1.Zhuluan Decoction Ameliorates Premature Ovarian Insufficiency by Inhibiting Excessive Autophagy of KGN Through Regulation of PI3K/Akt/mTOR Pathway
Yao CHEN ; Sainan TIAN ; Jing ZENG ; Xingxing YI ; Wen'e LIU ; Lei LEI ; Li TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):89-98
ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells (KGN) and ameliorates premature ovarian insufficiency (POI) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 (CCK-8) assay. Subsequently, the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined, KGN cells were categorized into the following groups: blank control (20% blank serum), model (20% blank serum + 5 μmol·L-1 cyclophosphamide), Zhuluan decoction-containing serum (20% Zhuluan decoction-containing serum + 5 μmol·L-1 cyclophosphamide), autophagy inhibitor (20% blank serum + 5 μmol·L-1 cyclophosphamide + 20 μmol·L-1 chloroquine phosphate), autophagy inhibitor + Zhuluan decoction-containing serum (20% Zhuluan decoction-containing serum + 5 μmol·L-1 cyclophosphamide + 20 μmol·L-1 chloroquine phosphate), and estradiol valerate (20% estradiol valerate-containing serum + 5 μmol·L-1 cyclophosphamide). Following 48 hours of incubation, flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K, phosphorylated (p)-Akt, Akt, p-mTOR, and mTOR, along with the expression levels of autophagy-related proteins such as Beclin1, autophagy-related 5 homolog (ATG5), and microtubule-associated protein 1 light chain 3 (LC3), in each group. Additionally, monodansylcadaverine (MDC) staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L-1 cyclophosphamide for 48 h successfully established a POI model, marked by a significant inhibition of KGN cell proliferation. Notably, the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation, with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group, the model group displayed an elevated apoptosis rate (P<0.01), reduced protein levels of PI3K, p-Akt, and p-mTOR (P<0.01), increased protein levels of Beclin1, LC3, and ATG5 (P<0.01), no significant alterations in the protein levels of Akt and mTOR, and an enhanced MDC autophagy fluorescence intensity (P<0.01). In comparison to that the model group, the apoptosis rates in the blank control group, model group, Zhuluan decoction-containing serum group, autophagy inhibitor group, autophagy inhibitor + Zhuluan decoction-containing serum group, and estradiol valerate group all reduced (P<0.05, P<0.01), with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K, p-Akt, and p-mTOR were higher in other groups than in the model group (P<0.05, P<0.01), being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group (P<0.01). The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group (P<0.05, P<0.01). The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group (P<0.05, P<0.01), while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model, thus managing POI.
2.Zhuluan Decoction Ameliorates Premature Ovarian Insufficiency by Inhibiting Excessive Autophagy of KGN Through Regulation of PI3K/Akt/mTOR Pathway
Yao CHEN ; Sainan TIAN ; Jing ZENG ; Xingxing YI ; Wen'e LIU ; Lei LEI ; Li TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):89-98
ObjectiveTo elucidate the underlying mechanism through which Zhuluan decoction suppresses excessive autophagy in human ovarian granulosa cells (KGN) and ameliorates premature ovarian insufficiency (POI) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsThe optimal concentration of cyclophosphamide for inducing a POI model in KGN cells was identified via the cell counting kit-8 (CCK-8) assay. Subsequently, the impacts of varying concentrations of Zhuluan decoction-containing serum on the viability of the KGN cell model were assessed. After the optimal drug concentration was determined, KGN cells were categorized into the following groups: blank control (20% blank serum), model (20% blank serum + 5 μmol·L-1 cyclophosphamide), Zhuluan decoction-containing serum (20% Zhuluan decoction-containing serum + 5 μmol·L-1 cyclophosphamide), autophagy inhibitor (20% blank serum + 5 μmol·L-1 cyclophosphamide + 20 μmol·L-1 chloroquine phosphate), autophagy inhibitor + Zhuluan decoction-containing serum (20% Zhuluan decoction-containing serum + 5 μmol·L-1 cyclophosphamide + 20 μmol·L-1 chloroquine phosphate), and estradiol valerate (20% estradiol valerate-containing serum + 5 μmol·L-1 cyclophosphamide). Following 48 hours of incubation, flow cytometry was utilized to measure the apoptosis rate of KGN cells in each group. Western blotting was employed to quantify the protein levels of PI3K, phosphorylated (p)-Akt, Akt, p-mTOR, and mTOR, along with the expression levels of autophagy-related proteins such as Beclin1, autophagy-related 5 homolog (ATG5), and microtubule-associated protein 1 light chain 3 (LC3), in each group. Additionally, monodansylcadaverine (MDC) staining was performed to evaluate the extent of autophagy in each group. ResultsIncubation of KGN cells with 5 μmol·L-1 cyclophosphamide for 48 h successfully established a POI model, marked by a significant inhibition of KGN cell proliferation. Notably, the inhibitory effect of cyclophosphamide on KGN cell proliferation exhibited a positive correlation with its concentration. Zhuluan decoction-containing serum at 20% and 30% promoted cell proliferation and mitigated the inhibitory effect of cyclophosphamide on KGN cell proliferation, with comparable therapeutic efficacy observed at both concentrations. Compared with the blank control group, the model group displayed an elevated apoptosis rate (P<0.01), reduced protein levels of PI3K, p-Akt, and p-mTOR (P<0.01), increased protein levels of Beclin1, LC3, and ATG5 (P<0.01), no significant alterations in the protein levels of Akt and mTOR, and an enhanced MDC autophagy fluorescence intensity (P<0.01). In comparison to that the model group, the apoptosis rates in the blank control group, model group, Zhuluan decoction-containing serum group, autophagy inhibitor group, autophagy inhibitor + Zhuluan decoction-containing serum group, and estradiol valerate group all reduced (P<0.05, P<0.01), with the most pronounced reduction observed in the autophagy inhibitor + Zhuluan decoction-containing serum group. The protein levels of PI3K, p-Akt, and p-mTOR were higher in other groups than in the model group (P<0.05, P<0.01), being the highest in the autophagy inhibitor + Zhuluan decoctio-containing serum group (P<0.01). The protein levels of Beclin1 and ATG5 were lower in other groups than in the model group (P<0.05, P<0.01). The expression level of LC3 declined in the Zhuluan decoction-containing serum group and the estradiol valerate group (P<0.05, P<0.01), while it decreased without statistical significance in the autophagy inhibitor group and the autophagy inhibitor + Zhuluan decoction-containing serum group. ConclusionZhuluan decoction may activate the PI3K/Akt/mTOR pathway to inhibit excessive autophagy and counteract the detrimental effects of cyclophosphamide on the KGN cell model, thus managing POI.
3.Regulatory effect of Jiedu Huayu granules on liver injury in mice with acute liver failure and its mechanism
Chengyu YA ; Tingshuai WANG ; Huiping YAN ; Yi WANG ; Qingrui ZHAO ; Shenglan ZENG ; Weiyu CHEN ; Rongzhen ZHANG
Journal of Clinical Hepatology 2026;42(1):143-150
ObjectiveTo investigate the mechanism of action of Jiedu Huayu granules in improving liver injury in mice with acute liver failure (ALF) by observing its effect on a mouse model of ALF after prophylactic administration, and to provide a basis for clinical medication. MethodsA total of 60 specific pathogen-free male C57BL/6J mice were divided into normal group, model group, Jiedu Huayu granules group (JDHY group), and farnesoid X receptor (FXR) agonist (GW4064) group using a random number table, with 15 mice in each group. The model of ALF was induced by a single intraperitoneal injection of D-galactosamine combined with lipopolysaccharide. The mice in the JDHY group were given prophylactic administration of 0.3 g/mL drug solution of Jiedu Huayu granules by gavage for 3 days before modeling, those in the normal group and the model group were given 0.9% NaCl solution by gavage, and those in the GW4064 group were given intraperitoneal injection of GW4064 for 3 consecutive days before modeling. The mice were sacrificed after modeling, and serum and liver tissue samples were collected. A veterinary automatic biochemical analyzer was used to measure the serum levels of total bilirubin (TBil), total bile acids (TBA), gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in mice from each group; HE staining was used to observe liver pathological changes; RT-PCR was used to measure the mRNA expression levels of FXR, fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), small heterodimer partner (SHP), and bile salt export pump (BSEP) in mice, and Western blot was used to measure the protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP. A one-way analysis of variance was used for comparison between groups, and the Dunett method was used for further comparison between two groups. ResultsCompared with the normal group, the model group had significant increases in the serum levels of TBil, ALT, AST, TBA, and GGT (all P<0.01), and compared with the model group, the JDHY group and the GW4064 group had significant reductions in the serum levels of TBil, ALT, AST, TBA, and GGT (all P <0.01). HE staining showed that compared with the model group, the JDHY group and the GW4064 group had milder pathological injury, a reduction in the area of hepatocyte necrosis, and alleviation of cellular swelling and edema. Compared with the normal group, the model group had significant reductions in the mRNA and protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP in liver tissue (all P <0.01), and compared with the model group, the JDHY group and the GW4064 group had significant increases in the mRNA and protein expression levels of FXR, FGF15, FGFR4, SHP, and BSEP in liver tissue (all P <0.05). ConclusionJiedu Huayu granules may alleviate liver injury in mice with ALF through the FXR/SHP axis.
4.Response to Comments on “Pretreatment 68Ga-PSMA-11 PET/CT to Predict the Response to Treatment With Immune Checkpoint Inhibitors Plus Tyrosine Kinase Inhibitors in Patients With Metastatic Renal Cell Carcinoma”
Shao-Hao CHEN ; Xiao-Hui WU ; Qian-Ren-Shun QIU ; Shao-Ming CHEN ; Jie ZANG ; Jun-Ming ZHU ; Cheng-Long ZENG ; Wei-Bing MIAO ; Xue-Yi XUE ; Ning XU
Korean Journal of Radiology 2026;27(2):188-190
5.The protein arginine methyltransferase PRMT1 ameliorates cerebral ischemia-reperfusion injury by suppressing RIPK1-mediated necroptosis and apoptosis.
Tengfei LIU ; Gan HUANG ; Xin GUO ; Qiuran JI ; Lu YU ; Runzhe ZONG ; Yiquan LI ; Xiaomeng SONG ; Qingyi FU ; Qidi XUE ; Yi ZHENG ; Fanshuo ZENG ; Ru SUN ; Lin CHEN ; Chengjiang GAO ; Huiqing LIU
Acta Pharmaceutica Sinica B 2025;15(8):4014-4029
Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.
6.Effects of Yiqi Huoxue Jiedu formula on the gut microbiota in elderly patients with pulmonary-derived sepsis based on 16S rDNA sequencing: a multicenter prospective randomized double-blind controlled trial.
Rui CHEN ; Jiahua LAI ; Minlin ZHONG ; Ruifeng ZENG ; Fang LAI ; Yi YU ; Yuntao LIU ; Xiaotu XI ; Jun LI
Chinese Critical Care Medicine 2025;37(5):416-423
OBJECTIVE:
To investigate the effects of the combined Yiqi Huoxue Jiedu formula (YHJF) on intestinal microbiota in elderly patients with pulmonary-derived sepsis and identify potential microbial targets.
METHODS:
A prospective randomized double-blind controlled trial was conducted. Elderly patients with pulmonary infection-induced sepsis admitted to the emergency department of Guangdong Provincial Hospital of Traditional Chinese Medicine (TCM), intensive care unit (ICU) of Fangcun Hospital, and ICU of Daxuecheng Hospital, from November 2020 to October 2021 were enrolled and randomized into two groups. Both groups received conventional Western medicine treatment. The observation group additionally received YHJF (composed of 15 g of Panax ginseng, 9 g of Panax notoginseng, and 3 g of Rheum palmatum, dissolved in 50 mL warm water) orally or via nasogastric tube twice daily for 7 days; while the control group received a placebo. Clinical data and fresh fecal samples were collected before treatment and on days 5-7 of treatment. Intestinal microbiota diversity and structure were analyzed via 16S rDNA sequencing and bioinformatics [α diversity, β diversity, and linear discriminant analysis effect size (LEfSe)].
RESULTS:
Fifty-five patients were included (29 in the control group, 26 in the observation group). There were no significantly differences in gender, age, comorbidities, and baseline sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), acute gastrointestinal injury (AGI) classification score, and gastrointestinal failure (GIF) score between the two groups. Compared to the control group, the observation group showed significantly lower serum procalcitonin, APACHE II score, and greater reduction in GIF score by day 7. Thirty fecal samples were collected pre-treatment (baseline group), 29 post-treatment from the control group, and 26 from the observation group. Gut microbiota α diversity analysis revealed that Simpson index in the observation group and control group were significantly decreased compared to the baseline group [0.75 (0.53, 0.91), 0.81 (0.32, 0.91) vs. 0.88 (0.87, 0.89), both P < 0.05], but there was no significantly difference between the observation group and the control group. There were no significantly differences in Chao1, Ace, and Shannon indices among three groups. β diversity analysis indicated that distinct microbiota structures among three groups (R2 = 0.096, P = 0.026). Species difference analysis showed that, at the phylum level, Firmicutes (53.69%), Actinobacteria (16.23%), Proteobacteria (15.39%), and Bacteroidetes (9.57%) dominated, with no significant intergroup differences. At the genus level, 38 taxa showed significant differences. Compared to the control group, the observation group exhibited increased Erysipelatoclostridium (P = 0.014) and Faecalibacterium (P = 0.013), and decreased Bacteroides (P = 0.009), Bilophila (P = 0.005), Eggerthella (P = 0.002), and Collinsella (P = 0.043). LEfSe analysis highlighted Lactobacillus salivarius, Erysipelatoclostridium, Collinsella, Cloacibacillus, and Bacteroides as key discriminators.
CONCLUSION
YHJF combined with conventional therapy alters intestinal microbiota structure in patients with elderly pulmonary-derived sepsis, with Bacteroides, Erysipelatoclostridium, and Collinsella identified as potential microbial targets.
Humans
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Gastrointestinal Microbiome/drug effects*
;
Drugs, Chinese Herbal/therapeutic use*
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Double-Blind Method
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Sepsis/drug therapy*
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Aged
;
Prospective Studies
;
RNA, Ribosomal, 16S/genetics*
;
Male
;
Female
;
Panax notoginseng
;
Rheum
7.Study on the efficacy of automatic-controlled pressure cupping for lumbar disc herniation.
Bo-Chen PENG ; Min-Shan FENG ; Li LI ; Gui-Ju REN ; Yi-Zhen YUAN ; Li-Jie CHANG ; Shu-Ying REN ; Liu ZENG ; Guang-Wei LIU ; Li-Guo ZHU ; Na YUAN
China Journal of Orthopaedics and Traumatology 2025;38(11):1133-1138
OBJECTIVE:
To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping.
METHODS:
A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety.
RESULTS:
All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001).
CONCLUSION
Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans
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Female
;
Male
;
Intervertebral Disc Displacement/physiopathology*
;
Middle Aged
;
Adult
;
Lumbar Vertebrae/physiopathology*
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Cupping Therapy/methods*
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Pressure
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Aged
;
Treatment Outcome
8.Buyang Huanwu Decoction promotes angiogenesis after oxygen-glucose deprivation/reoxygenation injury of bEnd.3 cells by regulating YAP1/HIF-1α signaling pathway via caveolin-1.
Bo-Wei CHEN ; Yin OUYANG ; Fan-Zuo ZENG ; Ying-Fei LIU ; Feng-Ming TIAN ; Ya-Qian XU ; Jian YI ; Bai-Yan LIU
China Journal of Chinese Materia Medica 2025;50(14):3847-3856
This study aims to explore the mechanism of Buyang Huanwu Decoction(BHD) in promoting angiogenesis after oxygen-glucose deprivation/reoxygenation(OGD/R) of mouse brain microvascular endothelial cell line(brain-derived Endothelial cells.3, bEnd.3) based on the caveolin-1(Cav1)/Yes-associated protein 1(YAP1)/hypoxia-inducible factor-1α(HIF-1α) signaling pathway. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to analyze the blood components of BHD. The cell counting kit-8(CCK-8) method was used to detect the optimal intervention concentration of drug-containing serum of BHD after OGD/R injury of bEnd.3. The lentiviral transfection method was used to construct a Cav1 silent stable strain, and Western blot and polymerase chain reaction(PCR) methods were used to verify the silencing efficiency. The control bEnd.3 cells were divided into a normal group(sh-NC control group), an OGD/R model + blank serum group(sh-NC OGD/R group), and an OGD/R model + drug-containing serum group(sh-NC BHD group). Cav1 silent cells were divided into an OGD/R model + blank serum group(sh-Cav1 OGD/R group) and an OGD/R model + drug-containing serum group(sh-Cav1 BHD group). The cell survival rate was detected by the CCK-8 method. The cell migration ability was detected by a cell migration assay. The lumen formation ability was detected by an angiogenesis assay. The apoptosis rate was detected by flow cytometry, and the expression of YAP1/HIF-1α signaling pathway-related proteins in each group was detected by Western blot. Finally, co-immunoprecipitation was used to verify the interaction between YAP1 and HIF-1α. The results showed astragaloside Ⅳ, formononetin, ferulic acid, and albiflorin in BHD can all enter the blood. The drug-containing serum of BHD at a mass fraction of 10% may be the optimal intervention concentration for OGD/R-induced injury of bEnd.3 cells. Compared with the sh-NC control group, the sh-NC OGD/R group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, significantly increased cell apoptotic rate, significantly lowered phosphorylation level of YAP1 at S127 site, and significantly elevated nuclear displacement level of YAP1 and protein expression of HIF-1α, vascular endothelial growth factor(VEGF), and vascular endothelial growth factor receptor 2(VEGFR2). Compared with the same type of OGD/R group, the sh-NC BHD group and sh-Cav1 BHD group had significantly increased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly decreased cell apoptotic rate, a further decreased phosphorylation level of YAP1 at S127 site, and significantly increased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC OGD/R group, the sh-Cav1 OGD/R group exhibited significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. Compared with the sh-NC BHD group, the sh-Cav1 BHD group showed significantly decreased cell survival rate, cell migration rate, mesh number, node number, and lumen length, a significantly increased cell apoptotic rate, a significantly increased phosphorylation level of YAP1 at the S127 site, and significantly decreased nuclear displacement level of YAP1 and protein expression of HIF-1α, VEGF, and VEGFR2. YAP1 protein was present in the protein complex precipitated by the HIF-1α antibody, and HIF-1α protein was also present in the protein complex precipitated by the YAP1 antibody. The results confirmed that the drug-containing serum of BHD can increase the activity of YAP1/HIF-1α pathway in bEnd.3 cells damaged by OGD/R through Cav1 and promote angiogenesis in vitro.
Drugs, Chinese Herbal/pharmacology*
;
Animals
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Mice
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Signal Transduction/drug effects*
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Glucose/metabolism*
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Caveolin 1/genetics*
;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
;
YAP-Signaling Proteins
;
Oxygen/metabolism*
;
Endothelial Cells/metabolism*
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Cell Line
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Adaptor Proteins, Signal Transducing/genetics*
;
Neovascularization, Physiologic/drug effects*
;
Cell Hypoxia/drug effects*
;
Angiogenesis
9.Inhibition GATA4 decreases susceptibility to age-related atrial fibrillation by regulating calcium cycling through NLRP3 signaling pathway
Yingqi YI ; Li LIU ; Zhanglan WANG ; Qingyi ZENG ; Wei LI ; Jingjing CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(10):1405-1412
Objective To investigate the impact of inhibiting GATA binding protein 4(GATA4)on the susceptibility to atrial fibrillation in elderly individuals and to elucidate the underlying mecha-nisms.Methods Fifteen 3-month-old young SD rats and 45 18-month-old SD rats were selected.According to the age and the injection of adeno-associated virus,the rats were divided into young group,elderly group,negative control group and interfering GATA4 group,with 15 rats in each group.Based on age and AAV injection,the rats were categorized into four groups:young group,elderly group,negative control group,and GATA4 interference group,with 15 rats in each group.Left atrial anteroposterior diameter was assessed via echocardiography.The extent of atrial fibro-sis was evaluated using Masson staining.Western blot analysis was employed to examine the ex-pression levels of GATA4,calcium cycling-related proteins,and NOD-like receptor pyrin domain-containing protein 3(NLRP3).Mouse atrial myocytes(HL-1 cells)were divided into five groups according to viral infection:control group,knockdown negative control group,GATA4 knock-down group,overexpression negative control group,and GATA4 overexpression group.The expression of GATA4 and NLRP3 was analyzed using Western blotting.Results The incidence of atrial fibrillation in the elderly group was significantly higher than that in the young group(80.0%vs 11.1%,P<0.01).Compared with the negative control group,the induction rate of atrial fibrillation in the GATA4 interference group was significantly decreased(22.2%vs 80.0%,P<0.05).Compared with the young group,the left atrial diameter,percentage of collagen vol-ume,activation time,absolute value of conduction dispersion,and expression of NLPR3 in the aged group were significantly increased,and the expression of calcium cycling protein was disor-dered(P<0.05,P<0.01).Compared with the negative control group,the left atrial diameter,per-centage of collagen volume,activation time,absolute value of conduction dispersion,and expres-sion of NLPR3 in the GATA4 interference group were significantly decreased,and the disturbance of calcium circulation was alleviated(P<0.05,P<0.01).Compared with the negative group of knockdown and overexpression,the expression of GATA4 and NLRP3 in HL1 cells in GATA4 knockdown group was significantly decreased,and the expression of GATA4 and NLPR3 in HL-1 cells in GATA4 overexpression group was significantly increased(P<0.01).Conclusion GATA4 inhibition decreases the susceptibility to atrial fibrillation and mitigates age-related structural remodeling,electrical remodeling,and inflammation in the atrium by regulating calcium cycling disorders and myocardial cell senescence via the NLRP3 pathway.
10.Health economics evaluation of inoculation of children with type b Haemophilus influenzae vaccine
Sisi CHEN ; Lu YANG ; Tian TANG ; Xinping ZHANG ; Huan QIN ; Chengfeng XIE ; Yi ZENG ; Fei CAO ; Hongying LI ; Feina DENG ; Zhengbo TU ; Xiuwen CHEN
Chinese Journal of Nosocomiology 2025;35(17):2651-2655
OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53%(42 cases)in both groups,and the female children accounted for 42.47%(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.

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