Objective To analyze the distribution characteristics of the single nucleotide polymorphism (SNP) site rs76206423 in the promoter region of the interleukin-2 receptor (IL-2R) β gene among Han males in a high radiation background area (HBRA) in Yangjiang City. Methods A total of 48 male participants from Tangkou Town, Yangxi County, Yangjiang City (HBRA group), and 51 male participants from Hengpo Town, Enping City (control group) were selected as the research subjects using the random number table method. Peripheral venous blood samples of participants from both groups were collected, and genomic DNA was extracted. The genotyping and allele frequency distribution of the rs76206423 (A/G) site in the IL-2R β promoter region was detected among the participants in both groups using the SNP detection method. The difference of allele frequencies between population in HBRA group and five area of East Asia, South Asia, Africa, Europe, and the Americas published in the Human Genome Project database from National Center for Biotechnology Information were analyzed. Results The allele frequencies of rs76206423 of population in both groups conformed to Hardy-Weinberg equilibrium (P>0.05). In the HBRA group, the AA genotype was predominant (64.6%), while the AG genotype was the most common in the control group (51.0%), with a significant difference (P<0.05). Population in both groups showed a predominance of the variant allele A (78.1% and 72.5%, respectively), with no significant difference (P>0.05). The frequency of the G allele of rs76206423 in the population in HBRA group was higher than those in South Asian, African, European, and American populations (all P<0.01), but showed no significant difference compared with East Asian populations (P>0.05). Conclusion In the Han male population from the HBRA in Yangjiang City, the rs76206423 site in the IL-2R β gene promoter region is predominantly composed of the wild-type A allele and AA genotype, indicating genetic stability and a relatively high degree of variation at this locus.

Through molecular docking and experimental validation,24 SPF male KM mice were ran-domly divided into four groups:the control group(CON),model group(LPS),high-dose Yang Shuhua group(YSH-H),which was gavaged with drug solution containing 1 g/mL crude Yang Shuhua,and the low-dose Yang Shuhua group(YSH-L),which was gavaged with drug solution containing 0.5 g/mL crude Yang Shuhua for a 17-day experimental period.Mouse body weight was recorded during the experiment,and fecal scoring was done 1 h after intraperitoneal injection of LPS.At the end of the experiment,histopathological changes in the jejunum tissue were examined,and the expression of tight junction protein-related genes was detected.Compared to the CON group,mice in the LPS group showed significant decreases in villus height,villus height/crypt depth(V/C)ratio(P＜0.01),and significant increase in crypt depth(P＜0.01).The mRNA ex-pression levels of ZO-1 and claudin-1 were significantly decreased(P＜0.01).Compared to the LPS group,mice in the YSH-H group showed significant decrease in crypt depth(P＜0.05),significant increase in villus height(P＜0.05),and significant increase in V/C ratio(P＜0.01).The YSH-L group showed a significant increase in V/C ratio(P＜0.05),a trend of decreased crypt depth,and an increasing trend of villus height.The mRNA expression of ZO-1 in the YSH-H group showed a significant increase(P＜0.05)and claudin-1 showed an increasing trend.Luteolin,quercetin,kaempferol,eriodictyol,and the top 5 potential key targets TP53,IL-1β,TNF,AKT1,and IL-10 exhibited molecular docking scores less than-20.95 kJ/mol,indicating strong activity.GO and KEGG enrichment analysis suggested that Yang Shuhua compounds might act on enteritis through the TNF signaling pathway,IL-17 signaling pathway,and PI3K-Akt signaling pathway.The qPCR results showed an upward trend in the mRNA expression levels of TLR4 and AKT1,significant in-crease in Caspase-1 and ASC(P＜0.05),and significantly increased expression of NF-κB and NL-RP3(P＜0.01).The mRNA expression level of AKT1,TLR4,NLRP3,ASC,Caspase-1,and NF-κB decreased compared to the LPS group,with significant differences in Caspase-1 and NF-κB(P＜0.05).This study suggests that Yang Shuhua exerts anti-enteritis effects through multiple compo-nents and pathways,with blockade of the TLR4-AKT-NF-κB pathway possibly being a key thera-peutic mechanism for treating enteritis.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

The objective of this study was to evaluate the protective effect and possible related mechanisms of Sophora subprostrate polysaccharide(SSP)on intestinal epithelial cell injury in-duced by Tert-Butyl hydroperoxide(TBHP).The optimal dose of TBHP and the safe concentra-tion range of SSP were determined using the MTT method.In this study,IPEC-J2 cells were divid-ed into five groups:the control group,the model group,the SSPL group,the SSPM group and the SSPH group,and the cell morphology,cell survival rate and LDH release rate were observed and measured.The content of intracellular reactive ROS was observed and determined by DCFH-DA staining.The content of MDA in the supernatant and the antioxidant index of cells were determined by the reagent kit.Transcriptome technology was employed to analyze the potential mechanisms by which SSP mitigates oxidative damage in IPEC-J2 cells.The results showed that treatment with 625 μmol/L TBHP for 2 h significantly reduced the activity of IPEC-J2 cells,markedly increased LDH release(P＜0.05),inhibited CAT superoxide SOD and glutathione GPX activities(P＜0.05),and significantly elevated MDA and ROS levels(P＜0.05).Compared to the model group,after SSP treatment,intracellular ROS levels were significantly reduced(P＜0.05),while CAT,SOD,and GPX activities were significantly increased(P＜0.05),and MDA content and LDH re-lease were significantly decreased(P＜0.05)in a dose-dependent manner.Transcriptome analysis revealed that TBHP treatment significantly altered the transcriptional profiles of IPEC-J2 cells,while SSP treatment could restore the transcriptional profiles of the damaged cells to a certain ex-tent.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)indicated that the differentially expressed genes between the CC and TBHP groups were significantly enriched in oxidative phosphorylation,ribosome,and other pathways.Meanwhile,the differentially expressed genes between the SSP and TBHP groups were mainly enriched in oxidative phosphorylation,ap-optosis,glyoxylate and dicarboxylate metabolism,and other pathways.These results suggest that TBHP may disrupt normal oxidative respiration in IPEC-J2 cells by affecting oxidative phospho-rylation and interfering with metabolism pathways involving glycine,serine,and threonine,leading to oxidative damage in intestinal epithelial cells.Conversely,SSP treatment may potentially restore oxidative phosphorylation processes,alleviate lysosomal damage,reduce cell apoptosis,and miti-gate oxidative damage in intestinal epithelial cells through modulation of oxidative phosphoryla-tion,apoptosis,and lysosomal pathways.This discovery provides a theoretical basis for the clinical application of SSP in alleviating oxidative damage in the porcine intestinal tract.

The objective of this study was to evaluate the protective effect and possible related mechanisms of Sophora subprostrate polysaccharide(SSP)on intestinal epithelial cell injury in-duced by Tert-Butyl hydroperoxide(TBHP).The optimal dose of TBHP and the safe concentra-tion range of SSP were determined using the MTT method.In this study,IPEC-J2 cells were divid-ed into five groups:the control group,the model group,the SSPL group,the SSPM group and the SSPH group,and the cell morphology,cell survival rate and LDH release rate were observed and measured.The content of intracellular reactive ROS was observed and determined by DCFH-DA staining.The content of MDA in the supernatant and the antioxidant index of cells were determined by the reagent kit.Transcriptome technology was employed to analyze the potential mechanisms by which SSP mitigates oxidative damage in IPEC-J2 cells.The results showed that treatment with 625 μmol/L TBHP for 2 h significantly reduced the activity of IPEC-J2 cells,markedly increased LDH release(P＜0.05),inhibited CAT superoxide SOD and glutathione GPX activities(P＜0.05),and significantly elevated MDA and ROS levels(P＜0.05).Compared to the model group,after SSP treatment,intracellular ROS levels were significantly reduced(P＜0.05),while CAT,SOD,and GPX activities were significantly increased(P＜0.05),and MDA content and LDH re-lease were significantly decreased(P＜0.05)in a dose-dependent manner.Transcriptome analysis revealed that TBHP treatment significantly altered the transcriptional profiles of IPEC-J2 cells,while SSP treatment could restore the transcriptional profiles of the damaged cells to a certain ex-tent.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)indicated that the differentially expressed genes between the CC and TBHP groups were significantly enriched in oxidative phosphorylation,ribosome,and other pathways.Meanwhile,the differentially expressed genes between the SSP and TBHP groups were mainly enriched in oxidative phosphorylation,ap-optosis,glyoxylate and dicarboxylate metabolism,and other pathways.These results suggest that TBHP may disrupt normal oxidative respiration in IPEC-J2 cells by affecting oxidative phospho-rylation and interfering with metabolism pathways involving glycine,serine,and threonine,leading to oxidative damage in intestinal epithelial cells.Conversely,SSP treatment may potentially restore oxidative phosphorylation processes,alleviate lysosomal damage,reduce cell apoptosis,and miti-gate oxidative damage in intestinal epithelial cells through modulation of oxidative phosphoryla-tion,apoptosis,and lysosomal pathways.This discovery provides a theoretical basis for the clinical application of SSP in alleviating oxidative damage in the porcine intestinal tract.

Objective To explore the therapeutic mechanism of berberine in atopic dermatitis(AD)rats based on PI3K/Akt/NF-kappa B signaling pathway.Methods Sixty adult male Wistar rats were randomly divided into the blank group(normal rats),the control group(AD model,50 mg/kg berberine treatment)and the experimental group(AD model,200 mg/kg berberine treatment),with 20 rats in each group.The levels of interleukin-4(IL-4),interleukin-13(IL-13)and tumor necrosis factor-α(TNF-α)were determined by enzyme-linked immunosorbent assay(ELISA)at 1 d,7 d and 14 d of intervention.The protein levels of PI3K,p-PI3K,Akt,p-Akt and NF-κB p65 were detected by Western blot assay.Pathological changes of rat skin tissue were analyzed by HE staining.Results After intervention for 1 d,7 d and 14 d,serum levels of IL-4,IL-13,TNF-α and PI3K,p-PI3K,Akt,p-Akt and NF-kappa B p65 were higher in the control group than those in the blank group(P＜0.05).After intervention for 7 d and 14 d,the levels of the above indicators were lower in the experimental group than those in the control group(P＜0.05).After 14 days of intervention,compared with the blank group,the skin tissue of rats in the control group and the experimental group showed obvious pathological changes,including thickening of epidermis layer,excessive keratinization of the stratum comeum,thickening of spinous layer and a large infiltration of inflammatory cells in dermis.The pathological damage of rat skin tissue was significantly alleviated in the experimental group.Conclusion Berberine can inhibit the activation of PI3K/Akt/NF-kappa B signaling pathway,reduce serum level of inflammatory factors and reduce pathological damage of skin tissue in AD rats.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.

Objective To compare the application value of direct arteriovenous fistula(AVF),after ultrasound-guided percutaneous transluminal angioplasty(PTA)dilation of radial artery AVF formation and reverse"J"arteriovenous graft(AVG)in hemodialysis patients with small diameter vessels.Methods Totally 96 end-stage renal disease patients with distal radial artery＜1.5 mm and cephalic vein≥2.0 mm who planning to receive hemodialysis were retrospectively enrolled.The patients were divided into AVF group(n=30),PTA+AVF group(n=34)and AVG group(n=32)according to fistulization methods.The technical success rate,clinical success rate,primary patency rate and secondary patency rate were compared among groups.Results The technical success rate of AVF group,PTA+AVF group and AVG group was 80.00%,94.12%and 100%,respectively,and the clinical success rate was 30.00%,82.35%and 93.75%,respectively,with significant differences among 3 groups(both P＜0.05).The primary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 80.00%,30.00%,27.59%,27.59%and 24.14%,respectively,in PTA+AVF group was 94.12%,82.35%,78.79%,68.75%and 62.50%,respectively,while in AVG group was 100%,93.33%,83.33%,76.67%and 66.67%,respectively,all being significant different among 3 groups(all P＜0.05).The secondary patency rate 1,3,6,9 and 12 months after fistulization in AVF group was 83.33%,75.00%,75.00%,70.83%and 58.33%,respectively,in PTA+AVF group was 93.33%,93.33%,83.33%,83.33%and 80.00%,respectively,while in AVG group was 100%,100%,93.33%,90.00%and 80.00%,respectively,also being significant different among 3 groups(all P＜0.05).Conclusion Compared with direct and after ultrasound-guided PTA dilation of radial artery AVF formation,AVG formation was more valuable for hemodialysis patients with small diameter vessels.

Objective To investigate the impact and underlying mechanism of curcumin(Cur)on the aberrant proliferation and migration of VSMC.Methods VSMC was treated with Ang Ⅱ to establish a cell proliferation model.The experiment included blank control group,model group,and low-,medium-and high-dose Cur treatment groups(1.5,3.0 and 4.5 pmol/L,n=11).To explore the effect of Cur on the AMPK/mTOR signaling pathway,VSMC was also assigned into blank control,Ang Ⅱ(10-6 mol/L),Cur(3.0 μmol/L)and Ang Ⅱ+Cur groups(n=3).Western blotting was employed to detect the expression of VSMC differentiation markers(α-SMA),dedif-ferentiation marker(OPN),autophagy-related proteins(P62 and Beclin-1),and proteins involved in the AMPK/mTOR pathway(AMPK,p-AMPK,mTOR,p-mTOR,p70S6K,p-p70S6K).Results Exposure to Ang Ⅱ enhanced the proliferation and migration of VSMC when compared with the blank control group(155％vs 100％,66％vs 48％,P＜0.05).When compared with the model group,the proliferative rate was significantly lower in the medium-and high-dose Cur groups,and the migratory rate was obviously decreased in the three Cur groups(P＜0.05).The α-SMA expression was increased in the medium-and high-dose Cur groups,and that of OPN was decreased in the three Cur groups when compared with the model group(P＜0.05).Enhanced Be-clin-1 and p-AMPK/AMPK and down-regulated P62,p-mTOR/mTOR,and p-p70S6K/p70S6K were observed in the Ang Ⅱ and Cur groups than the blank control group(P＜0.05).The Cur Ang Ⅱ and Cur+AngⅡ groups had notably higher Beclin-1 and p-AMPK/AMPK but lower P62,p-mTOR/mTOR,and p-p70S6K/p70S6K than the Ang Ⅱ group(P＜0.05).Conclusion Cur in-hibits the proliferation and migration of VSMC induced by Ang Ⅱ,potentially through its activa-ting the AMPK/mTOR signaling pathway and enhancing autophagy in VSMC.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.