One-day-old AA broilers were divided into five groups(15 chickens each,5 replicates per group):control(basic diet),three groups with low,medium,and high doses of crude extract of Flos sophorae and Fructus sophorae(100,150,200 mg/kg),and one group with Macleaya cordata extract(300 mg/kg).The 42-day trial measured intestinal enzyme activity,morphology,antioxidant and immune capacity,barrier function,and microbiota structure and diversity.Compared to the control and Macleaya cordata groups,the high-dose crude extract of Flos sophorae and Fructus sophorae group significantly increased trypsin activity in the duodenum,jejunum,and ileum(P＜0.05).It also reduced reactive oxygen species and malondialdehyde levels,increased glu-tathione peroxidase activity,reduced tumor necrosis factor-α,increased interleukin-10,and elevated mRNA expression of tight junction protein-1 and mucin-2 in the jejunum(P＜0.05).Microbial di-versity analysis showed higher Shannon index,increased Firmicutes and Bacteroidetes,decreased Proteobacteria,and more beneficial bacteria in the high-dose group(P＜0.05).Supplementing 200 mg/kg of crude extract of Flos sophorae and Fructus sophorae enhances intestinal morpholo-gy and function,and promotes intestinal health,thereby increasing farming efficiency.

Objectives:This study aimed to observe the disintegration of clopidogrel and ticagrelor in vitro solution with different pH levels and in human digestive tract.Methods:(1)In vitro study:0.9% normal saline was mixed with hydrochloric acid and sodium bicarbonate respectively to mimic fasting gastric fluid,postprandial gastric fluid,gastric fluid after taking acid-inhibiting agent,acid-free gastric fluid and small intestine fluid.The disintegration of clopidogrel and ticagrelor in different pH solutions was observed.(2)In vivo study:12 patients who were admitted to the Department of Geriatric,Peking University First Hospital from 2022.11 to 2023.6 were included and underwent magnetic controlled capsule endoscopy.We observed the disintegration of clopidogrel(n=6)and ticagrelor(n=6)in the digestive tract.Results:(1)In vitro study:clopidogrel began to disintegrate earlier than ticagrelor([21.67±7.53]s vs.[40.00±6.33]s,P=0.001),but clopidogrel disintegrated more slowly than ticagrelor([23.00±9.38]min vs.[8.33±1.97]min,P=0.011).Clopidogrel disintegrated faster in alkaline solution than in acidic and neutral solution([11.50±4.95]min vs.[28.75±2.50]min,P=0.004),and the disintegration rate of ticagrelor in alkaline solutions is comparable to that in acidic and neutral solutions([7.00±1.41]min vs.[9.00±2.00]min,P=0.285).(2)In vivo study:In the study population,the morphology of clopidogrel and ticagrelor began to change after passing through the esophagus,of which 3 cases(clopidogrel 1 case,ticagrelor 2 cases)were in powder state when passing through the cardia,and the remaining 9 cases were basically intact when entering the stomach and completely disintegrated in the stomach.The complete disintegration time of Clopidogrel varied significantly among individuals,ranging from 8 to 33 min,with an average of(18.80±10.38)min,while the complete disintegration time of ticagrelor ranged from 3 to 6 min,with an average of(4.25±1.26)min.Clopidogrel disintegrated slower than ticagrelor(P=0.034).Conclusions:In vitro study,clopidogrel disintegrated more slowly than ticagrelor in solutions at different pH levels.Compared with clopidogrel,the disintegration rate of ticagrelor was less affected by pH.After oral administration of clopidogrel and ticagrelor,clopidogrel disintegrated more slowly than ticagrelor.The difference of complete disintegration time between individuals of ticagrelor was smaller and the disintegration rate was faster.

Atherosclerosis is a severe disease threatening human health,leading to tremendous consequences such as acute coronary syndrome,myocardial infarction,and stroke.The onset and progression of atherosclerosis are attributed to a chronic inflammatory process,closely associated with the biological activities of various cells.Calpain,a Ca2+-dependent cysteine protease within cells,plays a pivotal role in this context by regulating a plethora of substrates through restricted catalysis of protein hydrolysis,thereby participating in pathological and physiological processes including endothelial damage,inflammatory response,and lipid metabolism.This review summarizes the role of calpain in the development of atherosclerosis and the latest research progress in the application of calpain inhibitors for treatment of atherosclerosis,offering new insights for the clinical realization of personalized and precise treatment of atherosclerosis.

Objective To explore the effect of tumor necrosis faction-α(TNF-α)gene rs1799964 and C-reactive protein(CRP)gene rs2794521 polymorphism and their interaction on the therapeutic effect of dagliaglozin in patients with heart failure.Meth-ods 98 patients with HF who received treatment in Chengdu Wenjiang District People's Hospital from January 2021 to October 2023 were retrospectively selected for the study.According to the different therapeutic effects,the patients were divided into effective group(n=61)and ineffective group(n=37).The laboratory indexes of the effective group and the ineffective group were compared.The polymorphism,genotype and allele distribution of TNF-α gene(rs1799964)and CRP gene(rs2794521)were analyzed.Multiple regression model was used to analyze the risk factors affecting the efficacy of dagaglizin in the treatment of HF.The association between TNF-α gene(rs1799964)and CRP gene(rs2794521)and cardiac function index was analyzed.To analyze the interaction between TNF-α polymorphism(rs1799964)and CRP polymorphism(rs2794521)on the efficacy of daglipzin in the treatment of HF.Results The frequencies of CC genotype,CT genotype and C allele of TNF-α gene(rs1799964)in ineffective group were 24.32%(9/37),54.05%(20/37)and 51.35%(38/74),respectively,which were higher than those in effective group 11.48%(7/61),40.98%(25/61)and 31.97%(39/122),the differences were statistically significant(χ2=7.284,7.256,7213,all P<0.05).The frequencies of CC genotype and C allele of CRP gene(rs2794521)in ineffective group were 24.32%(9/37)and 47.30%(35/74),respectively,which were higher than those in effective group 6.56%(4/61)and 28.69%(35/122),and the differences were statistically significant(χ2=7.578,6.947,all P<0.05).In the dominant mode and in the cumula-tive mode in the association between TNF-α gene(rs1799964)and CRP gene(rs2794521)was statistically significant(all P<0.05).TNF-α gene(rs1799964)CC genotype(β=1.134,95%CI:1.028～1.964),CRP gene(rs2794521)CT genotype(β=1.357,95%CI:1.239～2.154),CC genotype(β=2.017,95%CI:1.674～4.231)were independent risk factors for the efficacy of daglipzin in treating HF(all P<0.05).The association differences between TNF-α gene(rs1799964)and CRP gene(rs2794521)polymorphism and left ventricular end-systolic dimension(LVESd),left ventricular end diastolic dimension(LVEDd),left ventric-ular ejection fractions(LVEF)and stroke volume(SV)in additive and dominant models were statistically significant(all P<0.05).There were multiplicative and additive interactions between TNF-α gene(rs1799964)genotype CC and CRP gene(rs2794521)genotype CC(all P<0.05).Conclusion The TNF-α gene(rs1799964)genotype CC and CRP gene(rs2794521)genotype CC have a multiplicity and additional interaction,and the risk of daglaglizin in treating heart failure is higher when these two factors coexist.

Cardiovascular disease represent a significant global health threat,featured with continuously increased morbidity and mortality rates worldwide in recent years.Consequently,there is an urgent need for the development of safe and effective novel approaches for the prevention and treatment of cardiovascular disease.The advancements in nanotechnology within the medical field,including drug delivery and molecular imaging,have opened innovative avenues for the diagnosis and treatment of diseases.Due to their unique physicochemical and biological properties,metal-based nanoparticles have demonstrated remarkable potential and broad prospects in the diagnosis and treatment of cardiovascular disease.This review summarizes the latest research developments in the application of metal-based nanoparticles in cardiovascular disease and discusses the challenges associated with their clinical application,and presents new insights for the individualized and precise diagnosis and treatment of cardiovascular disease.

Objective To explore the effect of tumor necrosis faction-α(TNF-α)gene rs1799964 and C-reactive protein(CRP)gene rs2794521 polymorphism and their interaction on the therapeutic effect of dagliaglozin in patients with heart failure.Meth-ods 98 patients with HF who received treatment in Chengdu Wenjiang District People's Hospital from January 2021 to October 2023 were retrospectively selected for the study.According to the different therapeutic effects,the patients were divided into effective group(n=61)and ineffective group(n=37).The laboratory indexes of the effective group and the ineffective group were compared.The polymorphism,genotype and allele distribution of TNF-α gene(rs1799964)and CRP gene(rs2794521)were analyzed.Multiple regression model was used to analyze the risk factors affecting the efficacy of dagaglizin in the treatment of HF.The association between TNF-α gene(rs1799964)and CRP gene(rs2794521)and cardiac function index was analyzed.To analyze the interaction between TNF-α polymorphism(rs1799964)and CRP polymorphism(rs2794521)on the efficacy of daglipzin in the treatment of HF.Results The frequencies of CC genotype,CT genotype and C allele of TNF-α gene(rs1799964)in ineffective group were 24.32%(9/37),54.05%(20/37)and 51.35%(38/74),respectively,which were higher than those in effective group 11.48%(7/61),40.98%(25/61)and 31.97%(39/122),the differences were statistically significant(χ2=7.284,7.256,7213,all P<0.05).The frequencies of CC genotype and C allele of CRP gene(rs2794521)in ineffective group were 24.32%(9/37)and 47.30%(35/74),respectively,which were higher than those in effective group 6.56%(4/61)and 28.69%(35/122),and the differences were statistically significant(χ2=7.578,6.947,all P<0.05).In the dominant mode and in the cumula-tive mode in the association between TNF-α gene(rs1799964)and CRP gene(rs2794521)was statistically significant(all P<0.05).TNF-α gene(rs1799964)CC genotype(β=1.134,95%CI:1.028～1.964),CRP gene(rs2794521)CT genotype(β=1.357,95%CI:1.239～2.154),CC genotype(β=2.017,95%CI:1.674～4.231)were independent risk factors for the efficacy of daglipzin in treating HF(all P<0.05).The association differences between TNF-α gene(rs1799964)and CRP gene(rs2794521)polymorphism and left ventricular end-systolic dimension(LVESd),left ventricular end diastolic dimension(LVEDd),left ventric-ular ejection fractions(LVEF)and stroke volume(SV)in additive and dominant models were statistically significant(all P<0.05).There were multiplicative and additive interactions between TNF-α gene(rs1799964)genotype CC and CRP gene(rs2794521)genotype CC(all P<0.05).Conclusion The TNF-α gene(rs1799964)genotype CC and CRP gene(rs2794521)genotype CC have a multiplicity and additional interaction,and the risk of daglaglizin in treating heart failure is higher when these two factors coexist.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

BACKGROUND:Quercetin has anti-inflammatory,anti-cancer,anti-oxidation,anti-aging,anti-depression and other pharmacological effects,and has high medicinal value.Quercetin can promote wound healing in normal rats,but few drugs with quercetin as the main component have been developed,which limits its wide application in clinical practice. OBJECTIVE:To investigate the application effect of quercetin-carboxymethyl chitosan hydrogel on diabetic wound in rats by loading quercetin with hydrogel material. METHODS:(1)Carboxymethyl chitosan hydrogels and quercetin-carboxymethyl chitosan hydrogels were prepared respectively,and the micromorphology and in vitro drug release properties of the hydrogels were characterized.(2)Cell experiment:Mouse L929 fibroblasts were cultured in four groups.The blank control group was cultured conventionally.Carboxymethyl chitosan hydrogel,quercetin solution and quercetin-carboxymethyl chitosan hydrogel were added to pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively,to detect cell proliferation and migration ability.(3)Animal experiments:Diabetic models were established in 80 SD rats.After successful modeling,full-layer skin defect wounds with a diameter of 2 cm were made on the back of rats,and these models were randomly divided into four groups.Normal saline,carboxymethyl chitosan hydrogel,quercetin solution,and quercetin-carboxymethyl chitosan hydrogel were injected into the wounds of blank control group,pure hydrogel group,drug group,and drug-loaded hydrogel group,respectively.Each group contained 20 animals,which were bound with sterile gauze.Wound healing,pathological morphology,expression of inflammatory factors,and angiogenesis were observed after operation. RESULTS AND CONCLUSION:(1)Under scanning electron microscope,the microstructures of the two hydrogels were similar,both showed loose porous network structure,and quercetin-carboxymethyl chitosan hydrogels had good drug release performance in vitro.(2)Compared with blank control group,the cell proliferation and mobility of the other three groups were increased(P<0.05).The cell proliferation and mobility of drug-loaded hydrogel group were higher than those of pure hydrogel group and drug group(P<0.05).(3)The wound healing rate of the drug-loaded hydrogel group was higher than that of the other three groups at 5 and 11 days after operation.The wound healing rate of rats in the hydrogel group,pure hydrogel group,and drug group reached 100%18 days after operation,which was higher than that in the blank control group(P<0.05).Hematoxylin-eosin staining showed that intact skin and skin appendages were visible on the wounds of rats in the drug-loaded hydrogel group 18 days after surgery,while intact skin and skin appendages were visible on the wounds of rats in the blank control group,pure hydrogel group,and drug group 25 days after surgery.The levels of tumor necrosis factor α and interleukin-6 in the drug-loaded hydrogel group were lower than those in the blank control group at 5,11,and 18 days after surgery(P<0.05),and the levels of transforming growth factor β1 at 11 and 18 days after surgery were lower than those in the blank control group(P<0.05).The mRNA expressions of CD31 and vascular endothelial growth factor α in the drug-loaded hydrogel group were higher than those in the other three groups at 11 and 18 days after operation(P<0.05).(4)These findings indicate that quercetin in quercetin carboxymethyl chitosan hydrogel can regulate inflammatory response,accelerate angiogenesis,promote the proliferation and migration of fibroblasts,and enhance the healing of diabetic wounds in rats.