1.Efficacy evaluation of three objective refraction methods under cycloplegia in examination of refractive status among preschool children
SU Yu , XU Xiaohai, TANG Kaiyu, LI Zhongfu, FENG Mian, XU Shaojun
Chinese Journal of School Health 2026;47(7):1011-1014
Objective:
To explore the differences and consistency among three objective refraction methods, namely, retinoscopy after cycloplegia, the Spot binocular vision screener, and automated computer refractometry in preschool children, so as to provide evidence for optimizing refractive assessment strategies in this population.
Methods:
A total of 116 preschool children aged 2-6 years who were referred to the Ophthalmology Department of Anhui Women and Children s Medical Center because of abnormal vision screening results between August 2025 and March 2026 were enrolled by using purposive sampling. After adequate cycloplegia was achieved with 1% atropine ophthalmic gel, objective refraction was performed by using cycloplegic retinoscopy, the Spot Vision Screener, and an autorefractor. Differences in spherical equivalent (SE) among the three methods were compared using the Friedman test, while differences in myopia detection rates were assessed using Cochran s Q test. Cycloplegic retinoscopy was used as the reference standard to evaluate the diagnostic accuracy and reliability of the Spot Vision Screener and the autorefractor for myopia detection.
Results:
The median (interquartile range) spherical equivalent (SE) values for the right eye were identical across the three methods:1.50 (0.75, 2.50) D for cycloplegic retinoscopy, the Spot Vision Screener, and the autorefractor. For the left eye, the corresponding values were 1.50 (0.50, 2.50), 1.50 (0.50, 2.50), and 1.63 (0.75, 2.50) D, respectively. There were no significant differences in SE measurements among the three methods for either eye ( χ 2=3.77, 3.28, both P >0.05). The myopia detection rates of cycloplegic retinoscopy, the Spot Vision Screener, and the autorefractor were 13.79%, 12.07%, and 13.79%, respectively, for the right eye, and 13.79%, 14.66%, and 12.93%, respectively, for the left eye, with no significant differences among the three methods (Cochran s Q =1.60, 1.14, both P >0.05). Using cycloplegic retinoscopy as the reference standard, both the Spot Vision Screener and the autorefractor demonstrated high diagnostic accuracy and reliability for detecting myopia. Compared with the Spot Vision Screener, the autorefractor showed higher sensitivity (right eye:93.75%, 81.25%; left eye:88.24%, 76.47% ), Youden index (right eye:0.93, 0.80; left eye:0.86, 0.74), overall agreement (right eye:98.28%, 96.55%; left eye:96.55%, 94.83%), and Cohen s Kappa coefficient (right eye:0.93, 0.85; left eye:0.86, 0.78).
Conclusion
Under standardized cycloplegic conditions, the Spot Vision Screener and the autorefractor can serve as alternatives to retinoscopy for assessing refractive status, particularly in large scale screening and in children with poor cooperation.
2.Development and evaluation of a diagnostic model for autoimmune liver disease based on clinical indicators
Jia-Cheng JIN ; Jia-Chi YU ; Rui-Bing LI ; Mian-Yang LI
Medical Journal of Chinese People's Liberation Army 2025;50(8):976-983
Objective To develop and evaluate a diagnostic model for autoimmune liver disease(AILD)using clinical indicators.Methods A total of 181 AILD patients(AILD group)diagnosed in the Department of Gastroenterology or Rheumatology and Immunology,the First Medical Center of Chinese PLA General Hospital,from June 2019 to February 2024,133 patients with hepatitis B virus cirrhosis(HBVC)(HBVC group),and 100 healthy individuals(HC group)were included in the study cohort for retrospective analysis.Clinical data,blood routine tests,and biochemical indicators were compared among the groups.Propensity score matching was used to balance the effects of factors such as gender and age.Multivariate logistic regression analysis was applied to identify characteristic indicators for AILD.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic efficacy of single and combined indicators,and the optimal diagnostic model for AILD was constructed.The Hosmer-Lemeshow test was performed to assess the model's goodness-of-fit,while ROC analysis was employed to evaluate the predictive validity.Additionally,an independent validation cohort,including 91 AILD patients(AILD validation group),82 HBVC patients(HBVC validation group),and 40 healthy individuals(HC validation group)who visited during the same period,was used to validate the diagnostic model.False-positive and false-negative rates were calculated to assess the diagnostic efficacy and clinical utility of the model.Results The age and the proportion of male patients in AILD and HBVC groups were higher than those in HC group,and the proportion of male patients in AILD group was higher than in HBVC group,the differences were statistically significant(P<0.05).Prior to matching,compared with HC group,HBVC group and AILD group had significantly lower levels of hemoglobin(HB),red blood cell count(RBC),white blood cell count(WBC),platelet count(PLT),and albumin(ALB)(P<0.05),but significantly higher levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),gamma-glutamyl transferase(GGT),total bilirubin(TBIL),and direct bilirubin(DBIL)(P<0.05).Compared with HBVC group,AILD group had significantly higher levels of WBC,PLT,ALB,ALP,and GGT(P<0.05 or P<0.001)but significantly lower levels of TBIL and DBIL(P<0.001).After maching,compared with HC group,AILD group still had significantly lower levels of HB,RBC,WBC,PLT,and ALB,but significantly higher levels of ALT,AST,ALP,GGT,TBIL,and DBIL(P<0.05).Compared with HBVC group,AILD group had significantly higher levels of HB,RBC,WBC,PLT,ALB,ALT,ALP,and GGT,but significantly lower levels of DBIL(P<0.05).ROC analysis results showed that AST,GGT,ALP,and DBIL had high predictive values for differentiating AILD from HC(AUC=0.843,0.804,0.802,0.773),while PLT,WBC,GGT,and ALP had high predictive values for differentiating AILD from HBVC(AUC=0.780,0.739,0.729,0.702).For distinguishing AILD from HC,the combined model of AST,ALP,and DBIL(Model e)had an AUC of 0.887,with a sensitivity of 82.2%,and a specificity of 94.7%.For distinguishing AILD from HBVC,the combined model of ALP,GGT,and PLT(Model D)had an AUC of 0.829,with a sensitivity of 78.5%and a specificity of 80.6%.Conclusions The combined diagnostic model based on AST,ALP,and DBIL can effectively differentiate healthy individuals without liver diseases from AILD patients,while the combined diagnostic model based on PLT,ALP,and GGT can effectively distinguish HBVC from AILD patients.
3.PANoptosis:analyzing new dimension of cell death and its research progress in related diseases
Jun SHAO ; Na-qi LIAN ; Yu LI ; Mian-li BIAN
Chinese Pharmacological Bulletin 2025;41(2):214-218
Programmed cell death is known to play a crucial role in host defense,with various cell death pathways having u-nique regulatory mechanisms.In recent years,further research into cell death pathways has revealed crosstalk and coordination among them,leading to the proposition of a new cell death path-way:PANoptosis.PANoptosis is believed to be an inflammatory form of programmed cell death regulated by the PANoptosome complex,possessing key features of pyroptosis,apoptosis,and ne-croptosis,and it cannot be solely characterized by any single mode of cell death.PANoptosis is involved in various diseases,such as infectious diseases and tumor-related conditions,where specific triggers can induce host cell death via the PANoptosis pathway.In-depth investigation of PANoptosis promises a better understanding of the complex regulatory network of cell death and may offer new therapeutic targets for diseases.This review provides an overview of the specific mechanisms underlying PANoptosis and its potential roles in various diseases such as cancer,infectious diseases,and cardiovascular disorders.
4.Distribution of allergen components of dust mite in children with airway allergic diseases
Huijie HUANG ; Li XIANG ; Nannan JIANG ; Mian WEI ; Xiaoling HOU
Chinese Journal of General Practitioners 2025;24(5):581-586
Objective:To analyze the distribution of allergen components of dust mite in children with airway allergic diseases.Methods:This was a cross-sectional study. The clinical data of children with dust mite-induced allergic asthma (AA) complicated with allergic rhinitis (AR) or allergic rhinitis who were treated in Department of Allergy,Beijing Children′s Hospital from January 2019 to October 2022 were retrospectively analyzed. The spedific IgE (sIgE) levels to Der p1,Der p2,Der p5,Der p7,Der p10,Der p21,Der p23 and Der f1,Der f2 were detected by protein chip method. The distribution of dust mite sensitized components and the sIgE levels in children with different airway allergic diseases and different ages were compared.Results:Among 138 children with airway allergic diseases,there were 97 boys and 41 girls,age (6.86±2.61) years old,and there were 106 cases of AA combined AR (AAAR group) and 32 cases of AR alone (AR group). The sensitization rates of Der p2 was the highest (75.4%,104/138),followed by Der f2 (74.6%,103/138),Der f1 (73.9%,102/138),Der p1 (71.7%,99/138),Der p21 (19.6%,27/138),Der p5 (16.7%,23/138),Der p23 (14.5%,20/138),Der p7 (11.6%,16/138) and Der p10 (2.9%,4/138). The co-sensitization rate of Der p1,Der p2,Der f1 and Der f2 was the highest (31.2%,43/138). There was no significant difference in sensitization rate of dust mites components between AAAR group and AR group(all P>0.05). AAAR group had higher levels of sIgE to Der p23 than AR group [0.1 (0,0.1) IU/ml vs. 0 (0,0.1) IU/ml,Z=-2.819, P=0.005]. There were no significant differences in the positive rate of dust mite components and sIgE levels between children aged≤6 and>6 years old with airway allergic diseases(all P>0.05). Conclusions:Der p1,Der p2,Der f1 and Der f2 are the major components of dust mites sensitizing airway allergic diseases in children. Der p1,Der p2,Der f1 and Der f2 are the main co-sensitizing components in children with dust mite-induced airway allergic diseases. Compared with AR,the sIgE level to Der p23 in children with AAAR is higher.
5.The protective effect of low-dose L-carnitine on the reproductive function of male Wistar rats during acute exposure to simulated high-altitude environment
Jiahao LI ; Bin ZHANG ; Xingming JIANG ; Zihan BU ; Mian WANG ; Forong LI ; Dehui CHANG
Journal of Chongqing Medical University 2025;50(4):437-443
Objective:To investigate the interventional and protective effect of low-dose L-carnitine(LC)against reproductive system damage in male Wistar rats during acute exposure to simulated high-altitude environment.Methods:A total of 24 specific pathogen-free male Wistar rats,aged 12 weeks,were randomly divided into control group,high-altitude model group,and LC intervention group[intraperitoneal injection of LC at a dose of 50 mg/(kg·d)],with 8 rats in each group.The rats in the control group were fed under normal conditions(at an altitude of approximately 1 500 m),those in the high-altitude model group,and those in the LC intervention group were fed in a hypobaric oxygen chamber(at a simulated alti-tude of 6 000 m).The rats were sacrificed after 3 days.The testis was collected to calculate testicular index;the semen was collected from the epididymis,and the Weili sperm quality analysis system was used to assess sperm quality;blood samples were collected from the abdominal aorta,and ELISA kits were used to measure the serum levels of testosterone(T),luteinizing hormone(LH),and follicle-stimulating hormone(FSH);testicular tissue samples were collected,and biochemical kits were used to measure the activity of reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD);testicular tissue was collected to prepare HE and electron microscopy sections,and a light microscope and a transmission electron microscope were used for observation.Results:Com-pared with the blank control group,the high-altitude model group had significant increases in the levels of T,LH,and FSH(P<0.01),testicular tissue damage under the light microscope,and changes in the morphology of spermatogenic cells,including mitochondrial al-terations,membrane edema,loss of cristae,swelling of the matrix,and local dissolution,as well as significant increases in the levels of ROS and MDA(P<0.01)and a significant reduction in SOD activity(P<0.01).Compared with the high-altitude model group,the LC intervention group had a significant increase in the level of T(P<0.01),significant reductions in the levels of FSH and LH(P<0.01),and significant improvements in the pathological changes of testicular tissue,with no marked mitochondrial injury,and there were sig-nificant reductions in the levels of ROS and MDA(P<0.01)and a significant increase in SOD activity(P<0.01).There was no signifi-cant difference in testicular index between groups(P>0.05).The high-altitude model group had a significantly lower sperm count than the blank control group(P<0.05),while there was no significant difference in sperm count between the LC intervention group and the blank control group(P>0.05);there was no significant difference in sperm motility between groups(P>0.05).Conclusion:Low-dose LC can improve reproductive system damage in rats during acute exposure to simulated high-altitude environment,possibly by alleviat-ing oxidative stress response.
6.An animal model of temporomandibular joint osteoarthritis established by perforation of the articular disc
Zerou ZHANG ; Dan JIN ; Bingshuai JING ; Rui REN ; Mian ZHANG ; Fuwei LIU ; Yunpeng LI
Journal of Practical Stomatology 2025;41(3):328-335
Objective:This study aims to establish an animal model that accurately replicates the clinical symptoms and pathologi-cal changes of late-stage human TMJOA,with the goal of providing a standardized and reliable animal experimental method for sub-sequent research on the disease.Methods:Forty-eight male New Zealand rabbits aged 4 to 6 months were randomly divided into a model group and a sham group.The animals in the model group underwent bilateral temporomandibular joint disc perforation surgery,while the animals in the sham group underwent a sham surgery.The modeling effects were assessed at 4,8,and 12 weeks post-surgery using nociceptive behavior assessments,passive mouth opening measurements,histological analysis(HE,Safranin O-fast green staining),immunohistochemistry,immunofluorescence staining,and magnetic resonance imaging(MRI).Results:Animals in the model group exhibited distinct TMJOA symptoms,including joint pain and restricted mouth opening.Histologically,typical osteo-arthritis changes were evident.The Mankin osteoarthritis score was significantly higher(P<O.05).Conclusion:The TMJ disc perfo-ration model resmbled the same clinical manifestations and pathological changes seen in human TMJOA.
7.Neuroprotective mechanism of electroacupuncture in cerebral ischemia-reperfusion model rats
Haiyang WU ; Mian DUAN ; Chenglong LI ; Junyu ZHANG ; Haisheng JI ; Haitao WANG ; Wei MAO ; Ying WANG
Chinese Journal of Tissue Engineering Research 2025;29(18):3811-3818
BACKGROUND:Previous studies have demonstrated that acupuncture at the governor meridian has precise efficacy in the treatment of ischemic stroke and can improve cerebral ischemia-reperfusion injury by attenuating pyroptosis,but the upstream regulatory mechanisms are not yet fully clarified.OBJECTIVE:To observe the neuroprotective effect of electroacupuncture in model rats of cerebral ischemia-reperfusion injury.METHODS:Twenty-seven Sprague-Dawley rats were randomly divided into sham surgery,model,and electroacupuncture groups,with nine rats in each group.Modified suture method was used to establish cerebral ischemia-reperfusion model rats in the model and electroacupuncture groups.The electroacupuncture group was subjected to electroacupuncture at"Baihui,""Fengfu,"and"Dazhui"acupoints,20 minutes each,once a day,for 7 consecutive days.After treatment,neurological deficit scoring and pole test were performed to assess behavioral changes.Tri-phenyl tetrazolium chloride staining was used to assess cerebral infarction size in rats.Hematoxylin-eosin staining was performed to observe morphological changes in cerebral cortex tissue on the infarcted side of rats.Immunofluorescence analysis was used to determine Iba-1 and reactive oxygen species levels in cerebral cortex tissue on the infarcted side of rats,ELISA method was used for measuring interleukin-1β,interleukin-6 and tumor necrosis factor α levels in cerebral cortex tissue on the infarcted side of rats.Real-time fluorescence quantitative PCR and western blot were used to detect mRNA and protein expression levels of thioredoxin interaction protein,nod-like receptor associated protein 3(NLRP3),Caspase-1 and interleukin-1β in cerebral cortex tissue on the infarcted side of rats respectively,and the interaction between thioredoxin interaction protein and NLRP3 was analyzed by immunoprecipitation.RESULTS AND CONCLUSION:(1)Compared with the sham surgery group,rats in the model group showed an increase in neurological deficit score,pole test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining in the model group showed neuronal degeneration and necrosis,with fragmented and dissolved nuclei and cellular vacuoles.(2)Compared with the model group,rats in the electroacupuncture group showed a reduction in neurological deficit score,pole climbing test score,cerebral infarction volume(P<0.05),the immunofluorescence expression of Iba-1 and reactive oxygen species(P<0.05),the levels of interleukin-1β,interleukin-6 and tumor necrosis factor α(P<0.05),and the mRNA and protein expression of thioredoxin interaction protein,NLRP3,Caspase-1 and interleukin-1β in cerebral cortex tissue(P<0.05).Hematoxylin-eosin staining showed that the pathological damage of neurons in cerebral cortex tissue on the infarcted side of rats in the electroacupuncture group was significantly attenuated,with significantly reduced cell necrosis and vacuolation.(3)Immunoprecipitation assay showed an interaction between thioredoxin interaction proteins and NLRP3 in the cerebral cortical tissues on the infarcted side of rats in the model group.To conclude,electroacupuncture has a significant therapeutic effect against cerebral ischemia-reperfusion injury,possibly by inhibiting the reactive oxygen species/thioredoxin interaction protein/NLRP3 cell pyroptosis signaling pathway and activation of microglia to reduce the release of inflammatory factors.
8.Mechanism of action of Sterculiae Lychnophorae Semen against PM2.5-induced acute lung injury based on network pharmacology,molecular docking and experimental validation
Fan ZHANG ; Yi-fan DU ; Xiao-shu DENG ; Zu-feng ZHANG ; Xian-lei HAN ; Wei TIAN ; Xiu-mei LI ; Mian CHEN ; Fei LIU ; Nan WANG
Chinese Pharmacological Bulletin 2025;41(12):2362-2369
Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.
9.Feasibility and safety of surgery in patients with stageⅣ esophageal cancer following first-line therapies
Yan HUANG ; Hong YANG ; Kongjia LUO ; Yuhong LI ; Feng WANG ; Mian XI ; Qiaoqiao LI ; Jianhua FU
Chinese Journal of Gastrointestinal Surgery 2025;28(2):185-190
Objective:This study aimed to evaluate the feasibility and safety of surgical intervention for patients with stage Ⅳ esophageal cancer who demonstrated tumor regression following first-line treatment.Methods:This was a descriptive case series. The inclusion criteria for surgery were as follows: (1) an initial diagnosis of stage Ⅳ esophageal cancer, i.e. cT4b or cM1; (2) the presence of residual tumor following first-line therapy deemed potentially resectable upon reassessment; and (3) sufficient organ function to tolerate surgical procedures. Clinical data were retrospectively collected for 63 patients with stage Ⅳ esophageal cancer who underwent surgery following first-line therapy at Sun Yat-sen University Cancer Center between January 2014 and December 2023. Of these patients, 12 were initially staged as IVA, and 51 as IVB. Post-treatment restaging revealed that 9 patients achieved a clinical complete response, while 3 were downstaged to stage Ⅰ, 14 to stage Ⅱ, 24 to stage Ⅲ, and 13 to stage ⅣB (with regression of distant metastatic lesions enabling curative resection). Surgical approaches included right thoracic esophagectomy ( n=55), left thoracic esophagectomy ( n=4), and transmediastinal esophagectomy ( n=4). Additionally, 7 patients required extended organ resection. Two-field lymph node dissection was performed in 49 patients, while 14 underwent three-field lymph node dissection. Postoperative management varied: 31 patients received no adjuvant therapy, 11 underwent immunochemotherapy, 8 received immunotherapy alone, 8 underwent chemotherapy, 4 received chemoradiotherapy, and 1 received combined radiotherapy and immunotherapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS), with secondary endpoints including surgical outcomes and postoperative complications. Results:All 63 patients successfully underwent surgery without intraoperative mortality. R0 resection was achieved in 58 cases (92.1%), while R1 and R2 resections were performed in 1 case (1.6%) and 4 cases (6.3%), respectively. The mean operative time was 357±135 minutes. Postoperative complications were observed in 27 cases (42.9%), with 9 cases (14.3%) classified as Clavien-Dindo grade Ⅲ or Ⅴ. One patient (1.6%) died perioperatively. The median follow-up duration was 21 months (range: 4–107 months). The median OS was 64.8 months (95% CI: 50.9–78.6 months), and the median PFS was 68.0 months (95% CI: 53.9–82.3 months). Among 24 patients with supraclavicular lymph node metastases, 6 experienced recurrence and 8 died. Of 25 patients with abdominal metastases, 3 had recurrence and subsequently died. All 4 patients with lung metastases and both patients with bone metastases experienced recurrence and death.Conclusions:Surgical intervention is a feasible and safe treatment option for selected patients with stage Ⅳ esophageal cancer who demonstrate the potential for curative resection following first-line therapy.
10.Mechanism of vanillic acid against cardiac fibrosis induced by isoproterenol in mice based on Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways.
Hai-Bo HE ; Mian WU ; Jie XU ; Qian-Qian XU ; Fang-Zhu WAN ; Hua-Qiao ZHONG ; Ji-Hong ZHANG ; Gang ZHOU ; Hui-Lin QIN ; Hao-Ran LI ; Hai-Ming TANG
China Journal of Chinese Materia Medica 2025;50(8):2193-2208
This study investigated the effects and underlying mechanisms of vanillic acid(VA) against cardiac fibrosis(CF) induced by isoproterenol(ISO) in mice. Male C57BL/6J mice were randomly divided into control group, VA group(100 mg·kg~(-1), ig), ISO group(10 mg·kg~(-1), sc), ISO + VA group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig), ISO + dynamin-related protein 1(Drp1) inhibitor(Mdivi-1) group(10 mg·kg~(-1), sc + 50 mg·kg~(-1), ip), and ISO + VA + Mdivi-1 group(10 mg·kg~(-1), sc + 100 mg·kg~(-1), ig + 50 mg·kg~(-1), ip). The treatment groups received the corresponding medications once daily for 14 consecutive days. On the day after the last administration, cardiac functions were evaluated, and serum and cardiac tissue samples were collected. These samples were analyzed for serum aspartate aminotransferase(AST), lactate dehydrogenase(LDH), creatine kinase-MB(CK-MB), cardiac troponin I(cTnI), reactive oxygen species(ROS), interleukin(IL)-1β, IL-4, IL-6, IL-10, IL-18, and tumor necrosis factor-α(TNF-α) levels, as well as cardiac tissue catalase(CAT), glutathione(GSH), malondialdehyde(MDA), myeloperoxidase(MPO), superoxide dismutase(SOD), total antioxidant capacity(T-AOC) activities, and cytochrome C levels in mitochondria and cytoplasm. Hematoxylin-eosin, Masson, uranium acetate and lead citrate staining were used to observe morphological and mitochondrial ultrastructural changes in the cardiac tissues, and myocardial injury area and collagen volume fraction were calculated. Flow cytometry was applied to detect the relative content and M1/M2 polarization of cardiac macrophages. The mRNA expression levels of macrophage polarization markers [CD86, CD206, arginase 1(Arg-1), inducible nitric oxide synthase(iNOS)], CF markers [type Ⅰ collagen(Coll Ⅰ), Coll Ⅲ, α-smooth muscle actin(α-SMA)], and cytokines(IL-1β, IL-4, IL-6, IL-10, IL-18, TNF-α) in cardiac tissues were determined by quantitative real-time PCR. Western blot was used to detect the protein expression levels of Coll Ⅰ, Coll Ⅲ, α-SMA, Drp1, p-Drp1, voltage-dependent anion channel(VDAC), hexokinase 1(HK1), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), caspase-1, cleaved-caspase-1, gasdermin D(GSDMD), cleaved N-terminal gasdermin D(GSDMD-N), IL-1β, IL-18, B-cell lymphoma-2(Bcl-2), B-cell lymphoma-xl(Bcl-xl), Bcl-2-associated death promoter(Bad), Bcl-2-associated X protein(Bax), apoptotic protease activating factor-1(Apaf-1), pro-caspase-3, cleaved-caspase-3, pro-caspase-9, cleaved-caspase-9, poly(ADP-ribose) polymerase-1(PARP-1), and cleaved-PARP-1 in cardiac tissues. The results showed that VA significantly improved cardiac function in mice with CF, reduced myocardial injury area and cardiac index, and decreased serum levels of AST, CK-MB, cTnI, LDH, ROS, IL-1β, IL-6, IL-18, and TNF-α. VA also lowered MDA and MPO levels, mRNA expressions of IL-1β, IL-6, IL-18, and TNF-α, and mRNA and protein expressions of Coll Ⅰ, Coll Ⅲ, and α-SMA in cardiac tissues, and increased serum levels of IL-4 and IL-10, cardiac tissue levels of CAT, GSH, SOD, and T-AOC, and mRNA expressions of IL-4 and IL-10. Additionally, VA ameliorated cardiac pathological damage, inhibited myocardial cell apoptosis, inflammatory infiltration, and collagen fiber deposition, reduced collagen volume fraction, and alleviated mitochondrial damage. VA decreased the ratio of F4/80~+CD86~+ M1 cells and the mRNA expressions of CD86 and iNOS in cardiac tissue, and increased the ratio of F4/80~+CD206~+ M2 cells and the mRNA expressions of CD206 and Arg-1. VA also reduced protein expressions of p-Drp1, VDAC, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-1β, IL-18, Bad, Bax, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP-1, and cytoplasmic cytochrome C, and increased the expressions of HK1, Bcl-2, Bcl-xl, pro-caspase-3, pro-caspase-9 proteins, as well as the Bcl-2/Bax and Bcl-xl/Bad ratios and mitochondrial cytochrome C content. These results indicate that VA has a significant ameliorative effect on ISO-induced CF in mice, alleviates ISO-induced oxidative damage and inflammatory response, and its mechanism may be closely related to the inhibition of Drp1/HK1/NLRP3 and mitochondrial apoptosis signaling pathways, suppression of myocardial cell inflammatory infiltration and collagen fiber deposition, reduction of collagen volume fraction and CollⅠ, Coll Ⅲ, and α-SMA expressions, thus mitigating CF.
Animals
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Isoproterenol/adverse effects*
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Male
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Mice
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Signal Transduction/drug effects*
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Vanillic Acid/administration & dosage*
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Dynamins/genetics*
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Mice, Inbred C57BL
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Fibrosis/genetics*
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Apoptosis/drug effects*
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Mitochondria/metabolism*
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NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
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Myocardium/metabolism*
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Humans


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