistic regression analysis showed that age(P=0.006)and NT-proBNP(P=0.041)were influencing factors of cognitive im-pairment in non-dialysis patients with CKD.Receiver operating characteristic(ROC)curve analysis showed that the area under the curve(AUC),sensitivity,and specificity of age for prediction were 0.860,0.864 and 0.812 respectively,the AUC,sensitivity,and specificity of NT-proBNP for pre-diction were 0.808,0.795 and 0.875 respectively,and the combined prediction of age and NT-proBNP had an AUC,sensitivity,and specificity of 0.893,0.955,and 0.750,respectively.Conclusion As renal function deteriorates,the incidence rate and severity of cognitive impairment in non-dialysis patients with CKD tend to increase.Advanced age,renal function deterioration,high NT-proBNP level,and anemia are associated with the occurrence of cognitive impairment in non-di-alysis patients with CKD,among which age and NT-proBNP are influencing factors for cognitive im-pairment.