Background::Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to investigate the epigenetic mechanisms in IUGR.Methods::IUGR models were established in Sprague–Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF) 1–4 binding sites of the Igf2/H19 imprinting control region (ICR). The methylation states of CTCF1–4 binding sites were studied by pyrosequencing. Results::The IUGR models were constructed successfully. Igf2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group ( P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group ( P <0.05). In addition, knocking down Igf2 reduced the protein expression levels of AKT2-phosphorylation and PGC-1α ( P <0.05). In CTCF binding sites 1-4 of the Igf2/ H19 ICR, acetylated histones H3 (AcH3) enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. Histone H3 tri-methylated lysine 4 (H3K4me3) enrichment was significantly lower in the CTCF1–4 of newborn and 8-week-old IUGR groups ( P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group ( P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly ( P <0.05). Conclusion::The methylation status and histone modification in the Igf2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.

Objective To evaluate the clinical utility of the f-wave to QRS complex amplitude ratio(f/R ratio)in intracardiac electrogram(IC-ECG)-guided positioning of peripherally inserted central catheter(PICC)tips in patients with atrial fibrillation(AF),providing evidence to enhance clinical practice.Methods This study employed a conve-nience sampling method to enroll eligible AF patients admitted to a tertiary hospital in Suzhou from July 2023 to July 2024.During PICC placement,IC-ECG was utilized to monitor f-wave and QRS complex amplitude variations.Following successful catheterization,the f/R ratio was measured,and chest X-ray was performed to confirm the catheter tip position.The accuracy of PICC tip positioning across different f/R ratio ranges was analyzed,and the incidence of arrhythmias was recorded.A receiver operating characteristic curve was constructed to assess the diag-nostic performance of the f/R ratio in PICC tip localization.Results A total of 68 AF patients were included,with f/R ratios ranging from 20.63％to 91.24％.PICC tip positioning accuracy varied significantly across different f/R ratio ranges(P=0.006).The area under the ROC curve(AUC)for f/R ratio in PICC tip positioning was 0.784(P=0.009),with a maximum Youden index of 0.567,an optimal diagnostic threshold of 40.00％,a sensitivity of 81.7％,a speci-ficity of 75.0％,a positive predictive value of 96.1％,and a negative predictive value of 35.3％.No arrhythmias other than AF occurred during the procedure.Conclusion The f/R ratio provides reliable and safe guidance for PICC tip positioning in AF patients.An f/R ratio ≥40％is associated with higher accuracy in identifying the optimal catheter tip position.

Objective To investigate and analyze clinical characteristics and related factors of elderly patients with type 2 diabetes mellitus (T2DM) and frailty. Methods A total of 310 elderly patients with T2DM admitted to the hospital from January 2023 to June 2024 were selected as the research subjects. Their general information and disease-related information was collected through questionnaires. The Fried Frailty Scale was used to evaluate frailty status, and the patients were divided into frailty group and non-frailty group based on the Fried Frailty Scale score. Factors related to T2DM with frailty in the elderly were analyzed. Results The incidence of frailty in this study was 31.61% (98/310), and those without frailty accounted for 68.39% (212/310). There were statistically significant differences between the two groups in terms of age, body mass index (BMI), Self-rating Depression Scale (SDS) score, number of chronic complications, glycosylated hemoglobin (HbA1c) level, hemoglobin level, Mini-Nutritional Assessment-Short Form (MNA-SF) score, and Charlson Comorbidity Index (CCI) score (P<0.05). Multivariate logistic regression analysis showed that age, HbA1c level, SDS score, MNA-SF score, and CCI score were risk factors for frailty in elderly patients with T2DM (P<0.05). Conclusion The incidence of frailty is relatively high in elderly patients with T2DM. It is influenced by factors such as age , SDS score , HbA1c level , MNA-SF score and CCI score, and deserves clinical attention.

Objective:To screen differentially expressed genes in the retinas of mice with experimental autoimmune uveitis (EAU) through transcriptome sequencing.Methods:Twenty 8-week-old SPF grade male C57BL/6J mice were randomly divided into EAU group and control group by random number table method, with 10 mice in each group.In the EAU group, an emulsion of interphotoreceptor retinoid-binding protein 1-20 and complete Freund adjuvant was injected subcutaneously into the inner side of the hind limbs and intravenously into the tail vein of the mice, and pertussis toxin was injected intraperitoneally to establish the EAU model.In the control group, mice were subcutaneously injected with the corresponding volume of phosphate buffer solution.On the 21st day after model establishment, the anterior segment inflammation of the mouse eyes was examined using a slit-lamp microscope.Retinal blood vessels were observed by fundus photography and clinical inflammation was scored.Hematoxylin-eosin staining was used to observe the morphological changes in the retinal tissues of the two groups.Retinal tissues were collected from two groups of mice.RNA was extracted and cDNA libraries were constructed for transcriptome sequencing.The clusterProfiler package in R programming language was used to screen for differentially expressed genes in EAU, and to conduct GO and KEGG enrichment analyses.The expression of core differentially expressed genes in the retinal tissues was then verified using real-time fluorescent quantitative PCR.The breeding and use of experimental animals were in compliance with the relevant regulations of the Animal Ethics Committee of Anhui Medical University.The study protocol was approved by the Ethics Committee of Anhui Medical University (No.LLSC20221208).Results:On the 21st day after model establishment, the clinical score of the EAU group was 2.83±0.94, significantly higher than 1.89±0.93 of the control group, and the difference was statistically significant ( t=2.290, P<0.05). The retinal blood vessels of mice in the EAU group showed tortuosity and dilation.Histopathological examination revealed a large number of inflammatory cell infiltrations in the retina, indicating successful establishment of the EAU mouse model.Transcriptome sequencing of the mouse retinal tissues identified a total of 32 473 genes, and 154 differentially expressed genes were screened out.Among them, 79 genes were up-regulated with Gm38574, Tmem81, Ptpn7 being top three and 75 genes were down-regulated with Gm19802, Fga, Cyp3a11 being top three.GO enrichment analysis showed that the differentially expressed genes were mostly related to immune response and cytokine action.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in the Toll-like pathway and cytokine signaling pathway.Compared with the control group, the relative expression levels of Gm38574, Tmem81, and Ptpn7 in the retinal tissues of the EAU group were up-regulated, while the expression levels of Gm19802, Fga, and Cyp3a11 were down-regulated, and the differences were statistically significant ( t=9.755, 5.358, 6.289, 4.312, 6.577, 6.118; all P<0.05). Conclusions:There are significant differences in the key genes Gm38574, Tmem81, Ptpn7, Gm19802, Fga, and Cyp3a11 in the retinal tissues of EAU mice, mainly corelated with the cytokine interaction pathway, Toll-like receptor signaling pathway.

Objective To evaluate the clinical utility of the f-wave to QRS complex amplitude ratio(f/R ratio)in intracardiac electrogram(IC-ECG)-guided positioning of peripherally inserted central catheter(PICC)tips in patients with atrial fibrillation(AF),providing evidence to enhance clinical practice.Methods This study employed a conve-nience sampling method to enroll eligible AF patients admitted to a tertiary hospital in Suzhou from July 2023 to July 2024.During PICC placement,IC-ECG was utilized to monitor f-wave and QRS complex amplitude variations.Following successful catheterization,the f/R ratio was measured,and chest X-ray was performed to confirm the catheter tip position.The accuracy of PICC tip positioning across different f/R ratio ranges was analyzed,and the incidence of arrhythmias was recorded.A receiver operating characteristic curve was constructed to assess the diag-nostic performance of the f/R ratio in PICC tip localization.Results A total of 68 AF patients were included,with f/R ratios ranging from 20.63％to 91.24％.PICC tip positioning accuracy varied significantly across different f/R ratio ranges(P=0.006).The area under the ROC curve(AUC)for f/R ratio in PICC tip positioning was 0.784(P=0.009),with a maximum Youden index of 0.567,an optimal diagnostic threshold of 40.00％,a sensitivity of 81.7％,a speci-ficity of 75.0％,a positive predictive value of 96.1％,and a negative predictive value of 35.3％.No arrhythmias other than AF occurred during the procedure.Conclusion The f/R ratio provides reliable and safe guidance for PICC tip positioning in AF patients.An f/R ratio ≥40％is associated with higher accuracy in identifying the optimal catheter tip position.

Objective:To screen differentially expressed genes in the retinas of mice with experimental autoimmune uveitis (EAU) through transcriptome sequencing.Methods:Twenty 8-week-old SPF grade male C57BL/6J mice were randomly divided into EAU group and control group by random number table method, with 10 mice in each group.In the EAU group, an emulsion of interphotoreceptor retinoid-binding protein 1-20 and complete Freund adjuvant was injected subcutaneously into the inner side of the hind limbs and intravenously into the tail vein of the mice, and pertussis toxin was injected intraperitoneally to establish the EAU model.In the control group, mice were subcutaneously injected with the corresponding volume of phosphate buffer solution.On the 21st day after model establishment, the anterior segment inflammation of the mouse eyes was examined using a slit-lamp microscope.Retinal blood vessels were observed by fundus photography and clinical inflammation was scored.Hematoxylin-eosin staining was used to observe the morphological changes in the retinal tissues of the two groups.Retinal tissues were collected from two groups of mice.RNA was extracted and cDNA libraries were constructed for transcriptome sequencing.The clusterProfiler package in R programming language was used to screen for differentially expressed genes in EAU, and to conduct GO and KEGG enrichment analyses.The expression of core differentially expressed genes in the retinal tissues was then verified using real-time fluorescent quantitative PCR.The breeding and use of experimental animals were in compliance with the relevant regulations of the Animal Ethics Committee of Anhui Medical University.The study protocol was approved by the Ethics Committee of Anhui Medical University (No.LLSC20221208).Results:On the 21st day after model establishment, the clinical score of the EAU group was 2.83±0.94, significantly higher than 1.89±0.93 of the control group, and the difference was statistically significant ( t=2.290, P<0.05). The retinal blood vessels of mice in the EAU group showed tortuosity and dilation.Histopathological examination revealed a large number of inflammatory cell infiltrations in the retina, indicating successful establishment of the EAU mouse model.Transcriptome sequencing of the mouse retinal tissues identified a total of 32 473 genes, and 154 differentially expressed genes were screened out.Among them, 79 genes were up-regulated with Gm38574, Tmem81, Ptpn7 being top three and 75 genes were down-regulated with Gm19802, Fga, Cyp3a11 being top three.GO enrichment analysis showed that the differentially expressed genes were mostly related to immune response and cytokine action.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in the Toll-like pathway and cytokine signaling pathway.Compared with the control group, the relative expression levels of Gm38574, Tmem81, and Ptpn7 in the retinal tissues of the EAU group were up-regulated, while the expression levels of Gm19802, Fga, and Cyp3a11 were down-regulated, and the differences were statistically significant ( t=9.755, 5.358, 6.289, 4.312, 6.577, 6.118; all P<0.05). Conclusions:There are significant differences in the key genes Gm38574, Tmem81, Ptpn7, Gm19802, Fga, and Cyp3a11 in the retinal tissues of EAU mice, mainly corelated with the cytokine interaction pathway, Toll-like receptor signaling pathway.

Objective: To explore the damaging effect of the IP3-protein kinase C pathway on human retinal vascular endothelial cells under high glucose conditions. Methods: Human retinal vascular endothelial cells in the logarithmic growth phase were taken and divided into the experimental group(10 mmol/L glucose and 20 mmol/L glucose) and the control group(5 mmol/L glucose). The morphological changes of cells were observed under different concentrations of glucose culture medium. The apoptosis of human retinal vascular endothelial cells was detected by flow cytometry. Real-time fluorescent quantitative reverse transcription polymerase chain reaction was used to detect the RNA expression level of PKC in the IP3-protein kinase C(PKC) pathway, and Western blot was used to detect the protein expression level of PKC in cells. Results: Under high glucose conditions, the volume of human retinal vascular endothelial cells increased, the degree of extension decreased, and the apoptosis rate increased. Compared with the control group, the apoptosis rate of human retinal vascular endothelial cells in the 20 mmol/L glucose group increased(P<0.05); the IP3 level of human retinal vascular endothelial cells in the 20 mmol/L glucose group(587.9±15.2) ng/ml was lower than that of the control group(738.9±1.0) ng/ml(P<0.05). Under high glucose treatment, the expression levels of PKC mRNA and protein increased(P<0.05). Conclusion The IP3-PKC pathway may be involved in the damage process of human retinal vascular endothelial cells under high glucose conditions, and thus may play a role in diabetic retinopathy.

Objective To investigate the effectiveness of team-based learning(TBL)combined with research-based learning(RBL)in enhancing evidence-based nursing practice skills of undergraduate nursing interns.Methods A total of 114 undergraduate nursing students who interned in the operating room of a ⅢA hospital in Guangzhou from July 2021 to April 2022 were selected as study subjects.A randomized cluster sampling method based on a random number table was used to divide the students into a control group and a trial group.The control group received traditional teaching methods,while the trial group was taught using a combination of TBL and RBL.The two groups were compared in terms of evidence-based practice skills,critical thinking abilities,and their evaluations on the teaching methods.Results The differences in evidence-based practice skills and critical thinking abilities before and after the internship were significantly higher in the observation group compared to the control group(t=35.108,35.897;both P<0.05).Additionally,post-internship evaluation scores for the teaching methods in the trial group were significantly higher than those in the control group(t=-17.580,P<0.05).Conclusion TBL combined with RBL effectively enhances the evidence-based nursing practice skills and critical thinking abilities of undergraduate nursing interns.This approach also improves students'evaluations on the teaching methods and fosters the cultivation of excellent clinical evidence-based nursing professionals.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with adverse metabolic outcomes during adulthood. Histone modifications and changes in DNA methylation-affected genes are important for fetal development. This study aimed to confirm the epigenetic mechanisms in IUGR. METHODS: IUGR models were established in Sprague-Dawley rats using a maternal nutritional restriction approach during pregnancy. The abundance of insulin-like growth factor 2 (IGF2), phosphoinositide 3-kinase (PI3K), AKT serine/threonine kinase 2 (AKT2), and PPAR gamma coactivator 1 alpha (PGC-1α) was examined by real-time polymerase chain reaction (RT-PCR) and Western blotting analysis. Chromatin immunoprecipitation RT-PCR was employed to analyze histone modification in CCCTC-binding factor (CTCF)1-4 binding sites of the IGF2/H19 imprinting control region (ICR). The methylation states of CTCF1-4 binding sites were studied by pyrosequencing. RESULTS: The IUGR models were constructed successfully. IGF2 mRNA abundance in the placenta, fetal liver, and newborn liver was decreased in the IUGR group (P <0.01). Meanwhile, as compared with the control group, the expression levels of AKT2, PI3K, and PGC-1α were lower in newborn and 8-week-old livers in the IUGR group (P <0.05). In addition, knocking down IGF2 reduced the protein expression levels of AKT2-P and PGC-1α (P <0.05). In CTCF binding sites 1-4 of the IGF2/H19 ICR, AcH3 enrichment was significantly lower in CTCF1-3 in newborn and 8-week-old IUGR rats. H3K4me3 enrichment was significantly lower in the CTCF1-4 of newborn and 8-week-old IUGR groups (P <0.01). H3K9me2 enrichment was significantly higher in the IUGR group (P <0.01). The CpG dinucleotide methylation levels of CTCF1 and CTCF3, but not those of CTCF2 and CTCF4 binding sites in IUGR rat fetal, 4-week old, and 8-week-old livers decreased significantly (P <0.05). CONCLUSION The methylation status and histone modification in the IGF2/H19 ICR are related to growth and lipid metabolism via the PGC-1α/PI3K/AKT2 pathway in IUGR rats.