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.

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H₂S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H₂S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H₂S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.
Humans ; Mice ; Animals ; Gastrointestinal Microbiome ; Intestinal Barrier Function ; Mice, Inbred C57BL ; Colitis/metabolism* ; Inflammatory Bowel Diseases/drug therapy* ; Inflammation ; Anti-Inflammatory Agents/pharmacology* ; Disease Models, Animal

Objective:To explore the correlation between dietary N-glycolylneuraminic acid (Neu5Gc) intake and chronic inflammation state of body.Methods:A total of 306 samples of 102 types of food were purchased from a supermarket in Xiamen in September 2019, including grains, meat, poultry, seafood, eggs, beans, dairy products, vegetables and fruits. The content of Neu5Gc in food was determined by liquid chromatography-mass spectrometry. A total of 500 healthy freshmen from Xiamen University were selected by using a simple random sampling method. The food frequency questionnaire was used to investigate the food intake in the past year. The food intake was corrected by 3 consecutive 24-hour recalls, and the amount of Neu5Gc intake was calculated. The concentration of anti-Neu5Gc antibody, C-reactive protein (CRP) and interleukin-6 (IL-6) in serum was detected. Spearman correlation analysis was used to explore the correlation between Neu5Gc intake and anti-Neu5Gc antibody, CRP and IL-6 levels.Results:Neu5Gc was mainly found in red meat and liquid dairy products. The contents of Neu5Gc in beef, lamb and pork were (30.32±2.84), (20.39±4.73) and (5.58±1.04) mg/kg, respectively, and in liquid milk and yogurt were (10.87±1.54) and (6.91±0.24) mg/L, respectively. The M ( P25, P75) intake of Neu5Gc for all participants was 4.62 (2.20, 8.60) mg/d. The M( P25, P75) intake of Neu5Gc for males about 6.60(2.83, 10.20) was higher than that for females about [3.84 (1.84, 6.35) mg/d] ( P<0.001). The M ( P25, P75) of serum anti-Neu5Gc, CRP and IL-6 levels were 3.07 (2.17, 4.14) μg/ml, 0.37 (0.22, 0.87) mg/ml and 61.82 (12.23, 315.30) pg/ml, respectively. Spearman correlation analysis showed that the intake level of Neu5Gc was positively correlated with serum anti-Neu5Gc antibody, CRP and IL-6 levels, with r s values about 0.222, 0.102 and 0.126, respectively (all P values <0.05). Conclusion:Dietary Neu5Gc intake is mainly from red meat and liquid dairy products, and its intake level is positively correlated with chronic inflammatory state of body.

Objective:To explore the correlation between dietary N-glycolylneuraminic acid (Neu5Gc) intake and chronic inflammation state of body.Methods:A total of 306 samples of 102 types of food were purchased from a supermarket in Xiamen in September 2019, including grains, meat, poultry, seafood, eggs, beans, dairy products, vegetables and fruits. The content of Neu5Gc in food was determined by liquid chromatography-mass spectrometry. A total of 500 healthy freshmen from Xiamen University were selected by using a simple random sampling method. The food frequency questionnaire was used to investigate the food intake in the past year. The food intake was corrected by 3 consecutive 24-hour recalls, and the amount of Neu5Gc intake was calculated. The concentration of anti-Neu5Gc antibody, C-reactive protein (CRP) and interleukin-6 (IL-6) in serum was detected. Spearman correlation analysis was used to explore the correlation between Neu5Gc intake and anti-Neu5Gc antibody, CRP and IL-6 levels.Results:Neu5Gc was mainly found in red meat and liquid dairy products. The contents of Neu5Gc in beef, lamb and pork were (30.32±2.84), (20.39±4.73) and (5.58±1.04) mg/kg, respectively, and in liquid milk and yogurt were (10.87±1.54) and (6.91±0.24) mg/L, respectively. The M ( P25, P75) intake of Neu5Gc for all participants was 4.62 (2.20, 8.60) mg/d. The M( P25, P75) intake of Neu5Gc for males about 6.60(2.83, 10.20) was higher than that for females about [3.84 (1.84, 6.35) mg/d] ( P<0.001). The M ( P25, P75) of serum anti-Neu5Gc, CRP and IL-6 levels were 3.07 (2.17, 4.14) μg/ml, 0.37 (0.22, 0.87) mg/ml and 61.82 (12.23, 315.30) pg/ml, respectively. Spearman correlation analysis showed that the intake level of Neu5Gc was positively correlated with serum anti-Neu5Gc antibody, CRP and IL-6 levels, with r s values about 0.222, 0.102 and 0.126, respectively (all P values <0.05). Conclusion:Dietary Neu5Gc intake is mainly from red meat and liquid dairy products, and its intake level is positively correlated with chronic inflammatory state of body.

OBJECTIVE： To provide reference for pharmaceutical manufacturers improving the quality system of GMP and drug regulatory departments improving their supervision level. METHODS： Through analyzing and summarizing the problems existing in the 28 pharmaceutical enterprises which had been published on the website in the National Medical Products Administration from February 6th， 2018 to January 25th， 2019， the common problems were found and their causes were analyzed， then the regulatory countermeasures were put forward. RESULTS & CONCLUSIONS： Pharmaceutical enterprises have some problems of inadequate implementation of GMP， such as the inadequate performance of personnel in key positions and the unsatisfactory training effect of relevant personnel， the inconsistency between actual production technology and approved legal technology， the non-standard management of enterprise materials， the incomplete batch production records and the inability to effectively monitor the production cycle. However， there are also some problems in the supervision department， such as the large difference in the scale of inspectors’ on-site inspection， the need to strengthen the inspectors’ inspection ability and level， and the lack of innovation in the means of supervision. It is suggested that pharmaceutical manufacturers should improve the construction of GMP quality management system and strengthen the training of relevant personnel； the regulatory authorities should continue to promote the reform of “release， control and service”， strictly enforce the access conditions of inspectors， strengthen the training of inspectors and ideological construction of the inspector team，further strengthen the construction of supervision system and enhance the innovation of supervision means， so as to jointly maintain the safety， effectiveness and quality controllability of medicines.

Vaccination, one of the greatest inventions of mankind, prevents millions of people from infectious diseases and death each year. With the continuous improvement in immunization coverage, the safety of vaccines has attracted widespread attention. Common adverse reactions to vaccinations are mainly caused by inflammation, but the immune responses and biological damages following immunization are so complicated that the possible mechanisms have not been completely unveiled. Exploring the relationship between inflammation and immunogenicity after vaccination is of great significance for the monitoring and management of vaccines after marketing. This article reviewed the mechanism of inflammatory responses after vaccination and its potential impact on immunogenicity.

BACKGROUND: Nasal mucosa fibroblasts are reported to involve in inflammation and wound repair of various nasal diseases by secreting a variety of cytokines and chemokines. Guinea pig is a most suitable experimental animal for the study of allergic diseases. OBJECTIVE: To investigate the effective methods of isolation, culture, purification and identification of guinea pig nasal mucosa fibroblasts. METHODS: Guinea pig nasal mucosa fibroblasts were isolated by collagenase digestion, and purified by differential velocity adherence. The morphology of fibroblasts was observed by inverted phase contrast microscope, fibroblasts were identified by vimentin immunocytochemical staining, and the cell growth was detected by MTT assay to draw the growth curve. RESULTS AND CONCLUSION: (1) Under inverted phase contrast microscope, there were cells with different shapes in the primary nasal mucosa fibroblasts, most of which showed spindle-like and applanate shape, and cells were scattered distribution in cluster. The purified fibroblasts were homogeneous, mainly were long spindle-shaped, and distributed in fish shoal-like and radial-like. (2) Immunocytochemical staining indicated that fibroblasts were positive for vimentin. (3) The cell growth curve appeared to be typical S-shaped. (4) To conclude, the isolated and cultured cells exhibit typical biological characteristics of fibroblasts.