[Objective] To validate and optimize the platelet transfusion refractoriness (PTR) prediction model for patients with hematological disorders established by our center. [Methods] The data of patients with hematological diseases who received platelet transfusions from December 2021 to December 2022 were used as the training set, and data from January 2023 to December 2023 as the validation set. The validation set data was used to validate the predictive model constructed on the training set. Relevant risk factors for PTR were collected through literature review and preliminary studies。 The patients were divided into effective and ineffective groups according to the corrected count increment (CCI) of platelet counts. Predictive factors were screened using univariate and multivariate logistic regression. The calibration of the model were assessed via calibration curves, while discrimination, accuracy, sensitivity, and specificity were evaluated using receiver operating characteristic (ROC) curves Clinical utility was further analyzed with decision curve analysis (DCA). [Results] The Hosmer-Lemeshow (H-L) goodness-of-fit test for the validation set yielded S: P=0.000, indicating that the original model needs optimization. Baseline comparisons and logistic regression identified the number of red blood cell units (RBCU) and platelet units (PLT-U) transfused as key predictors for the optimized model. The H-L goodness-of-fit test S: P values for the training and validation sets were 0.930 and 0.056, respectively; the ROC areas were 0.793 5 and 0.809 4, specificities 90.95% and 84.21%, sensitivities 59.26% and 70.04%, and accuracies 78.14% and 74.10%, respectively. DCA demonstrated clinical net benefit within a prediction probability threshold range of 0.2-0.8. [Conclusion] Transfusion volumes of RBC-U and PLT-U were inversely associated with PTR in hematological patients. The resulting PTR prediction model exhibits moderate predictive efficacy and clinical benefit.

Objective: To explore the associations between caregivers nutrition literacy and pediatric nonalcoholic fatty liver disease (NAFLD), so as to provide scientific evidence for the key contents of family intervention measures. Methods: In September 2022, a study involving 1 609 thirdgrade students and their caregivers from six schools in Yinzhou, Haishu, and Zhenhai Districts of Ningbo City, Zhejiang Province, was conducted. Venous blood samples were collected to measure lipid profiles and investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) among the children. Family Food Environment Questionnaire was used to assess the nutrition literacy levels of the caregivers. Generalized linear regression analysis was employed to explore the correlation between caregivers nutrition literacy levels and the prevalence of NAFLD in children. Results: Among the surveyed students, 191 were in the NAFLD group, whereas 1 418 were in the nonNAFLD group. The median nutrition literacy score of caregivers in the NAFLD group and nonNAFLD group all were 11.00 (9.00,12.00), which was not significantly different (Z=-0.40, P=0.71). The generalized linear regression results revealed that the level of nutrition literacy of caregivers had no significant effect on childrens Triglyceride-glucose (TyG) index and Triglyceride-glucose-Waisttoheight ratio (TyG-WHtR) [β(95%CI) were 0.001(-0.005-0.006) and 0.000(-0.014-0.014), P>0.05]. Conclusions The nutrition literacy level of caregivers has no significant correlation with the direct incidence of NAFLD in children. As for family intervention measures, it is necessary not only to improve the nutrition literacy level of caregivers but also to effectively apply nutritional knowledge in practice to optimize health management.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.

Objective To investigate the sputum metabolic profiles of patients with occupational coal workers' pneumoconiosis (CWP) by an untargeted metabolomics method, and to identify relevant differential metabolic pathways and potential biomarkers. Methods A total of 12 male patients with stage Ⅰ CWP were selected as the CWP group, and 16 healthy male individuals were selected as the control group, using a judgmental sampling method. Sputum metabolites of individuals in both groups were detected to perform non-targeted metabolomic analysis using the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Differential metabolites (DMs) and their pathways were screened using principal component analysis, partial least squares discriminant analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Potential biomarkers were analyzed and identified via the receiver operating characteristic curve (ROC). Results There were apparent metabolic alterations observed in sputum of CWP patients compared with healthy controls. In the positive ion mode, a total of 42 DMs were identified in sputum from CWP patients, including 19 downregulated and 23 upregulated metabolites. In the negative ion mode, a total of 25 DMs were identified in sputum from CWP patients, including 16 downregulated and 9 upregulated metabolites. KEGG enrichment analysis of sputum from CWP patients showed that seven DMs pathways were enriched in ABC transporters, histidine metabolism, phenylalanine metabolism, arachidonic acid metabolism, linoleic acid metabolism, purine metabolism, and oxidative phosphorylation, involving 26 DMs. ROC analysis indicated that 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate of these 26 DMs may serve as potential biomarkers for CWP. Conclusion Sputum metabolomic profiles were altered in CWP patients compared with healthy controls. The potential biomarkers of CWP prevention and treatment are 16(R)-hydroxyarachidonic acid, pyrophosphate, and 2-hydroxyphenylacetate.

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective To investigate the correlation between serum leptin level and body mass index(BMI)in in-fants with cyanosis congenital heart disease,and the relationship between leptin and Ob gene receptor(Ob-R)and hypoxia-inducible factor 1α(HIF-1α)in myocardium.Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery,Fuwai Hospital from January 2019 to October 2020 were included in this study.According to the arterial partial pressure of oxygen(PaO2)of 90 mmHg,they were divided into cyanotic group(n=30)and acyanotic group(n=22).Their height and weight were collected to calculate BMI.The serum leptin level was measured by ELISA.The ex-pressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot.In animal mod-el,SD rats were divided into normoxia group and hypoxia intervention group,which were subjected to continuous hypoxia(10％ O2)for 4 weeks.The hypoxia intervention group received intraperitoneal injection of HIF-1α in-hibitor digoxin(2 mg/kg)daily from the 14 th to 21st day of hypoxia,respectively.The body weight of rats was recorded,and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot.Results Com-pared with the acyanosis group,the cyanosis group had a significantly lower BMI(P<0.05)and a lower leptin/BMI ratio(leptin/BMI)(P<0.05).Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI(P<0.05).In the cyanosis group,the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation.In animal model,with the down-regulation of HIF-1α expression in digoxin injection,the Ob-R level was significantly lower than that in the control group(P<0.05),the trend of weight loss was significantly inhibited(P<0.05).The right ventricular hypertrophy in-dex was significantly lower than that in the control group(P<0.05).Conclusions HIF-1α regulates the expres-sion of Ob-R in myocardial tissue,and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Objective To explore the risk factors for platelet transfusion refractoriness(PTR)in patients with hemato-logical disorders,construct a prediction model and validate the model efficacy.Methods Patients with hematological disor-ders who received platelet transfusion therapy in the Chengdu Second People's Hospital from December 2021 to December 2022 were retrospectively included to judge the effectiveness of platelet transfusion and screened for risk factors by univariate and multivariate logistic regression.A prediction model for PTR was constructed using receiver operating characteristic(ROC)curve,calibration curve and decision curve(DCA)to assess the differentiation,calibration and clinical value of the model,respectively.Results A total of 334 hematological patients were included,including 168 males and 176 females,with a PTR incidence of 40.4%.Univariate and multivariate logistic regression analysis showed that platelet transfusion vol-ume,erythrocyte transfusion volume,and neutrophil ratio were risk factors for PTR(P<0.05).A prediction model for PTR in hematological patients was established based on these risk factors.The area under the model's curve was 0.8377(95%CI:0.723-0.772),the sensitivity was 58.52%,and the specificity was 89.95%.The calibration curve showed that the S∶P was 0.964,the maximum absolute difference Emax was 0.032,and the average absolute difference Eavg was 0.009.The DCA a-nalysis showed that the model had clinical application value when the risk threshold ranged from 0.2 to 0.9.Conclusion The PTR prediction model based on platelet transfusion volume,erythrocyte transfusion volume and neutrophil ratio can pro-vide a basis for effective platelet transfusion in hematological patients.

Objective To explore the status of knowledge graph-based research into breast cancer micro-environment and to predict future research hotspots.Methods The literature related to breast cancer microenvironment in recent 20 years was retrieved from CNKI and Web of Science Core Collection database and analyzed with CiteSpace and VOSviewer.Results A total of 825 Chinese articles and 16,221 English articles were retrieved.Visual analysis showed that research focus has gradually shifted from cellular research to molecular research and drug innovation.Cancer stem cells,PD-1,PD-L1,immune checkpoint inhibitors,and nanoparticles are the main subjects of interest in research on breast cancer microenvironment,and the United States has the largest number of studies on breast cancer microenvironment,followed by China and Italy.Conclusion Current research mainly focuses on tumor stemness,immunotherapy,and nanodeli-very.Owing to deepening research in this field,the targeting of the breast cancer microenvironment for the prevention of tumor development and metastasis and improvement of tumor prognosis has emerged as a new research direction.

Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication after cerebral revascularization, which may lead to catastrophic consequences. The mechanism of CHS is not fully understood, and it may be related to cerebral autoregulation dysfunction and the increase of blood pressure after operation. Timely detection and treatment of cerebral hyperperfusion can avoid CHS. This article reviews the pathogenesis, diagnosis, clinical manifestations, prevention and treatment of CHS.

Objective:To observe the toxic and side effects of TCM syndrome differentiation and treatment combined with abemaciclib and endocrine drugs in the treatment of hormone receptor ( HR ) positive and human epidermal growth factor receptor 2 ( HER2 ) negative advanced breast cancer and the dose of abemaciclib under the influence of toxic and side effects.Methods:Patients with HR+/HER2- advanced breast cancer who received TCM combined with abemaciclib and endocrine therapy in Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2021 to February 2023 were selected, and the relevant data of East Asian population in MONARCH 2 and MONARCH 3 of abemaciclib random phase Ⅲ clinical study were extracted for retrospective cohort study. The TCM exposure cohort was divided into 20 cases of TCM + abemaciclib + fulvestrant group (EXP 1) and 22 cases of TCM + abemaciclib + aromatase inhibitor (AI) group (EXP 2). The East Asian populations in MONARCH 2 and 3 were non-exposed cohorts, which were divided into NEXP 1 group ( 146 cases ) and NEXP 2 group (102 cases). The safety analysis of the 2 cohorts was carried out, and the reduction and termination of abemaciclib taken by patients under the influence of toxic and side effects were counted.Results:①There were significant differences in CTCAE any grade, grade 2 ( χ2 values were 8.11, 4.59, respectively ) between EXP 1 group and NEXP 1 group, as well as in CTCAE any grade ( χ2=18.57) between EXP 2 group and NEXP 2 group compare the incidence rate of diarrhoea ( P<0.05 or P<0.01). There was significant differences in CTCAE ≥ grade 2 EXP 1 group compare the incidence rate of diarrhoea ( χ2=5.56, P=0.02). The incidence of grade ≥ 3 neutropenia in EXP 1 was [ 5 cases (27.78%) ] and in EXP 2 was [ 2 cases (13.33%)]. There were 65 cases (44.52%) in NEXP 1 and 30 cases (29.41%) in NEXP 2, and the exposed cohort were lower than those in the non-exposed cohort. The increase of GPT, GOT and SCr in the exposed cohort were lower than those in the non-exposed cohort. ② Compared with the non-exposed cohort, the first occurrence time of diarrhea and neutropenia was prolonged and the duration was shortened in the exposed cohort. ③ The patients in the exposed cohort were less likely to take abemaciclib reduction and discontinuation due to diarrhea, neutropenia, impaired liver function, and elevated SCr than those in the non-exposed cohort. Conclusion:TCM syndrome differentiation and treatment combined with abemaciclib and endocrine drugs is safe in the treatment of HR+/HER2- advanced breast cancer, which can effectively prevent and treat the toxic and side effects caused by abemaciclib, and reduce the drug reduction and discontinuation.