The occurrence and development of atherosclerotic cardiovascular diseases is closely related to abnormally elevated plasma low density lipoprotein cholesterol(LDLC)level.Low density lipoprotein receptor(LDLR)plays a central role in the maintenance of cholesterol homeostasis by mediating the endocytotic clearance of LDLC,and the abundance of LDLR on the surface of the cell membrane is closely related to the expression level and recirculation of LD-LR.Recent studies have found that RING-E3 ubiquitin ligase can regulate LDLR levels through a dual mechanism:on the one hand,it directly ubiquitinates and modifies LDLR to promote its degradation via the endosome-lysosome pathway;on the other hand,it reduces LDLR synthesis through activation of the liver X receptor(LXR)pathway or inhibition of the nuclear translocation of sterol regulatory element-binding protein(SREBP).Together,these two mechanisms lead to a decrease in cell membrane LDLR abundance,impairing cholesterol metabolic homeostasis and exacerbating LDLC accumu-lation.Therefore,targeted inhibition of RING-E3 ubiquitin ligase activity may be a novel strategy to regulate LDLR ex-pression,reduce plasma LDLC levels,and combat cardiovascular disease.This article reviews the mechanism of action of RING-E3 ubiquitin ligase in regulating LDLR and its related research progress.

Objective This study aimed to investigate the effect of acupoint injection on glycometabolism in patients with Polycystic ovary syndrome(PCOS).Methods Eighty patients who were newly diagnosed with polycystic ovary syndrome(PCOS)in our hospital were randomly allocated into two groups:a control group and a treatment group,with 40 cases in each group.The two groups were treated with dietary exercise lifestyle and dietary exercise lifestyle+acupoint injection intervention for 3 months,respectively.The basal disposition index(DI0),early-phase disposition index(DI30),and total disposition index(DI120)represented β-cell function at fasting,early phase,and 120 minutes during the oral glucose tolerance test(OGTT).The homeostatic model assessment for insulin resistance(HOMA-IR)and the M value obtained from the high insulin-euglycemic clamp(HEC)test indicated insulin sensitivity.The changes in anthropometric indicators[waist-to-hip ratio(WHR),body mass index(BMI)],blood glucose and insulin levels[fasting blood glucose(Glu0),2 h post-OGTT blood glucose(Glu120),fasting insulin(Ins0),2 h post-OGTT insulin(Ins120),and glycated hemoglobin A1c(HbA1c)],sex hormones[free testosterone index(FAI),luteinizing hormone/follicle-stimulating hormone(LH/FSH)],pancreatic β-cell function and insulin sensitivity,oxidative stress[malondialdehyde(MDA),Cu/Zn superoxide dismutase(Cu/Zn SOD),glutathione peroxidase 1(GPX1)],and inflammation[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)]were compared before and after treatment,and safety observations were conducted.Results The baseline levels of the two groups were consistent(P>0.05);after treatment,the Glu0,Ins0,HOMA-IR,MDA,IL-6,IL-1β,and TNF-α in the treatment group were significantly reduced compared to those observed in the control group(P<0.05,P<0.01),while DI0,DI120,M value,Cu/Zn SOD,and GPX1 were higher than those in the control group(P<0.05,P<0.01).However,there were no statistically significant differences in anthropometric indicators,sex hormones,and other glucose metabolism indicators(P>0.05),and the incidence of adverse reactions between the two groups was not statistically significant(P>0.05).Conclusion Acupoint injection can alleviate glycometabolism in patients with PCOS of kidney deficiency and blood stasis to a certain extent,improve systemic oxidative stress and inflammatory status,and provide a possible external treatment method in traditional Chinese medicine for these patients.

Objective This study aimed to investigate the effect of acupoint injection on glycometabolism in patients with Polycystic ovary syndrome(PCOS).Methods Eighty patients who were newly diagnosed with polycystic ovary syndrome(PCOS)in our hospital were randomly allocated into two groups:a control group and a treatment group,with 40 cases in each group.The two groups were treated with dietary exercise lifestyle and dietary exercise lifestyle+acupoint injection intervention for 3 months,respectively.The basal disposition index(DI0),early-phase disposition index(DI30),and total disposition index(DI120)represented β-cell function at fasting,early phase,and 120 minutes during the oral glucose tolerance test(OGTT).The homeostatic model assessment for insulin resistance(HOMA-IR)and the M value obtained from the high insulin-euglycemic clamp(HEC)test indicated insulin sensitivity.The changes in anthropometric indicators[waist-to-hip ratio(WHR),body mass index(BMI)],blood glucose and insulin levels[fasting blood glucose(Glu0),2 h post-OGTT blood glucose(Glu120),fasting insulin(Ins0),2 h post-OGTT insulin(Ins120),and glycated hemoglobin A1c(HbA1c)],sex hormones[free testosterone index(FAI),luteinizing hormone/follicle-stimulating hormone(LH/FSH)],pancreatic β-cell function and insulin sensitivity,oxidative stress[malondialdehyde(MDA),Cu/Zn superoxide dismutase(Cu/Zn SOD),glutathione peroxidase 1(GPX1)],and inflammation[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)]were compared before and after treatment,and safety observations were conducted.Results The baseline levels of the two groups were consistent(P>0.05);after treatment,the Glu0,Ins0,HOMA-IR,MDA,IL-6,IL-1β,and TNF-α in the treatment group were significantly reduced compared to those observed in the control group(P<0.05,P<0.01),while DI0,DI120,M value,Cu/Zn SOD,and GPX1 were higher than those in the control group(P<0.05,P<0.01).However,there were no statistically significant differences in anthropometric indicators,sex hormones,and other glucose metabolism indicators(P>0.05),and the incidence of adverse reactions between the two groups was not statistically significant(P>0.05).Conclusion Acupoint injection can alleviate glycometabolism in patients with PCOS of kidney deficiency and blood stasis to a certain extent,improve systemic oxidative stress and inflammatory status,and provide a possible external treatment method in traditional Chinese medicine for these patients.

Objective To map the super-enhancers remodeling of intestinal gastric cancer and reveal the tumor biological functions of the super-enhancers and the downstream target genes that may be activated.Methods A total of 31 normal gastric mucosal tissues,23 intestinal gastric cancer tissues and 9 intestinal gastric cancer organoids were collected from the Department of Gastroenterology of Army Medical Center of PLA from January to December 2022.Chromatin targeting histone H3K27ac modified chromatin targeting cleavage under targets and tagmentation(CUT&Tag)sequencing was conducted on above tissues.The remodeling profiles of super-enhancers in intestinal gastric cancer were analyzed and the key target genes were identified based on bioinformation tools.CRISPRi technology was used to intervene with the super-enhancers,the expression of target genes was detected with Western blotting,and the proliferation,migration and invasion abilities were detected by CCK-8 assay and Transwell chambers in the control group and the intervention group.Results There was a significant difference in the signal of super-enhancers between intestinal gastric cancer tissues and normal gastric mucosal tissues(P<0.05),and the active super-enhancers in cancer tissues may be involved in biological processes such as negative regulation of the immune system and cell adhesion.The expression of up-regulated cell migration-inducing protein(CEMIP)in tumor cells was regulated by the super-enhancers,and intervening the super-enhancers down-regulated the expression of CEMIP(P<0.05),and inhibited the cell proliferation,invasion and migration abilities of tumor cells(P<0.05).Conclusion Super-enhancer remodeling is observed in intestinal gastric cancer,and they can up-regulate the expression of CEMIP gene and promote the growth,migration and invasion of cancer cells.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Objective:To explore the value of 3D reconstruction combined with watershed analysis in thoracoscopic anatomical partial lobectomy for peripheral early stage lung cancer.Methods:A retrospective cohort study was used to analyze the case data of 152 patients with early peripheral lung cancer who received targeted treatment in Hai′an People′s Hospital of Jiangsu Province from January 2022 to April 2023. All patients were treated with thoracoscopic anatomical partial lung resection. According to different preoperative analysis methods, they were divided into an observation group ( n=79) and a control group ( n=73). The observation group underwent three-dimensional reconstruction combined with venous drainage analysis, and the control group underwent routine analyze. The surgical indicators, pulmonary function indicators, C-reactive protein (CRP), interleukin-6 (IL-6) and complications were compared between the two groups. Normally distributed measurement data were expressed as mean±standard deviation ( ± s), independent samples t-test was used for comparison between groups, and paired-sample t-test was used for comparison within groups. Comparison of enumeration data between groups was performed using the chi-square test. Results:The operation time, postoperative drainage time, postoperative hospital stay, and intraoperative blood loss in the observation group were (76.57±11.94) min, (2.15±0.24) d, (4.32±0.75) d, and (27.63±3.54) mL respectively. The control group was (112.64±13.67) min, (3.76±0.31) d, (5.16±0.81) d, (53.26±4.61) mL, respectively. The observation group was smaller than the control group, and the differences between the two groups were statistically significant ( P<0.05). At discharge, the observation group had maximum ventilation per minute as a percentage of predicted value (MVV% pred), forced expiratory volume in 1 second as a percentage of predicted value (FEV1% pred), and forced vital capacity as a percentage of predicted value (FVC% pred) were (83.33±7.51)%, (85.22±7.44)%, (84.16±7.26)%, and those of the control group were (77.19±7.46)%, (76.47±7.36)%, and (79.38±7.20)%, respectively. The observation group was greater than that of the control group, and the differences between the two groups were statistically significant ( P<0.05). The CRP and IL-6 in the observation group were(47.53±6.34) mg/L, (32.21±5.14) mg/L, (144.53±20.84) ng/L, (180.82±21.17) ng/L, respectively on the 1st and 3rd days after surgery, while those in the control group were (57.84±6.71) mg/L, (38.77±5.23)mg/L, (155.14±22.83) ng/L, (200.97±25.52) ng/L, the observation group was lower than that of the control group, and the difference was statistically significant ( P<0.05). The incidence rate of complications in the observation group was 5.06%, and that in the control group was 10.96%, There was no statistically significant difference between the two groups ( P>0.05). Conclusion:Preoperative 3D reconstruction combined with venous drainage analysis can better promote the recovery of patients with early peripheral lung cancer and retain more lung function after thoracoscopic anatomical partial pulmonary resection.

Objective:To assess the efficacy of "three-step" strategy for preparing autologous pedicled nasal mucosal flaps in repairing cerebrospinal fluid（CSF） leaks following transsphenoidal pituitary adenoma surgery. Methods:A retrospective study was conducted on the clinical data of 25 patients who developed CSF leaks after transsphenoidal pituitary adenoma surgery at the First Affiliated Hospital of Kunming Medical University between July 2012 and June 2022. Surgical repair was selected step by step using nasal septal mucosal flap with either the posterior septal artery or septal branch of the sphenopalatine artery as the pedicle, or a pedicled middle turbinate mucosal flap. All patients underwent ≥2-year endoscopic follow-up to assess flap viability and CSF leak recurrence. Results:The median postoperative hospital stay was 4 days. Five patients developed intracranial infections postoperatively. The follow-up period ranged from 2 to 12 years. Nasal endoscopic examinations showed good mucosal flap growth, with no recurrence of CSF leakage in any of the patients. Conclusion:High-flow cerebrospinal fluid（CSF） leaks following pituitary tumor surgery pose significant challenges for clinical repair. Based on intraoperative nasal septal mucosal preservation and the condition of sellar base CSF leakage, the "three-step" strategy for preparing autologous pedicled nasal mucosal flaps-utilizing posterior septal artery, ethmoidal artery-based, or pedicled middle turbinate mucosal flaps sequentially-is a safe and effective repair method.
Humans ; Retrospective Studies ; Pituitary Neoplasms/surgery* ; Surgical Flaps ; Nasal Mucosa/surgery* ; Cerebrospinal Fluid Leak/surgery* ; Adenoma/surgery* ; Postoperative Complications/surgery* ; Male ; Female ; Middle Aged ; Adult ; Aged

The occurrence and development of atherosclerotic cardiovascular diseases is closely related to abnormally elevated plasma low density lipoprotein cholesterol(LDLC)level.Low density lipoprotein receptor(LDLR)plays a central role in the maintenance of cholesterol homeostasis by mediating the endocytotic clearance of LDLC,and the abundance of LDLR on the surface of the cell membrane is closely related to the expression level and recirculation of LD-LR.Recent studies have found that RING-E3 ubiquitin ligase can regulate LDLR levels through a dual mechanism:on the one hand,it directly ubiquitinates and modifies LDLR to promote its degradation via the endosome-lysosome pathway;on the other hand,it reduces LDLR synthesis through activation of the liver X receptor(LXR)pathway or inhibition of the nuclear translocation of sterol regulatory element-binding protein(SREBP).Together,these two mechanisms lead to a decrease in cell membrane LDLR abundance,impairing cholesterol metabolic homeostasis and exacerbating LDLC accumu-lation.Therefore,targeted inhibition of RING-E3 ubiquitin ligase activity may be a novel strategy to regulate LDLR ex-pression,reduce plasma LDLC levels,and combat cardiovascular disease.This article reviews the mechanism of action of RING-E3 ubiquitin ligase in regulating LDLR and its related research progress.

Objective To explore the factors influencing the occurrence of cardiac complications after endoscopic surgery in patients with non-small cell lung cancer(NSCLC)and construct the prediction model.Methods A total of 312 patients with non-small cell lung cancer who were diagnosed and underwent thoracoscopic treatment in our hospital from January 2020 to January 2023 were selected as the objects of this study,and were divided into cardiac complication group and non-cardiac complication group according to whether cardiac complications occurred after surgery.The clinical data of patients in each group were analyzed,and the factors affecting the occurrence of cardiac complications in patients with non-small cell lung cancer after endoscopic surgery were discussed by multivariate Logistic regression analysis.A full-variable risk prediction model for the occurrence of cardiac complications was constructed,and the predictive model was verified by receiver operating characteristic curve(ROC)analysis.Results The incidence of postoperative cardiac complications in 312 patients with non-small cell lung cancer was 24.04％.Univariate analysis showed that Age,smoking history,smoking history,comorbidities,intraoperative blood loss,operative time,systolic blood pressure,FEV1,FEV1％,FPG,HbA1c and urinary microalbumin were correlated with the incidence of cardiac complications in patients with non-small cell lung cancer after endoscopic surgery(P＜0.05).Multivariate Logistic stepwise regression analysis showed:age,comorbidities,operation time and HbA1c were independent risk factors for postoperative cardiac complications in patients with non-small cell lung cancer(P＜0.05).A risk prediction model for cardiac complications was established based on multiple factors,that is,P=1/(1+e-y),y=-3.114+0.881 × age+0.754 × complications+1.285 × operation time+1.185 × HbA1c,and the ROC curve diagnosis showed that the risk prediction model predicted the occurrence of cardiac complications with an AUC of 0.847,95％CI of 0.769-0.925,sensitivity of 82.5％,specificity of 83.2％.Conclusion Age,complications,operation time,and HbA1c are all independent risk factors affecting the occurrence of cardiac complications in patients with non-small cell lung cancer after endoscopic surgery,and the risk prediction model constructed by the above factors has a good predictive value for the occurrence of cardiac complications.

Population based health data collection and analysis are important in epidemiological research. In recent years, with the rapid development of big data, Internet and cloud computing, artificial intelligence has gradually attracted attention of epidemiological researchers. More and more researchers are trying to use artificial intelligence algorithms for genome sequencing and medical image data mining, and for disease diagnosis, risk prediction and others. In recent years, machine learning, a branch of artificial intelligence, has been widely used in epidemiological research. This paper summarizes the key fields and progress in the application of machine learning in epidemiology, reviews the development history of machine learning, analyzes the classic cases and current challenges in its application in epidemiological research, and introduces the current application scenarios and future development trends of machine learning and artificial intelligence algorithms for the better exploration of the epidemiological research value of massive medical health data in China.