Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding developed a strategy for platelet and plasma infusion management in critically ill children based on systematic reviews and consensus meetings of international multidisciplinary experts. One good practice statement and six expert consensus statements were proposed for plasma and platelet transfusions in critically ill children following severe trauma, traumatic brain injury, and/or intracranial hemorrhage. This article introduces the specific methods and basis for the formation of recommendations in this part of the guide.

AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

AIM:To compare and analyze the effectiveness and safety of reducing the diameter of the back optical zone diameter(BOZD)of orthokeratology lens designed by CRT and VST in controlling the progression of myopia in children and adolescents.METHODS:Retrospective study. The study subjects were 400 myopia patients aged 8-16 years who were admitted to the orthokeratology fitting center of our hospital from June 2019 to May 2022, with 400 eyes(including right eye data analysis). The subjects were divided into CRT-S group(BOZD<6.0 mm), CRT group(BOZD=6.0 mm), VST-S group(BOZD<6.2 mm), VST group(BOZD=6.2 mm)according to the brand of orthokeratology lens and BOZD group, with 100 cases in each group. Uncorrected visual acuity(UCVA), corneal flat K value, axial length, spherical equivalent, and incidence of corneal injury were collected and analyzed at 1 d, 1 wk, 1 and 6 mo, 1 and 2 a, respectively.RESULTS:After wearing lenses for 1 d, the UCVA of the VST-S group improved the fastest, but after 1 wk, all groups reached a good UCVA, and there was no significant difference between groups. The corneal flat K value of the CRT-S group decreased the most after wearing lenses for 6 mo, and there was no significant difference in the corneal flat K value of all groups after 1 year of lens wearing. At each time point, the axial length growth decreased significantly after reducing the BOZD of the same brand of orthokeratology lens. At 6 mo, there was no significant difference in the axial length growth and defocus ring diameter between the CRT-S group and the VST-S group, but at 1 and 2 a, the VST-S group had significantly lower axial length growth and defocus ring diameter than the CRT-S group. The growth of the diopter sphere and spherical equivalent(SE)was significantly reduced when the BOZD of the same brand of orthokeratology lens was reduced at 2 a follow-up. The VST-S group had the smallest changes in the degree of SE and had the best myopia control effect. There was no significant difference in the change value of the diopter cylinder and the incidence of corneal injury among the four groups.CONCLUSION:Reducing the BOZD of the orthokeratology lens can effectively control the growth of the axial length and the progression of myopia degree. The myopia control effect of the VST lens is better than that of the CRT lens after reducing the BOZD. Reducing the BOZD of the orthokeratology lens does not increase the risk of additional corneal injury.

OBJECTIVE: To investigate the effects of histone deacetylase (HDAC) levels on the proliferation and apoptosis of Burkitt lymphoma cells, and the changes in related signaling molecules in the PI3K/AKT/mTOR signaling pathway, so as to explore the pathogenesis of Burkitt lymphoma. METHODS: HDAC levels in Burkitt lymphoma were detected by RT-PCR and Western blot. CA46 and RAJI cells were treated with the HDAC selective inhibitor VPA. CCK8 assay was used to detect the proliferation ability of cells. Western Blot was used to measure the expression of apoptosis-related proteins, PI3K/AKT/mTOR signaling pathway proteins and their phosphorylation levels. RESULTS: The expression levels of classⅠ HDAC in Burkitt lymphoma were higher than those in normal cells, and the HDAC1 inhibitor VPA could inhibit the proliferation of CA46 and RAJI cells. VPA decreased HDAC expression in CA46 and RAJI cells, inhibited the phosphorylation of PI3K/AKT/mTOR pathway molecules AKT and p70S6K, increased the expression of apoptotic proteins Cleaved Caspase-3, Cleaved Caspase-8, Cleaved Caspase-9 and Bax, and decreased the expression of anti-apoptotic proteins Bcl-2 and PARP. CONCLUSION Inhibition of HDAC activity can Attenuate the proliferation of Burkitt lymphoma cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway activity.
Humans ; Burkitt Lymphoma/pathology* ; Apoptosis ; Cell Proliferation ; Signal Transduction ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Histone Deacetylases/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Phosphorylation

OBJECTIVE: To explore the role of semaphorin 4D (Sema4D) in immunoglobulin A (IgA) -mediated immune abnormalities in B lymphocytes of pediatric Henoch-Schonlein purpura (HSP). METHODS: One hundred HSP children admitted to Hengshui People's Hospital from January 2022 to January 2023 were selected as HSP group, and one hundred healthy children as control group. Sema4D expression was detected, and the relationship between Sema4D expression in children's serum and skin lesions and clinical characteristics of children was analyzed. Sema4D expression on the surface of lymphocytes of HSP children was detected. Different concentrations of human recombinant Sema4D protein was used to stimulate peripheral blood mononuclear cells in HSP children in vitro. The expression level of IgA in the supernatant was detected to verify whether Sema4D mediates immune abnormalities through IgA secreted by B lymphocytes. RESULTS: The Sema4D level in the HSP group was significantly higher than that in the control group (P <0.001). Sema4D level in HSP children with severe, renal involvement, and joint involvement was higher than those with mild to moderate disease, and no renal or joint involvement (all P <0.001). Compared with control group, IgA level, CD8 ⁺ T lymphocyte proportion, and CD19 ⁺ B lymphocyte proportion in the HSP group were significantly higher but CD4 ⁺ T lymphocyte proportion was lower (all P <0.001). The expression levels of Sema4D on the surface of CD4 ⁺ T lymphocytes, CD8 ⁺ T lymphocytes, and CD19 ⁺ B lymphocytes in the HSP group were significantly higher than those in the control group (all P <0.001). With the increase of human recombinant Sema4D protein concentration, the level of IgA expression in HSP children gradually increased (P <0.05). Correlation analysis showed that Sema4D was significantly positively correlated with IgA (r =0.667). CONCLUSION HSP children show high expression of Sema4D, especially on the surface of T and B lymphocytes. The shedding of Sema4D from membrane surface may stimulate B lymphocytes to secrete IgA by binding to CD72, leading to immune abnormalities.
Humans ; IgA Vasculitis/immunology* ; Semaphorins/metabolism* ; B-Lymphocytes/metabolism* ; Immunoglobulin A/immunology* ; Child ; Antigens, CD/metabolism* ; Male ; Female ; Child, Preschool

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Objective To explore a deep learning-based automatic bone age estimation model for elbow joint X-ray images of Chinese Han adolescents and children and evaluate its performance.Methods A total of 943(517 males and 426 females)elbow joint frontal view X-ray images of Chinese Han ado-lescents and children aged 6.00 to<16.00 years were collected from East,South,Central and North-west China.Three experimental schemes were adopted for bone age estimation.Scheme 1:Directly in-put preprocessed images into the regression model;Scheme 2:Train a segmentation network using"key elbow joint bone annotations"as labels,then input segmented images into the regression model;Scheme 3:Train a segmentation network using"full elbow joint bone annotations"as labels,then in-put segmented images into the regression model.For segmentation,the optimal model was selected from U-Net,UNet++and TransUNet.For regression,VGG16,VGG19,InceptionV2,InceptionV3,ResNet34,ResNet50,ResNet101 and DenseNet121 models were selected for bone age estimation.The dataset was randomly split into 80%(754 samples)for training and validation for model fitting and hyperparameter tuning,and 20%(189 samples)as an internal test set to test the performance of the trained model.An additional 104 elbow joint X-ray images from the same demographic and age group were col-lected and used as an external test set.Model performance was evaluated by comparing the mean ab-solute error(MAE),root mean square error(RMSE),accuracies within±0.7 years(P±0.7 years)and±1.0 years(P±1.0 years)between the estimated age and the actual age,and by drawing radar charts,scat-ter plots,and heatmaps.Results When segmented with Scheme 3,the UNet++model achieved good segmentation performance with a segmentation loss of 0.000 4 and an accuracy of 93.8%at a learning rate of 0.000 1.In the internal test set,the DenseNet121 model with Scheme 3 yielded the best results with MAE,P±0.7 years and P±1.0 years being 0.83 years,70.03%,and 84.30%,respectively.In the external test set,the DenseNet121 model with Scheme 3 also performed best,with an average MAE of 0.89 years and an average RMSE of 1.00 years.Conclusion When performing automatic bone age estima-tion using elbow joint X-ray images in Chinese Han adolescents and children,it is recommended to use the UNet++model for segmentation.The DenseNet121 model with Scheme 3 achieves optimal per-formance.Using segmentation networks,especially that trained with annotation areas encompassing the full elbow joint including the distal humerus,proximal radius,and proximal ulna,can improve the ac-curacy of bone age estimation based on elbow joint X-ray images.

Objective To explore a deep learning network model suitable for bone age estimation using shoulder joint X-ray images in Chinese Han adolescents.Methods A retrospective collection of 1 286 shoulder joint X-ray images of Chinese Han adolescents aged 12.0 to<18.0 years(708 males and 578 females)was conducted.Using random sampling,approximately 80%of the samples(1 032 cases)were selected as the training and validation sets for model learning,selection and optimization,and the other 20%samples(254 cases)were used as the test set to evaluate the model's generalization ability.The original single-channel shoulder joint X-ray images and dual-channel inputs combining original images with segmentation labels(manually annotated shoulder joint regions multiplied pixel-by-pixel with original images,followed by segmentation via the U-Net++network to retain only key shoulder joint region information)were respectively input into four network models,namely VGG16,ResNet18,ResNet50 and DenseNet121 for bone age estimation.Additionally,manual bone age estimation was con-ducted on the test set data,and the results were compared with the four network models.The mean absolute error(MAE),root mean square error(RMSE),coefficient of determination(R2),and Pear-son correlation coefficient(PCC)were used as main evaluation indicators.Results In the test set,the bone age estimation results of the four models with dual-channel input of shoulder joint X-ray images outperformed those with single-channel input in all four evaluation indicators.Among them,DenseNet121 with dual-channel input achieved best results with MAE of 0.54 years,RMSE of 0.82 years,R2 of 0.76,and PCC(r)of 0.88.Manual estimation yielded an MAE of 0.82 years,ranking second only to dual-channel DenseNet121.Conclusion The DenseNet121 model with dual-channel input combined with original images and segmentation labels is superior to manual evaluation results,and can effectively estimate the bone age of Chinese Han adolescents.