BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

BACKGROUND:Autophagy,as a key regulatory mechanism of cell development,plays an important role in different stages of embryonic development.The mechanism of how autophagy regulates embryonic development through histone modifications is currently unclear.OBJECTIVE:To investigate the effect of autophagy on trimethylation of lysine 4 on histone H3(H3K4me3)modification in embryos and its effect on embryonic development.METHODS:Mouse fertilized eggs were divided into control and autophagy inhibitor-treated groups(chloroquine phosphate-treated group and 3-methyladenine-treated group),and cultured in vitro to different periods of time,and were then classified as early 2-cell embryos,middle 2-cell embryos,late 2-cell embryos,4-cell embryos,8-cell embryos,morula stage,and blastocyst stage.Levels of reactive oxygen species,autophagy marker proteins LC3B and P62,DNA loss marker γH2AX,and H3K4me3 were analyzed by immunofluorescence assay in late 2-cell embryos of each group.Changes in H3K4me3 modification in late 2-cell embryos of each group were detected by CUT&Tag.RESULTS AND CONCLUSION:(1)Autophagy inhibition caused embryo development arrest.(2)There was no significant difference in reactive oxygen species and γH2AX between the autophagy inhibitor-treated groups and control group.(3)H3K4me3 levels were significantly elevated in the autophagy inhibitor-treated group compared with the control group.(4)CUT&Tag results showed a significantly increased H3K4me3 peaks on the proximal promoter region of the genes after autophagy inhibition and an increase of H3K4me3-specific modification genes.These findings suggest that autophagy may affect embryonic development by regulating the level of H3K4me3 modification.

Objective To characterize the properties of Hepa1-6-derived microparticles (Hepa1-6-MPs), investigate their stimulatory effects on dendritic cells (DCs) and their cellular uptake pathways, and explore the specific cytotoxic effects of CD8⁺ T cells induced by Hepa1-6-MP-loaded DCs on hepatoma cell lines, with the aim of developing a novel immunotherapeutic model for hepatocellular carcinoma (HCC). Methods The isolated Hepa1-6-MPs were identified using Western blotting, transmission electron microscopy (TEM) and dynamic light scattering (DLS). Flow cytometry was used to assess the uptake pathways of Hepa1-6-MPs by DCs. Subsequently, enzyme-linked immunosorbent assay (ELISA) was used to measure the effects of Hepa1-6-MP-loaded DCs on the release levels of tumor necrosis factor α(TNF-α) and interferon γ(IFN-γ) into the supernatant of CD8⁺ T cells. Lactate dehydrogenase (LDH) tests were conducted to evaluate the cytotoxic effects of CD8⁺ T cells stimulated by Hepa1-6-MP-loaded DCs on hepatoma cells. Results The morphology, size and protein markers of Hepa1-6-MPs met the established criteria. Hepa1-6-MPs enhanced the expression of DC maturation markers CD80 and CD86, and were internalized by DCs via clathrin-mediated endocytosis and phagocytosis pathways. Subsequently, Hepa1-6-MP-loaded DCs stimulated CD8⁺ T cells to release high levels of TNF-α and IFN-γ, which induced their specific cytotoxicity against HCC cells. Conclusion These findings suggest that Hepa1-6-MP-loaded DCs may be a promising HCC immunotherapeutic tool.
Carcinoma, Hepatocellular/therapy* ; Liver Neoplasms/therapy* ; Dendritic Cells/immunology* ; Humans ; Cancer Vaccines/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cell Line, Tumor ; Tumor Necrosis Factor-alpha/immunology* ; Interferon-gamma/immunology* ; Cell-Derived Microparticles/immunology* ; Animals

Objective To investigate short-term clinical efficacy of autologous leukocyte-poor platelet-rich plasma(LP-PRP)treatment of knee osteoarthritis(KO A).Methods 85 cases of patients with Keligren Lawrence grade Ⅰ-Ⅲ knee os-teoarthritis in Peking University First Hospital Taiyuan Hospital(Taiyuan Central Hospital)from 2022 to 2023 were collect-ed for autologous LP-PRP collection and quality assessment using a blood component separator,and all patients were treated with autologous LP-PRP.The degree and function of knee pain were assessed by visual analog scale(VAS)and knee arthri-tis index scale(WOMAC)at 1,3 and 6 months after injection.Knee MRI was performed after 6 months of treatment,and the MRI imaging changes before and after treatment were compared.Different influencing factors in the treatment results were grouped and analyzed,mainly including platelet concentration in LP-PRP and K-L grading of knee joint.According to the platelet concentration in LP-PRP,it was divided into three grades,which are low concentration[(＜800)×109/L],medium concentration[(800-1 000)×109/L],and high concentration[(＞1 000)× 109/L];According to the K-L grade of the knee joint,the severity of knee osteoarthritis was divided into three grades:Ⅰ、Ⅱ、Ⅲ.Results The VAS and WOMAC scores at 1,3 and 6 months after LP-PRP treatment were significantly lower than those before treatment,and the difference was sta-tistically significant(P＜0.05).There was a statistically significant difference in the therapeutic effect of different levels of platelet concentration,and when the platelet concentration was more than 1 000×109/L,the significant effect was the most obvious(P＜0.05).The therapeutic effect of different levels of platelet concentration was statistically significant(P＜0.05).MRI showed that the articular cartilage signal was significantly improved after treatment.Conclusion Autologous LP-PRP injection into knee cavity for the treatment of KO A has a good short-term clinical effect in relieving knee pain.

OBJECTIVE To optimize hematopoietic stem cell transplantation therapy and provide support for drug research by investigating the dynamic process of hematopoietic and immune system reconstitution after bone marrow transplantation(BMT)in mice.METHODS CD45.2+C57BL/6 mice were used as recipient mice and randomly divided into the normal control group and transplantation group,with 30 mice in each.The transplantation group was irradiated by a lethal dose of cobalt-60 rays.Bone marrow cells were prepared from CD45.1+C57BL/6 mice and transfused into recipient mice through the tail vein.Peripheral blood,spleens,lymph nodes,thymuses and bone marrow were collected at 1,2,4,8 and 16 weeks after transplantation.Blood routine examination was performed with peripheral blood and total cell numbers in suspensions of other organs were counted by an automated cell counter.Cell classification analysis of white blood cells in peripheral blood,cell suspensions of other organs was performed by flow cytometry.RESULTS Four weeks after BMT,the numbers of white blood cells and red blood cells in peripheral blood of recipient mice returned to the same level of or higher level than normal control(P<0.05).Although the number of platelets recovered significantly,it was still mark-edly lower than that of normal control until 16 weeks post BMT(P<0.05).In addition,the percentages of myeloid leukocytes and B cells in peripheral blood,spleens,lymph nodes,and bone marrow,as well as megakaryocytes and erythrocyte progenitor cells in bone marrow also returned to normal,and the majority of myeloid leukocytes and B cells were CD45.1+cells from the donors.Eight weeks after BMT,T cells in peripheral blood,spleens,lymph nodes,thymuses,and bone marrow of recipient mice returned to normal,and CD45.1+T cells were dominating.CONCLUSION The hematopoietic and immune reconstitution of recipient mice is nearly completed eight weeks after BMT.However,the reconstruction speed of different kinds of cells and the reconstruction status of same kind of cell in different organs vary widely.

Objective: We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. Methods: Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. Results: A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. Conclusion The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

Objective To investigate the value of dual-energy CT quantitative parameters combined with CT features for predicting perineural invasion(PNI)of colorectal adenocarcinoma.Methods Preoperative whole-abdominal CT data of 79 patients with colorectal adenocarcinoma confirmed by postoperative pathology were retrospectively analyzed.The patients were divided into PNI group(n=31)or no PNI group(n=48).Univariate analysis was used to compare CT features and dual-energy CT quantitative parameters between groups,and the variables with significant differences were included in binary logistic regression analysis to construct a combined model.Receiver operating characteristic(ROC)curves were drawn and area under the curve(AUC)were calculated,the efficacy of single CT parameters and combined model for predicting PNI of colorectal adenocarcinoma were evaluated.Results There were significant differences of the location of the primary lesion,the maximum thickness of the diseased intestinal wall,the presence or absence of peritumoral lymph node metastases,peritumoral mesenteric streak shadow and tumor deposits shown on CT between groups(all P＜0.05).Significant differences of the arterial phase slope of energy spectrum curve(λHU),iodine concentration(IC),normalized IC(NIC),dual energy index and the venous phase NIC of dual energy index were found between groups(all P＜0.05).AUC of the above single parameters for predicting PNI of colorectal adenocarcinoma ranged from 0.615 to 0.698,while of the combined model was 0.864.Conclusion Dual-energy CT quantitative parameters combined with CT features could be used to effectively predict PNI of colorectal adenocarcinoma.

Objective:To investigate the risk factors of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients in plain-sand areas and loess hilly areas of Gansu province.Methods:A total of 1 599 T2DM patients who participated in chronic disease and risk factors monitoring and basic public health service management were selected by multi-stage stratified random sampling method in the sandy plain areas and loess hilly areas of Gansu province. Questionnaire survey, physical measurement and laboratory tests were performed. Multivariate binary logistic model was used to analyze the influencing factors.Results:The prevalence of DKD was 22.1% (174/787) among T2DM patients in the sandy plain areas and 19.1%(155/812) in the loess hilly area, respectively. Hypertension ( OR=3.022), hyperuricemia ( OR=2.114) and HbA1c≥7%( OR=2.231) were the risk factors for DKD in the plain-sand areas, and the risk of DKD increased with age. In the loess hilly areas, female sex ( OR=0.379) was the protective factor for DKD; while duration of disease≥10 years ( OR=2.476), hyperuricemia ( OR=1.907), HbA1c≥7% ( OR=1.927) were the risk factors for DKD; and the risk of DKD increased with the increase of age, and decreased with the increase of per capita monthly income. Conclusions:The prevalence of DKD and its influencing factors are different between sandy plain areas and loess hilly areas in Gansu province. The prevention and treatment of hypertension should be given more attention in sandy plain areas. In addition, the screening of DKD should be conducted among T2DM patients, particularly for those with old age, hyperuricemia and HbA1c≥7% in both areas of the province.

【Objective】 To investigate the relationship between maternal oral health behavior during pregnancy and premature birth. 【Methods】 A total of 248 preterm and 700 non-preterm pregnant women who delivered in Northwest Women’s and Children’s Hospital in Shaanxi Province from January to December 2022 were included in case group and control group, respectively. General demographic characteristics and oral health behavior during pregnancy were collected by questionnaires, and the oral health impact profile-14 (OHIP-14) was used to assess the oral health related life quality of pregnant women. Logistic regression model was used to analyze the relationship between maternal oral health behavior during pregnancy and premature birth. 【Results】 During pregnancy, maternal frequent eating after brushing teeth (OR=1.62, 95% CI: 1.03-2.57), unused fluoride toothpaste (OR=2.03, 95%CI: 1.25-3.05), late visit to the doctor for oral discomfort (OR=1.41, 95%CI: 1.02-1.96), brushing teeth less than twice one day (OR=1.77, 95%CI: 1.13-2.78) or less than 3 minutes each time (OR=1.52, 95%CI: 1.09-2.11), and elevated OHIP-14 score (OR=1.07, 95%CI: 1.04-1.10) increased the risk of premature birth. 【Conclusion】 Poor oral health behavior during pregnancy may increase the risk of premature birth. Therefore, more efforts should be made to publicize oral health knowledge and guide pregnant women to establish good oral health habits so as to improve oral health and promote maternal and child health.

Objective:To analyze the literature on electric burns published at home and abroad, and to explore the research hotspots and frontiers of electric burns.Methods:The bibliometric method was used. The Chinese and English literature related to electric burns published in China National Knowledge Infrastructure, Wanfang database, VIP database and the core collection of Web of Science database from January 1, 2013 to December 31, 2022 were searched respectively, and the CiteSpace 6.2.R2 software was used for analysis. The number of papers, authors, countries, and institutions of Chinese and English literature were counted respectively, and the co-occurrence analysis of keywords and mutation analysis and cluster analysis on the basis of the co-occurrence analysis were conducted, besides, the clustering time line figure was obtained after the keywords were sorted by time to explore the current research status and the evolution process of hotspots in the field of electric burns.Results:A total of 398 English papers were retrieved from the core collection of Web of Science database, and a total of 523 Chinese papers were retrieved from China National Knowledge Infrastructure, Wanfang database, and VIP database after duplicate check. From 2013 to 2022, the number of English literature published in the field of electric burns showed a steadily upward trend, and the number of published Chinese literature showed a downward trend and tended to be stable. In Chinese literature, a total of 302 authors as the first author published papers related to electric burns, with 17 core authors published ≥3 papers; in English literature, a total of 320 authors as the first author published papers related to electric burns. Researches on electric burns were carried out in 65 countries, with United States having the most cooperation with other countries and the largest number of papers published. A total of 512 institutions at home and abroad published papers related to electric burns, and the institutions with the largest number of Chinese and English papers were Shanghai Electric Power Hospital in China ( n=14) and Hallym University in Korea ( n=11), respectively. A total of 1 176 Chinese keywords and 1 068 English keywords were included for co-occurrence analysis after excluding keywords related to the searching words. The top three keywords in frequency in Chinese literature were surgical flap, wound repair, and nursing, and the top three keywords in frequency in English literature were management, epidemiology, and children. Ten clusters were obtained by keyword analysis in Chinese literature, and the largest cluster was wound healing, followed by clinical effects and surgical flaps. Seven clusters were obtained by keyword analysis in English literature, and the largest cluster was reconstructive surgical procedures, followed by chronic pain and shock. The persistent clusters in Chinese literature were wound healing and clinical outcomes, etc., and the prominent nodes in the recent two years were surgical timing, limb electric burns, and hypertrophic scars; the persistent clusters in English literature were reconstructive surgical procedures and chronic pain, etc., and the prominent nodes in the recent two years were predictors and burn management, etc. In Chinese literature, the keyword with the longest duration of mutation (2017—2021) was wrist electric burns, and the keyword with the highest intensity of mutation was flap repair; in English literature, the keyword with the longest duration of the mutation (2019—2022) was voltage, and the keyword with the highest intensity of mutation was prevention. Conclusions:There are similarities and differences in the research directions and hotspots of electric burns at home and abroad. Surgical flap repair is a common research hotspot at home and abroad. At present, domestic research focuses on wound healing, wrist electric burns, and other aspects, while international research focuses on treatment management, epidemiology, reconstruction, and other aspects.