Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

Background: The immune system plays a critical role in the development and progression of osteoporosis and fractures. However, the causal relationships between antibody immune responses, immune cells, and these bone conditions remain unclear. This study aimed to explore these relationships using Mendelian randomization (MR) analysis. Methods: We collected complete blood count data from patients with fractures and healthy individuals and analyzed their differences. Then, we conducted a 2-sample, 2-step MR analysis to investigate the causal effects of antibody immune responses on osteoporosis and fractures, using inverse-variance weighted (IVW) as the primary method. We also explored whether immune cells mediate the pathway between antibodies and osteoporosis or fractures. Finally, we analyzed the functions and expression levels of key genes involved. Results: Overall, the fracture group exhibited increased white blood cell count, absolute neutrophil count, absolute monocyte count, platelet count, and their respective proportions, while absolute lymphocyte count, absolute eosinophil count, absolute basophil count, red blood cell count, and their proportions were decreased. We identified 44 causal relationships between antibodies and osteoporosis or fractures, with 7 supported by multiple MR methods, and 5 showing odds ratios significantly deviating from 1 in the IVW analysis. Epstein-Barr virus-related antibodies had a notable impact on osteoporosis and fractures. The human leukocyte antigen (HLA) gene family, particularly HLA-DPB1, emerged as a significant risk factor. However, immune cells were not found to mediate these effects. Conclusions This study elucidated the causal relationships between antibody immune responses, immune cells, and osteoporosis or fractures. The HLA gene family plays a crucial role in the interaction between antibodies and these bone conditions, with HLA-DPB1 identified as a key risk gene. Immune cells do not serve as mediators in this process. These findings provide valuable insights for future research.

BACKGROUND:Multiple clinical observational studies have suggested a close relationship of serum trace elements and nutrients with osteonecrosis,but it remains unclear whether there is a genetic causal effect between serum trace elements and nutrients on osteonecrosis. OBJECTIVE:To investigate the causal effects of serum trace elements and nutrients on osteonecrosis using the Mendelian randomization approach. METHODS:The exposure factors of serum trace elements and vitamins with mononucleotide polymorphisms were obtained from the published UK Biobank database and publicly available databases of genome-wide association studies.The outcome event of osteonecrosis was derived from the FinnGen Biobank database.Mendelian randomization methods were employed to explore the causal relationship between seven trace elements and three nutrients with osteonecrosis.Causal inference was conducted using inverse variance weighting,MR-Egger,and weighted median methods.F-statistic was calculated to ensure the robustness of instrumental variables.Cochran's Q test and leave-one-out method were used for heterogeneity testing.MR-Egger regression and MR-PRESSO were employed for horizontal pleiotropy testing.PhenoScanner database was utilized to remove mononucleotide polymorphisms with horizontal pleiotropy to ensure the reliability of the results. RESULTS AND CONCLUSION:Causal relationships were found between serum selenium,phosphate,vitamin C,vitamin E,and osteonecrosis through Mendelian randomization analysis.Serum selenium,vitamin C,and vitamin E were found to have a protective effect on osteonecrosis,while excessive intake of phosphate increased the risk of osteonecrosis.No heterogeneity or horizontal pleiotropy was observed during the study,and Mendelian randomization statistical power(Power value>80%)indicated the reliability of the aforementioned four results.These findings have important clinical implications for the development of targeted preventive and therapeutic measures for osteonecrosis.

Cohort study of children and adolescents health is an ideal method to explore health-related problems from childhood to adulthood, to which more attention has been paid. This paper summarizes the progress in cohort study of children and adolescents health conducted both at home and abroad by introducing the study design, main contents. Emphasizing the international exchange and cohort integration, continuously expanding cohort research field, and using multi-source data for high-quality follow-up have become the trend of cohort study of children and adolescents health.

Purpose: This study aimed to evaluate changes in ultrafast pulse wave velocity (ufPWV) in individuals with arterial stiffness and subclinical atherosclerosis (subAS), and to provide cutoff values. Methods: This retrospective study recruited 231 participants, including 67 patients with subAS. The pulse wave velocity was measured at the beginning and end of systole (PWV-BS and PWVES, respectively) using ultrafast ultrasonography to assess arterial stiffness. The right and left common carotid arteries were measured separately, and laboratory metabolic parameters were also collected. Participants were balanced between groups using propensity score matching (PSM) at a 1:1 ratio, adjusting for age, sex, and waist-to-hip ratio as potential confounders. Cutoff values of ufPWV for monitoring subAS were determined via receiver operating characteristic (ROC) curve analysis. Results: PWV-ES, unlike PWV-BS, was higher in the subAS subgroup than in the subAS-free group after PSM (all P<0.05). For each 1 m/s increase in left, right, and bilateral mean PWV-ES, the risk of subAS increased by 23% (95% confidence interval [CI], 1.04 to 1.46), 26% (95% CI, 1.07 to 1.52), and 38% (95% CI, 1.12 to 1.72), respectively. According to ROC analyses, predictive potential was found for left PWV-ES (cutoff value=7.910 m/s, P=0.002), right PWV-ES (cutoff value=6.615 m/s, P=0.003), and bilateral mean PWV-ES (cutoff value=7.415 m/s, P<0.001), but not for PWV-BS (all P>0.05). Conclusion PWV-ES measured using ultrafast ultrasonography was significantly higher in individuals with subAS than in those without. Specific PWV-ES cutoff values showed potential for predicting an increased risk of subAS.

AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.

Objective:To investigate the efficacy and safety of tocilizumab in the treatment of critically ill children with acute necrotizing encephalopathy (ANE).Methods:It is a retrospective cohort study. The children with ANE admitted to the pediatric intensive care unit of 4 Chinese tertiary hospitals from December 2022 to November 2023 were divided into conventional treatment group and tocilizumab group, and the comparison between groups was performed by using Mann ‐ Whitney U test or Chi-square test. Results:Among 21 cases of severe ANE, there were 11 males with the onset age of 65 (27, 113) months. The duration from onset to PICU admission was 2 (1, 2) days. There were 13 cases of ultra-high fever (greater than 40 ℃), including 18 cases of convulsions, and 19 cases with a GCS score of less than 8 points. The causative agent was novel coronavirus Omicron in 7 cases and influenza A in 14 cases. All cases had central respiratory failure requiring mechanical ventilation. Of the 21 cases, 18 were shock, 15 were coagulopathy, 10 were kidney injury and 13 were liver dysfunction. Of these hospitalized patients, 8 children with ANE were treated with tocilizumab. Eight cases received continuous blood purification (CBP) treatment, 5 of them were combined with plasmapheresis. Serum cytokine levels were elevated in 21 children with ANE, including (interleukin, IL)-6 and IL-8 (61 (22, 1 513) and 68 (5, 296) ng/L). There were 14 cases (67%) deaths, including 11 cases in the conventional treatment group and 3 cases in the tocilizumab group. There was no significant difference in the mortality rate between the two groups ( P=0.056). Tocilizumab-related rash or other adverse events were not observed. Conclusions:The motality of critically ill ANE patients was high. The combination of Tocilizumab with conventional treatment did not reduce the motality of severe ANE patients, and no adverse reactions of tocilizumab were observed.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.