Objective To investigate the potential therapeutic effects,targets,and pathways of wogonoside in hypertension-induced renal injury using the Gene Expression Omnibus(GEO)database and network pharmacology,and to validate the effects of wogonoside intervention on the renal tissues of spontaneously hypertensive rats(SHR),angiotensin Ⅱ(Ang Ⅱ)-stimulated NRK-52E cell apoptosis,and the regulation of relevant pathways through in vivo and in vitro experiments.Methods GEO dataset and network pharmacology analyses were performed to investigate the key therapeutic targets of wogonoside for hypertensive nephropathy.The STRING database was used to analyze protein-protein interactions.Biological functions were annotated via Gene Ontology(GO),and the potential signaling pathways were enriched using the Kyoto Encyclopedia of Genes and Genomes(KEGG).SHR were randomly divided into groups and given low,medium,or high doses of wogonoside(0.075,0.75,and 7.5 mg/kg)via gastric gavage for 10 weeks.Morphological changes in the kidney tissue were assessed by hematoxylin-eosin(HE)staining.Serum levels of inflammatory cytokines,including tumor necrosis factor α(TNF-α),interleukin(IL)-1 β,and IL-6,were measured using ELISA.Apoptosis rates were evaluated by TUNEL staining,and Western blot was performed to determine the expression of Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the expression of phosphorylated and total extracellular signal-regulated kinases(ERK)and p38 mitogen-activated protein kinase(MAPK)proteins.An in vitro model of Ang Ⅱ-stimulated NRK-52E cells was constructed and was treated with wogonoside at different concentrations(25,50,or 100 μmol/L)for 24 h.The apoptosis rates were then assessed by Annexin V staining,and Western blot was performed to validate the expression of apoptosis-related and pathway-associated proteins.Results Analysis of dataset GSE41453 revealed 11673 upregulated and 5902 downregulated genes in the renal tissues of SHR compared to the Wistar Kyoto(WKY)rats,or the WKY control group.Through the analysis of multiple databases,371 potential targets of wogonoside were identified,resulting in 98 overlapping targets.From these,45 core therapeutic targets were identified through further analysis,including TNF,CASP3,etc.GO analysis significantly enriched processes such as the negative regulation of apoptosis.KEGG pathway enrichment analysis highlighted the apoptosis pathway,IL-17 signaling pathway,and MAPK signaling pathway as being significantly enriched.Wogonoside treatment effectively mitigated pathological damage in SHR kidney tissues and significantly inhibited the expression of inflammatory cytokines,including TNF-α,IL-1 β,and IL-6(P＜0.05).It also decreased cell apoptosis rates in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells,downregulated the expression of Bax and cleaved caspase-3,and upregulated Bcl-2 expression(P＜0.05).Furthermore,wogonoside treatment inhibited the phosphorylation of ERK and p38 MAPK in SHR kidney tissues and Ang Ⅱ-stimulated NRK-52E cells(P＜0.05).Conclusion Wogonoside may exert its protective effects against hypertension-induced renal injury by suppressing the inflammatory response and cell apoptosis,potentially through the regulation of the MAPK signaling pathway.

Objective To investigate the potential therapeutic effects of trifolin on hypertension-induced renal injury,as well as the key targets and pathways involved.Methods The mRNA transcriptional profiles of peripheral blood clinical samples from hypertensive patients were analyzed using Gene Expression Omnibus(GEO),a high-throughput gene expression database.The network pharmacology method was employed to screen key targets of trifolin in treating hypertension-induced renal injury.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted.NRK-52E cells,a rat renal proximal tubular cell line,were used to construct an angiotensin Ⅱ(Ang Ⅱ)-stimulated cell model.Flow cytometry was performed to assess cell apoptosis rates and Western blotting was performed to determine the expression levels of apoptosis-related proteins,including Bax,Bcl-2,cleaved caspase-3,and caspase-3,and the phosphorylation and total protein levels of the key MAPK pathway proteins,including ERK,p38 MAPK,and JNK.Results Analysis of the dataset GSE75360 revealed that,compared with healthy controls,3 331 genes were upregulated and 3 197 genes were downregulated in peripheral blood mononuclear cells of hypertensive patients.According to network pharmacology analysis,472 potential targets of trifolin were identified,including CASP3 and MAPK1.Protein-protein interaction network analysis showed that these targets were closely associated with apoptosis regulatory signaling pathways.GO and KEGG pathway enrichment analyses indicated that trifolin was significantly enriched in pathways associated with negative regulation of apoptosis,apoptotic signaling pathways,and the MAPK signaling pathway.The in vitro experiments confirmed that,compared with the Ang Ⅱ group,trifolin intervention inhibited apoptosis in Ang Ⅱ-stimulated NRK-52E cells,suppressed the expression of Bax and cleaved caspase-3,promoted Bcl-2 expression,and inhibited the phosphorylation of p38 MAPK,ERK,and JNK(P<0.05).Conclusion Trifolin may exert its protective effect against hypertension-induced renal injury by inhibiting Ang Ⅱ-induced NRK-52E cell apoptosis and regulating the MAPK signaling pathway,representing an important mechanism underlying its therapeutic action.

Objective:To compare the efficacies of robot-assisted unilateral and manual unilateral/bilateral puncture kyphoplasty (PKP) for the treatment of osteoporotic thoracolumbar fracture (OTLF).Methods:A retrospective cohort study was conducted to analyze the clinical data of 64 OTLF patients admitted to First Affiliated Hospital of Kunming Medical University from April 2021 to May 2022. The patients included 28 males and 36 females, aged 57-88 years [(74.5±5.6)years]. Fracture segments were 12 patients from T 1-T 9, 32 from T 10-L 2, and 20 from L 3-L 5. All the patients were treated with PKP. Among them, 25 patients underwent manual unilateral puncture (manual unilateral group), 18 patients underwent manual bilateral puncture (manual bilateral group), and 21 patients underwent robot-assisted unilateral puncture (robot-assisted unilateral group). The operation time, channel establishment time, intraoperative blood loss, intraoperative fluoroscopy times, bone cement injection volume, and bone cement spatial distribution score were compared among the three groups. The visual analogue score (VAS), Oswestry disability index (ODI) and Cobb angle of kyphosis were compared among the three groups before operation, at 3 days and 3 months after operation, and at the last follow-up. The incidence of complications was compared. Results:All the patients were followed up for 6-10 months [(7.0±0.9)months]. The operation time of the manual unilateral group was (30.2±6.1)minutes, which was shorter than (37.9±8.9)minutes of the robot-assisted unilateral group and (49.0±10.2)minutes of the manual bilateral group; the operation time of the robot-assisted unilateral group was markedly shorter than that of the manual bilateral group (all P<0.05). The channel establishment time of the robot-assisted unilateral group was (4.7±1.4)minutes, which was markedly shorter than (10.4±4.4)minutes of the manual unilateral group and (21.7±6.2)minutes of the manual bilateral group (all P<0.05). The intraoperative blood loss of the robot-assisted unilateral group was (23.8±7.2)ml, which was less than (34.3±7.7)ml of the manual unilateral group and (55.9±18.7)ml of the manual bilateral group (all P<0.05). The number of intraoperative fluoroscopy of the robot-assisted unilateral group was (12.1±2.5)times, which was markedly less than (21.2±5.9)times of the manual unilateral group and (39.6±9.5)times of the manual bilateral group (all P<0.05). The channel establishment time, intraoperative blood loss and intraoperative fluoroscopy times of the manual unilateral group were markedly shorter or less than those of the manual bilateral group (all P<0.05). The bone cement injection volume and bone cement distribution score of the robot-assisted unilateral group were (4.7±1.3)ml and (7.9±1.2)points, which were not statistically different from (5.7±1.3)ml and (8.7±1.1)points of the manual bilateral group (all P>0.05), but were markedly higher than (3.0±1.3)ml and (5.1±1.8)points of the manual unilateral group (all P<0.05). There were no significant differences in VAS, ODI and Cobb angle among the three groups at 3 days, 3 months after operation and at the last follow-up (all P>0.05), but which were all lower than those before surgery (all P<0.05). There were no significant differences in VAS, ODI and Cobb angle among three groups before operation, at 3 days, 3 months after surgery and at the last follow-up (all P>0.05). The complication rate was 4.8% (1/21) of the robot-assisted unilateral group, 32.0% (8/25) of the manual unilateral group, and 33.3% (6/18) of the manual bilateral group, with no significant difference between the manual unilateral group and the manual bilateral group ( P>0.05), but both of which was markedly higher than that of the robot-assisted unilateral group ( P<0.05). Conclusion:Robot-assisted unilateral puncture and manual unilateral/bilateral puncture PKP can both achieve satisfactory results for the treatment of OTLF, but robot-assisted unilateral puncture has shorter channel establishment time, less intraoperative blood loss and intraoperative fluoroscopy times, and lower complication rate.

Objective To evaluate the effect of early surgical treatment for primary lower limb varicose veins complicated by thrombophlebitis.Methods The clinical date of 42 patients with primary lower extremity varicose veins complicated by thrombophlebitis treated in 4 years were analyzed retrospectively.The CEAP classification was adopted to establish the diagnoses of the all patieats.In the early stage,high ligation and stripping of the varicase veins were performed.After removal of varicose veins and thrombi,both anti-inflammation therapy and anticoagulant therapy were applied.Results All patients made a good recovery.After surgery,3 patients had skin callous and swelling,and 3 patients had foot nerve paresthesia.But,no serious complications,such as deep venous thrombosis or pulmonary embolism,were observed.The was no recurrence during 2 months to 4 years follow-up.Conclusions Early surgical treatment for primary lower limb varicose veins complicated by superficial thrombophlebitis not only has good results but also helps control of deep venous thrombosis and pulmonary embolism,and other serious complications that can result from superficial venous thrombosis.