1.Study on synergistic promotion of ferroptosis in human hypertrophic scar fibroblasts by erastin combined with shikonin
Jian-jun WANG ; Yan-hua WANG ; Yu-ting TANG ; Jing-yi ZHANG ; Fang MA ; Xi HE ; Hui-xia YANG ; Qi-peng ZHAO ; Zhi-gang BAI ; Yin-ju HAO ; Gui-zhong LI ; Yi-deng JIANG ; Jiang-yong SHEN
Chinese Pharmacological Bulletin 2025;41(2):268-276
Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50%).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P<0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P<0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P<0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P<0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.
2.Effect of metformin on epithelial-mesenchymal transition in A549 lung cancer cells and its underlying mechanisms
Xi CHEN ; Tao TANG ; Peng-yi YU ; Yuan-yuan HU ; Wen-ying XIE ; Qing LI ; Hui WANG
Chinese Pharmacological Bulletin 2025;41(2):348-355
Aim To investigate the effect of metformin on epithelial-mesenchymal transition(EMT)of lung cancer A549 cells and its underlying mechanism.Methods Lung cancer A549 cells were cultured in vitro and treated with metformin.Cell morphology was observed by fluorescence staining.The mRNA expres-sion levels of E-cadherin,N-cadherin,SMA and Vimen-tin were detected by RT-PCR.The regulatory effects of metformin on EMT in A549 cellswere examined by high-throughput sequencing.An EMT model was estab-lished through TGF-β1 induction.Following metformin treatment,the morphology of A549 cells was observed.Western blot was employed to determine the expression levels of NGF,E-cadherin,N-cadherin,SMA and Vim-entin.Additionally,si-NGF transfection was performed to evaluate the protein expressions of E-cadherin,N-cadherin,SMA and Vimentin in A549 cells,and a cell scratch assay was conducted to assess cell migration.Results After metformin treatment,A549 cells exhibi-ted a loss of mesenchymal-like morphology,character-ized by a transition to a round shape,a reduction in colony formation,and decreased adherence.RT-PCR and high-throughput sequencing revealed a down-regu-lation in the expression of genes associated with mesen-chymal transition,including N-cadherin,SMA,and Vim-entin,and an up-regulation in the expression of genes associated with epithelial transformation,such as ZO-1 and E-cadherin.Additionally,the expression of nerve growth factor(NGF)was significantly up-regulated.Following transfection with si-NGF,A549 cells treated with metformin exhibited a down-regulation in the ex-pression of the epithelial marker E-cadherin,concomi-tant with an up-regulation in the expression of stromal markers N-cadherin,Vimentin,and SMA.Conclusions Metformin can up-regulate the expression of E-cad-herin and down-regulate the expression of N-cadherin,Vimentin and SMA in lung cancer A549 cells,thereby inhibiting EMT.Additionally,NGF signaling molecules may play a significant role in this process.
3.Effects of Rutong Ruanjian Tablets on angiogenesis in a rat model of preneoplastic breast cancer of Liver-Qi Stagnation and Blood Stasis Pattern via DLL4/Notch1/Hes1 pathway
Hua YANG ; Jun-yao LONG ; Jie GONG ; Bing-bing LU ; Xi ZOU ; Yu-rong WU ; Li-fang LIU ; Hui LIU ; Qi-hua CHEN
Chinese Traditional Patent Medicine 2025;47(3):774-781
AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P<0.05,P<0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P<0.05,P<0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P<0.05,P<0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.
4.Epidemiological distribution characteristics and transmission patterns of Campylobacter in a Shandong broiler slaughterhouse
Shuai MIAO ; Xiu-mei HUANG ; Lin WANG ; Jun-hui LIU ; Jian-mei ZHAO ; Yu-bin GAO ; Shi-ping SONG ; Si-yu ZHANG ; Na LIU ; Ge ZHAO ; Xi-yue ZHANG ; Jun-wei WANG ; Juan WANG ; Zhi-na QU
Chinese Journal of Zoonoses 2025;41(6):583-591
This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.
5.Application of ultrasound-guided needling assisted the motor evoked potentials and electromyography monitoring in spinal surgery
Jing HU ; Hai-lin LI ; Zhi-qiang WU ; Jia-cheng LU ; Zi-xuan YUAN ; Yu-xi SUN ; Hui-bo WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):960-964
Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.
6.Diagnostic value of ET-1,Apelin combined with ECG for hypertrophic cardiomyopathy and their as-sociation with prognosis
Yu-yue SHEN ; Geng-xin SUN ; Xia-li WANG ; Xi-hui WANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(2):205-211
Objective:To investigate levels of endothelin-1(ET-1)and Apclin in patients with hypertrophic car-diomyopathy(HCM)and diagnostic value of their combination with ECG for HCM,and their association with prognosis.Methods:A total of 150 HCM patients admitted in the Second Affiliated Hospital of Xi'an Medical Uni-versity between June 2020 and June 2022 were selected as observation group.According to death during follow-up,the observation group was divided into survival group(n=64)and death group(n=86),and another 100 healthy volunteers who underwent physical examination in our hospital simultaneously were selected as control group.ET-1,Apelin and ECG indexes were compared between above-mentioned groups.Diagnostic value of ET-1,Apelin and ECG combined detection for HCM was analyzed by receiver operating characteristic(ROC)curve.Multivariate Logistic regression was used to analyze influencing factors of death within 6-month follow-up in HCM patients,and nomogram model was established.Results:Compared with participants in control group,those in the observa-tion group had significant higher ET-1[(0.64±0.15)pmol/L vs.(0.39±0.07)pmol/L],QRS wave group(∑QRS)[(23.60±3.96)mm vs.(14.02±1.78)mm],Cornell voltage index(SV3+RaVL)[(2.12±0.40)mV vs.(1.05±0.20)mV]and S-wave on V1 lead+R-wave on V5 lead(SV1+RV5)[(3.88±0.73)mV vs.(2.24±0.34)mV],and significant lower Apelin[(1.10±0.25)pg/ml vs.(1.58±0.17)pg/ml]level(P<0.001 all).ROC curve indicated that the area under the curve(AUC)of combined detection of above five indexes diagno-sing HCM was 0.933(95%CI 0.895~0.961),significantly higher than any single detection(Z=3.681~6.428,P<0.001 all),the H-L goodness of fit test showed P=0.056,suggesting that the model was well accepted,and DCA showed that ET-1 and Apelin combined ECG detection model had good clinical application value in HCM.Multivariate Logistic regression indicated that ET-1,∑QRS,SV3+RaV and SV1+RV5 were independent risk factors for death within 6-month in HCM patients(OR=2.617~3.600,P<0.001 all),and Apelin was its inde-pendent protective factor(OR=0.271,P<0.001).The nomogram model of HCM patients dying within 6 months was 4.627+0.452 × ET-1+0.536 × Apelin+0.575 × ∑QRS+0.541 × SV3+RaVL+0.352 × SV1+RV5.Conclusion:Serum ET-1 and Apelin levels significantly change in HCM patients,and the combination of ECG detection and both indexes have good performance diagnosing HCM and are independent influential factors for the death of HCM patients within 6 months.
7.Effect of Circadian Clock Genes on Circadian Rhythm of Allergic Rhinitis Based on Weiyang Theory
Xi CHEN ; Ran JING ; Yu LI ; Man YIN ; Hui ZHANG ; Jianfeng ZHANG ; Xinrong LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(2):431-436
Allergic rhinitis(AR)affects 10%-40%of the population in the world.Because CLOCK genes regulate the circadian rhythms of AR,the symptoms in parts of the patients are aggravated in the morning and evening and relieved at moon.Although lots of studies showed that traditional Chinese medicine is effective for AR,further explores are still needed to analyze the circadian rhythm of AR based on Chinese Chronological Medicine for controlling the circadian outbreak point of symptoms of AR in daily cycle.We supposed that Weiyang might play an important role for controlling the circadian rhythm of AR with closed similarities with the tidal variation of the expressions of CLOCK genes.Thus based on Weiyang theory,we tried to clarify the mechanism of circadian rhythm of AR and explore the relationship between Weiyang and the CLOCK genes so as to further expand the treatment methods of adjusting the circadian cycle of AR with TCM and improve the corresponding therapeutic efficacy.
8.Application of ultrasound-guided needling assisted the motor evoked potentials and electromyography monitoring in spinal surgery
Jing HU ; Hai-lin LI ; Zhi-qiang WU ; Jia-cheng LU ; Zi-xuan YUAN ; Yu-xi SUN ; Hui-bo WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(11):960-964
Objective To explore the effect and predictive value of ultrasound-guided needling assisted motor evoked potentials(MEP)and electromyography(EMG)monitoring on neurological recovery in spinal surgery.Methods A retrospective analysis was conducted on the clinical data of 80 patients who underwent spinal surgery at Jiangsu Province Hospital of Chinese Medicine from January 2020 to December 2024.A total of 41 patients in the observation group received ultrasound-guided needling assisted MEP and EMG monitoring,and 39 patients in the control group received conventional method for MEP and EMG monitoring.The operative time,intraoperative blood loss,and the proportions of intraoperative MEP and EMG warnings were compared between the two groups,and the sensitivity and specificity of intraoperative MEP monitoring were compared between the two groups.The receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to analyze the efficiency of MEP warning in predicting the dysfunction of postoperative spinal cord.Results There were no significant differences in the operative time,intraoperative blood loss,or the proportions of intraoperative MEP and EMG warnings(P>0.05).The sensitivity,specificity and AUC of intraoperative MEP monitoring in the observation group were significantly higher than those in the control group,with statistically significant differences(P<0.05).The sensitivity,specificity,and AUC of postoperative MEP warning in predicting the dysfunction of spinal cord in the observation group were higher than those in the control group,with statistically significant differences(P<0.05).Conclusion Ultrasound-guided needling assisted MEP and EMG monitoring can effectively enhance the intraoperative neural monitoring accuracy,and postoperative MEP warning demonstrates superior predictive value for postoperative neurological dysfunction.
9.Prevalence and related factors of screening myopia among students in special education schools in Tianjin
XI Wei, HAN Hui, XIONG Wenjuan, HAN Yu, WANG Hui, ZHANG Xin
Chinese Journal of School Health 2025;46(3):443-446
Objective:
To understand the current situation and related factors of screening myopia among students in special education schools, so as to provide evidence for promoting the health level of this population.
Methods:
From November 2021 to December 2023, a total of 281 students from 6 special education schools in 5 districts of Tianjin were selected by cluster random sampling method for computer optometry visual acuity examination for non ciliary paralysis and questionnaire survey. Multiple Logistic regression was performed to analyze the influencing factors of screening myopia among special education students.
Results:
The screening myopia detection rate among these special education students in Tianjin was 27.0%, and the screening myopia detection rates of students with autism, developmental delays, and intellectual disabilities were 22.4%, 12.5%, and 33.0%, respectively. The degree of myopia increased with age ( χ 2 trend =22.65, P <0.01). Multivariate Logistic regression analysis showed that age(10-13 years old: OR =5.40, 14-17 years old: OR =8.40, 18-23 years old: OR =6.02), accommodation(non resident: OR =0.29), daily mobile phone usage ≥2 hours ( OR =2.37), and daily computer/tablet usage ≥2 hours ( OR =2.70) were the risk factors for screening myopia among special education students ( P <0.05).
Conclusions
The detection rate and degree of screening myopia increase with age in special education students. Prolonged screen time exposure is a primary risk factor for screening myopia in special education students. Effective myopia prevention and control strategies should be designed according to the characteristics of special education students.
10.Effects of Rutong Ruanjian Tablets on angiogenesis in a rat model of preneoplastic breast cancer of Liver-Qi Stagnation and Blood Stasis Pattern via DLL4/Notch1/Hes1 pathway
Hua YANG ; Jun-yao LONG ; Jie GONG ; Bing-bing LU ; Xi ZOU ; Yu-rong WU ; Li-fang LIU ; Hui LIU ; Qi-hua CHEN
Chinese Traditional Patent Medicine 2025;47(3):774-781
AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P<0.05,P<0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P<0.05,P<0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P<0.05,P<0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.


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