Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To investigate the effect of total fla-vones of Coreopsis tinctoria Nutt(CF)on cognitive im-pairment in vascular dementia(VD).Methods The VD rat models were established by modified bilateral common carotid arteries ligation method.SD rats were divided into the sham operation group,model group,positive control group(nicergoline),and low,medium,and high dose CF groups.After eight weeks of admin-istration,the short term memory and spatial learning and memory abilities were evaluated by the platform jumping test,dark avoidance test and Morris water maze test.The pathological changes of the hippocam-pal tissues were inspected by HE and Nissl staining.The contents of TNF-α and IL-1β in the hippocampal were examined by ELISA.The protein expression lev-els of TLR4,MyD88,NF-κB p65,and p-NF-κB p65 in the hippocampal were detected by Western blot.The mRNA expression levels of miR-93,TLR4,MyD88,and NF-κB p65 in the hippocampal were determined by qRT-PCR.Results CF obviously improved the short term memory and spatial learning and memory abilities of VD rats,and alleviated the pathological damage of the hippocampus.CF also obviously decreased the lev-els of TNF-α and IL-1β,declined the protein expres-sion levels of TLR4,MyD88,and p-NF-κB p65,and re-duced the miR-93,TLR4,and MyD88 mRNA expres-sion in the hippocampus.Conclusion CF has a nota-ble protective effect on the neuroinflammation and cog-nitive impairments in VD rats by inhibiting the miR-93-mediated TLR4 signaling pathway.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Aim To investigate the mechanism of in-testinal mucosal barrier protective effect of Qingjie Huagong decoction(QJHGD)on rats with severe acute pancreatitis(SAP).Methods The SAP rat model was constructed,and the sham-operation group,the model group,the group administered with different dosages of QJHGD,and the positive control group were set up respectively.HE staining was used to observe the histopathological changes.ELISA was employed to detect the serum levels of diamine oxidase(DAO)and D-lactic acid(D-LA)in rats.Transmission electron microscopy was utilized to observe the mitochondria of ileal tissues.qRT-PCR and Western blot were applied to detect the mRNA and protein expression of PGAM5,Drp1,PINK1,Parkin,LC3B in ileal tissues of rats.Results Compared with the sham-operated group,the pancreas and ileum tissues of rats in the model group showed obvious pathological changes,with abnormal mitochondrial structure and reduced number of autoph-agic vesicles in the ileum tissues.The levels of DAO and D-LA in serum increased(P＜0.01),and the mRNA and protein expression of PGAM 5,Drp 1,PINK1,Parkin,and LC3B in the ileum tissues de-creased significantly.Compared with the model group,pancreatic and ileal pathology were improved,mito-chondrial damage in the ileum was reduced,and the number of autophagic vesicles increased in the QJHGD group.The serum levels of DAO and D-LA were re-duced,and the expression of PGAM5,Drp1,PINK1,Parkin,and LC3B mRNA and protein in the ileal tis-sues increased significantly.Conclusions QJHGD may exert a protective effect on the SAP intestinal mu-cosal barrier by regulating the PGAM5/Drp1/PINK1/Parkin axis in order to elevate the level of mitochondri-al autophagy in the intestinal epithelial cells,thereby improving the level of repair of the intestinal epithelial cells.

Objective To evaluate the efficacy,safety and patient compliance of a quadruple therapy containing minocycline compared with the traditional quadruple therapy in the treatment of Helicobacter(H.)pylori.Methods This study included 200 H.pylori positive patients,with 100 assigned to the minocycline-containing bismuth quadruple therapy group(LBMC group)and the other 100 to the amoxicillin-containing bismuth quadruple therapy group(LBAC group).After matching the two groups of patients using the propensity score matching(PSM)method,there were 86 cases in each group.Telephone follow-up was conducted on the 14th day after the start of treatment to record patient medication compliance and adverse drug reactions.A 13C urea breath test was performed for re-examination at least one month after completing the treatment plan and discontinuing medication.The intention-to-treat(ITT)and per-protocol(PP)analyses were used to compare the H.pylori eradication rates between the two groups,and Chi-square test and t-test were used for intergroup comparison.Results In the ITT analysis,the eradication rates of the LBMC group and the LBAC group were 89.5%(77/86,95%CI:82.9%～96.1%)and 82.6%(71/86,95%CI:74.4%～90.7%),respectively.In the PP analysis,the eradication rates were 92.6%(75/81,95%CI:86.8%～98.4%)and 88.8%(71/80,95%CI:81.7%～95.8%),respectively.The adverse reaction rate of the LBMC group was 27.9%(24/86),and that of the LBAC group 31.4%(27/86),showing no statistically significant difference(P>0.05).In terms of compliance,the LBMC group was 94.2%(81/86),and the LBAC group 93.0%(80/86),revealing no statistically significant difference(P>0.05).Conclusion As a first-line treatment for eradicating H.pylori,regimens containing minocycline demonstrate equivalent eradication rates to those containing amoxicillin,with similar safety and compliance.They can be used as an alternative treatment for patients allergic to penicillin.

Objective To explore the effects of microscopic total resection on cerebral blood flow perfusion and cognitive function in patients with glioma.Methods The clinical data of 80 glioma patients admitted to our hospital were retrospectively analyzed.The grouping were conducted according to different surgical methods,among which 38 patients treated with traditional craniotomy were included in the traditional group,and 42 patients treated with microscopic total resection were included in the microscopic group.The surgery-related indicators,cerebral blood perfusion indexes,cognitive function and recurrence of patients in the two groups were compared.Results The surgical time,time to get out of bed,and hospital stay of patients in the microscopic group were shorter than those in the traditional group,the intraoperative blood loss was lower than that in the traditional group,and the incision length was smaller than that in the traditional group,with statistically significant differences(P<0.05).Six months after surgery,the standard uptake value of 13N-NH3 in the cerebral cortex of patients in the microscopic group was higher than that in the traditional group(P<0.05).Six months after surgery,the scores of directional ability,immediate memory,attention and calculation ability,delayed memory,and language function,and total mini-mental state examination score of patients in the microscopic group were higher than those in the traditional group(P<0.05).One year after surgery,the recurrence rate of patients in the microscopic group was 4.76%,which was lower than that in the traditional group of 23.68%,with statistically signifi-cant difference(P<0.05).Conclusion Compared with traditional craniotomy,microscopic total resection is more advantageous for patients with glioma,which can optimize surgical indicators,ameliorate postoperative cerebral blood flow perfusion,and restore cognitive function,with a lower postoperative recurrence rate.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.

Pancreatic cancer is highly aggressive and often diagnosed at an advanced stage,leaving most patients ineligible for radical resection.This study retrospectively analyzed four patients with locally advanced or advanced pancreatic cancer to evaluate the clinical efficacy and safety of high-intensity focused ultrasound(HIFU)ablation combined with chemotherapy as a neoadjuvant and conversion therapy.All cases were reviewed and individualized treatment plans were formulated through a multidisciplinary team evaluation.All patients received HIFU plus gemcitabine and nab-paclitaxel chemotherapy,with assessments of tumor volume,vascular involvement,surgical conversion,symptom relief,and adverse events.Three patients achieved marked tumor shrinkage and reduction of vascular invasion,enabling successful R0 resection without recurrence during follow-up.The remaining patient achieved disease stability,significant pain relief,and maintained good quality of life under repeated HIFU therapy.All treatments were well tolerated,and no severe adverse reactions occurred.The combination of HIFU and chemotherapy demonstrated synergistic local and systemic effects,effectively achieving tumor downstaging,improving resectability,and alleviating symptoms.As a safe,noninvasive,and repeatable therapeutic approach,this strategy offers a promising option for patients with advanced pancreatic cancer.Further large-scale prospective studies are warranted to validate its long-term efficacy and elucidate underlying mechanisms.