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.

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 investigate the causes of abnormal decrease in maximum amplitude(MA)of thromboelastog-raphy(TEG)and its effect on prognosis by monitoring the changes of coagulation-related indexes in emergency trauma pa-tients.Methods A total of 319 cases of trauma patients admitted to our hospital from September 2020 to September 2023 were retrospectively analyzed,and the coagulation-related indexes of 0 h and 24 h after admission were observed.According to the MA results,they were divided into normal MA group(>50 mm)and reduced MA group(≤50 mm)to compare the hemoglobin(Hb),platelets count(Plt),activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(Fib),thrombin time(TT),D-dimer(D-D),coagulation reaction time(R),clot formation kinetics(Angle),30 min clot dissolution rate(Ly30),MA,thrombine-antithrombin complex(TAT)and plasminase-α2 plasminase inhibitor complex(PIC).The correlation between MA and fibrinolysis indexes in 319 trauma patients was analyzed.According to whether tranexamic acid(TXA)was used,the reduced MA group was divided into a TXA group and a non-drug group.The differ-ences in the change of the above coagulation-related indexes,mortality rate and changes in blood product dosage were com-pared between the two groups.Results Compared with the normal MA group,Hb,Plt,Fib,diastolic blood pressure and GCS scores decreased,while heart rate,ISS score and mortality increased significantly in the reduced MA group(P<0.05).The R,PT and TT were prolonged significantly(P<0.05),and PIC and D-D increased significantly(P<0.05)in the re-duced MA group.Correlation analysis found that MA had no correlation with Ly30,TAT and APTT,but was correlated with Angle(r=0.803),Plt(r=0.544),Fib(r=0.581),PIC(r=-0.443)and D-D(r=-0.343).Compared with the non-drug group,the change of Angle,MA and FIB in the TXA group increased significantly(P<0.05),while the change of PIC de-creased(P<0.05).Cryoprecipitate and platelet transfusion in the TXA group reduced significantly(P<0.05),and red blood cell transfusion had a decreasing trend,but the difference was not significant(P>0.05).The mortality rate in the TXA group was reduced significantly(P<0.05).Conclusion Hyperfibrinolysis may be an important factor in the abnormal decrease of MA in emergency trauma patients.Treatment with TXA can improve its effect on MA,and reduce the transfusion of blood products and the patient mortality.

Early detection and treatment are essential to improve the prognosis of patients with psoriatic arthritis. Nail psoriasis is a known risk factor and a predictive symptom for psoriatic arthritis. Assessment of clinical manifestations of nail psoriasis together with evaluation using advanced technology has made it possible to achieve early diagnosis of psoriatic arthritis. This review summarizes diagnostic methods of psoriatic arthritis and nail psoriasis in recent years, and analyzes the latest studies on the correlation between psoriatic arthritis and nail psoriasis, in order to facilitate early diagnosis of psoriatic arthritis through clues of nail psoriasis.

Objective:To investigate the effect of empagliflozin on diabetic kidney disease in db/db mice and the potential mechanisms.Methods:db/db mice were randomly divided into db/db group and Empa group. C57BL/6J mice were used as normal control group. We measured the level of serum biochemistry and inflammatory cytokines. Pathological changes of kidney were observed by pathological staining. The protein expression levels of NLRP3, cleaved caspase-1 and GSDMD were detected.Results:Compared with db/db group, the level of fasting blood glucose, blood lipids, serum biochemistry, and urinary protein-to-creatinine ratio in Empa group were significantly decreased ( P<0.05). HE staining and Masson staining showed that empagliflozin could significantly improve glomerular pyknosis and renal interstitial fibrosis in db/db mice. Meanwhile, the expressions of NLRP3, cleaved caspase-1, and GSDMD protein were down-regulated ( P<0.05). Conclusion:Empagliflozin improves kidney damage in diabetic model mice, and the possible mechanism is to inhibit the cell pyroptosis signal pathway of NLRP3/caspase-1/GSDMD.

Objective To discuss the accuracy of three-dimensional (3D) sonography in diagnosing arcuate uterus and septate uterus and propose a quantitative indicator in distinguishing arcuate uterus and septate uterus.Methods Ninety-six patients with suspected congenital uterine malformation underwent 3D sonography to assess uterine anomalies at Obstetrics and Gynecology Hospital of Fudan University from August 2011 to March 2013.Uterine coronal section was reconstructed and measured in onmi view imaging mode of 3D sonography.Then qualitative diagnosis and categorization was done.The results were compared with diagnosis of hysteroscopy,hysteroscopy combined with laparoscope to determine the sensitivity,specificity,positive predictive values,negative predictive values and total accuracy of 3D sonography in diagnosing arcuate uterus,partial and complete septate uterus respectively.The variable was created in coronal section of uterus constructed through 3D imaging mode to differentiate arcuate uterus from septate uterus.Results There were 33 cases (34.4％,33/96) of arcuate uterus,54 cases (56.2％,54/96) of partial septate uterus and 9 cases (9.4％,9/96) of complete uterus in 96 cases diagnosed by 3D sonography.The accuracy of 3D sonography in diagnosing arcuate uterus and septate uterus was 86.5％.We concluded that 3D sonography had 100％ sensitivity,82.9％ specificity,60.6％ positive predictive value and 100％negative predictive value in the diagnosis of arcuate uterus.The sensitivity of 3D sonography for diagnosis of partial septate uterus was 80.6％,the specificity was 100％,the positive predictive value was 100％,and the negative predictive value was 69.1％.The sensitivity,specificity,positive and negative predictive values of 3D sonography for detecting complete septate uterus were all 100％.The ratio of depth of uterine internal indentation and depth from uterine fundus to the top of intemal indentation was more than 50％ for septate uterus,while less than 50％ for most of the arcuate uterus.Conclusions The diagnostic efficiency of 3D sonography in specific uterine malformation is different.The new quantitative indicator maybe helpful in improving the accuracy of 3D sonography in diagnosing arcuate uterus and septate uterus.