AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology* ; Humans ; Atherosclerosis/immunology* ; Neutrophils/physiology* ; Leukocyte Elastase/metabolism* ; Peroxidase/physiology* ; Matrix Metalloproteinases/physiology* ; Cathepsin G/metabolism* ; Cathelicidins ; HMGB1 Protein/physiology* ; Histones ; Animals ; Endothelium, Vascular

Objective: To investigate the relationship between relative grip strength and hyperuricemia (HUA) levels in university freshmen, and to explore the potential value of muscle function indicators in HUA prevention among young populations, so as to provide new scientific evidences for HUA control in the demographic. Methods: Utilizing health examination data from 1 744 freshmen enrolled in a Shaanxi Province university in September 2024, absolute grip strength was measured using CAMRY electronic dynamometers, with relative grip strength subsequently calculated. Spearman correlation analysis was employed to examine relationships between student characteristics and relative grip strength, and binary Logistic regression models assessed the association strength between relative grip strength and HUA. Results: The overall HUA detection rate among freshmen was 29.8%, with significant gender differences (male:43.1%; female:24.0%; χ 2=64.62, P <0.01). Correlation analysis revealed significant associations between relative grip strength, body weight, height, body mass index (BMI) and HUA in both genders (boys: r =-0.27, 0.54, 0.11 , 0.53; girls: r =-0.18, 0.33, 0.08, 0.33, all P <0.05). Binary Logistic regression demonstrated that each standard deviation increase in relative grip strength reduced HUA risk by 77% in males ( OR=0.23, 95%CI =0.14-0.37) and 80% in females ( OR=0.20, 95%CI =0.11-0.36) (both P <0.01). Conclusions Relative grip strength represents a significant factor associated with HUA in university students. Incorporating muscle strength training into HUA prevention programs and establishing muscle function based HUA risk warning systems should be considered.

AIM:To elucidate the pharmacody-namic and network pharmacological mechanisms of total flavonoids of Carthamus tinctorius L.,to ex-plore their key targets and related pathways,and to clarify their mechanism of action against hepatic fibrosis.METHODS:The total flavonoids of Cartha-mus tinctorius L.were determined by LC-MS/MS and analysed for their compositions;the active in-gredients were screened by TCMSP database,SWISS ADME database and literature search;the targets related to total flavonoids of Carthamus tinctorius L.were screened by Swiss Target Predic-tion database;and the targets related to hepatic fi-brosis were screened by GeneCards database;the anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained by taking the intersection of Venny.2.1.0;the protein interac-tions were analysed by STRING database;the visu-alization analysis was carried out by Cytoscape soft-ware;the GO function and KEGG pathway analysis was carried out by Metascape platform;and molec-ular docking was verified by using AutoDock soft-ware for the core targets and active ingredients.The mechanism of anti-hepatic fibrosis of total fla-vonoids of Carthamus tinctorius L.was verified by animal model and in vitro cell experiments.RE-SULTS:A total of 41 flavonoid components were identified in Carthamus tinctorius L.Through the network pharmacological analysis,149 anti-hepatic fibrosis targets of total flavonoids of Carthamus tinctorius L.were obtained,including 23 core tar-gets.The GO enrichment analyses involved a total of three aspects,namely,biological process(BP),cellular component(CC),and molecular function(MF).KEGG enrichment results showed that PI3K/Akt and MAPK are pathways involved in the devel-opment of hepatic fibrosis.Molecular docking veri-fied that the active ingredients Quercetin,Acacetin and Glabridin were tightly bound to Akt1 and HI-FIA,respectively.In animal model experiments,it was observed by HE and Masson staining that fibro-plasia was reduced,collagen deposition was re-duced,inflammatory cell infiltration was reduced,and fibrotic liver tissues were improved in total fla-vonoids of Carthamus tinctorius L.administration group.In isolated cell experiments:Western blot-ting results suggested that total flavonoids of Car-thamus tinctorius L.could decrease the hepatic fi-brosis marker factor α-SMA,Collagen1(P＜0.01)and PI3K,Akt protein expression(P＜0.01).CONCLU-SION:Total flavonoids of Carthamus tinctorius L.ex-erted anti-hepatic fibrosis effects through multi-components,multi-targets and multi-pathways,and their mechanism of action may be achieved by regulating the PI3K/Akt signalling pathway.

Objective:To investigate the effects of early postoperative nutritional management under enhanced recovery after surgery (ERAS) guidelines on nutritional biochemical indicators and length of hospital stay in patients undergoing lumbar fusion surgery. Method:Ninety-four patients who underwent lumbar posterior internal fixation + intervertebral fusion surgery in Department of Orthopedics Ⅲ of Ningxia Medical University General Hospital from January 2020 to March 2021 were randomly divided into an intervention group (n=47) and a control group (n=47). The intervention group received nutritional intervention by a clinical nutritionist at 2 hours after anesthesia recovery, and the control group started to eat liquid diet at 6 hours after anesthesia recovery. The protein-calorie intake, blood glucose, total protein, albumin, hemoglobin, postoperative hospitalization time and total hospitalization time of the two groups were observed. Results:The protein-calorie intake of the intervention group was higher than that of the control group on the day of surgery and the first 3 days after surgery, with statistically significant differences (P<0.05). The blood glucose level of the intervention group was lower than that of the control group on the first day after surgery, with statistically significant differences (P<0.05). The total protein level of the intervention group was higher than that of the control group on the third day after surgery, with statistically significant differences (P<0.05). The albumin and hemoglobin levels of the intervention group were higher than those of the control group on the first and third days after surgery, with statistically significant differences (P<0.05). The incidence of abdominal distension and the length of hospital stay in the intervention group were lower than those in the control group, with statistically significant differences (P<0.05). Conclusion:Early postoperative nutritional management has a certain effect on improving nutritional and biochemical indicators and shortening the length of hospital stay in patients undergoing lumbar fusion surgery.

Objective To investigate the neuroprotective effect and potential mechanism of rehabilitation training combined with citicoline on cerebral hemorrhage model in mice based on Keap1/Nrf2/ARE signaling pathway.Methods The C57BL/6 male mice were randomly divided into sham operation group(sham operation treatment),model group(right caudate putamen hemorrhage model induced by type Ⅶcollagenase),choline group(model+choline 64 mg·kg-1),rehabilitation training group(rehabilitation training)and combined group(model+rehabilitation training+choline 64 mg·kg-1).The study observed the modified neurological severity score(mNSS)in mice with cerebral hemorrhage;colorimetric assays were used to detect the expression of malondialdehyde(MDA),superoxide dismutase(SOD)and catalase(CAT)in brain tissues;protein imprinting and reverse transcription-quantitative polymerase chain reaction were employed to assess the expression of Kelch-like ECH-associated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE),heme oxygenase-1(HO-1),quinone oxidoreductase 1(NQ01)proteins and mRNA in brain tissues.Results The mNSS scores of sham operation group,model group,citicoline group,rehabilitation training group and combined group were 0,1.56±0.73,1.00±0.00,0.78±0.44 and 0.67±0.50;the MDA contents were(6.93±0.92),(22.97±0.77),(19.26±1.73),(13.21±0.78)and(7.25±0.97)nmol·mgprot-1;the relative expression of Keap1 protein were 0.79±0.03,1.02±0.04,0.95±0.10,0.90±0.09 and 0.86±0.05;the relative expression levels of Nrf2 protein were 0.94±0.12,0.71±0.08,0.90±0.07,0.98±0.12 and 1.33±0.25.There were significant differences in the above indexes between the model group and the sham operation group(P＜0.05,P＜0.01);there were significant differences between the citicoline group and the rehabilitation training group,the model group(P＜0.05,P＜0.01);there were significant differences between the combined group and the citicoline group,the rehabilitation training group except for protein expression of Keap1(all P＜0.01).Conclusion Rehabilitation training and citicoline can reduce the symptoms of neurological deficits in mice with cerebral hemorrhage.The mechanism way be that they can activate the Keap1/Nrf2/ARE signaling pathway to exert anti-oxidative stress,and the combined effect is the best.

Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Objective To study the mechanism of Sanhuang Decotion in the treatment of ulcerative colitis(UC)under Candida albicans colonization in mice based on Dectin-1-Syk-CARD9 signaling pathway.Methods Mice model of UC with fungal colonization were established with dextran sodium sulfate free drinking and C.albicans intragastric administration.Mice were divided into normal control group,model group,sulfasalazine group,fluconazole group,and Sanhuang Decotion low-and high-dosage groups,and receive corresponding drug interventions.General state of mice were observed,and the disease activity index(DAI)score of mice were calculated.The load of C.albicans in intestine was detected,the length of the colon was measured,and pathological scoring of the colon tissue was performed.The ultrastructural changes of colon epithelium were observed under transmission electron microscopy.The contents of TNF-α,IL-6 and IL-12 in serum and colon tissues were detected by ELISA.The mRNA and protein expression of Dectin-1,Syk,CARD9,NF-κBp65 and inflammation factors in intestinal epithelial cells and colon tissues were detected by qPCR,Western blot and immunohistochemistry.Results Compared with the normal control group,the model group mice showed reduced activity,decreased food intake,accompanied by loose stools,significantly increased DAI score,increased load of C.albicans in the intestine,shortened colon length,and increased histopathological score,with widening of gap between colon epithelial cells,cytoplasmic dissolution,mitochondrial swelling;TNF-α,IL-6 and IL-12 in serum and colon tissue increased,the expressions of Dectin-1 and CARD9 mRNA and protein in colon epithelial cells increased,p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein expression in colon tissue increased(P<0.01,P<0.05).Compared with the model group,the Sanhuang Decotion high-dosage group mice showed a significant decrease in DAI score,decreased intestinal C.albicans load,increased colon length,decreased histopathological score,more complete and orderly arrangement of microvilli in colon epithelial cells,mild mitochondrial swelling,TNF-α,IL-6 and IL-12 in serum and colon tissue decreased,and the mRNA and protein expression of Dectin-1 and CARD9 in colon tissue increased,the expression of p-Syk,p-NF-κBp65,CARD9,TNF-α,IL-1β,IL-6 protein in colon tissue decreased(P<0.01,P<0.05).Conclusion Sanhuang Decotion may exert an anti C.albicans colonization UC effect by inhibiting the Dectin-1-Syk-CARD9 signaling pathway and reducing the release of inflammatory factors.

Objective To investigate the antioxidant activity of bamboo stem extracts and the therapeutic effect of bamboo stem water extract on oxidative inflammation induced by tert butyl hydroperoxide (t-BHP) in human colon adenocarcinoma cells (Caco-2). Methods In this study, ABTS, DPPH, and FRAP assays were used to determine the extracellular antioxidant activity of petroleum ether extract, ethyl acetate extract, n-butanol extract, 95% ethanol extract, and distilled water extract from bamboo stems. The human intestinal Caco-2 cell line was used as the model cell, and t-BHP was selected as the oxidative stress modeling agent. The CCK-8 assay was used to detect cell viability and the optimal oxidative damage concentration of t-BHP. The content of MDA, 8-OHdG, TNF-α and IL-1β were detected to assess antioxidant stress effect. Results The five extracts of bamboo all had certain antioxidant activity, among which the water extract of bamboo stem had the best comprehensive antioxidant activity with high cell viability in Caco-2 cells. The optimal modeling concentration of t-BHP was 200 μMol/L. The water extract of bamboo stem significantly reduced the content of oxidative stress related biomarkers and inflammatory factors in Caco-2 cells induced by t-BHP. Conclusion The stem extracts of bamboo in Xianning City have strong in vitro antioxidant activity. Among them, the water extract of bamboo stem has a protective effect on t-BHP induced oxidative damage in Caco-2 cells, suggesting that the water extract possesses a potential to be developed as new antioxidant products for clinical prevention and treatment of oxidative damage related diseases.