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.

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.

【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.

Objective The study aimed to compare the diagnostic efficacy of QuantiFERON-TB Gold(QFT-TB)detection of specific cellular immune IGRAs in tuberculosis diagnostic laboratory for pulmonary tuberculosis,extrapulmonary tuberculosis and special population samples in vitro,which may provide evidence for clinical diagnosis and treatment.Methods A total of 546 patients with tuberculosis(AFB + 146 cases,AFB-247 cases),117 patients with molecular biology positive tuberculosis(Xpert 69 cases,TB-DNA 48 cases)and 36 patients with histopathological positive were collected from January to July 2023.There were 72 cases of extrapulmonary tuberculosis,276 cases of pleural effusion and 25 cases of ascites.QFT-TB method was used for detection,chi-square test was applied for com-parison between groups,and the methodological evaluation of positive rate and coincidence rate were all compared.Results The positive rates of QFT-TB in pulmonary tuberculosis,extrapulmonary tuberculosis and close contacts were 83.69%,69.44%,and 32.41%,respectively.The coincidence rates of QFT-TB in AFB +,GeneXpert,TB-DNA and pathological confirmed tuberculosis patients were 91.09%,88.40%,81.25%,and 72.22%,respectively.The positive rate of pleural effusion in patients with tuberculous pleurisy was 60.50%,and the uncertainty rate was 29.71%.The positive rate of ascites was 44.00%and the uncertainty was 36.00%.Conclusion QFT-TB test has good value in the auxiliary diagnosis of pulmonary tuberculosis,and has certain reference significance for the diagnosis of extrapulmonary tuberculosis based on the detection of pleural fluids and ascites.

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.

Background::Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).Method::The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).Results::MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI= 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions::These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.

[Objective]Depression is a common mental illness with a profound impact on physical health.Depression has been associated with a higher risk of bacterial infection;however,whether this relationship is causal and how depression affects infection remains unclear.Therefore,we aimed to investigate the effects of depressive phenotype in infected mice by constructing a chronic unpredictable mild stress(CUMS)model.[Methods]Mice were induced with CUMS for 4 weeks.The depressive phenotype was evaluated using behavioral tests.Subsequently,the mice were intraperitoneally injected with Klebsiella pneumoniae to establish bacterial infection.Serum and abdominal tissues were collected 48 h after infection.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the tissues,and enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of inflammatory factors.In addition,the fecal samples collected before infection were analyzed for 16S rDNA gene of gut microbiota,and the expression levels of NF-κB/NLRP3 signaling pathway in colon tissues of uninfected mice were detected.[Results]Behavioral tests showed that compared with the control mice,CUMS mice had significantly lower body weight(P<0.0001,t=5.426),lower sucrose preference rate(P<0.001,t=4.937),increased swimming stationary time(P<0.001,t=16.37),and decreased time spent in the central area of the open field(P<0.01,t=3.575).Survival analysis showed that compared with the control mice,the survival rate of CUMS mice significantly decreased after infection(P<0.05).Additionally,histochemical staining showed that tissue damage in the liver(P<0.05,t=4.025),kidney(P<0.05,t=2.828),and mesentery(P<0.01,t=5.367)significantly increased.Furthermore,ELISA results showed that the levels of the inflammatory cytokines IL-6(P<0.01,t=3.365),IL-1β(P<0.01,t=4.061),TNF-α(P<0.01,t=4.460)and LPS(P<0.0001,t=27.24)were elevated.The difference was statistically significant.According to 16S rDNA sequencing,CUMS-induced changes in the intestinal bacterial community structure of mice,making them significantly different from the control mice.Compared with the control mice,the expression levels of NF-κB(P<0.01,t=6.825)and NLRP3(P<0.001,t=9.561)were upregulated in CUMS mice.[Conclusion]The CUMS model was successfully constructed and CUMS mice developed more severe bacterial infection.Gut microbiota was dysregulated and the expression of NF-κB/NLRP3 signaling pathway was up-regulated in CUMS mice,which was related to the susceptibility to bacterial infection.

Objective:To explore the feasibility of artificial intelligence(AI)technology in predicting placental in-sufficiency in the first trimester.Methods:High risk pregnant women with singleton and anterior wall placenta were selected as the research subjects.Data of ultrasound parameters were collected in the first trimester,including u-terine arterial pulsatility index(UTPI)and placental vascular hemodynamics index(PVIs).Patients that developed into preeclampsia(PE)and fetal growth restriction(FGR)were defined as the placental insufficiency group.The placental images in the first trimester were asymmetrically amplified and divided into a training set and a testing set.The placental texture features were extracted from the training set images to create a placental insufficiency machine learning model based on ultrasound imaging technology.The model was validated using the testing set images,and the diagnostic test results of ultrasound and AI were compared.Results:A total of 164 pregnant women were included,with 147 normal cases and 17 cases with placental insufficiency.The sensitivity,specificity,positive predictive value,negative predictive value,positive likelihood ratio and negative likelihood ratio of the AI test set were 73.33％,60.85％,58.93％,74.87％,1.87 and 0.44,respectively.The area under the receiver operat-ing characteristic(ROC)curve was 0.67,with an accuracy rate of 58.93％,a recall rate of 73.33％,and an F1 score of 0.65.The comparison of diagnostic test results between ultrasound and AI:AI had the highest positive predictive value(58.93％),while other diagnostic test results were lower than PVIs.Conclusions:The positive predictive value of AI technology based on placental ultrasound texture analysis is superior to ultrasound parame-ters.Given that PVIs values are easily affected by many technical or physiological parameters,AI is a promising tool for predicting placental dysfunction.

Objective:To explore the feasibility of artificial intelligence(AI)technology in predicting placental in-sufficiency in the first trimester.Methods:High risk pregnant women with singleton and anterior wall placenta were selected as the research subjects.Data of ultrasound parameters were collected in the first trimester,including u-terine arterial pulsatility index(UTPI)and placental vascular hemodynamics index(PVIs).Patients that developed into preeclampsia(PE)and fetal growth restriction(FGR)were defined as the placental insufficiency group.The placental images in the first trimester were asymmetrically amplified and divided into a training set and a testing set.The placental texture features were extracted from the training set images to create a placental insufficiency machine learning model based on ultrasound imaging technology.The model was validated using the testing set images,and the diagnostic test results of ultrasound and AI were compared.Results:A total of 164 pregnant women were included,with 147 normal cases and 17 cases with placental insufficiency.The sensitivity,specificity,positive predictive value,negative predictive value,positive likelihood ratio and negative likelihood ratio of the AI test set were 73.33％,60.85％,58.93％,74.87％,1.87 and 0.44,respectively.The area under the receiver operat-ing characteristic(ROC)curve was 0.67,with an accuracy rate of 58.93％,a recall rate of 73.33％,and an F1 score of 0.65.The comparison of diagnostic test results between ultrasound and AI:AI had the highest positive predictive value(58.93％),while other diagnostic test results were lower than PVIs.Conclusions:The positive predictive value of AI technology based on placental ultrasound texture analysis is superior to ultrasound parame-ters.Given that PVIs values are easily affected by many technical or physiological parameters,AI is a promising tool for predicting placental dysfunction.

Background::Growth differentiation factor-15 (GDF-15) is a stress response protein and is related to cardiovascular diseases (CVD). This study aimed to investigate the association between GDF-15 and pre-eclampsia (PE).Method::The study involved 299 pregnant women, out of which 236 had normal pregnancies, while 63 participants had PE. Maternal serum levels of GDF-15 were measured by using enzyme-linked immunosorbent assay kits and then translated into multiple of median (MOM) to avoid the influence of gestational week at blood sampling. Logistic models were performed to estimate the association between GDF-15 MOM and PE, presenting as odd ratios (ORs) and 95% confidence intervals (CIs).Results::MOM of GDF-15 in PE participants was higher compared with controls (1.588 vs. 1.000, p < 0.001). In the logistic model, pregnant women with higher MOM of GDF-15 (>1) had a 4.74-fold (95% CI= 2.23-10.08, p < 0.001) increased risk of PE, adjusted by age, preconceptional body mass index, gravidity, and parity. Conclusions::These results demonstrated that higher levels of serum GDF-15 were associated with PE. GDF-15 may serve as a biomarker for diagnosing PE.