OBJECTIVE To mine and analyze adverse event signals associated with inebilizumab， and to provide reference for safe and rational clinical use. METHODS Reports of adverse event related to inebilizumab were collected from the FDA adverse event reporting system （FAERS） database， from Q2 2020 to Q4 2024. Adverse events were standardized and categorized according to the preferred term （PT） and system organ class （SOC） of the Medical Dictionary for Regulatory Activities （MedDRA） version 26.0. Signals were mined using the reporting odds ratio （ROR） method and the Bayesian confidence propagation neural network （BCPNN） method. RESULTS A total of 783 adverse event reports with inebilizumab as the primary suspected drug were identified， involving 297 patients. Most reports originated from the United States and Japan， with physicians being the primary reporters. Female patients outnumbered males， and the most common age group was 45-64 years. Using the ROR method and BCPNN method， a total of 29 valid adverse event signals were detected， involving 12 SOCs and comprising 225 adverse event reports. The five most frequently reported PTs were headache， nausea， fatigue， infectious pneumonia and arthralgia. The five PTs with the strongest signal intensity were： B-cell recovery， decreased blood immunoglobulin G， spinal compression fracture， COVID-19 and acute respiratory distress syndrome. Among the 29 valid signals for adverse event， 19 were not documented in the drug package inserts， involving 10 SOCs and comprising 107 adverse event reports. These encompassed nervous system disorders， general disorders and administration site conditions， eye disorders， among others. CONCLUSIONS Inebilizumab treatment not only causes adverse events documented in the product information， such as infections， immunoglobulin reduction and infusion-related reactions but also leads to potential signals， including B-cell recovery， spinal compression fracture. When using this drug in clinical practice， the patient’s risk of infection and baseline immune status should be assessed， relevant indicators should be closely monitored， and targeted preventive measures should be considered when necessary.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background: Bone cancer pain (BCP) is not adequately addressed by current treatment methods, making the exploration of effective management strategies a topic of significant interest. Bone marrow mesenchymal stem cells (BMSCs) seem to be a potential way for managing BCP, yet little is known about the mechanisms underlying the efficacy of this potential treatment. Methods: We established the male C57BL/6 mice BCP models. Behavioral tests, X-ray, bone histology, western blotting, and immunofluorescence were used to verify the analgesic effect of BMSCs. Results: Intramedullary injection of Lewis lung carcinoma cells into the femur successfully generated the mice BCP models. The number of c-Fos-positive neurons and phosphorylated mitogen-activated protein kinase (MAPK) proteins in the spinal dorsal horn of the BCP mice increased. Intrathecal injection of BMSCs temporarily improved the BCP mice’s mechanical and thermal hyperalgesia without affecting motor function. This effect may be related to inhibiting spinal microglia and p-p38 MAPK activation. The analgesic effect of BMSCs may be related to the homing effect mediated by CXCR4. Conclusions Intrathecal injection of BMSCs can temporarily inhibit mechanical and thermal hyperalgesia in BCP mice without affecting motor function. This effect may be related to the inhibition of p-p38 protein expression and the inhibition of microglia but not to p-ERK and p-JNK.

Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Objective To evaluate the accuracy and reproducibility of AlignRT-guided positioning by comparing two positioning workflows for pelvic tumor radiotherapy,and to further explore the feasibility of using it to replace skin marker alignment.Methods Forty cases of pelvic tumor treated with radiotherapy using Infinity accelerator in Sun Yat-sen University Cancer Center between March 2022 and March 2023 were included in the study,with 20 cases using the skin marker alignment workflow and the other 20 adopting AlignRT-guided positioning workflow.The translational errors(LAT,LNG,VRT)and rotational errors(Yaw,Pitch,Roll)were determined by the registration of pre-treatment cone-beam CT(CBCT)with planned CT.Both CBCT shifts and error offset distributions were analyzed;planning target volume(PTV)margins were calculated;and correlation analyses were conducted among six-dimensional errors,and between body mass index and setup errors.Results The median translational and rotational setup errors of skin marker alignment workflow vs AlignRT-guided positioning workflow were 0.19-0.34 cm vs 0.10-0.15 cm and 0.50°-1.30°vs 0.50°-0.70°,with the maximum offset ranges of 1.20-1.70 cm vs 0.42-0.47 cm and 2.00°-5.50° vs 1.80°-2.00°,respectively.Additionally,for skin marker alignment workflow,inter-fractional errors>0.5 cm and>3° were observed in 23.3%and 9.8%of fractions.The PTV margins of AlignRT-guided positioning workflow were 0.37,0.38 and 0.34 cm in the left-right,superior-inferior and anterior-posterior directions,respectively,which were much smaller than those of skin marker alignment workflow(0.67,1.22 and 0.95 cm).No correlation was found between six-dimensional errors in two positioning workflows.When using AlignRT-guided positioning workflow,the setup errors in LAT,LNG and Pitch directions had low correlations with body mass index.Conclusion In pelvic tumor radiotherapy,AlignRT-guided positioning can reduce translational and rotational errors,achieve precise setup and excellent inter-fractional reproducibility and stability,and replace traditional skin marker alignment while being used in conjunction with CBCT.

Silver nanoparticles(AgNPs)are employed as disinfectants due to their extensive antimi-crobial properties,but their biosafety in the livestock industry has not been comprehensively as-sessed.In this study,16 Black-skin Red-crowned chickens aged 32 weeks were randomly divided in-to four groups and sprayed with AgNP solution at the concentration of 0,0.064,0.128 or 0.256 g/L,respectively,every 72 h in their coops for 30 d.The effects of AgNPs as the disinfectant on lung tissue in chicken were investigated through calculation of organ coefficients,observation of lung tissue sections,analysis of bronchoalveolar lavage fluid,measurement of inflammatory factors,de-tection of silver residue in lung tissue,and exploration of signaling pathways in pulmonary fibrosis.The results indicated that chickens in the 0.128 and 0.256 g/L AgNPs treatment groups showed the blurred pulmonary lobule boundaries,the destroyed alveolar structure,and the significant in-crease in pulmonary fibrosis.These pathological changes were accompanied by the decrease in lung organ coefficient,the reduced SP-C content,the increased total protein concentration in lavage flu-id,and the elevated LDH and silver content in lung tissue.The levels of IL-6 and TNF-α in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than the control group,which suggested that AgNPs exposure could induce the pulmonary inflammatory responses.High concentrations of AgNPs can trigger pulmonary tissue fibrosis,damaging the structure and func-tions of lungs.The relative mRNA expression levels of NF-κB in all AgNPs treatment groups,TGF-β in the 0.128 g/L AgNPs treatment group,and Smad3 in the 0.128 and 0.256 g/L AgNPs treatment groups were significantly higher than these in the control group,respectively.Spraying chickens with 0.128 or 0.256 g/L AgNPs for disinfection led to pulmonary deposition of AgNPs,causing direct structural and functional damages to the lungs.It could also induce the chronic pul-monary inflammation through the NF-κB pathway and promote the TGF-β/Smad3 pathway to in-crease collagen synthesis,leading to pulmonary fibrosis.Therefore,the application of high concen-trations of AgNPs in livestock farming requires careful consideration of their potential biological safety issues.

Objective:To explore the latent pattern characteristics of adolescent prosocial behavior and their relationship with the sense of life meaning.Methods:A total of 1 500 students from primary and secondary schools were selected.The Adolescent Prosocial Behavior Questionnaire and the Meaning in Life Questionnaire were admin-istered.Latent profile analysis was used to investigate the potential categories of prosocial behavior,and variance a-nalysis was employed to compare the relationship between prosocial behavior and life meaning.Results:Adolescent prosocial behavior was classified into 3 latent categories,namely negative prosocial behavior type(5.7％),altruistic relationship behavior type(36.7％),and positive prosocial behavior type(57.6％).The score differences in each dimension of the variables among the 3 categories were statistically significant(P＜0.01).Among the three latent categories,the positive prosocial behavior type scored higher on all dimensions than the altruistic relationship behav-ior type(P＜0.05),and the altruistic relationship behavior type scored higher than the negative prosocial behavior type(P＜0.05).Conclusion:There are three distinct latent profiles in adolescent prosocial behavior,which are closely associated with the sense of life meaning.

Objective:To analyze the intention to receive influenza vaccination and its associated factors among urban and rural residents aged≥50 in Zhejiang Province, China, in 2024.Methods:This cross-sectional study was conducted between March and May 2024 through a multi-stage intercept survey in 35 counties (cities, districts) selected from a total of 90 in Zhejiang Province, involving 175 communities/villages. The survey targeted residents visiting local hospitals and community health service centers/community health clinics. The questionnaire included basic demographic information, knowledge related to influenza prevention and treatment, chronic disease status, history of influenza vaccination, and intention to vaccinate. Urban and rural residents were classified based on their registered residence, according to the "Rules for Compilation of Statistical Regional Code and Urban-Rural Division Code" issued by the National Bureau of Statistics. Chi-square tests, ANOVA, and multivariate logistic regression models were used to analyze the factors influencing the intention to receive the influenza vaccine.Results:A total of 10 500 participants were surveyed, comprising 4 885 rural residents (46.52%) and 5 615 urban residents (53.48%). Of these, 3 430 rural residents (70.21%) and 3 718 urban residents (66.22%) expressed intention to receive the influenza vaccine. Multivariate logistic regression analysis revealed that for rural residents aged≥50, younger age groups (50-59 years: OR=1.747, 95% CI: 1.290-2.366; 60-69 years: OR=1.838, 95% CI: 1.401-2.411), history of influenza vaccination ( OR=6.721, 95% CI: 5.152-8.767), doctor′s recommendation for vaccination ( OR=3.788, 95% CI: 3.078-4.662), and higher scores on knowledge related to influenza prevention and treatment ( OR=1.090, 95% CI: 1.054-1.128) were significant promoting factors for vaccination intent. For urban residents aged≥50, belonging to the 60-69 age group ( OR=1.264, 95% CI: 1.023-1.563), history of influenza vaccination ( OR=5.392, 95% CI: 4.309-6.748), doctor′s recommendation for vaccination ( OR=5.307, 95% CI: 4.420-6.371), and higher scores on knowledge related to influenza prevention and treatment ( OR=1.051, 95% CI: 1.021-1.082) were significant promoting factors for vaccination intent. Conclusions:The intention to receive the influenza vaccination is notably high among residents aged≥50 in both urban and rural areas of Zhejiang Province, yet there remains potential for improvement. Age, history of influenza vaccination, doctor recommendation, and knowledge related to influenza prevention and treatment are significant factors influencing the intention to receive the influenza vaccination.