1.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
2.Anti-inflammatory and Antioxidant Effects and Mechanisms of Baicalin in Rat Model of COPD via NF-κB/Nrf2 Signaling Pathway
Feixue HU ; Genfa WANG ; Guoliang DONG ; Jun XIONG ; Xinzhong KANG ; Zhongjuan PENG ; Caiqiu SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):117-126
ObjectiveTo investigate the anti-inflammatory and antioxidant effects of baicalin for treating chronic obstructive pulmonary disease (COPD) in rats and decipher the molecular mechanisms via the nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MethodsSixty SPF-grade male Sprague-Dawley rats were randomly assigned into six groups: normal control, COPD model, low-dose baicalin, medium-dose baicalin, high-dose baicalin, and budesonide. The normal control group received no treatment, whereas COPD was modeled in other groups with a combined modeling approach involving intratracheal lipopolysaccharide instillation and passive cigarette smoke exposure. The model establishment was evaluated through behavioral observation combined with pathological examination. Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in the lung. Serum levels of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-17, IL-22, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β)], reactive oxygen species (ROS), and vascular endothelial growth factor (VEGF) were quantified by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the levels of IL-6, IL-17, and IL-22 in the bronchoalveolar lavage fluid (BALF) and IL-10, IL-22, and TNF-α in the lung tissue were measured via ELISA. Immunohistochemistry (IHC) was employed to detect the expression of histone deacetylase 2 (HDAC2) and Nrf2. Western blot was performed to evaluate the expression of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glucocorticoid receptor (GR), NF-κB, HDAC2, and Nrf2 in the lung tissue. Additionally, real-time PCR was conducted to assess the mRNA levels of PI3K, Akt, HDAC2, Nrf2, GR, and NF-κB in the lung tissue. ResultsHE staining revealed that the airway mucosal epithelium in the COPD model group appeared extensive shedding, structural disorganization, and diffuse infiltration of inflammatory cells within the lumen. And goblet cells showed compensatory proliferation with pathological hypertrophy of mucus glands. In contrast, inflammatory infiltration and alveolar overdistension were significantly alleviated in the medium- and high-dose baicalin groups. The COPD model group exhibited mucus plug formation within the terminal bronchioles, along with fibrotic narrowing of the bronchial wall. Moreover, the smooth muscle bundles of the bronchial wall were hypertrophic, with concomitant collagen deposition. Progressive dissolution and rupture of alveolar septa were observed, leading to the formation of abnormally enlarged air-filled cavities. However, the bronchial wall structure was largely restored with only mild thickening of the smooth muscle layer in the baicalin groups. Compared with the COPD model group, the medium- and high-dose baicalin groups showed declined ROS and VEGF levels (P<0.05), and all the baicalin groups presented lowered levels of IL-6, IL-8, IL-17, IL-22, TGF-β, and TNF-α and elevated level of IL-10 (P<0.05). Baicalin upregulated the protein levels of HDAC2, Nrf2, GR, PI3K, and Akt, while suppressing the protein level of NF-κB (P<0.05). Furthermore, baicalin increased the mRNA levels of Nrf2 and GR while down-regulating the mRNA level of NF-κB (P<0.05). ConclusionBaicalin exerts anti-inflammatory and antioxidant effects by inhibiting the pro-inflammatory factor NF-κB while enhancing the expression of the anti-inflammatory factor HDAC2 and activating the antioxidant factor Nrf2, thereby alleviating the lung tissue damage in COPD rats. The therapeutic effects of baicalin may be closely associated with its regulatory role in the NF-κB/Nrf2 signaling pathway.
3.Application of TEG-PM and drug-related gene detection in guiding the selection of antiplatelet regimens in patients with intracranial aneurysms after receiving stenting
Xuerou MENG ; Wenqiu PAN ; Cheng WAN ; Genfa YI ; Junchao WANG ; Jihong HU ; Wei ZHAO
Journal of Interventional Radiology 2025;34(5):461-467
Objective To discuss the application of partial antiplatelet drug genotype detection and thromboelastography-platelet mapping(TEG-PM)in guiding the selection of antiplatelet regimens in patients with intracranial aneurysms(IAs)after receiving stenting.Methods A total of 106 patients with IAs in the First Affiliated Hospital of Kunming Medical University,who underwent implantation of stent and received the testings of platelet-endothelial aggregation receptor 1(PEAR 1)and clopidogrel-related gene-cytochrome P450 enzyme 2C19(CYP2C19),and some of whom received TEG-PM testing from January 2019 to August 2022,were collected for this study.The patients were divided into group A(gene detection group,according to the drug-related gene detection results to adjust the medication)and group B(combination group,according to the two testing results to guide the medication).The patient's gender,age,testing data were collected,and the occlusion of IAs,stent intimal hyperplasia,drug-related hemorrhagic and ischemic complications during follow-up period were recorded.Results A total of 123 IAs lesions in 106 patients were treated.The patient's mean age was(53.67±6.66)years,67 patients were female.Group A had 41 patients and group B had 65 patients.No statistically significant differences in the baseline data,IAs features,stent types used,and medication regimen existed between the two groups(all P>0.05).In Group A,the ischemic complications and hemorrhagic complications occurred in two patients each.In Group B,no ischemic complications occurred and 4 patients developed hemorrhagic complications.The difference in the incidence of related complications between the two groups was not statistically significant(P=0.287 and P=0.782 respectively).There were no statistically significant differences in the postoperative one-month and 3-month intimal hyperplasia grade and the aneurysm occlusion rate between the two groups(all P>0.05).The postoperative 6-month overall intimal hyperplasia grade in Group A was slightly higher than that in Group B,and the difference was statistically significant(P=0.034).Conclusion In order to improve the precision and individualized treatment of antiplatelet therapy,it is suggested that clinicians should adopt TEG-PM-guided conventional double-antibody therapy first when making selection of testing items.For patients with insufficient inhibition rate indicated by TEG-PM,testing of the genes associated with antiplatelet drugs should be used.Based on the genetic test results it is necessary to determine the reasons for the insufficient inhibition rate as well as to adjust the medication promptly according to the specific situation of the patient,so as to ensure the effectiveness of antiplatelet therapy and achieve the purpose of individualized precision therapy.
4.Comparative study of triple therapy and double therapy in intermediate or advanced stage hepatocellular carcinoma
Gang LI ; Genfa YI ; Wei ZHAO ; Xiaodong ZHANG ; Xuerou MENG ; Junchao WANG
Journal of Practical Radiology 2024;40(9):1503-1507
Objective To compare the differences in efficacy and safety between transarterial chemoembolization(TACE)com-bined with lenvatinib and camrelizumab(triple therapy)and TACE combined with lenvatinib(double therapy)in intermediate or advanced stage hepatocellular carcinoma(HCC).Methods The clinical data of 145 patients who were diagnosed with HCC and received triple therapy or double therapy were retrospectively collected.The differences of objective response rate(ORR),disease control rate(DCR),median progression-free survival(mPFS),median overall survival(mOS),and adverse events were compared between the two groups.Results The ORR and DCR in 1,3 and 6 months of the triple therapy group were higher than those of the double therapy group,and the differences were statistically significant in 3 and 6 months.The mPFS and mOS of the triple therapy group were higher than those of the double therapy group,and the differences were statistically significant.The Cox proportional hazards model results showed that the therapy methods,maximum tumor diameter and alpha-fetoprotein(AFP)were independent risk factors of progres-sion-free survival(PFS)and overall survival(OS).Besides,Barcelona Clinic Liver Cancer(BCLC)staging was independent risk fac-tor of OS.In terms of adverse events,the incidence of reactive cutaneous capillary endothelial proliferation(RCCEP)and hypothy-roidism in the triple therapy group were higher than those in the double therapy group,and the differences were statistically signifi-cant.Conclusion Compared with double therapy,triple therapy can significantly improve the efficacy of intermediate or advanced stage HCC,prolong patients'PFS and OS,and its safety can be well controlled.
5.The influence of uterus position on HIFU ablation effect of uterine fibroids
Genfa YI ; Wei ZHAO ; Hongjie FAN ; Xuancheng XIE ; Jiangping CUN ; Tao WANG
Journal of Interventional Radiology 2019;28(3):280-283
Objective To compare high-intensity focused ultrasound (HIFU) ablation effect on uterine fibroids between patients with different uterus positions. Methods The clinical data of 372 patients with symptomatic uterine fibroids, who were treated with HIFU at authors' hospital, were retrospectively analyzed. According to the position of the uterus, the patients were divided into anteverted group, mid-position group and retroverted group. Single factor analysis of variance was used to compare the baseline data of fibroids and HIFU ablation results between each other among the three groups. Results Successful HIFU treatment was accomplished in all patients. The average age of the patients was (39±6) years. Single factor analysis of variance indicated that no statistically significant difference in baseline data of fibroids existed between each other among the three groups (P>0.05) . The one cm3 sonication time and energy efficiency factor (EEF) in the anteverted group were significantly smaller than those in the retroverted group, the differences were statistically significant (P =0.007 and P =0.017 respectively) . Conclusion Uterine fibroids within an anteverted uterus are more likely to be ablated by HIFU.
6.EffectofhighGintensityfocusedultrasoundablationonuterinefibroidswithdifferentsignalintensityonT2WI
Genfa YI ; Wei ZHAO ; Hongjie FAN ; Xuancheng XIE ; Jiangping CUN ; Tao WANG
Journal of Practical Radiology 2019;35(3):437-440
Objective ToinvestigatetheeffectofhighGintensityfocusedultrasound (HIFU)ablationonuterinefibroidswithdifferent withdifferentT2Gweightedimage(T2WI)signalintensity.Methods 357patientswithsymptomaticuterinefibroidstreatedwith HIFU wereretrospectivelyanalyzed.AccordingtoT2WIsignalcharacteristics,fibroidsweredividedinto4groups:hypointensity,isointensity, hyperintensityand mixedintensity.The HIFUtreatmentparametersandablationeffectsofeachgroup werecomparedby O n eG W a y analysisofvariance.Results Theaverageageofthepatientswas(38.5±6.2)y,andtherewerenosignificantdifferencesinbaseline data(P>0.05).AllpatientssuccessfullycompletedHIFUtreatment,withtheaveragetreatmenttimeof(128.3±60.9)min,theaverage nonGperfusionvolumerate(NPVR)of(74.4±14.7)%,andtheaverageenergyefficiencyfactor(EEF)of(7.1±4.8)j/mm3.Theresults of O n eG W a y analysisofvarianceshowedthattheT2WIhypointensitygrouphadshortersonicationtime,treatmenttimeand1cm3 sonicationtime,smallertreatmentpowerandEEF,largerNPVR,comparingwiththehyperintensitygroup withstatisticallysignificant differences(P<0.05).Conclusion UterinefibroidswithT2WIhypointensityhavelowwatercontentandhighenergydepositionefficiency, whicharemoresuitableforHIFUablation.
7.Effects of pubertal timing on eating disorders among adolescents in Bengbu
HAN Hui,TANG Jianjun,HUA Haichen,HUANG Qing,WANG Chao,LIU Genfa
Chinese Journal of School Health 2019;40(8):1166-1168
Objective:
To explore the effects of pubertal timing on eating disorders among adolescents in Bengbu.
Methods:
Totally 831 students from grade five to eight in two nine-year schools were selected and surveyed with Pubertal Development Scale (PDS) and Eating Disorder Inventory(EDI).
Results:
The score of female on drive for thinness and body dissatisfaction was higher than male’s. The score of different grade on drive for thinness, bulimia, perfectionism,maturity fears and ineffectiveness was significant difference between them(P<0.05 ).The score of interpersonal distrust was highest in delay pubertal timing in schoolboys, and the score of drive for thinness,body dissatisfaction and diet of schoolgirl in early pubertal timing was highest,there was significant difference between them(F=2.68,4.87,6.46,3.07,5.49,P<0.05 ).
Conclusion
There are close relationship between the pubertal timing and eating disorders.The eating disorders will be offected in early and delay pubertal timing of adolescents.
8.Embolization of unruptured intracranial aneurysms combined with brain arteriovenous malformations
Kun WANG ; Wei ZHAO ; Jihong HU ; Genfa YI ; Ying SHI
Chinese Journal of Interventional Imaging and Therapy 2017;14(6):355-359
Objective To explore the value of interventional therapy in unruptured intracranial aneurysms combined with brain arteriovenous malformations (BAVM).Methods Data of 23 patients with unruptured aneurysms combined with BAVM were retrospectively analyzed.All patients were treated with interventional embolization,and the embolization methods were choosen according to the Redekop classification.The proximal or distal hemodynamic aneurysms were embolized with coils,and the intranidal aneurysms were embolized with Onyx.The outcome was assessed by the Glasgow outcome score (GOS) one week after treatment.DSA scan was used to observe whether there was recurrence during 3-6 months after embolization.Results Totally there were 36 aneurysms in 23 patients,including 8 intranidal aneurysms,16 proximal flow-related aneurysms,11 distal flow-related aneurysms and 1 unrelated aneurysm.Embolizations of 16 proximal hemodynamic aneurysms and l0 distal hemodynamic aneurysms were done with coils.And embolization of 8 intranidal aneurysms were done with Onyx.One distal hemodynamic aneurysm was not embolized due to the difficulty of embolization and the regular shap of aneurysm;and the patient died of cerebral hernia caused by intracranial hemorrhage on the sixth day after embolization.Because it was more suitable for surgical clipping,1 unrelated hemodynamic aneurysm was not embolized.In 23 cases,BAVM were completely embolized in 7 cases and incompletely embolized in 16 cases.A week after operation,the GOS score were 5 in 19 cases and 4 in 3 cases.The GOS score was not evaluated in the dead case.Except for 1 cases of death,the other 22 cases were followed up after embolization.No recurrence and intracranial hemorrhage occurred.Conclusion Interventional treatment of unruptured intracranial aneurysms combined with BAVM is safe and effective.Making treatment plan according to the hemodynamic characteristics of lesions and completely embolizing all lesions to prevent postoperative bleeding is helpful to improve the prognosis of patients.
9.Effects of activating silent information regulator 1 on early myocardial damage in severely burned rats.
Lei FAN ; Xiaozhi BAI ; Longlong YANG ; Shuyue WANG ; Chen YANG ; Chao LI ; Linlin SU ; Genfa LYU ; Dahai HU
Chinese Journal of Burns 2014;30(3):194-198
OBJECTIVETo explore the effects of activating silent information regulator 1 (SIRT1) on early myocardial damage in severely burned rats.
METHODSTwenty-four healthy male SD rats were divided into sham injury group (SI), scald group (S), and resveratrol (RSV) treatment group (RT) according to the random number table, with 8 rats in each group. Rats in groups S and RT were inflicted with 30% TBSA full-thickness scald on the back by immersing in 95 °C water for 18 s. Immediately after injury, rats in group S were intraperitoneally injected with 10 mL normal saline (50 mL/kg) and those in group RT with 10 mL normal saline (50 mL/kg)+10 µL RSV in the concentration of 1 g/mL (50 mg/kg). Backs of rats in group SI were immersed in 20 °C room temperature water for 18 s to simulate the scald process. Heart tissues and aorta abdominalis blood samples were collected at post injury hour (PIH) 6. The histomorphology of heart tissues was observed with HE staining. The serum contents of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined with ELISA. The protein expressions of SIRT1 and caspase-3 and mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue specimens were determined with Western blotting and real-time fluorescent quantitative RT-PCR (with protein level denoted as gray value). Data were processed with one-way analysis of variance and LSD- t test.
RESULTS(1) In group SI, myocardial fibers were in irregularly cylindrical shape, neatly arranged, and the transverse striation were distinct. In group S, myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were observed. In group RT, the degrees of myocardial interstitial edema, disorder of myocardial fiber arrangement, and cytoplasm destruction were alleviated in comparison with those of group S. (2) The serum contents of CK and LDH of rats in group S were respectively (2 385 ± 712) and (2 551 ± 196) U/L, which were significantly higher than those in the group SI [(290 ± 59) and (759 ± 60) U/L, with t values respectively 9.466 and 25.452, P values below 0.01]. The serum contents of CK and LDH of rats in group RT were respectively (1 336 ± 149) and (2 209 ± 133) U/L, which were significantly lower than those of group S (with t values respectively -4.506 and -4.860, P values below 0.01). (3) The protein expressions of SIRT1 and caspase-3 in heart tissue of rats in group S were respectively 0.47 ± 0.11 and 0.48 ± 0.12, which were significantly higher than those in group SI [0.18 ± 0.06 and 0.09 ± 0.05, with t values respectively 4.813 and 9.014, P values below 0.01]. The protein expression of SIRT1 in heart tissue of rats in group RT was 0.74 ± 0.18, which was significantly higher than that of group S (t = 4.561, P < 0.01); the protein expression of caspase-3 in heart tissue of rats in group RT was 0.21 ± 0.08, which was significantly lower than that of group S (t = -6.239, P < 0.01). (4) The mRNA expressions of SIRT1, caspase-3, IL-1β, and TNF-α in heart tissue of rats in group S were respectively 2.33 ± 0.24, 1.96 ± 0.20, 2.46 ± 0.21, 1.89 ± 0.37, which were significantly higher than those in group SI (1.00 ± 0.07, 1.00 ± 0.06, 1.00 ± 0.08, 1.00 ± 0.09, with t values respectively 14.961, 12.823, 18.559, 6.679, P values below 0.01). The mRNA expression of SIRT1 in heart tissue of rats in group RT was 2.89 ± 0.31, which was significantly higher than that of group S (t = 3.997, P < 0.01). The mRNA expressions of caspase-3, IL-1β, and TNF-α in heart tissue of rats in group RT were respectively 1.31 ± 0.08, 1.64 ± 0.09, 1.25 ± 0.08, which were significantly lower than those of group S (with t values respectively -8.264, -10.245, -4.818, P values below 0.01).
CONCLUSIONSThe expression of SIRT1 in heart tissue is upregulated in the early stage of severely burned rats. Activation of SIRT1 by RSV can alleviate myocardial tissue injury and reduce apoptosis of cardiac myocytes and secretion of IL-1β and TNF-α.
Animals ; Antioxidants ; Apoptosis ; Burns ; Caspase 3 ; genetics ; metabolism ; Edema ; metabolism ; Interleukin-1beta ; Male ; Myocardium ; metabolism ; pathology ; Myocytes, Cardiac ; RNA, Messenger ; genetics ; Rats ; Serum ; Sirtuin 1 ; genetics ; metabolism ; Stilbenes ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Up-Regulation ; physiology
10.The establishment of animal models with secondary hypersplenism by using percutaneous embolism of splenic vein technique and the study on radiofrequency ablation
Su WANG ; Wei ZHAO ; Jihong HU ; Genfa YI ; Tao WANG
Journal of Interventional Radiology 2014;(9):792-796
Objective To introduce a method for fast establishment of pig models with secondary hypersplenism, and using this model to study the effect of radiofrequency ablation (RFA). Methods Congestive splenomegaly was created by CT- guided percutaneous embolization of splenic vein and its collateral branches in pigs. Then radiofrequency ablation was employed in the models to observe the changes of peripheral blood as well as the spleen changes in its morphology and histopathology. The blood cell count for peripheral venous blood was determined once a week, and the spleen size was measured by CT scanning. Results One week after splenic vein embolization, the counts of peripheral erythrocytes and platelets showed a reduction, which became more obvious in three weeks (P < 0.05). Erythropenia, thrombocytopenia and splenomegaly could last for over six weeks. At the second week after the procedure , pathologically the spleen assumed passive congestion appearance. The thermal energy produced by radiofrequency ablation could cause local splenic coagulation necrosis, splenic vessels occlusion and splenic thrombotic infarction due to diffuse micro-vascular thrombosis. Conclusion To establish an animal model with secondary hypersplenism, the method of CT-guided percutaneous embolism of splenic vein is simple and reliable. The animal models can be used for surgical or interventional researches. Radiofrequency ablation is an effective intervention means.


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