1.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
2.Investigating Effect of Xianglian Huazhuo Prescription on Cell Cycle and Proliferation in Rats with Chronic Atrophic Gastritis Through TGF-β1/Smads Signaling Pathway
Yican WANG ; Jie WANG ; Yirui CHENG ; Xiaojing LI ; Yibin MA ; Qiuhua LIU ; Ziwei LIU ; Yuxi GUO ; Pengli DU ; Yanru CAI ; Yao DU ; Zheng ZHI ; Bolin LI ; Qian YANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):128-136
ObjectiveTo explore the potential mechanism of Xianglian Huazhuo prescription (XLHZ) in treating chronic atrophic gastritis (CAG) by regulating cell cycle and inhibiting proliferation, using bioinformatics technology and animal experiments. MethodsDifferential expressed genes (DEGs) related to CAG were screened using GEO database and GEO2R tool. Weighted gene co-expression network analysis (WGCNA) was employed to search for hub genes of CAG. These hub genes were intersected with cell cycle proliferation based on GeneCards database. Eenrichment analysis of the intersecting genes was performed to obtain signaling pathways and biological processes related to CAG. Protein protein interaction (PPI) analysis of genes was conducted using the Protein Interaction Platform (STRING) database to search the super hub gene (hub 2.0), and animal experiments were conducted for further validation. Fourteen of 70 male Wistar rats were randomly selected as the normal group, and the remaining 56 rats were prepared by the combined modeling method of "starvation disorder+N-methyl-N-nitro-N-nitrosoguanidine (MNNG) + sodium salicylate". The successfully modeled rats were randomly divided into the model group, XLHZ-H, XLHZ-M, and XLHZ-L groups (36, 18, 9 g·kg-1, respectively), and Morodan group (1.4 g·kg-1). Each group was given corresponding intervention for 60 days. Hematoxylin-eosin (HE) staining was used to observe the histopathological changes of gastric mucosa in rats. The ultrastructure of gastric mucosal tissue cells was observed by transmission electron microscopy. The relative expression levels of TGF-β1, Smad2 and Smad3 proteins, S/G2/M phase marker geminin and proliferation marker MCM2 were detected by Western blot in gastric mucosal tissue, and Spearman correlation analysis was performed. ResultsA total of 15 hub 2.0 genes were identified, including TGF-β1, suggesting the involvement of the TGF-β1 signaling pathway in the CAG pathogenesis. Compared with the normal group, the expressions of TGF-β1, Smad2, geminin and MCM2 proteins in the gastric mucosa tissue of the model group were increased (P<0.05), and the expression of Smad3 protein was decreased (P<0.05). Compared with the model group, the expressions of TGF-β1 and geminin in the gastric mucosa were decreased in the drug groups (P<0.05). The XLHZ-M group, XLHZ-H group and Morodan group had significantly decreased protein expression of Smad2 and MCM2 (P<0.05). The protein expression of Smad3 was significantly increased in XLHZ-M, XLHZ-H, and Morodan groups (P<0.05). Spearman correlation analysis showed that Smad3 was negatively correlated with other indicators, and positively correlated with other indicators (P<0.01). ConclusionXLHZ may inhibit TGF-β1/Smads signaling pathway, regulate cell cycle, and inhibit proliferation in the treatment of CAG.
3.Adhesion,proliferation,and vascular smooth muscle differentiation of bone marrow mesenchymal stem cells on different electrospinning membranes
Xianjuan SUN ; Qiuhua WANG ; Jinyi ZHANG ; Yangyang YANG ; Wenshuang WANG ; Xiaoqing ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(4):661-669
BACKGROUND:Small diameter artificial vessels are urgently needed to treat coronary artery and peripheral artery diseases in clinical practice.At present,vascular tissue engineering has become the main method for preparing small diameter artificial vessels.Selecting suitable biomaterials and cell sources is the key factor for successful construction of small diameter tissue engineered vessels. OBJECTIVE:To observe the effect of four kinds of electrospinning membrane materials on proliferation,adhesion and differentiation of bone marrow mesenchymal stem cells into vascular smooth muscle cells. METHODS:Bone marrow mesenchymal stem cells were isolated and extracted from SD rats.The bone marrow mesenchymal stem cells were inoculated separately on polycaprolactone(PCL),polycaprolactone-hyaluronic acid(PCL-HA),polycaprolactone-silk-filament proteins(PCL-SF),and polycaprolactone-gelatin(PCL-GEL)electrospinning membrane materials.After 1,3,and 7 days of culture,the cell arrangement on the material was observed under scanning electron microscope.The proliferation and adhesion of the material were observed by phalloidin staining.The mRNA expressions of CD90,Meflin,and transforming growth factor β were detected by qRT-PCR.After 7 days of induced differentiation into vascular smooth muscle cells,the mRNA expression ofɑ-smooth muscle actin on the material was detected by qRT-PCR. RESULTS AND CONCLUSION:(1)Bone marrow mesenchymal stem cells were arranged along the fibers of the four kinds of electrospinning membranes under scanning electron microscopy.(2)Phalloidin staining showed the regular distribution of bone marrow mesenchymal stem cells on the four kinds of electrospinning membranes and parallel distribution along the fiber direction.Moreover,PCL-HA,PCL-SF,and PCL-GEL electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells than PCL electrospinning membranes.Compared with PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes were more conducive to the proliferation and adhesion of bone marrow mesenchymal stem cells.(3)qRT-PCR showed that the four kinds of electrospun membrane materials could maintain the mRNA expression of CD90 and Meflin in bone marrow mesenchymal stem cells,but there was no significant difference between groups(P>0.05).The mRNA expression of transforming growth factor β in PCL-HA,PCL-SF,and PCL-GEL groups was higher than that in PCL group on days 1 and 7(P<0.05),and the mRNA expression of transforming growth factor β in PCL-SF group was higher than that in the other three groups on days 3 and 7(P<0.05).The mRNA expression of transforming growth factor β in PCL-HA group was higher than that in PCL-GEL group on day 7(P<0.05).(4)qRT-PCR showed that the mRNA expression of ɑ-smooth muscle actin in PCL-SF group was higher than that in the other three groups(P<0.05),and that in PCL-HA group was higher than that in PCL group(P<0.05).(5)The results indicate that compared with PCL,PCL-HA and PCL-GEL electrospinning membranes,PCL-SF electrospinning membranes combined with bone marrow mesenchymal stem cells are more suitable for the preparation of small diameter tissue engineered vessels.
4.Interpretation of the Disinfection Effects Testing and Evaluation Methods Section in Test Methods for Disinfection Products(WS/T 10009-2023)
Yanyan WANG ; Jiaqi WANG ; Qiuhua WEI ; Li YU ; Jin SHEN
Journal of Sichuan University (Medical Sciences) 2025;56(5):1184-1188
Test Methods for Disinfection Products(WS/T 10009-2023),a health industry standard,was officially released by the National Disease Control and Prevention Administration on December 15,2023.The standard came into effect on May 1,2024.This standard systematically specifies the testing and evaluation methods for disinfection products,covering three core components—disinfection effect testing and evaluation,physical and chemical testing techniques,and toxicological testing methods.The standard provides an important technical basis for the testing of disinfection products in China.To promote an accurate understanding and effective implementation of the standard,this article focuses on the in-depth interpretation of the section concerning the testing and evaluation methods of disinfection effects.It provides a detailed explanation of the major updates,technical highlights,and scientific rationale behind the standard.The article incorporates discussions on optimizing the validation test methods for the disinfection and sterilization effects of disinfectants,simulated field testing of disinfectants,evaluation of air disinfection effects,and the supplementation and improvement of testing methods for disinfection devices(including sterilization devices).This article aims to provide clear technical guidance for disinfection product inspection personnel,researchers,and other professionals involved,promote the standardized application of the standard,improve the quality of disinfection products,and ensure scientific,effective,and safe disinfection practices.
5.Mesenchymal stem cells combined with polycaprolactone-hyaluronic acid electrospinning membrane in repair of endometrial injury
Jiangru AN ; Jinyi ZHANG ; Qiuhua WANG ; Yangyang YANG ; Wenshuang WANG ; Xiaoqing ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(16):3369-3379
BACKGROUND:Human endometrial mesenchymal stem cells can directly repair the damaged endometrium,promote angiogenesis,and restore the morphological structure of the uterus.However,after the direct injection of stem cells into the damaged endometrium,the cell survival rate is low,the retention time is short,and the repair effect is limited.OBJECTIVE:To observe the effect of polycaprolactone-hyaluronic acid electrospinning membrane combined with human endometrial mesenchymal stem cells on endometrial injury in rats.METHODS:(1)Cell experiment:Human endometrial mesenchymal stem cells were extracted by collagenase digestion method.Polycaprolactone-hyaluronic acid electrospinning membrane was prepared by electrospinning technology.The human endometrial mesenchymal stem cells were inoculated on polystyrene culture plate and polycaprolactone-hyaluronic acid electrospinning membrane.The proliferation and adhesion of the cells were observed by DNA quantitative analysis,WST-1 cell activity test,phalloidin staining,and scanning electron microscopy.The mRNA expressions of CD90 and Meflin in electrospun membrane were detected by qRT-PCR.(2)Animal experiments:27 female SD rats in estrus were selected to establish uterine adhesion model by mechanical scratching method and randomly divided into three groups with nine rats in each group:The blank control group did not receive any treatment;the control group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane;the experimental group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell mesh.Samples were collected at 3,7,and 14 days after surgery.Hematoxylin-eosin staining was used to observe the morphological structure of uterus and the number of glands.qRT-PCR and immunofluorescence staining were used to observe the expression of CD31 and vascular endothelial growth factor in uterine tissue.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with polystyrene culture plate,polycaprolactone-hyaluronic acid electrospinning membrane could promote the proliferation and adhesion of human endometrial mesenchymal stem cells.Polycaprolactone-hyaluronic acid electrospinning membrane supported the expression of CD90 and Meflin genes of human endometrial mesenchymal stem cells.(2)Animal experiments:Hematoxylin-eosin staining showed that polycaprolactic-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell patch could promote the recovery of endometrial morphological structure after injury.The endometrial thickness and number of gland on day 14 after surgery were higher than those in blank control group and control group(P<0.05).qRT-PCR and immunofluorescence staining showed that the mRNA and protein expressions of CD31 and vascular endothelial growth factor in the experimental group were higher than those in the blank control group and the control group at 7 and 14 days after surgery(P<0.05).(3)The results showed that polycaprolacton-hyaluronic acid electrospinning membrane could improve the survival rate of stem cells and prolong the contact time between stem cells and the damaged tissue,and the composite transplantation of the two could better repair the damaged endometrial tissue.
6.Mesenchymal stem cells combined with polycaprolactone-hyaluronic acid electrospinning membrane in repair of endometrial injury
Jiangru AN ; Jinyi ZHANG ; Qiuhua WANG ; Yangyang YANG ; Wenshuang WANG ; Xiaoqing ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(16):3369-3379
BACKGROUND:Human endometrial mesenchymal stem cells can directly repair the damaged endometrium,promote angiogenesis,and restore the morphological structure of the uterus.However,after the direct injection of stem cells into the damaged endometrium,the cell survival rate is low,the retention time is short,and the repair effect is limited.OBJECTIVE:To observe the effect of polycaprolactone-hyaluronic acid electrospinning membrane combined with human endometrial mesenchymal stem cells on endometrial injury in rats.METHODS:(1)Cell experiment:Human endometrial mesenchymal stem cells were extracted by collagenase digestion method.Polycaprolactone-hyaluronic acid electrospinning membrane was prepared by electrospinning technology.The human endometrial mesenchymal stem cells were inoculated on polystyrene culture plate and polycaprolactone-hyaluronic acid electrospinning membrane.The proliferation and adhesion of the cells were observed by DNA quantitative analysis,WST-1 cell activity test,phalloidin staining,and scanning electron microscopy.The mRNA expressions of CD90 and Meflin in electrospun membrane were detected by qRT-PCR.(2)Animal experiments:27 female SD rats in estrus were selected to establish uterine adhesion model by mechanical scratching method and randomly divided into three groups with nine rats in each group:The blank control group did not receive any treatment;the control group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane;the experimental group was implanted with polycaprolacton-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell mesh.Samples were collected at 3,7,and 14 days after surgery.Hematoxylin-eosin staining was used to observe the morphological structure of uterus and the number of glands.qRT-PCR and immunofluorescence staining were used to observe the expression of CD31 and vascular endothelial growth factor in uterine tissue.RESULTS AND CONCLUSION:(1)Cell experiment:Compared with polystyrene culture plate,polycaprolactone-hyaluronic acid electrospinning membrane could promote the proliferation and adhesion of human endometrial mesenchymal stem cells.Polycaprolactone-hyaluronic acid electrospinning membrane supported the expression of CD90 and Meflin genes of human endometrial mesenchymal stem cells.(2)Animal experiments:Hematoxylin-eosin staining showed that polycaprolactic-hyaluronic acid electrospinning membrane/human endometrial mesenchymal stem cell patch could promote the recovery of endometrial morphological structure after injury.The endometrial thickness and number of gland on day 14 after surgery were higher than those in blank control group and control group(P<0.05).qRT-PCR and immunofluorescence staining showed that the mRNA and protein expressions of CD31 and vascular endothelial growth factor in the experimental group were higher than those in the blank control group and the control group at 7 and 14 days after surgery(P<0.05).(3)The results showed that polycaprolacton-hyaluronic acid electrospinning membrane could improve the survival rate of stem cells and prolong the contact time between stem cells and the damaged tissue,and the composite transplantation of the two could better repair the damaged endometrial tissue.
7.Effects of formononetin on malignant biological behaviors and angiogenesis of gallbladder cancer cells via regulating the JAK/STAT signaling pathway
Gang WANG ; Qiuhua LIU ; Ke GUO ; Zhencheng ZHU ; Hao SHEN
Chinese Journal of Cancer Biotherapy 2025;32(9):941-947
Objective:To investigate the effects of formononetin on the malignant biological behavior and angiogenesis of gallbladder cancer GBC-SD cells through regulation of the JAK2/STAT3 signaling pathway.Methods:GBC-SD cells were cultured routinely,and their xenograft nude mouse models were constructed.The cells and mice were divided into control group,formononetin group,colivelin(JAK2/STAT3 activator)group,and formononetin+colivelin group.Cell proliferation,migration and invasion,and apoptosis were assessed using MTT,Transwell,and flow cytometry assays,respectively.ELISA was applied to measure the secretion levels of vascular endothelial growth factor(VEGF)in cells of each group.Vasculogenic mimicry(VM)formation assay was used to detect the tube formation ability of each group of cells.In vivo,the effects of formononetin on xenograft tumor growth were examined,and CD31 and VEGF expression in xenograft tissues were detected by immunohistochemistry.Western blotting was applied to analyze JAK2/STAT3 phosphorylation levels in both cells and tumor tissues.Results:Formononetin significantly inhibited the proliferation,migration,and invasion of GBC-SD cells and promoted apoptosis(all P<0.05).It also suppressed VEGF secretion and VM formation in GBC-SD cells(all P<0.05),inhibited the growth and vascular formation of GBC-SD xenograft tumors(all P<0.05),reduced VEGF expression in transplanted tumor tissues,and decreased phosphorylation of the JAK2/STAT3 pathway in both GBC-SD cells and their xenograft tissues.These effects of formononetin were partially reversed by colivelin(all P<0.05).Conclusion:Formononetin inhibits GBC-SD cell proliferation,migration,invasion,and angiogenesis,and promotes apoptosis by suppressing the JAK2/STAT3 signaling pathway.The JAK2/STAT3 signaling pathway may serve as a potential therapeutic target for gallbladder cancer.
8.Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients.
Jiang XIAO ; Guiju GAO ; Yi DING ; Jialu LI ; Chengyu GAO ; Qiuhua XU ; Liang WU ; Hongyuan LIANG ; Liang NI ; Fang WANG ; Yujiao DUAN ; Di YANG ; Hongxin ZHAO
Chinese Medical Journal 2023;136(24):2931-2937
BACKGROUND:
This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.
METHODS:
We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.
RESULTS:
Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P <0.001).
CONCLUSION
The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.
Humans
;
Antiretroviral Therapy, Highly Active/adverse effects*
;
Anti-HIV Agents/adverse effects*
;
HIV Infections/drug therapy*
;
Tenofovir/therapeutic use*
;
Retrospective Studies
;
Emtricitabine/pharmacology*
;
Adenine/therapeutic use*
;
Lipids
9.Effects of ceftriaxone on Nrf2/GPX4 pathway and ferroptosis of cerebral cortex in early brain injury of rats with subarachnoid hemorrhage
Juan DU ; Haifeng QU ; Zehua GONG ; Liang WANG ; Yichao WANG ; Qiuhua ZHANG ; Jianmin LI ; Junjie LIU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):15-23
Objective:To investigate the effects of ceftriaxone(CTX) on nuclear factor erythroid 2-related factor 2(Nrf2)/glutathione peroxidase 4(GPX4) pathway and ferroptosis in early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Forty-eight clean grade male SD rats were randomly divided into sham operation group (Sham group), SAH group, SAH+ CTX group and SAH+ CTX+ Nrf2 inhibitor group (SAH+ CTX+ ML385 group) according to the random number table with 12 rats in each group.Seven days before modeling, rats in SAH+ CTX+ ML385 group were injected intraperitoneally with ML385 (30 mg · kg -1) once a day for consecutive 7 days.And 5 days before modeling, rats in SAH+ CTX group and SAH+ CTX+ ML385 group were treated with CTX(200 mg · kg -1) by intraperitoneal injection once a day for five consecutive days.Rats in Sham group and SAH group were intraperitoneally injected with the same amount of 0.9% sodium chloride solution.After 24 hours of modeling, the neurological function score and brain tissue water content of rats in each group were measured.HE staining was used to observe the morphology of neurons in CA1 and CA3 regions of hippocampus.Prussian blue staining was used to observe the iron deposition in cerebral cortex.Spectrophotometer was used to determine the iron content, malonic dialdehyde(MDA) content, glutathione(GSH) content and GPX4 activity in cerebral cortex.Western blot was used to detect the expression levels of Nrf2 and GPX4 proteins in cerebral cortex.SPSS 23.0 was used for statistical analysis.One-way ANOVA was used to compare the mean of multiple groups of samples, and Dunnett- t test was used for further pairwise comparison between groups. Results:There was a statistically significant difference in the neurological function scores of rats in the four groups 24 hours after SAH ( F=48.40, P<0.001). The neurological function score of rats in the SAH group 24 hours after SAH was significantly lower than those in Sham group and SAH+ CTX group (both P<0.05). The brain water content of rats in the four groups 24 h after SAH was statistically significant ( F=49.61, P<0.001). The brain water content of rats in the SAH group 24 h after SAH was significantly higher than that in Sham group and SAH+ CTX group(both P<0.05). There was statistically significant differences in the number of neuronal necrosis in CA1 and CA3 regions of hippocampus in the four groups 24 hours after SAH ( F=17.44, 246.50, both P<0.001). The numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH group were significantly higher than those in Sham group and SAH+ CTX group, and the numbers of neuronal necrosis in CA1 and CA3 regions of hippocampus in SAH+ CTX+ ML385 group were significantly higher than those in SAH+ CTX group (all P<0.05). Twenty-four hours after SAH, the amount of iron deposited in the cerebral cortex of rats in the four groups was statistically significant ( F=2 363.0, P<0.001). The iron deposition in the cerebral cortex of rats in the SAH group was significantly higher than those in Sham group and SAH+ CTX group (both P<0.05). There were significant differences in iron content, MDA content, GSH content and GPX4 activity in the cerebral cortex of the four groups 24 h after SAH( F=2 380.0, 1 322.0, 789.1, 815.5, all P<0.001). The content of iron and MDA in the cerebral cortex of rats in SAH group were significantly higher than those in Sham group, while the content of GSH and the activity of GPX4 were significantly lower than those in Sham group (all P<0.05). The content of iron and MDA in the cerebral cortex of rats in SAH+ CTX group were lower than those in SAH group, and the content of GSH and the activity of GPX4 were higher than those in SAH group (all P<0.05). At 24 h after SAH, the expression levels of Nrf2 and GPX4 protein in the cerebral cortex of the four groups were statistically significant ( F=888.7, 1 556.0, both P<0.001). The protein expression levels of Nrf2 (0.382±0.014) and GPX4 (0.329±0.019) in the cerebral cortex in SAH group were lower than those in Sham group ((0.746±0.009), (0.953±0.009)) (both P<0.05). The expression levels of Nrf2 (0.631±0.006) and GPX4 (0.833±0.008) protein in the cerebral cortex in the SAH+ CTX group were significantly higher than those in the SAH group (both P<0.05). The expression levels of Nrf2 (0.427±0.009) and GPX4 (0.525±0.011) protein in the cerebral cortex in SAH+ CTX+ ML385 group were significantly lower than those in SAH+ CTX group (both P<0.05). Conclusion:Ceftriaxone may inhibit ferroptosis during EBI in SAH rats by regulating Nrf2/GPX4 signal axis.
10.The effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab for patients with inoperable esophageal squamous cell carcinoma
Lichen DAI ; Jianfeng HUANG ; Lijun HU ; Jia WU ; Jianlin WANG ; Qinghong MENG ; Fei SUN ; Qiuhua DUAN ; Jingping YU
Chinese Journal of Radiological Medicine and Protection 2023;43(3):182-188
Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.

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