Objective: To compare and analyze the antibacterial effects of platelets against five common clinical pathogenic bacteria including MRSA, SE, SA, E. coli, and CRKP, and to preliminarily explore the role of DCD sensitivity in the observed variations of antibacterial effects. Methods: The same number of platelets were used to establish co-culture systems of platelets and platelet lysates with the five pathogenic bacteria. The antibacterial effects of platelets and platelet lysates on the five pathogenic bacteria were evaluated by observing the turbidity of the bacterial solution, measuring the OD value of the bacterial solution and counting the colonies. The supernatant protein of platelets co-cultured with MRSA was collected for quantitative proteomics analysis to explore the important antibacterial proteins of platelets. The content of DCD in the supernatant after co-culture of platelets and platelet lysates with the five pathogenic bacteria was detected by ELISA to preliminarily analyze the reasons for the different antibacterial effects of platelets on the five pathogenic bacteria. Results: Compared with the control group of MRSA, SA, and SE, the turbidity of the bacterial solution decreased after co-culture of platelets and platelet lysates with MRSA, SA, and SE for 12 h, and the OD value and colony count were significantly reduced (P<0.05). The turbidity of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with E. coli for 24 h, but the OD value decreased (P<0.05), and the colony count decreased to 10 CFU/mL but the difference was not statistically significant (P>0.05). Compared with the control group of CRKP, the turbidity, OD value, and colony count of the bacterial solution did not change significantly after co-culture of platelets and platelet lysates with CRKP (P>0.05). Proteomics results showed that after co-culture with MRSA, important proteins related to platelet activation, including collagen, fibrinogen, von Willebrand factor, integrin αIIbβ3, platelet glycoprotein V and IV were significantly up-regulated. ELISA results showed that after co-culture with the five pathogenic bacteria, platelets could secrete a large amount of DCD, with the content around 3 μg/mL. Conclusion: The antibacterial effect of platelets on Gram-positive bacteria MRSA, SA, and SE is better than that on Gram-negative bacteria E. coli and CRKP, and platelets have the best antibacterial effect on MRSA. The differences in antibacterial effects of platelets on the five pathogenic bacteria may be related to the sensitivity of DCD antibacterial peptides to the five pathogenic bacteria.

【Objective】 To explore the relationship between polygenic risk score (PRS) and the sustainability of childhood obesity intervention, in order to provide scientific basis for future sustainable and personalized childhood obesity intervention based on genetic background. 【Methods】 A total of 148 children with overweight/obesity at baseline were selected as study subjects from a cluster randomized controlled trial (September 2018 to April 2021) regarding the effect of a childhood obesity intervention in Beijing, China. Saliva was collected to detect the whole genome sequencing. Four PRSs were built: weighted and unweighted PRS69, weighted and unweighted PRS67. The interactions between PRS and study arms on the sustainability of intervention effect (the changes in obesity-related indicators between the end of the intervention and the last follow-up) were analyzed. 【Results】 There were interactions between PRS and study arms on the rebound degree of waist circumference adjusted for body mass index (BMI), waist-to-hip ratio adjusted for BMI, and systolic blood pressure after the intervention. Compared with the control group, children in the intervention group carried each additional unit (standard deviation) of weighted PRS69, the waist circumference adjusted for BMI rebounded more by 0.34 (95%CI: 0.05 - 0.63, P=0.020), and waist-to-hip ratio adjusted for BMI rebounded more by 0.29 (95%CI: 0.03 - 0.56, P=0.031) at the last follow-up survey. When children in the intervention group carried each additional unit (standard deviation) of weighted PRS67 and unweighted PRS67, systolic blood pressure at the last follow-up survey rebounded more by 3.58 (95%CI:0.50 - 6.66, P=0.023) and 3.75 (95%CI: 0.78 - 6.71, P=0.014), respectively. 【Conclusions】 The higher PRS (the more risk alleles) children with overweight/obesity carried, their waist circumference, waist-to-hip ratio and systolic blood pressure are more likely to rebound after the intervention. Findings from this study suggest that future studies should focus more on these high-risk children after the intervention to prevent and control obesity rebound.

Biological hydroxyapatite(BHA)is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity.The clinical application of mateiral size is based on the principle of bone defect area adaptation,which contributes to diversity of BHA sizes.However,different sizes correspond to different hierarchi-cal levels of bone biomimicry.As the size changes,the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation,leading to unstable bone graft outcomes.Therefore,this paper reviews the size effect of clinical BHA,analyzes the multilevel structure of natural bone,proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA,and further analyzes the size-media-ted osteo-coagulo-immunomodulation.Based on the hierarchical levels of bone and its osteo-coagulo-immunomodula-tion effect,we provide a new understanding of the biolog-ical principle of the size effect of biomaterials and a theo-retical basis for the basic research and clinical application of different size BHA materials.

There is increasing evidence that the activation of glucagon-like peptide-1 receptor(GLP-1R)can be used as a therapeutic intervention for cognitive disorders.Here,we have screened GLP-1 R targeted com-pounds from Scutellaria baicalensis,which revealed baicalein is a potential GLP-1 R small-molecule agonist.Mitophagy,a selective autophagy pathway for mitochondrial quality control,plays a neuro-protective role in multiple cognitive impairment diseases.We noticed that Glp1r knock-out(KO)mice present cognitive impairment symptoms and appear worse in spatial learning memory and learning capacity in Morris water maze(MWM)test than their wide-type(WT)counterparts.Our mechanistic studies revealed that mitophagy is impaired in hippocampus tissue of diabetic mice and Glp1r KO mice.Finally,we verified that the cognitive improvement effects of baicalein on diabetic cognitive dysfunction occur through the enhancement of mitophagy in a GLP-1 R-dependent manner.Our findings shed light on the importance of GLP-1 R for cognitive function maintenance,and revealed the vital significance of GLP-1R for maintaining mitochondrial homeostasis.Furthermore,we identified the therapeutic potential of baicalein in the treatment of cognitive disorder associated with diabetes.

Objective To evaluate the effectiveness of tumor cell Vimentin combined with endoscopic ultrasound-guided fine-needle biopsy(EUS-FNB)in diagnosing solid pancreatic tumors.Methods Clinical data from 110 patients who underwent EUS-FNB from October 2021 to December 2023 were retrospectively analyzed.Solid pancreatic tumors including but not limited to pancreatic cancer and pancreatic neuroendocrine tumors.The sensitivity,specificity,and accuracy of EUS-FNB were assessed by comparing its results with the final pathological diagnoses.Result Clear histopathological diagnoses were obtained in 106 cases,accounting for 96.37%.Among them,87 cases were definitively diagnosed as adenocarcinoma or pancreatic ductal adenocarcinoma.Immunohistochemical staining showed that Vimentin was expressed in the tumor cells.There was no statistically significant difference in positive rates among biopsies from different anatomical sites(P>0.05),but significant differences were observed in lesions of different diameters(P<0.05).Immunohistochemical staining suggested that Vimentin expression levels might be associated with the nature of the lesions.The overall diagnostic accuracy,sensitivity,and specificity of Vimentin combined with EUS-FNB for pancreatic masses were 86.09%,84.57%,and 100.00%,respectively.Specifically,for solid masses,the diagnostic accuracy,sensitivity,and specificity were 87.67%,86.55%,and 100.00%,respectively.For pancreatic cystic tumors,the diagnostic accuracy,sensitivity,and specificity were 65.42%,69.79%,and 100.00%,respectively.Conclusion The combination of tumor cell Vimentin and EUS-FNB demonstrates high diagnostic accuracy for solid pancreatic tumors,making it a valuable tool for clinical application.

Objective To explore the optimal method for preparing fresh and fixed skeletal muscle tissues,and to lay an experimental foundation for the rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.Methods The tibialis anterior muscle was extracted from C57BL/6J mice.Fresh tissue was treated by direct rapid freezing in liquid nitrogen,embedding combined with liquid nitrogen freezing,and foreign body alkane treatment combined with liquid nitrogen freezing.Fixed tissues were pre-treated by direct embedding with embedding agent combined with rapid liquid nitrogen freezing.The frozen sections were stained with hematoxylin and eosin.The cross-sectional areas of ice crystals and muscle fibers were calculated to evaluate the effects of the different pre-treatment method.Results The morphology of the muscle fiber bundles was disrupted and numerous ice crystal vacuoles were observed in fresh tissues after direct liquid nitrogen freezing and foreign body alkane treatment combined with liquid nitrogen freezing.In contrast,the muscle fiber bundles were intact and dense and there were no ice crystals in tissues treated with embedding agent combined with rapid liquid nitrogen freezing,indicating that this pre-treatment method was suitable for preparing fresh skeletal muscle tissue.Fixed tissue treated with embedding agent and liquid nitrogen freezing also showed complete muscle fiber bundles and no ice crystals.Conclusions Treatment of fresh and fixed skeletal muscle tissues with embedding agent combined with rapid liquid nitrogen freezing preserves muscle fiber bundles,with no ice crystals.Tissues prepared by this method are thus suitable for further examinations,such as immunohistochemistry and immunofluorescence.This method will therefore aid the accurate and rapid diagnosis of and research into the pathogenesis of skeletal muscle diseases.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Objective: To study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity, so as to provide scientific basis for formulating personalized intervention measures based on genetic background in children with obesity. Methods: From September 2018 to June 2019, a total of 393 children aged 8-10 years in Beijing were enrolled in a cluster randomized controlled trial. Eight schools were randomly allocated into intervention group and control group at a ratio of 1∶1. Saliva DNA samples were collected to detect rs 12145833 polymorphism of SDCCAG 8 gene. The intervention group received a comprehensive intervention, while the control group received usual practice. Intervention measures included diet improvement, sports, school amd family sport. The obesity related indicators were measured at baseline and after the end of intervention 1 academic year. Multiple linear regression and Logistic regression were used to analyze the interaction between genes and intervention on obesity indicators. Results: In the intervention group, children with TT genotype of rs 12145833 of the SDCCAG 8 gene had less increase in systolic( β=4.56, 95%CI=1.84-7.28, P <0.01) and diastolic blood pressure( β=2.59, 95%CI=0.45-4.73, P <0.05) than those with GT and GG genotypes. In the control group, the systolic blood pressure of children with TT genotype increased more than those with GT and GG genotype( β=-2.86, 95%CI=-5.63--0.83, P <0.05). There was an interaction between rs 12145833 polymorphism of SDCCAG 8 gene and intervention on systolic blood pressure, diastolic blood pressure and body fat percentage in children( P <0.05). Conclusion Children with TT genotype of rs 12145833 in the SDCCAG 8 gene are more sensitive to obesity intervention than those with GG and GT genotypes, especially in the improvement of systolic blood pressure, diastolic blood pressure and body fat percentage. Further trials to study the role of rs 12145833 polymorphism of SDCCAG 8 gene in the intervention of childhood obesity among different ethnic populations are needed.

Objective To explore the association between iron metabolism indexes and the risk of gestational diabetes mellitus(GDM)in pregnant women with advanced age.Methods A total of 292 pregnant women,whose age were≥35 years old and gave birth in Taicang First People's Hospital from April 2021 to April 2023,were retrospectively included and divided into GDM group and non-GDM group.The differences of iron metabolism indexes[serum ferritin(SF),serum iron(SI)and hemoglobin(Hb)]measured from the 20 to 24 weeks of gestation were compared between the two groups.Multivariable Logistic regression model was used to explore the association of SF,SI and Hb with GDM.Based on the data of single nucleotide polymorphism from IEU OpenGWAS(http://gwas.mr-cieu.ac.uk/)and FinnGen datasets,two samples Mendelian randomization analysis were conducted to explore the causal relationship between iron metabolism indexes and GDM by using the methods of Inverse Variance Weighted(IVW).Results In the maximally ad-justed multi-factor logistic models,the statistically significant association between SF measured from 20 to 24 weeks of gestation and the risk of GDM was found[odds ratio(95％confident interval)=1.02(1.01-1.04),P=0.001].The association between Hb and GDM was marginally significant[odds ratio(95％confident interval)=1.04(1.00-1.07),P=0.044],but no association between SI and GDM reached statistical significance.However,Mendelian randomization analysis showed there was no significant evidence for causal association between SF,Hb and GDM.Conclusion SF examined at 20 to 24 weeks of gestation could be used as a biomarker of GDM in the pregnant women with advanced age,but no evidence supported the causal association between SF and GDM.

Abstract In recent decades, the prevalence of childhood obesity has increased at a alarming rate. The health hazards of childhood obesity are substantial, which has become an important public health problem. Lifestyle intervention is an effective means to prevent childhood obesity. However, individuals varied in their response to the intervention program, which may be associated with genetic factors. This paper systematically reviews the research progress of the effects of FTO, MC4R and other genetic variants on childhood obesity interventions, summarizes the limitations of current research and sheds light on the future research, so as to provide scientific evidence for individualized childhood obesity interventions based on genetic backgrounds.