1.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
2.Study on the Correlation between Serum CXCL4,CXCR3 Levels and Postoperative Cerebral Vascular Spasm in Patients with Ruptured Intracranial Aneurysms
Kui WANG ; Ke PAN ; Gaofeng TAN
Journal of Modern Laboratory Medicine 2025;40(5):131-135
Objective To explore the predictive value of serum levels of CXC chemokine ligand 4(CXCL4),CXC receptor 3 chemokine(CXCR3)for postoperative cerebral vasospasm(CVS)in patients with ruptured intracranial aneurysms.Methods The clinical data of 106 patients with intracranial aneurysms rupture who under went craniotomy and clipping surgery at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2020 to December 2022 were collected.The incidence of CVS was observed.Serum CXCL4 and CXCR3 levels were compared at 1,3,7 days after surgery between patients without CVS and patients with CVS.Spearman correlation coefficient was used to analyze the relationship between serum CXCL4,CXCR3 levels and CVS degree.ROC curve was used to analyze the value of serum CXCL4 and CXCR3 levels in predicting postoperative CVS.Results Among 106 patients with ruptured intracranial aneurysms,a total of 38 cases(35.85%)developed CVS after surgery,and 68 cases(64.15%)did not develop CVS.There was no statistically obvious difference in preoperative serum levels of CXCL4 and CXCR3 between the CVS group and the non CVS group(t=0.104,0.141,all P>0.05).The serum levels of CXCL4 and CXCR3 in the non CVS group were lower than those before surgery 1,3,and 7 day after surgery,and the differences were statistically significant(q=14.867,17.525,24.384;16.274,20.251,34.237,all P<0.05).Compated with preoperative levels,the levels of serum CXCL4 and CXCR3 in the CVS group decreased on postoperative 1 and 7 days,and the differences were statistically significant(q=9.486,4.858;10.760,9.104,all P<0.05).Compared with the mild CVS group,the serum levels of CXCL4 and CXCR3 in the moderate and severe CVS groups were obviously increased(q=2.982,5.992;2.961,3.465),and the serum levels of CXCL4 and CXCR3 in the severe CVS group were higher than those in the moderate CVS group(q=3.564,4.036),and the differences were statistically significant(all P<0.05),respectively.Spearman results showed that serum levels of CXCL4 and CXCR3 were positively correlated with the severity of CVS(r=0.491,0.483,all P<0.05).The ROC curve results showed that the AUC of CXCL4 and CXCR3 combined in predicting postoperative CVS in patients with intracranial ruptured aneurysms was higher than that of CXCL4,CXCR3 alone,and the differences were statistically significant(Z=2.937,2.750,all P<0.05).Conclusion The serum levels of CXCL4 and CXCR3 in ruptured intracranial aneurysms patients with postoperative CVS are obviously elevated,and the combined detection of the two can effectively predict the occurrence of CVS.
3.Mechanism of total salvianolic acid improving myeloid macrophage infiltration in liver cancer bearing mice by regulating TLR4/MyD88/NF-κB pathway
Yunan DU ; Zhibo DANG ; Xiqian ZHANG ; Gaofeng TAN ; Honglin LI ; Yunfei JIA
Chinese Journal of Immunology 2025;41(11):2624-2630
Objective:To investigate the impacts of total salvianolic acid(TSA)on macrophage polarization and mesenchymal macrophage infiltration in liver cancer bearing mice by regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)pathway.Methods:Mice were randomly separated into liver cancer group,TSA low concentra-tion group,TSA medium concentration group,TSA high concentration group,TSA high concentration+TLR4 inhibitor(TAK242)group and control group,with 12 mice in each group.Except for control group,mice in all other groups were injected subcutaneously into the right axilla to construct liver cancer models by intraperitoneal transmission of third-generation H22 cell suspension.After suc-cessful modeling,administration was carried out once a day for 2 weeks.Changes in tumor weight,tumor volume,spleen index and thymus index were detected.Immunofluorescence was applied to detect proportions of CD86 and CD206 positive cells in tumor tissue.ELISA was applied to detect levels of inducible nitric oxide synthase(iNOS),IL-6 and IL-10 in tumor tissues.Flow cytometry was ap-plied to detect proportion of CD11b+F4/80+in tumor tissue.Western blot was applied to detect TLR4,p-NF-κB P65 and MyD88 pro-teins in tumor tissue.The life quality and survival rate of mice were observed.Results:Compared with control group,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were reduced in liver cancer group,while proportion of CD206 positive cells and level of IL-10 in tumor tissue were increased(P<0.05).Compared with liver cancer group,tumor weight and volume of mice in TSA low,medium,high concentration groups were decreased,while survival rate,spleen index,thymus index,proportion of CD86 positive cells in tumor tissue,levels of iNOS and IL-6,and expressions of TLR4,p-NF-κB P65 and MyD88 proteins were increased,proportion of CD206 positive cells,level of IL-10,and proportion of CD11b+F4/80+in tumor tissue decreased(P<0.05).TAK242 reversed the effects of high concentration TSA on macrophage polarization and myeloid macrophage infiltration in liver cancer bearing mice.Conclusion:TSA may promote M1 polari-zation of macrophages in liver cancer bearing mice and inhibit myeloid macrophage infiltration by activating the TLR4/MyD88/NF-κB pathway.
4.Study on the Correlation between Serum CXCL4,CXCR3 Levels and Postoperative Cerebral Vascular Spasm in Patients with Ruptured Intracranial Aneurysms
Kui WANG ; Ke PAN ; Gaofeng TAN
Journal of Modern Laboratory Medicine 2025;40(5):131-135
Objective To explore the predictive value of serum levels of CXC chemokine ligand 4(CXCL4),CXC receptor 3 chemokine(CXCR3)for postoperative cerebral vasospasm(CVS)in patients with ruptured intracranial aneurysms.Methods The clinical data of 106 patients with intracranial aneurysms rupture who under went craniotomy and clipping surgery at the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from October 2020 to December 2022 were collected.The incidence of CVS was observed.Serum CXCL4 and CXCR3 levels were compared at 1,3,7 days after surgery between patients without CVS and patients with CVS.Spearman correlation coefficient was used to analyze the relationship between serum CXCL4,CXCR3 levels and CVS degree.ROC curve was used to analyze the value of serum CXCL4 and CXCR3 levels in predicting postoperative CVS.Results Among 106 patients with ruptured intracranial aneurysms,a total of 38 cases(35.85%)developed CVS after surgery,and 68 cases(64.15%)did not develop CVS.There was no statistically obvious difference in preoperative serum levels of CXCL4 and CXCR3 between the CVS group and the non CVS group(t=0.104,0.141,all P>0.05).The serum levels of CXCL4 and CXCR3 in the non CVS group were lower than those before surgery 1,3,and 7 day after surgery,and the differences were statistically significant(q=14.867,17.525,24.384;16.274,20.251,34.237,all P<0.05).Compated with preoperative levels,the levels of serum CXCL4 and CXCR3 in the CVS group decreased on postoperative 1 and 7 days,and the differences were statistically significant(q=9.486,4.858;10.760,9.104,all P<0.05).Compared with the mild CVS group,the serum levels of CXCL4 and CXCR3 in the moderate and severe CVS groups were obviously increased(q=2.982,5.992;2.961,3.465),and the serum levels of CXCL4 and CXCR3 in the severe CVS group were higher than those in the moderate CVS group(q=3.564,4.036),and the differences were statistically significant(all P<0.05),respectively.Spearman results showed that serum levels of CXCL4 and CXCR3 were positively correlated with the severity of CVS(r=0.491,0.483,all P<0.05).The ROC curve results showed that the AUC of CXCL4 and CXCR3 combined in predicting postoperative CVS in patients with intracranial ruptured aneurysms was higher than that of CXCL4,CXCR3 alone,and the differences were statistically significant(Z=2.937,2.750,all P<0.05).Conclusion The serum levels of CXCL4 and CXCR3 in ruptured intracranial aneurysms patients with postoperative CVS are obviously elevated,and the combined detection of the two can effectively predict the occurrence of CVS.
5.Study on the Improvement Effect and Mechanism of Saikosaponin A on Insomnia Rats by Regulating cAMP/PKA/CREB Signaling Pathway
Mingliang QIAO ; Shuo LIANG ; Yi MENG ; Fengsen LI ; Gaofeng TAN ; Dandan QI ; Haopan CHEN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(5):633-638
Objective To explore the improving effect and mechanism of saikosaponin A on insomnia rats based on cAMP/PKA/CREB pathway.Methods Seventy-five SD rats were randomly divided into blank group,model group,low-dose saikosaponin A group(0.625 mg·kg-1),high-dose saikosaponin A group(2.500 mg·kg-1)and Estazolam group(0.1 mg·kg-1),with 15 rats in each group.Insomnia rat model was established by intraperitoneal injection of Phenylalanine(PCPA,0.1 mg·kg-1).The general condition and circadian rhythm of rats were observed;the sleep latency and sleep duration of rats were measured by pentobarbital sodium righting experiment.The sleep phase of rats was observed,and the duration of slow wave sleep phase 1(SWS1),slow wave sleep phase 2(SWS2),rapid eye movement sleep phase(REMS)and total sleep time(TST)were recorded.The mRNA expression levels of hypothalamic circadian genes Clock,Bmal1 and clock-controlled genes Rev-erbα and Rorα were determined by qRT-PCR.The expression level of NeuN in hippocampus was determined by immunofluorescence.The level of cAMP in brain tissue was determined by ELISA.The expression levels of Clock,Bmal1,Rev-erbα,Rorα and cAMP/PKA/CREB pathway-related proteins in brain tissue were determined by Western Blot.Results Compared with the blank group,the rats in the model group had disordered circadian rhythms,extreme excitement,irritability,and reduced sleep;the sleep latency was significantly prolonged(P<0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly shortened(P<0.05).The arrangement of neurons was disordered,and the IOD value of NeuN positive neurons was significantly decreased(P<0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly decreased(P<0.05).The expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly decreased(P<0.05).Compared with the model group,the aggressiveness of the rats in the administration group was significantly weakened,the circadian rhythm was rhythmic,the activity was reduced,and the sleep was increased.The sleep latency was significantly shortened(P<0.05),and the sleep duration and SWS1,SWS2,REMS and TST were significantly prolonged(P<0.05).The disorder of neuronal arrangement was restored,and the IOD value of NeuN positive neurons was significantly increased(P<0.05).The mRNA and protein expression levels of Clock,Bmal1,Rev-erbα and Rorα in brain tissue were significantly increased(P<0.05).The protein expression levels of cAMP,p-PKA/PKA and p-CREB/CREB in brain tissue were significantly increased(P<0.05).Conclusion Saikosaponin A may improve the circadian rhythm of insomnia rats by activating cAMP/PKA/CREB pathway.
6.Analysis of the Current Situation and Causes of Retention of Emergency Rescue Patients in the People's Hospital
Shuanglong CHEN ; Yao TAN ; Gaofeng ZHENG
Chinese Hospital Management 2024;44(7):50-54
Objective To investigate the current situation of emergency rescue patient retention in Jianyang People's Hospital and explore its causes.Methods A retrospective analysis was conducted on the data of 4 834 patients rescued in the emergency room of Jianyang People's Hospital in 2022.They were divided into retention group and non retention group based on whether the emergency detention time exceeded 6 hours.With detention as the dependent variable and factors that may lead to emergency detention as the independent variable,binary logistic regression method was applied to screen for factors related to emergency detention.Results The median retention time for emergency rescue patients was 4.84 hours,with 3 721 cases(76.98%)having a retention time≤6 hours and 1 113 cases(23.02%)having a retention time>6 hours;the main influencing factors for emergency detention included age,visit time,visit season,admission method,involving two or more departments,diversion direction,and treatment compliance(P<0.05).Conclusion Emergency patients aged≥41 years old,treated from 17:00 to<08:00 the next day,visited in winter,admitted on their own,involving two or more departments,diverted to hospitalization,and with average or poor treatment compliance are prone to emergency detention.Therefore,the emergency department of the hospital should develop appropriate management measures based on the above factors to reduce emergency detention time.
7.Analysis of the Current Situation and Causes of Retention of Emergency Rescue Patients in the People's Hospital
Shuanglong CHEN ; Yao TAN ; Gaofeng ZHENG
Chinese Hospital Management 2024;44(7):50-54
Objective To investigate the current situation of emergency rescue patient retention in Jianyang People's Hospital and explore its causes.Methods A retrospective analysis was conducted on the data of 4 834 patients rescued in the emergency room of Jianyang People's Hospital in 2022.They were divided into retention group and non retention group based on whether the emergency detention time exceeded 6 hours.With detention as the dependent variable and factors that may lead to emergency detention as the independent variable,binary logistic regression method was applied to screen for factors related to emergency detention.Results The median retention time for emergency rescue patients was 4.84 hours,with 3 721 cases(76.98%)having a retention time≤6 hours and 1 113 cases(23.02%)having a retention time>6 hours;the main influencing factors for emergency detention included age,visit time,visit season,admission method,involving two or more departments,diversion direction,and treatment compliance(P<0.05).Conclusion Emergency patients aged≥41 years old,treated from 17:00 to<08:00 the next day,visited in winter,admitted on their own,involving two or more departments,diverted to hospitalization,and with average or poor treatment compliance are prone to emergency detention.Therefore,the emergency department of the hospital should develop appropriate management measures based on the above factors to reduce emergency detention time.
8.Analysis of the Current Situation and Causes of Retention of Emergency Rescue Patients in the People's Hospital
Shuanglong CHEN ; Yao TAN ; Gaofeng ZHENG
Chinese Hospital Management 2024;44(7):50-54
Objective To investigate the current situation of emergency rescue patient retention in Jianyang People's Hospital and explore its causes.Methods A retrospective analysis was conducted on the data of 4 834 patients rescued in the emergency room of Jianyang People's Hospital in 2022.They were divided into retention group and non retention group based on whether the emergency detention time exceeded 6 hours.With detention as the dependent variable and factors that may lead to emergency detention as the independent variable,binary logistic regression method was applied to screen for factors related to emergency detention.Results The median retention time for emergency rescue patients was 4.84 hours,with 3 721 cases(76.98%)having a retention time≤6 hours and 1 113 cases(23.02%)having a retention time>6 hours;the main influencing factors for emergency detention included age,visit time,visit season,admission method,involving two or more departments,diversion direction,and treatment compliance(P<0.05).Conclusion Emergency patients aged≥41 years old,treated from 17:00 to<08:00 the next day,visited in winter,admitted on their own,involving two or more departments,diverted to hospitalization,and with average or poor treatment compliance are prone to emergency detention.Therefore,the emergency department of the hospital should develop appropriate management measures based on the above factors to reduce emergency detention time.
9.Analysis of the Current Situation and Causes of Retention of Emergency Rescue Patients in the People's Hospital
Shuanglong CHEN ; Yao TAN ; Gaofeng ZHENG
Chinese Hospital Management 2024;44(7):50-54
Objective To investigate the current situation of emergency rescue patient retention in Jianyang People's Hospital and explore its causes.Methods A retrospective analysis was conducted on the data of 4 834 patients rescued in the emergency room of Jianyang People's Hospital in 2022.They were divided into retention group and non retention group based on whether the emergency detention time exceeded 6 hours.With detention as the dependent variable and factors that may lead to emergency detention as the independent variable,binary logistic regression method was applied to screen for factors related to emergency detention.Results The median retention time for emergency rescue patients was 4.84 hours,with 3 721 cases(76.98%)having a retention time≤6 hours and 1 113 cases(23.02%)having a retention time>6 hours;the main influencing factors for emergency detention included age,visit time,visit season,admission method,involving two or more departments,diversion direction,and treatment compliance(P<0.05).Conclusion Emergency patients aged≥41 years old,treated from 17:00 to<08:00 the next day,visited in winter,admitted on their own,involving two or more departments,diverted to hospitalization,and with average or poor treatment compliance are prone to emergency detention.Therefore,the emergency department of the hospital should develop appropriate management measures based on the above factors to reduce emergency detention time.
10.Analysis of the Current Situation and Causes of Retention of Emergency Rescue Patients in the People's Hospital
Shuanglong CHEN ; Yao TAN ; Gaofeng ZHENG
Chinese Hospital Management 2024;44(7):50-54
Objective To investigate the current situation of emergency rescue patient retention in Jianyang People's Hospital and explore its causes.Methods A retrospective analysis was conducted on the data of 4 834 patients rescued in the emergency room of Jianyang People's Hospital in 2022.They were divided into retention group and non retention group based on whether the emergency detention time exceeded 6 hours.With detention as the dependent variable and factors that may lead to emergency detention as the independent variable,binary logistic regression method was applied to screen for factors related to emergency detention.Results The median retention time for emergency rescue patients was 4.84 hours,with 3 721 cases(76.98%)having a retention time≤6 hours and 1 113 cases(23.02%)having a retention time>6 hours;the main influencing factors for emergency detention included age,visit time,visit season,admission method,involving two or more departments,diversion direction,and treatment compliance(P<0.05).Conclusion Emergency patients aged≥41 years old,treated from 17:00 to<08:00 the next day,visited in winter,admitted on their own,involving two or more departments,diverted to hospitalization,and with average or poor treatment compliance are prone to emergency detention.Therefore,the emergency department of the hospital should develop appropriate management measures based on the above factors to reduce emergency detention time.

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