Objective Objective To investigate the expression levels of long non-coding RNA HCG11(LncHCG11)and miR-214-5p in pancreatic cancer tissues and their potential molecular regulatory mechanisms.Methods Ten patients with pancreatic cancer admitted between January 2022 and January 2025 were included,and post-operative cancer tissue and paired adjacent tissue samples were collected.Real-time quantitative PCR technology was used to detect the transcription levels of LncHCG11 and miR-214-5p,and the expression level of sirtuin 2(SIRT2)protein was measured by Western blot.The relationship of miR-214-5p with LncHCG11 and SIRT2 was predicted through a biological database.Results Compared with the adjacent non-cancerous tissues,the expression of LncHCG11 and SIRT2 was significantly reduced in pancreatic cancer tissues,while the level of miR-214-5p was significantly increased(P<0.01).In vitro experiments showed that overexpression of LncHCG11 in the Panc1 cell line could upregulate the expression of SIRT2 protein and simultaneously inhibit the proliferative activity of Panc1 cells(P<0.05).Both miR-214-5p and LncHCG11,SIRT2 had binding sites.Conclusion LncHCG11 may act as a competing endogenous RNA to sponge miR-214-5p,releasing its transcriptional inhibition on SIRT2,thereby inhibiting the progression of pancreatic cancer.

Objective:To explore the correlation between triglyceride glucose index (TyGI) and hyperuricemia (HUA) in theindividuals undergoing physical examinations.Methods:It was a cross-sectional study. A total of 21 720 individuals who underwent health examinations at the Health Management Center of Xiangya Hospital, Central South University from October 2020 to March 2021 were selected as the research subjects. Based on whether uric acid levels exceeded the normal range, the participants were divided into a HUA group and a control group (normal uric acid group). The independent correlation between TyGI and HUA was determined with multiple logistic regression analysis, and stratified analysis was conducted to investigate population differences in the correlation. And finally, a further evaluation was conducted to determine whether there was a nonlinear relationship between TyGI and HUA through smooth curve fitting and threshold saturation effect analysis.Results:The TyGI in the HUA group was significantly higher than that in the control group ( t=-41.787, P<0.001). After adjusting for relevant factors, the multiple logistic regression analysis showed that there was a significant positive correlation between TyGI and risk of HUA ( OR=1.755, 95% CI: 1.632-1.887); and as TyGI increased, the risk of HUA gradually increased. Stratified analysis and interaction tests were conducted based on age, gender, body mass index, blood glucose abnormalities, hypertension, and estimated glomerular filtration rate (eGFR), it′s indicated that TyGI was positively correlated with the risk of HUA in various populations except for in the individuals with a eGFR less than 60 ml·min -1·(1.73 m 2) -1 and in females (all P>0.05). The smooth curve fitting between TyGI and HUA suggested that as TyGI increased, the risk of HUA tended to increase. However, when TyGI reached a certain threshold, the risk of HUA no longer increased. Further analysis of threshold saturation effects suggested that the inflection point of TyGI was 9.871. Conclusion:The correlation between TyGI and HUA in the population undergoing health examinations is nonlinear.

Objective:To explore the correlation between hyperuricemia (HUA) and chronic kidney disease (CKD) in the individuals undergoing physical examinations.Methods:It was a retrospective cohort study. The study selected 6 910 individuals who received health check-ups at the Xiangya Hospital Health Management Center of Central South University in 2012 and 2022, with none of them having developed CKD in 2012. Using the presence of HUA in 2012 as the independent variable and the occurrence of CKD in 2022 as the outcome variable, four Cox proportional hazards regression models were constructed, with baseline age, gender, body mass index, waist circumference, glomerular filtration rate, presence of hypertension, presence of diabetes, presence of dyslipidemia, white blood cell count, hemoglobin level, direct bilirubin level, alanine aminotransferase level, and blood uric acid level in 2013 as confounding variables. These models were used to analyze the correlation between HUA and CKD, and sensitivity analyses were conducted. The percentile bootstrap method was employed to conduct mediation effect testing, analyzing the intermediary risk factors that influence the correlation between HUA and CKD.Results:Among the 6 910 participants included in the study, the overall baseline detection rate of HUA was 8.78% (607/6 910). In 2022, the incidence of CKD was 7.2% (498/6 910). Cox regression analysis showed a positive correlation between HUA and the occurrence of CKD in the overall population ( HR=1.586, 95% CI: 1.224-2.055). However, after gradually adjusting for confounding factors, the correlation between HUA and CKD was not statistically significant. Stratified by gender, the occurrence of HUA was positively correlated with the incidence of CKD in women ( HR=2.599, 95% CI: 1.069-6.316), but the correlation became non-significant after adjusting for confounding factors. In contrast, there was no significant correlation between HUA and CKD in men. In sensitivity analysis, When uric acid levels were analyzed by grouping participants into two categories based on thresholds of>420 μmol/L for men and>360 μmol/L for women, or as a continuous variable, the results showed a positive correlation between HUA and CKD in the overall population and in women, the HR (95% CI) value was 1.627 (1.282-2.064), 2.465 (1.552-3.914), 1.004 (1.003-1.005) and 1.006 (1.004-1.008), respectively. However, after adjusting for confounding factors, the correlation between HUA and CKD became non-significant in both cases. In the males, there was no correlation between uric acid and the occurrence of CKD, regardless of whether uric acid was treated as a categorical or continuous variable. Mediation analysis revealed that diabetes and hypertension were full mediators between HUA/blood uric acid levels and CKD in the overall population. Among males, diabetes and hypertension were full mediators between blood uric acid levels and CKD. In females, hypertension was a full mediator between HUA/blood uric acid levels and CKD, with an effect proportion of 100%. Conclusion:HUA is positively correlated with the risk of CKD, particularly in females, but HUA is not an independent predictor of CKD. HUA influences the occurrence of CKD through conditions such as diabetes and hypertension.

Objective:To investigate the effects of the expanded lateral thoracic artery perforator flap in the reconstruction of breast scar contracture deformity after burns in minor females.Methods:The study was a retrospective observational study. From July 2018 to October 2023, 8 female children aged 4 to 12 years and with breast scar contracture deformity after burns, who met the inclusion criteria, were admitted to the Department of Burns and Plastic Surgery of Guangzhou Red Cross Hospital of Jinan University. The skin and soft tissue expander (hereinafter referred to as expander) was placed in the first stage. The contracture scar was removed and released in the second stage, and the wound formed after the scar was removed measured between 9 cm×8 cm and 15 cm×10 cm. The expanded lateral thoracic artery perforator flap was designed and transferred to repair the wound with resected flap area of 10 cm×9 cm to 16 cm×11 cm, and the wound at the flap donor area was directly sutured. The complications such as incision infection, hematoma, and expander exposure were observed after stage Ⅰ surgery. After stage Ⅱ surgery, the survival of the flap and the wound healing at the flap donor area were observed. During the 1-year follow-up after the stage Ⅱ surgery, the breast development was evaluated according to tanner staging performance of female pubertal breast development, the aesthetic effect of the affected breast was evaluated by using the aesthetic effect evaluation standard after breast surgery, the Vancouver scar scale (VSS) was used to score the scar condition at the flap donor and recipient areas, and the satisfaction of the children's families with the surgical outcomes was investigated by using a self-made scale.Results:After stage Ⅰ surgery, no incision infection, hematoma, expander exposure, or other complications occurred in 8 children. After stage Ⅱ surgery, only one child had tissue necrosis at the distal end of the flap with a size of about 2 cm×1 cm, which healed after dressing change, and the flap in other children had good blood supply, soft texture, moderate thickness, and similar color to the skin at the recipient area. The wounds at all flap donor areas healed well. During the 1-year follow-up after stage Ⅱ surgery, 7 children had normal breast development, with their breast volume, height, and shape being almost the same as or similar to the healthy side, with the aesthetic effect of all being grade Ⅰ; the breast in one child had not yet developed, and these indicators were not evaluated. The locations of nipple areola complex in 8 children were almost the same as or similar to those in the healthy side, and their skin color, integrity, texture, and elasticity of the partial breast repaired by the transferred flap were similar to those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The shapes of nipple and areola in 5 children were inconsistent with those in the healthy side because of the original scar, with the aesthetic effect of all being grade Ⅱ, and the shapes of nipple and areola in the other 3 children were consistent with those in the healthy side, with the aesthetic effect of all being grade Ⅰ. The VSS score of the scar at the flap recipient area was 2-5, and the VSS score of the scar at the flap donor area was 1-3. Seven children's families were satisfied with the surgical effect, and one child's family was basically satisfied with the surgical effect.Conclusions:For the breast scar contracture deformity of minor females after burns, the expanded lateral thoracic artery perforator flap is used for reconstruction before puberty, which results in fewer postoperative complications, good breast shape, and hidden scar at the flap donor area. It is beneficial for the normal development of adolescent breasts, and is one of the safe and effective methods for the treatment of breast scar contracture deformity in minor females after burns.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

OBJECTIVES: Pyroptosis plays a critical role in tubulointerstitial lesions of diabetic kidney disease (DKD). Annexin A2 (ANXA2) is involved in cell proliferation, apoptosis, and adhesion and may be closely related to DKD, but its specific mechanism remains unclear. This study aims to investigate the role and molecular mechanism of ANXA2 in high glucose-induced pyroptosis of renal tubular epithelial cells, providing new targets for DKD prevention and treatment. METHODS: Human renal tubular epithelial HK-2 cells were divided into a normal glucose group (5.5 mmol/L), a high glucose group (30.0 mmol/L), and a osmotic control group (24.5 mmol/L mannitol+5.5 mmol/L glucose). ANXA2 expression was modulated by overexpression of plasmids and small interfering RNA (siRNA). Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, apoptosis by flow cytometry, and ANXA2, p50, and p65 subcellular localization by immunofluorescence. Western blotting was employed to detect α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type IV (Col-IV). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to analyze nuclear factor-κB (NF-κB) subunits p50/p65 and the pyroptosis pathway factors NLR family Pyrin domain containing 3 (NLRP3), caspase-1, inferleukin (IL)-1β, and IL-18. Protein interactions between ANXA2 and p50/p65 were examined by co-immunoprecipitation, while chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to examine NF-κB binding to the ANXA2 promoter. RESULTS: High glucose upregulated ANXA2 expression and promoted its nuclear translocation (P<0.01). High glucose reduced cell proliferation, increased apoptosis, and elevated α-SMA, FN, and Col-IV expression (all P<0.05); ANXA2 overexpression aggravated these effects (all P<0.05), while ANXA2 knockdown reversed them (all P<0.05). High glucose activated NF-κB and increased NLRP3, caspase-1, L-1β, and IL-18 mRNA and protein expression (all P<0.05); ANXA2 overexpression further enhanced this, whereas knockdown suppressed NF-κB activation and downstream factors (all P<0.05). Co-immunoprecipitation confirmed ANXA2 directly binds the NF-κB subunit p65. ChIP assays revealed p65 binds specifically to ANXA2 promoter regions (ChIP-2, ChIP-4, and ChIP-6), and luciferase activity in corresponding mutant constructs (M2, M4, and M6) was significantly increased versus controls (all P<0.05), confirming positive transcriptional regulation of ANXA2 by p65. CONCLUSIONS ANXA2 and NF-κB form a positive feedback loop that sustains NLRP3 inflammasome activation, promotes pyroptosis pathway activation, and aggravates high glucose-induced renal tubular epithelial cell injury. Targeting ANXA2 or blocking its interaction with p65 may be a novel strategy to slow DKD progression.
Humans ; Pyroptosis/drug effects* ; Annexin A2/physiology* ; Epithelial Cells/cytology* ; Kidney Tubules/cytology* ; Glucose/pharmacology* ; Diabetic Nephropathies/metabolism* ; NF-kappa B/metabolism* ; Cell Line ; Cell Proliferation ; Transcription Factor RelA/metabolism* ; Feedback, Physiological

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Aim To systematically elucidate the molecular regulatory network of thermogenic function in brown adipose tissue(BAT)through multi-omics integrative analysis,to discover novel thermogenic regulatory genes and provide novel therapeutic targets for metabolic disorders.Methods A novel methodology for screening key genes regulating thermogenesis in BAT was constructed:First,differential expression analysis was performed on bulk RNA-seq data from murine BAT.Genes meeting the thresholds of ABS(log2FoldChange)＞1 and Padj＜0.05 were identified as differentially expressed genes.Intersectional analysis was then applied to obtain consensus upregulated and downregulated gene sets.Subsequently,scRNA-seq data of brown adipocytes were partitioned into high-expression group and low-expression group based on the expression levels of candidate genes.Differential analysis and gene set enrichment analysis(GSEA)were conducted between these groups to assess the correlation between candidate genes and thermogenic function.Finally,ex-perimental validation of selected candidate genes was performed using quantitative real-time PCR and Western blot.Results Bioinformatics analysis identified 65 thermogenesis-positive correlated genes and 7 thermogenesis-negative corre-lated genes.Subsequent quantitative PCR validation demonstrated that candidate genes Mfsd2a,Me1,Slc25a34,Pfkp,Ankrd9,Hsd17b12,Aldoa,Ctsz and Pcyt2 exhibited upregulation exceeding 5-fold,while Pid1 and Angpt1 showed down-regulation over 50％.All observed expression changes demonstrated statistical significance(P＜0.01)through rigorous hypothesis testing.These findings highlight the potential involvement of these genes in thermogenic regulation,warranting further functional investigations to elucidate their molecular mechanisms in energy metabolism pathways.Conclusions This study established a novel"computational screening → in silico knockout → experimental validation"paradigm for tar-get discovery,systematically unveiling the molecular network involved in BAT thermogenic regulation.This methodology is equally applicable for identifying key regulatory genes in other physiological or pathological processes.The study identi-fied 11 core genes that may play pivotal regulatory roles during BAT thermogenic activation,which could potentially offer novel pharmacological intervention targets to improve energy metabolism and treat obesity-related complications.

Objective Objective To investigate the expression levels of long non-coding RNA HCG11(LncHCG11)and miR-214-5p in pancreatic cancer tissues and their potential molecular regulatory mechanisms.Methods Ten patients with pancreatic cancer admitted between January 2022 and January 2025 were included,and post-operative cancer tissue and paired adjacent tissue samples were collected.Real-time quantitative PCR technology was used to detect the transcription levels of LncHCG11 and miR-214-5p,and the expression level of sirtuin 2(SIRT2)protein was measured by Western blot.The relationship of miR-214-5p with LncHCG11 and SIRT2 was predicted through a biological database.Results Compared with the adjacent non-cancerous tissues,the expression of LncHCG11 and SIRT2 was significantly reduced in pancreatic cancer tissues,while the level of miR-214-5p was significantly increased(P<0.01).In vitro experiments showed that overexpression of LncHCG11 in the Panc1 cell line could upregulate the expression of SIRT2 protein and simultaneously inhibit the proliferative activity of Panc1 cells(P<0.05).Both miR-214-5p and LncHCG11,SIRT2 had binding sites.Conclusion LncHCG11 may act as a competing endogenous RNA to sponge miR-214-5p,releasing its transcriptional inhibition on SIRT2,thereby inhibiting the progression of pancreatic cancer.

Objective:To explore the correlation between triglyceride glucose index (TyGI) and hyperuricemia (HUA) in theindividuals undergoing physical examinations.Methods:It was a cross-sectional study. A total of 21 720 individuals who underwent health examinations at the Health Management Center of Xiangya Hospital, Central South University from October 2020 to March 2021 were selected as the research subjects. Based on whether uric acid levels exceeded the normal range, the participants were divided into a HUA group and a control group (normal uric acid group). The independent correlation between TyGI and HUA was determined with multiple logistic regression analysis, and stratified analysis was conducted to investigate population differences in the correlation. And finally, a further evaluation was conducted to determine whether there was a nonlinear relationship between TyGI and HUA through smooth curve fitting and threshold saturation effect analysis.Results:The TyGI in the HUA group was significantly higher than that in the control group ( t=-41.787, P<0.001). After adjusting for relevant factors, the multiple logistic regression analysis showed that there was a significant positive correlation between TyGI and risk of HUA ( OR=1.755, 95% CI: 1.632-1.887); and as TyGI increased, the risk of HUA gradually increased. Stratified analysis and interaction tests were conducted based on age, gender, body mass index, blood glucose abnormalities, hypertension, and estimated glomerular filtration rate (eGFR), it′s indicated that TyGI was positively correlated with the risk of HUA in various populations except for in the individuals with a eGFR less than 60 ml·min -1·(1.73 m 2) -1 and in females (all P>0.05). The smooth curve fitting between TyGI and HUA suggested that as TyGI increased, the risk of HUA tended to increase. However, when TyGI reached a certain threshold, the risk of HUA no longer increased. Further analysis of threshold saturation effects suggested that the inflection point of TyGI was 9.871. Conclusion:The correlation between TyGI and HUA in the population undergoing health examinations is nonlinear.