To investigate the protective effect of Lycium barbarum glycopeptide(LbGp)on testicu-lar injury induced by D-galactose(D-gal)in aging rats,male SD rats were randomly divided into 6 groups:the blank control group(Control),aging model group(Model),positive control group(β-nicotinamide mononucleotide,NMN),low dose LbGp group(LLbGp),medium dose LbGp group(MLbGp)and high dose LbGp group(HLbGp).The testicular mass of rats was counted,the morphological changes of testicular tissue were observed by hematoxylin-eosin(HE)staining,the testicular senescence was detected by β-galactosidase(SA-β-gal)staining,and the levels of testos-terone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)in serum were de-tected.The levels of oxidative factors such as glutathione peroxidase(GSH-Px),superoxide dis-mutase(SOD),malondialdehyde(MDA),catalase(CAT)and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in rat tissues were measured.TUNEL staining was used to detect the apoptosis of testicular cells,epididymal sperm quality,and the expression of Keap1,Nrf2 and Nqo1 mRNA were analyzed.The results showed that compared with the Model group,the testicular coefficient of Lycium barbarum glycopeptide rats in MLbGp and HLbGp groups increased(P＜0.01),the level of T in serum and sperm quality increased(P＜0.05),the structural degeneration and aging of testicular tissue decreased(P＜0.01),the level of antioxidant factors increased,and the levels of inflammatory factors and apopto-sis decreased(P＜0.05).The expression of Keap1 decreased significantly(P＜0.01),while the ex-pression of Nrf2 and Nqo1 mRNA increased(P＜0.05).The above results indicate that Lycium barbarum glycopeptide can improve D-gal-induced testicular senescence,attenuate oxidative stress,reduce inflammatory response,decrease apoptosis,and exert a protective effect on testicular injury in rats due to senescence through the Keap1-Nrf2 signaling pathway.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

Objective:To study effect of matrine on TNF-α induced proliferation of human umbilical vein endothelial cells(HUVEC),as well as to explore whether its mechanism is related to regulation of miR-125b-5p and STAT3 expressions.Methods:HUVEC proliferation model was established by TNF-α stimulating.After matrine treatment,miR-125b-5p level was detected by real-time fluorescent quantitative PCR,proliferating cell nuclear antigen(PCNA),cell cycle protein D1(CyclinD1),matrix metallopro-teinase 2(MMP2),MMP9,STAT3 levels were detected by real-time fluorescent quantitative PCR and Western blot.Targeting rela-tionship between miR-125b-5p and STAT3 was verified by dual luciferase reporter gene assay.Results:Matrine inhibited TNF-α in-duced HUVEC proliferation(P<0.05),decreased PCNA,CyclinD1,MMP2,MMP9,STAT3 expressions(P<0.05),and increased miR-125b-5p expression(P<0.05).Overexpression of miR-125b-5p could reduce cell proliferation and PCNA,CyclinD1,MMP2,MMP9 expressions HUVEC induced by TNF-α(P<0.05).miR-125b-5p targeted STAT3 expression negatively in HUVEC,and inhi-biting miR-125b-5p expression could reverse effect of matrine on TNF-α induced cell proliferation and PCNA,CyclinD1,MMP2,MMP9 and STAT3 expressions.Conclusion:Matrine inhibits TNF-α induced proliferation of HUVEC,which is related to regulation of miR-125b-5p/STAT3 pathway.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

To investigate the protective effect of Lycium barbarum glycopeptide(LbGp)on testicu-lar injury induced by D-galactose(D-gal)in aging rats,male SD rats were randomly divided into 6 groups:the blank control group(Control),aging model group(Model),positive control group(β-nicotinamide mononucleotide,NMN),low dose LbGp group(LLbGp),medium dose LbGp group(MLbGp)and high dose LbGp group(HLbGp).The testicular mass of rats was counted,the morphological changes of testicular tissue were observed by hematoxylin-eosin(HE)staining,the testicular senescence was detected by β-galactosidase(SA-β-gal)staining,and the levels of testos-terone(T),luteinizing hormone(LH)and follicle stimulating hormone(FSH)in serum were de-tected.The levels of oxidative factors such as glutathione peroxidase(GSH-Px),superoxide dis-mutase(SOD),malondialdehyde(MDA),catalase(CAT)and inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)in rat tissues were measured.TUNEL staining was used to detect the apoptosis of testicular cells,epididymal sperm quality,and the expression of Keap1,Nrf2 and Nqo1 mRNA were analyzed.The results showed that compared with the Model group,the testicular coefficient of Lycium barbarum glycopeptide rats in MLbGp and HLbGp groups increased(P＜0.01),the level of T in serum and sperm quality increased(P＜0.05),the structural degeneration and aging of testicular tissue decreased(P＜0.01),the level of antioxidant factors increased,and the levels of inflammatory factors and apopto-sis decreased(P＜0.05).The expression of Keap1 decreased significantly(P＜0.01),while the ex-pression of Nrf2 and Nqo1 mRNA increased(P＜0.05).The above results indicate that Lycium barbarum glycopeptide can improve D-gal-induced testicular senescence,attenuate oxidative stress,reduce inflammatory response,decrease apoptosis,and exert a protective effect on testicular injury in rats due to senescence through the Keap1-Nrf2 signaling pathway.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

Objective:To study effect of matrine on TNF-α induced proliferation of human umbilical vein endothelial cells(HUVEC),as well as to explore whether its mechanism is related to regulation of miR-125b-5p and STAT3 expressions.Methods:HUVEC proliferation model was established by TNF-α stimulating.After matrine treatment,miR-125b-5p level was detected by real-time fluorescent quantitative PCR,proliferating cell nuclear antigen(PCNA),cell cycle protein D1(CyclinD1),matrix metallopro-teinase 2(MMP2),MMP9,STAT3 levels were detected by real-time fluorescent quantitative PCR and Western blot.Targeting rela-tionship between miR-125b-5p and STAT3 was verified by dual luciferase reporter gene assay.Results:Matrine inhibited TNF-α in-duced HUVEC proliferation(P<0.05),decreased PCNA,CyclinD1,MMP2,MMP9,STAT3 expressions(P<0.05),and increased miR-125b-5p expression(P<0.05).Overexpression of miR-125b-5p could reduce cell proliferation and PCNA,CyclinD1,MMP2,MMP9 expressions HUVEC induced by TNF-α(P<0.05).miR-125b-5p targeted STAT3 expression negatively in HUVEC,and inhi-biting miR-125b-5p expression could reverse effect of matrine on TNF-α induced cell proliferation and PCNA,CyclinD1,MMP2,MMP9 and STAT3 expressions.Conclusion:Matrine inhibits TNF-α induced proliferation of HUVEC,which is related to regulation of miR-125b-5p/STAT3 pathway.

Objective:To examine the safety and effectiveness of a novel domestic transcatheter aortic valve system in addressing severe aortic valve stenosis.Methods:This prospective, multicenter, single-arm target-value clinical trial enrolled patients with severe aortic stenosis meeting inclusion criteria from 13 Chinese centers between July 2021 and April 2022. The primary endpoint was all-cause mortality at 1-year post-procedure. Secondary endpoints included safety outcomes (30-day all-cause mortality, 1-year major adverse cardiovascular events, device success) and efficacy parameters (transvalvular pressure gradient, paravalvular leak severity, New York Heart Association(NYHA)class improvement, and quality of life). Survival analysis was performed using the Kaplan-Meier analysis.Results:The study included 134 patients, 85 males and 49 females, with an age of (73.6±5.6)years (range: 65.1 to 91.8 years). Bicuspid aortic valve morphology was present in 59.7% (80/134). Device success rate was 99.3%, with one case converted to open surgery due to coronary obstruction. All-cause mortality was 0.8% (95% CI: 0.1% to 5.3%) at both 30-day and 1-year follow-up, significantly lower than the 25% target value ( P<0.01). Permanent pacemaker implantation rates remained 2.2% (3/134) at both timepoints. Stroke incidence was 0.7% (1/134) at 30 days and 1.5% (2/134) at 1 year. Myocardial infarction rates were 0.7% (1/134) at both intervals. The postoperative transvalvular pressure gradient of the aortic valve was (6.6±3.1) mmHg(1 mmHg=0.133 kPa) (range: 4 to 8 mmHg). Among the patients, 32 cases (23.9%) had mild paravalvular leakage, 4 cases (3.0%) had moderate paravalvular leakage, and no severe paravalvular leakage was observed. NYHA class Ⅰ and Ⅱ patients increased from 18.7% preoperatively to 99.3% postoperatively. Conclusion:The novel domestic transcatheter aortic valve system demonstrates satisfactory 1-year safety and efficacy outcomes in treating severe aortic stenosis.

BACKGROUND:Inflammation and oxidative stress contribute to the barriers of regeneration in chronic wound.Oxymatrine has various biological activities,such as anti-oxidation,anti-inflammation and so on,which may have the potential effect of promoting wound healing. OBJECTIVE:To investigate the effect of oxymatrine on wound healing and the protective effect on H2O2-induced oxidative stress injury in human keratinoid cell line HaCaT cells. METHODS:(1)In vivo experiment:Hyaluronic acid methacryloyl hydrogels containing 0,0.05,0.1,0.2 g/L oxymatrine were prepared.A full-layer skin defect model with a diameter of 12 mm was made in the back of 75 diabetic mice and randomly divided into five groups for intervention,with 15 mice in each group.The wounds of the model group were bandaged and fixed.The wounds of the hydrogel group were covered with hyaluronic acid methacryloyl hydrogel.The wounds of the low-dose,moderate-dose and high-dose oxymatrine groups were covered with hyaluronic acid methacryloyl hydrogel containing 0.05,0.1,and 0.2 g/L oxymatrine,respectively,and then bandaged and fixed after light curing.Relevant indicators were detected within 14 days.(2)In vitro experiment:Human keratinocyte line HaCaT was divided into five groups.The normal group was cultured conventionally.H2O2 group and low-,moderate-and high-concentration oxymatrine groups were treated with H2O2 for 4 hours,and then the medium was replaced with medium containing 0,0.05,0.1,and 0.2 g/L oxymatrine,respectively,and the relevant indexes were detected after 24 hours of culture. RESULTS AND CONCLUSION:(1)In vivo experiment:Compared with the model group,the wound healing rate of mice in the hydrogel group had no significant change.The wound healing rate of mice in the low-,moderate-and high-dose oxymatrine group was increased at 7 and 14 days after treatment(P<0.05).Pathological observation of wound section 14 days after treatment showed that compared with the model group,the thickness of regenerated epidermal layer,the number of microvessels,and collagen deposition in the moderate-and high-dose oxymatrine groups were increased(P<0.05).Western blot assay analysis of wound samples 7 days after surgery showed that compared with the model group,the protein expressions of tumor necrosis factor α and interleukin 6 in the moderate-and high-dose oxymatrine groups were decreased(P<0.05).(2)In vitro experiment:CCK8 assay,EdU and Ki67 staining showed that compared with the H2O2 group,the cell proliferation ability of the moderate-and high-concentration oxymatrine groups was significantly increased(P<0.05).Compared with the H2O2 group,mitochondrial membrane potential was increased(P<0.05)and reactive oxygen species content was decreased(P<0.05)in the moderate-and high-concentration oxymatrine groups.Western blot assay results showed that compared with the H2O2 group,the expression levels of Nrf2 nuclear protein,Nrf2 total protein,HO-1 protein,and superoxide dismutase 1 protein were increased in the high-concentration oxymatrine group(P<0.05).(3)These findings confirm that oxymatrine can alleviate oxidative stress damage in HaCat cells and accelerate wound healing by upregulating the levels of Nrf2 and HO-1 protein.

Important anatomical structures such as mandibular incisive canal,tongue foramen,and mouth floor vessels may be damaged during implant surgery in the mandibular anterior region,which may lead to mouth floor hematoma,asphyxia,pain,paresthesia and other symptoms.In severe cases,this can be life-threatening.The insufficient alveolar bone space and the anatomical variation of blood vessels and nerves in the mandibular anterior region increase the risk of blood vessel and nerve injury during implant surgery.In case of vascular injury,airway control and hemostasis should be performed,and in case of nerve injury,implant removal and early medical treatment should be performed.To avoid vascular and nerve injury during implant surgery in the mandibular anterior region,it is necessary to be familiar with the anatomical structure,take cone-beam computed tomography,design properly before surgery,and use digital technology during surgery to achieve accurate implant placement.This article summarizes the anatomical structure of the mandibular anterior region,discusses the prevention strategies of vascular and nerve injuries in this region,and discusses the treatment methods after the occurrence of vascular and nerve injuries,to provide clinical reference.