[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 characteristics and rules of the locations of acupoints selected in weight loss after syndrome differentiation of acupuncture and moxibustion, and provide quantitative evidence for the location specificity of acupoint selection in weight loss. METHODS: Clinical research articles on acupoint selection based on syndrome differentiation of acupuncture and moxibustion in weight loss were retrieved in China National Knowledge Infrastructure (CNKI), from the inception to September 20th, 2024, and the data about acupoints and differentiated syndromes were extracted. Based on graph theory, the acupoint-syndrome network was established and its topological parameters such as node degree, value of betweenness centrality, description length and number of community were calculated. RESULTS: ①The description length of the limbs was 4 255.592, and that of the trunk was 3 274.312. The information contained in the acupoint-syndrome network for the acupoints on the limbs was greater than that for those on the trunk. ②The value of betweenness centrality and node degree showed a nonlinear relationship, with R²of 0.812 1 for the trunk and 0.321 8 for the limbs. The values of betweenness centrality for the acupoints on the trunk were uniformly distributed, and the difference among these values was much smaller than that for the acupoints on the limbs. It suggested that the distance from each trunk acupoint to network center was similar, and the importance among these acupoints to network was similar, while the importance among acupoints located on the limbs was different significantly. ③The frequency proportion of acupoints on the trunk showed uniform distribution among different syndromes, while that of some acupoints located on the limbs such as Taichong (LR3), Neiting (ST44) and Taixi (KI3) presented a correlation with the syndromes. CONCLUSION In weight loss with acupuncture and moxibustion, the correlation between the limb acupoints and syndromes is more diverse and specific than that between the trunk acupoints and syndromes. The differences in acupoint selection for simple obesity treated with acupuncture and moxibustion are mostly reflected in the acupoints on the four limbs rather than those on the trunk. It provides an approach to acupoint selection for "local weight loss" and "general regulation" in treatment with acupuncture and moxibustion.
Humans ; Acupuncture Points ; Moxibustion ; Weight Loss ; Acupuncture Therapy ; Obesity/physiopathology*

BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

OBJECTIVES: To assess the effectiveness of the comparison between pit and fissure sealants and fluoride varnishes, as well as various types of sealants, in preventing caries on the occlusal surface of children's first permanent molars (FPM). METHODS: Conduct a comprehensive search of literature published between January 1, 1988, and May 30, 2024, in the following databases: China National Knowledge Infrastructure, Web of Science, Cochrane Library, Embase, PubMed, China Science Periodical Database and China Biology Medicine database. Meta-analysis and subgroup analyses were performed on the literature that met the inclusion criteria. RESULTS: A total of 5 618 pieces of literature were retrieved, resulting in the inclusion of 14 in the study. Meta-analysis showed that there was no statistically significant difference in the efficacy between varies pit and fissure sealants compared to fluoride varnishes, and between varies types of sealants in preventing caries on the occlusal surface of children's first permanent molars within 24 months post-surgery (P>0.05). CONCLUSIONS Within 24 months, there was no significant difference in the effectiveness of using resin-based or glass iomomer pit and fissure sealants compared with fluoride varnishes in preventing occlusal caries in FPM in children; within 24 months, there was no significant difference in the effectiveness of using resin-based sealants compared with ART sealants in preventing occlusal caries in FPM in children. ART sealants are recommended over resin-based sealers for children who have no conditions for chair-side manipulation or who are poorly co-operative.
Humans ; Pit and Fissure Sealants/therapeutic use* ; Dental Caries/prevention & control* ; Molar ; Child ; Fluorides, Topical/therapeutic use* ; Dentition, Permanent

Objective To analyze the risk factors of critically ill patients infected with Acinetobacter bau-mannii(AB)and carbapenem resistant Acinetobacter baumannii(CRAB).Methods From January 2022 to June 2023,the data of Intensive Care Unit(ICU)patients admitted to Second Hospital of Shanxi Medical Uni-versity in Shanxi Province were collected.According to whether they were infected with AB,the patients were divided into an observation group and a control group(98 cases each).The observation group was further di-vided into a carbapenem sensitive Acinetobacter baumannii(CSAB)group(72 cases)and a CRAB group(26 cases).Mann-Whitney U test,chi-square test and other univariate and multivariate binary Logistic regression were used to analyze the risk factors of AB and CRAB infection for critically ill patients.The prognosis was analyzed by Kaplan Meier survival analysis.Results Long stay in ICU,previous use of carbapenem drugs and high Acute Physiology and Health Evaluation(APACHE Ⅱ)score were independent risk factors for AB sus-ceptibility(P＜0.05),while the independent risk factors for CRAB susceptibility were invasive ventilation and delayed surgery(P＜0.01).In addition,CRAB infection,COVID-19 and shock was risk factors for death in critically ill patients,and invasive ventilation,indwelling drainage tube and operation could reduce the risk of death in critically ill patients(P＜0.05).Conclusion ICU stay time,APACHE Ⅱ score,previous use of car-bapenem drugs and invasive ventilation increase the risk of AB and CRAB infection in critically ill patients.In-vasive ventilation,indwelling drainage and early surgery could reduce the risk of death from AB and CRAB in-fection in critically ill patients.

Cerebral blood flow directly affects the metabolism of substances and neural activity in the brain, and is closely associated with the occurrence and development of cerebral small vessel disease (CSVD). Multiple studies have revealed that various imaging biomarkers in patients with CSVD, such as lacunar infarction, enlarged perivascular spaces, cerebral microbleeds, cerebral atrophy, and white matter hyperintensities, are closely associated with cerebral autoregulation (CA) function. Therefore, understanding the regulatory mechanism of CA in patients with CSVD is of great significance for delaying the further development of CSVD, improving cerebral ischemia and cognitive impairment. This article reviews the correlation and mechanism between CA and CSVD.

Objective To discuss the efficacy of transcatheter arterial chemoembolization(TACE)in combination with targeted therapy and immune checkpoint inhibitors for advanced hepatocellular carcinoma(HCC),and to identify the influencing factors.Methods A total of 60 patients with advanced HCC,who were admitted to the Air Force Medical Center of China from January 2016 to December 2022,were enrolled in this study.Thirty patients received TACE combined with targeted therapy and immune checkpoint inhibitors(TACE-L-P group),and the other 30 patients received TACE combined with targeted therapy(TACE-L group).The progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and objective response rate(ORR)were compared between the two groups.Results In the TACE-L group and TACE-L-P group,the median PFS(mPFS)was 7 months and 10 months respectively(P=0.011),the median OS(mOS)was 15.5 months and 29 months respectively(P=0.014).Child-Pugh class B(HR=3.89,95％CI:1.27-11.94,P=0.018)and Barcelona Clinic Liver Cancer(BCLC)stage C(HR=2.83,95％CI:1.32-6.03,P=0.007)were the independent risk factors for OS,while micro wave ablation(HR=0.21,95％CI:0.07-0.63,P=0.005)and TACE-L-P(HR=0.09,95％CI:0.03-0.3,P=0.001)were the independent protection factors for OS.Besides,elevated bilirubin level(HR=1.03,95％CI:1-1.06,P=0.032)and elevated gamma-glutamyl transferase(GGT)level(HR=1.01,95％CI:1-1.01,P=0.002)were the independent risk factors for disease progression,and TACE-L-P(HR=0.27,95％CI:0.09-0.79,P=0.017)was the independent protection factor for disease progression.The ORR and DCR in TACE-L-P group were remarkably higher than those in TACE-L group,which were 43.4％vs 13.3％and 63.4％vs 23.3％respectively,the differences between the two groups were statistically significant(both P＜0.05).Conclusion In treating advanced HCC,TACE combined with targeted therapy and immune checkpoint inhibitors is superior to TACE combined with targeted therapy in therapeutic efficacy.