Objective To investigate the effect and molecular mechanism of tRF-1:30-Gln-CTG-4(tRF-1:30)on the expression of inflammatory factors in high glucose(HG)-induced renal tubular epithelial cells(RTECs).Methods RTECs were divided into the control group,the HG group,the HG+tRF-1:30 mimic group,the HG+tRF-1:30 negative control(NC)group,the HG+si-IKZF2 group and the HG+si-NC group.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of tRF-1:30,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),monocyte chemoattractant protein-1(MCP-1)and IKAROS family zinc finger protein 2(IKZF2).Enzyme-linked immunosorbent assay(ELISA)was used to detect levels of TNF-α,IL-6 and MCP-1.Protein expression of IKZF2 was detected by Western blot assay.Dual-luciferase reporter assay was used to detect the targeting relationship between tRF-1:30 and IKZF2.Results The expression levels of inflammatory factors were elevated in HG-induced RTECs,and the expression level of tRF-1:30 was decreased(P＜0.05).Overexpression of tRF-1:30 significantly decreased expression levels of inflammatory factors in HG-induced RTECs(P＜0.05),and the expression level of IKZF2 was significantly increased(P＜0.05).Further knockdown of IKZF2 can inhibit the release of inflammatory factors,and the expression level of IKZF2 was down-regulated after overexpression of tRF-1:30.Double luciferase reporting experiment further verified the possible targeting relationship between tRF-1:30 and IKZF2.Conclusion Overexpression of tRF-1:30 inhibits the expression of inflammatory factors in HG-induced RTECs by target binding and negatively regulating the expression of IKZF2.

Objective To evaluate the effects of matrine on the inflammatory,oxidative and migratory responses of HaCaT keratinocytes in an in vitro atopic dermatitis(AD)model.Methods HaCaT cells were divided into the control group(no treatment)and the model group(0.05,0.1 and 0.2 mmol/L).HaCaT cells in the model group were stimulated with 10 μg/L tumor necrosis factor-α(TNF-α)/interferon-γ(IFN-γ)for 24 h.Cells in the model group were pretreated with 0.05,0.1 and 0.2 mmol/L matrine for 1 h and then stimulated with 10 μg/L TNF-α/IFN-γ for 24 h.MTT assay was used to assess the cytotoxicity of matrine.Enzyme-linked immunosorbent(ELISA)assay was performed to determine levels of cytokines(IL-6,IL-8 and IL-1β)and chemokines(TARC,MDC and RANTES).mRNA expression levels of antioxidant genes were detected by real-time quantitative PCR(RT-qPCR).Cell migration was analyzed by scratch closure assay.Immunohistochemistry was commended to analyze the nuclear translocation of NF-κB p65.Western blot assay was used to detect the phosphorylation levels of p38,ERK and p65 proteins.Results Compared with the model group,matrine 0.1 and 0.2 mmol/L significantly decreased the expression levels of IL-6,IL-1β,IL-8 and chemokines,and matrine significantly enhanced the expression levels of superoxide dismutase-1(SOD1),SOD2,catalase(CAT)and glutathione peroxidase(GPx),and promoted scratch wound healing(P＜0.05).In addition,matrine 0.1 and 0.2 mmol/L inhibited the phosphorylation levels of p38,ERK and p65 proteins and the nuclear translocation of p65.Conclusion Matrine possesses anti-inflammatory and antioxidant properties,and stimulates wound closure in eratinocyte AD model,which may be related to the inhibition of the activation of MAPK and NF-κB pathways.

Objective To explore the regulatory mechanism of emodin on pain behavior in a mouse model of osteoarthritis based on mitochondrial key genes.Methods Thirty C57BL/6J mice were randomly divided into the control group,the osteoarthritis(OA)model group and the emodin-treated(OA+emodin)group,10 mice per each group.The mice in the OA group and the OA+emodin group were intra-articular injection of complete Freund's adjuvant(20 μL)in knee to establish the OA model,and mice in the OA+emodin group were treated by intraperitoneal emodin(10 mg/kg)injection.After behavioral testing,knee tissue of mice was collected for hematoxylin-eosin staining.Western blot analysis was used to detect expression levels of proinflammatory factors interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and mitochondria-related proteins NADH dehydrogenase(ubiquinone)flavoprotein 1(NDUFV1),cytochrome C oxidase subunit 5B(COX5B),cytochrome C oxidase assembly protein COX15 homolog(COX15),NADH dehydrogenase(ubiquinone)1 alpha subcomplex subunit 10(NDUFA10)in knee tissue.Results Compared with the control group,mice in the OA group showed decreased mechanical nociceptive threshold(PWT),reduced latency and distance in rotarod test(P＜0.05).Compared with the OA group,mice in the OA+emodin group showed increased PWT,latency,and distance(P＜0.05).In the control group,the structures of cartilage and subchondral bone were intact,while in the OA group,the cartilage was thinner and the subchondral trabeculae was deteriorated.The treatment with emodin alleviated cartilage degeneration.The expression levels of IL-1β,TNF-α,COX15 and NDUFA10 were increased while expression levels of NDUFV1 and COX5B were decreased in the OA group compared with the control group.The emodin treatment restored the above-mentioned protein expression levels(P＜0.05).Conclusion Emodin can alleviate pain behavior in OA mice by regulating the expressions of inflammatory factors and mitochondrial related proteins.

Objective To investigate the impact of acacetin(Aca)on angiogenesis in diabetes retinopathy(DR)rats by regulating Hippo signaling pathway.Methods Sixty SD rats were grouped into the control group,the DR group,the Aca low dose group(10 mg/kg),the Aca medium dose group(20 mg/kg),the Aca high dose group(30 mg/kg)and Hippo-YAP signaling pathway inhibitor Verteporfin group(Aca high dose 30 mg/kg+Verteporfin 0.8 pmol/kg),with 10 rats in each group.Except the control group,streptozotocin and high-fat feed were used to construct the DR model.Body weight and fasting blood glucose(FBG)levels of rats were measured.Fluorescein angiography(FFA)was applied to observe retinal angiogenesis and fluorescein leakage.Enzyme linked immunosorbent assay was applied to detect serum levels of vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2).Pathological changes of retinal tissue were observed by hematoxylin-eosin staining.Western blot assay was applied to detect expression levels of VEGF,hypoxia-inducible factor 1 alpha(HIF-1α),vascular cell adhesion molecule-1(VCAM-1)and Hippo signaling pathway proteins.Results Compared with the control group,retinal cells of rats in the DR group were arranged in a disordered and loose manner,with neovascularization and a large amount of fluorescein leakage,and body weight,the expression of large tumor suppressor homolog 2(LATS2),p-Yes-associated protein(YAP)were reduced.FBG and expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,transcription activator with PDZ binding motif(TAZ),TEA domain family member 1(TEAD1)were increased(P＜0.05).Compared with the DR group,retina cells of rats in the Aca low,medium and high-dose groups and the Verteporfin group were arranged neatly,with reduced neovascularization and fluorescence leakage,body weight and the expression levels of LATS2 and p-YAP were increased,and FBG,expression levels of VEGF,Ang-2,HIF-1α,VCAM-1,YAP,TAZ and TEAD1 were reduced(P＜0.05).The effect was more obvious in the Aca high dose group.However,there was no significant difference in each indicator between the Verteporfin group and the Aca high dose group.Conclusion Aca can inhibit angiogenesis and improve retinal pathological damage in DR rats,and its mechanism of action may be related to regulating the Hippo signaling pathway.

Objective To investigate the effect and mechanism of sodium ferulate in the treatment of Ménière disease(MD)model mice.Methods BALB/c mice were selected,and an MD model was constructed using posterior fossa epidural approach combined with intraperitoneal injection of aldosterone.Sixty model mice were randomly grouped into the model group,the low dose sodium ferulate group,the medium dose sodium ferulate group,the high dose sodium ferulate group and the dexamethasone group,with 12 mice in each group.Another 12 BALB/c mice were selected as the sham operation group.After grouping and tympanic administration,auditory evoked brainstem response(ABR)was applied to detect the hearing level of mice in each group.HE staining and magnetic resonance imaging(MRI)were applied to observe the morphology of cochlea and membranous labyrinth hydrops of mice in each group.Enzyme-linked immunosorbent assay was applied to detect serum levels of lipoprotein a[Lp(a)],pro-inflammatory factor interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in each group.Immunohistochemical staining and Western blot assay were applied to detect the expression of Lp(a)in each group.Results Compared with the sham operation group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,serum levels of Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly increased in the model group(P＜0.05).Compared with the model group,the ABR threshold,the score of membranous labyrinth hydrops,the proportion of middle stage area,levels of serum Lp(a),IL-6 and TNF-α,the IOD value of Lp(a)positive expression and the expression of Lp(a)protein in the cochlea of mice were significantly decreased in the low,medium and high dose sodium ferulate groups and the dexamethasone group(P＜0.05),and the effect of high dose sodium ferulate was more obvious.Conclusion Sodium ferulate can down regulate the expression of Lp(a)protein,reduce the production of proinflammatory factors,inhibit the inflammatory reaction,thereby alleviating the symptoms of membranous labyrinth hydrops in MD mice,and improving their auditory function.

Objective To investigate the effect and potential mechanism of early exercise intervention on cerebral myelin in cerebral ischemia rats.Methods A total of 18 SD rats were randomly divided into the sham group,the middle cerebral artery occlusion resting group(MCAO-SED)and the middle cerebral artery occlusion exercise group(MCAO-EX),with 6 rats in each group.Except the sham group,the middle cerebral artery occlusion model was prepared by modified Longa line embolization method in other groups.After modeling,rats in the MCAO-EX group were placed on a treadmill for exercise intervention for 28 days.Neurological function was assessed by modified neural function deficit score(mNSS).Infarct volume was detected by MRI scanning(T2),myelin basic protein(MBP)expression was detected by immunofluorescence.Myelin sheath structure was detected by transmission electron microscopy.Western blot assay was used to detect endoplasmic reticulum stress-related protein expression.Apoptosis was detected by TUNEL staining.Results After 28 days of intervention,compared with the MCAO-SED group,the nerve function recovered well in the MCAO-EX group,infarct volume decreased,myelin integrity increased,MBP fluorescence intensity expression increased and MBP expression level increased.The expression levels of ATF6,p-IRE1,p-PERK and cleaved caspase 3 were significantly decreased,and apoptosis was reduced.Conclusion Early exercise can inhibit endoplasmic reticulum stress-induced apoptosis,promote cerebral myelin repair,reduce infarct size and improve nerve function.

Objective To investigate the effect of Jaceosidin on inflammatory response in gestational diabetes mellitus(GDM)rats and its mechanism.Methods The GDM rat model was established by intraperitoneal injection of streptozotocin into pregnant rats.The successfully established rats were separated into the GDM group,the Jaceosidin L,M,H groups and the Jaceosidin+CTCE-0214[stromal cell-derived factor-1α(SDF-1α)/C-X-C chemokine receptor 4(CXCR4)activator]group,with 10 rats in each group.Meantime,10 healthy pregnant rats were taken as the control group.The Jaceosidin L,M and H groups were gavaged with 2,3 and 4 mg/kg Jaceosidin,respectively.The Jaceosidin+CTCE-0214 group was intraperitoneally injected with 10 mg/kg CTCE-0214 and gavaged with 4 mg/kg Jaceosidin.The control group and the GDM group were given equal amounts of physiological saline.The fasting blood glucose,fasting insulin and insulin resistance index were compared between each group of rats.Enzyme-linked immunosorbent assay was applied to detect levels of IL-1β and TNF-α in placental tissue.HE staining was applied to observe pathological changes of placental tissue.Apoptosis of placental tissue was detected by TUNEL.Western blot assay was applied to detect levels of SDF-1α/CXCR4 pathway related proteins in placental tissue.Results The intervention of different doses of Jaceosidin in GDM rats reduced levels of fasting blood glucose,fasting insulin,insulin resistance index and proinflammatory cytokines,improved the placental injury and apoptosis of GDM rats,and inhibited the activation of SDF-1α/CXCR4 signaling pathway in a dose-dependent manner(P＜0.05).SDF-1α/CXCR4 activator combined Jaceosidin could inhibit the above effects of Jaceosidin.Conclusion Jaceosidin can reduce inflammation and insulin resistance in GDM rats by suppressing the activation of SDF-1 α/CXCR4 signaling pathway.

Objective To compare the effect of rubber ring versus dental floss combined with hemoclipping assisted en-doscopic submucosal dissection(ESD)in the treatment of early gastrointestinal tumor.Methods A total of 103 patients with early gastrointestinal cancer were divided into the rubber band traction group(rubber band group,n=51)and the dental floss traction assist group(dental floss group,n=52)according to different assisted traction techniques during ESD.The basic con-ditions of the two groups were compared before operation,as well as the amount of submucosal injection,installation time of the traction device,the amount of bleeding during operation,the time of operation,the delayed bleeding after operation,one-time complete resection rate of tumor,days in hospital after operation and complication rate at 72 hours after operation.The degree of postoperative pain(VAS pain Score),follow-up quality of life(SF-36 Score)and complications 12 months after op-eration were also recorded.Results The intraoperative submucosal injection volume,intraoperative bleeding volume,num-ber of hemostatic clamp detachment,surgical time,complication rate 72 hour after operation and postoperative hospital stay were lower in the rubber band group than those in the dental floss group(P＜0.05).There was no significant difference in the number of delayed postoperative bleeding between the two groups(P＞0.05).After 12 months of follow-up,patients in the rubber band group had mild postoperative pain and good quality of life.The incidence of complications decreased within 12 months after surgery in the rubber band group(P＜0.05).Conclusion Compared with floss traction aid,rubber ring traction aid ESD can shorten the operation time and reduce postoperative complications,which is worth popularizing.

Objective To compare the efficacy and safety of large volume ligation device and tissue glue injection in the treatment of GOV gastric varicose veins,and to provide reference for the treatment of GOV gastric varicose veins.Methods A total of 150 patients with GOV type gastric varicose veins were prospectively included.Patients were divided into the endoscopic varicose vein ligation(EBL)group(78 cases)and the endoscopic varicose vein embolization(EVO)group(72 cases)according to their condition and willingness.In EBL group,GOV type gastric varices were treated by endoscopic ligation with a large volume ligation device.The EVO group was treated with tissue glue combined with cinnamyl alcohol injection.All patients were re-examined with gastroscopy 2-3 weeks after the first operation to observe whether varicose veins were residual and bleeding(if so,treatment should be repeated at this follow-up visit).Gastroscopy was performed at 1,3 and 6 months after surgery to evaluate the main outcome measures after endoscopic treatment,including success rate of varicose vein hemostasis,technical success rate,eradication rate,recurrence rate and related complications(secondary indicators):endoscopy-related bleeding,fever,sepsis and distant embolization.Results There were no significant differences in technical success rate,hemostasis success rate,average treatment times and 6-month eradication rate of gastric varices between the EBL group and the EVO group.The recurrence rate was higher in the EVO group than that of EBL group(P＜0.05).The endoscopy-related bleeding rate and fever rate were lower in the EBL group than those in the EVO group(P＜0.05).In the EVO group,1 patient developed pulmonary embolism after injection and 3 patients developed septicemia.Conclusion The short-term efficacy of high volume ligation device is similar to that of endoscopic injection of tissue glue in eradicating GOV gastric varices,but the former is safer than the latter.

Objective To investigate the clinical significance and serum changes of asprosin(ASP)levels in patients with essential hypertension and early renal damage.Methods According to urinary albumin/creatinine ratio(UACR),160 patients with essential hypertension were divided into the simple hypertension group(78 cases)and the early renal damage group(82 cases).Another 60 healthy subjects were selected as the control group.The differences of serum ASP,interleukin-6(IL-6)and UACR levels were compared between groups.The correlation between ASP and blood pressure,IL-6 and UACR was analyzed.Logistic regression analysis was used to analyze the factors influencing early renal damage in essential hypertension.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of each index for early renal injury.Results The serum levels of ASP,IL-6 and UACR were higher in the early renal damage group than those in the control group and the simple hypertension group(all P＜0.05).The serum levels of ASP and IL-6 showed an increasing trend with the increase of blood pressure.ASP was positively correlated with systolic blood pressure(SBP),diastolic blood pressure(DBP)and IL-6 levels in patients with essential hypertension(all P＜0.05).Serum ASP was positively correlated with SBP,UACR and IL-6 levels in essential hypertension patients(P＜0.05),and serum ASP was positively correlated with UACR and IL-6 levels in the early renal damage group(P＜0.05).Logistic regression analysis showed that higher levels of SBP,ASP and IL-6 were independent risk factors for early renal damage.ROC curve showed that ASP had the largest area under the curve(AUC)of 0.972(95%CI:0.950-0.993).The AUC of combined detection of ASP+IL-6+SBP was 0.986(95%CI:0.972-0.999).Conclusion The increased serum ASP level in patients with early renal damage in essential hypertension is a good predictor of early renal damage.The combined detection of ASP+IL-6+SBP is better than single detection.