1.Efficacy and safety of botulinum toxin type A injection combined with sacral neuro-modulation in the treatment of idiopathic non-obstructive urinary retention
Yongkun ZENG ; Qingwei WANG ; Wen ZHU ; Zikai LI ; Shuo XU ; Chuanyu WANG ; Ke JIN
Journal of Modern Urology 2025;30(12):1069-1074
Objective To evaluate the efficacy and safety of botulinum toxin A (BTX-A) injection into the external urethral sphincter in combination with sacral neuromodulation (SNM) for the treatment of idiopathic non-obstructive urinary retention (INOUR). Methods A total of 57 INOUR patients treated in our hospital during May 2022 and May 2024 were enrolled. Patients were divided into the BTX (n=30) and combined groups (n=27) according to whether they chose SNM after BTX-A injection. The baseline, postoperative 1-month and 6-month consecutive 3-day voiding diaries, quality of life score (QoL), and post-void residual (PVR), preoperative and postoperative 1-month urodynamic results, and postoperative complications were recorded and compared between the two groups. Results One month after surgery, the average number of voiding frequency per day and PVR were lower in both groups than those before surgery (P<0.05), while the average daily urine volume and maximum flow rate (MFR) were higher (P<0.05). There was no statistically significant difference between the maximum detrusor pressure during micturition in both groups before and after surgery (P>0.05). One month after surgery, the average number of voiding frequency per day, average daily urine volume, PVR, QoL, MFR, bladder compliance (BC), and maximum cystometric capacity (MCC) were better in the combined group than in the BTX group (P<0.05), and the efficiency was higher in the combined group (88.9% vs.63.3%, P<0.05). Six months after surgery, the efficacy of the BTX group returned to the baseline level with no statistically significant difference, whereas the efficacy of the combined group was stable (not different from the postoperative 1-month indicators, but better than the baseline level). During the follow-up, there was no difference in the incidence of complications between the BTX group and combined group [43.3% (13/30) vs. 48.1% (13/27), P>0.05]. Conclusion BTX-A injection into the external urethral sphincter combined with SNM improves the short-term outcomes of INOUR patients and maintains the efficacy 6 months postoperatively, which is a safe and reliable treatment option.
2.Clinical effect and safety of modified injection approach in temporal area depression
Mingzi ZHANG ; Zhijin LI ; Wenbo XIA ; Zikai QIU ; Xuda MA ; Sichao CHEN ; Loubin SI ; Zhifei LIU ; Xiaojun WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(2):138-142
Objective:To investigate the clinical efficacy and safety of a modified injection technique for improving temporal concavity deformities.Methods:A prospective study was conducted on 157 female patients who underwent temporal concavity augmentation at the Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, from June 2019 to June 2022. The patients were aged from 32 to 48 (38.2±3.1) years. Granular fat was obtained through liposuction and purification. Using the midpoint of the frontotemporal line as the entry point, the granular fat tissue was injected evenly at multiple points under the skin and superficial temporal fascia. Additional granular fat was injected in the temporal edge area to ensure a smooth appearance. The visual analogue scale (VAS) was used to assess the patients' intraoperative pain levels. Follow-up visits were conducted for one year postoperatively to assess patient satisfaction with the improvement in temporal concavity, local pigmentation, and fine lines in the lateral orbital area based on preoperative and postoperative photographs. Complications, including swelling, ecchymosis, hematoma, fat embolism, infection, fat liquefaction, and subcutaneous induration, were recorded immediately after surgery and at the one-year follow-up.Results:All the 157 patients experienced mild swelling in the injection area postoperatively, which resolved within 3 to 6 days. Ecchymosis occurred in 15 patients and spontaneously resolved within 10 days. Eleven patients had asymmetry in the filled area, with 3 recovering after local massage and observation, and the remaining 8 undergoing a second fat grafting procedure. A total of 25 patients underwent more than two fat grafting procedures, including 4 who underwent three procedures. Mild local hematoma occurred in 3 patients postoperatively. The intraoperative pain VAS was (1.8±0.5) score. After treatment, the improvement scores for temporal concavity, local pigmentation, and fine lines in the lateral orbital area were (7.4±0.7), (6.8±0.7), and (7.9±0.7) scores, respectively. After one year of follow-up, no complications such as fat embolism, infection, fat liquefaction, or subcutaneous induration were observed in the 157 patients.Conclusion:The modified injection technique for improving temporal concavity deformities is safe and effective, with high patient satisfaction.
3.Primary regional disparities in clinical characteristics, treatments, and outcomes of a typically designed study of valvular heart disease at 46 tertiary hospitals in China: Insights from the China-VHD Study.
Xiangming HU ; Yunqing YE ; Zhe LI ; Qingrong LIU ; Zhenyan ZHAO ; Zheng ZHOU ; Weiwei WANG ; Zikai YU ; Haitong ZHANG ; Zhenya DUAN ; Bincheng WANG ; Bin ZHANG ; Junxing LV ; Shuai GUO ; Yanyan ZHAO ; Runlin GAO ; Haiyan XU ; Yongjian WU
Chinese Medical Journal 2025;138(8):937-946
BACKGROUND:
Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China.
METHODS:
Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan-Meier survival analysis was used to compare the cumulative incidence rate.
RESULTS:
Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P <0.05).
CONCLUSIONS:
This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics.
REGISTRATION
ClinicalTrials.gov , NCT03484806.
Aged
;
Female
;
Humans
;
Male
;
Middle Aged
;
China/epidemiology*
;
Heart Valve Diseases/therapy*
;
Kaplan-Meier Estimate
;
Tertiary Care Centers
;
Treatment Outcome
4.Potential effects of ornidazole on intracanal vascularization in endodontic regeneration
Zikai LI ; Chengcheng ZHANG ; Jiaying XIONG ; Xirui YANG ; Jing YANG ; Haishan SHI
Chinese Journal of Tissue Engineering Research 2025;29(14):2892-2898
BACKGROUND:In endodontics,revascularization and effective control of bacterial infection are prerequisite for regenerative repair of tissues and further development of the root apex.Ornidazole,carried in pulp-capping materials or vascularized scaffolding materials may control pulpal infections,but its effect on vascularization need to be investigated.OBJECTIVE:To investigate the residual concentration pattern of ornidazole in root canals and to evaluate the effects of ornidazole on endothelial cell proliferation,migration,and differentiation,as well as on vascular irritation.METHODS:(1)Ornidazole was encapsulated in the isolated pulp cavity and then immersed in Hank's balanced salt solution for 7 days.Ornidazole was then removed from the pulp cavity,reencapsulated in sterile water,and again immersed in Hank's balanced salt solution.The mass concentration of ornidazole in the pulp cavity fluid was measured periodically by colorimetric method.(2)Human umbilical vein endothelial cells were inoculated into well plates.Adherent cells were stimulated by the addition of lipopolysaccharide for 24 hours,and then co-cultured by the addition of 0,1,2,5,8,10 μg/mL ornidazole,to detect the cellular activity and migratory ability.Human umbilical vein endothelial cells were inoculated in well plates and co-cultured with different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole or stimulated by lipopolysaccharide for 24 hours followed by the addition of different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole.The gene expression of vascular endothelial growth factor and basic fibroblast growth factor as well as the protein expression of vascular endothelial growth factor was detected.(3)The chorioallantoic membrane assay was employed to assess the vascular irritation of 2 and 10 μg/mL ornidazole.RESULTS AND CONCLUSION:Residual ornidazole in exfoliated teeth was rapidly released within the initial 6 days,with a subsequent decrease in release rate,maintaining a concentration of approximately 2 μg/mL at the root apex after 8 days.Under lipopolysaccharide-induced inflammatory conditions,cell counting kit-8 and cell live-dead fluorescence staining showed that ornidazole(1-10 μg/mL)had no significant effect on the activity of human umbilical vein endothelial cells,and the cell scratch assay showed that ornidazole(1-10 μg/mL)had no obvious effect on the migratory ability of human umbilical vein endothelial cells.RT-qPCR assay showed that,after co-cultivation with ornidazole alone,the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells showed an overall decreasing trend.After co-culturing with ornidazole under lipopolysaccharide-induced inflammation,the mRNA expression of the two factors showed a rising trend in human umbilical vein endothelial cells.Western blot assay showed that vascular endothelial growth factor protein expression had an elevating trend in human umbilical vein endothelial cells after co-culture with ornidazole under lipopolysaccharide-induced inflammatory conditions.The chorioallantoic membrane assay showed that 2 and 10 μg/mL ornidazole were non-vascular irritating.To conclude,1-10 μg/mL ornidazole is non-cytotoxic and non-vascular irritating,promotes the expression of angiogenesis-related genes and proteins in inflammatory endothelial cells,and serves as a potential therapeutic agent for pulpal infection control.
5.Effect and mechanism of Penthorum chinense Pursh extract on alleviating diarrhea in weaned piglets
Shicheng BI ; Hanlin ZHOU ; Zikai LI ; Lin DU ; Aishi XU ; Weidong HU ; Hongsheng OUYANG
Chinese Journal of Veterinary Science 2025;45(9):1999-2007
To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25%),medium-dose prevention group(0.50%)and high-dose pre-vention group(1.00%).Starting from the 14 th day,0.25%,0.50%and 1.00%PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25%),the medium-dose prevention group(0.50%),and the high-dose prevention group(1.00%)was significantly reduced at 28-62 d(P<0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P<0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.
6.Effect and mechanism of Penthorum chinense Pursh extract on alleviating diarrhea in weaned piglets
Shicheng BI ; Hanlin ZHOU ; Zikai LI ; Lin DU ; Aishi XU ; Weidong HU ; Hongsheng OUYANG
Chinese Journal of Veterinary Science 2025;45(9):1999-2007
To observe the effect of penthorum chinense pursh(PCP)on diarrhea in weaned pig-lets,and to explore its mechanism through network pharmacology and in vivo animal experiments.Animal experiment 1 A total of 160 1-day-old piglets were randomly divided into control group,low-dose prevention group(0.25%),medium-dose prevention group(0.50%)and high-dose pre-vention group(1.00%).Starting from the 14 th day,0.25%,0.50%and 1.00%PCP were added to the basal diet of the three prevention groups and weaned.PCP was stopped on the 29th day,and the diarrhea rate of piglets was recorded for 35 d.In animal experiment 2,35 4-week-old male Kunming mice were randomly divided into 5 groups(control group,LPS group,low-dose group,medium-dose group and high-dose group)for 8 d.The low-dose group,the medium-dose group and the high-dose group were intragastrically administered with 200,400 and 800 mg/kg PCP for 7 consecutive days,respectively.The control group and the LPS group were intragastrically administered with the same amount of sterile saline.On the 8th day of the experiment,except that the Control group was intraperitoneally injected with sterile normal saline,the other groups were intraperitoneally injec-ted with the same amount of LPS(15 mg/kg)to establish an intestinal injury model.HE staining was used for ileal histopathological observation,and fluorescence quantitative PCR was used to de-tect the expression levels of inflammatory factors and tight junction protein mRNA.The TCMSP database was used to screen the active components and targets of PCP,and the GeneCards database was used to obtain the targets of diarrhea.The targets of PCP and diarrhea were imported into Li-anchuan biological cloud platform,and the Venn diagram was obtained after intersection.The pro-tein-protein interaction(PPI)network was constructed by combining Cytoscape 3.7.1 and STRING database,and GO and KEGG enrichment analysis was performed by KOBAS-i platform.The results showed that compared with the control group,the diarrhea rate of weaned piglets in the low-dose prevention group(0.25%),the medium-dose prevention group(0.50%),and the high-dose prevention group(1.00%)was significantly reduced at 28-62 d(P<0.05).According to the prediction of network pharmacology,there were 32 corresponding targets of 145 potential com-ponents of PCP,6 332 targets of diarrhea,and 118 intersection targets.The protective mechanism of PCP in the treatment of diarrhea may be related to NF-κB and PI3k-Akt signaling pathways.Further experiments confirmed that compared with the LPS group,PCP can significantly improve the pathological state of ileum in mice,the mRNA expression level of intestinal tight junction pro-tein Occludin(P<0.05)was reversed.At the same time,PCP also significantly down-regulated the mRNA level of NF-κB.The results showed that PCP may alleviate diarrhea in piglets through multiple targets and multiple pathways.The main mechanism may be related to the inhibition of Akt-NF-κB signaling pathway.This study is conducive to providing a theoretical basis for the clini-cal application of PCP.
7.Potential effects of ornidazole on intracanal vascularization in endodontic regeneration
Zikai LI ; Chengcheng ZHANG ; Jiaying XIONG ; Xirui YANG ; Jing YANG ; Haishan SHI
Chinese Journal of Tissue Engineering Research 2025;29(14):2892-2898
BACKGROUND:In endodontics,revascularization and effective control of bacterial infection are prerequisite for regenerative repair of tissues and further development of the root apex.Ornidazole,carried in pulp-capping materials or vascularized scaffolding materials may control pulpal infections,but its effect on vascularization need to be investigated.OBJECTIVE:To investigate the residual concentration pattern of ornidazole in root canals and to evaluate the effects of ornidazole on endothelial cell proliferation,migration,and differentiation,as well as on vascular irritation.METHODS:(1)Ornidazole was encapsulated in the isolated pulp cavity and then immersed in Hank's balanced salt solution for 7 days.Ornidazole was then removed from the pulp cavity,reencapsulated in sterile water,and again immersed in Hank's balanced salt solution.The mass concentration of ornidazole in the pulp cavity fluid was measured periodically by colorimetric method.(2)Human umbilical vein endothelial cells were inoculated into well plates.Adherent cells were stimulated by the addition of lipopolysaccharide for 24 hours,and then co-cultured by the addition of 0,1,2,5,8,10 μg/mL ornidazole,to detect the cellular activity and migratory ability.Human umbilical vein endothelial cells were inoculated in well plates and co-cultured with different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole or stimulated by lipopolysaccharide for 24 hours followed by the addition of different mass concentrations(0,1,2,5,8,10 μg/mL)of ornidazole.The gene expression of vascular endothelial growth factor and basic fibroblast growth factor as well as the protein expression of vascular endothelial growth factor was detected.(3)The chorioallantoic membrane assay was employed to assess the vascular irritation of 2 and 10 μg/mL ornidazole.RESULTS AND CONCLUSION:Residual ornidazole in exfoliated teeth was rapidly released within the initial 6 days,with a subsequent decrease in release rate,maintaining a concentration of approximately 2 μg/mL at the root apex after 8 days.Under lipopolysaccharide-induced inflammatory conditions,cell counting kit-8 and cell live-dead fluorescence staining showed that ornidazole(1-10 μg/mL)had no significant effect on the activity of human umbilical vein endothelial cells,and the cell scratch assay showed that ornidazole(1-10 μg/mL)had no obvious effect on the migratory ability of human umbilical vein endothelial cells.RT-qPCR assay showed that,after co-cultivation with ornidazole alone,the mRNA expression of vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells showed an overall decreasing trend.After co-culturing with ornidazole under lipopolysaccharide-induced inflammation,the mRNA expression of the two factors showed a rising trend in human umbilical vein endothelial cells.Western blot assay showed that vascular endothelial growth factor protein expression had an elevating trend in human umbilical vein endothelial cells after co-culture with ornidazole under lipopolysaccharide-induced inflammatory conditions.The chorioallantoic membrane assay showed that 2 and 10 μg/mL ornidazole were non-vascular irritating.To conclude,1-10 μg/mL ornidazole is non-cytotoxic and non-vascular irritating,promotes the expression of angiogenesis-related genes and proteins in inflammatory endothelial cells,and serves as a potential therapeutic agent for pulpal infection control.
8.Clinical effect and safety of modified injection approach in temporal area depression
Mingzi ZHANG ; Zhijin LI ; Wenbo XIA ; Zikai QIU ; Xuda MA ; Sichao CHEN ; Loubin SI ; Zhifei LIU ; Xiaojun WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(2):138-142
Objective:To investigate the clinical efficacy and safety of a modified injection technique for improving temporal concavity deformities.Methods:A prospective study was conducted on 157 female patients who underwent temporal concavity augmentation at the Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, from June 2019 to June 2022. The patients were aged from 32 to 48 (38.2±3.1) years. Granular fat was obtained through liposuction and purification. Using the midpoint of the frontotemporal line as the entry point, the granular fat tissue was injected evenly at multiple points under the skin and superficial temporal fascia. Additional granular fat was injected in the temporal edge area to ensure a smooth appearance. The visual analogue scale (VAS) was used to assess the patients' intraoperative pain levels. Follow-up visits were conducted for one year postoperatively to assess patient satisfaction with the improvement in temporal concavity, local pigmentation, and fine lines in the lateral orbital area based on preoperative and postoperative photographs. Complications, including swelling, ecchymosis, hematoma, fat embolism, infection, fat liquefaction, and subcutaneous induration, were recorded immediately after surgery and at the one-year follow-up.Results:All the 157 patients experienced mild swelling in the injection area postoperatively, which resolved within 3 to 6 days. Ecchymosis occurred in 15 patients and spontaneously resolved within 10 days. Eleven patients had asymmetry in the filled area, with 3 recovering after local massage and observation, and the remaining 8 undergoing a second fat grafting procedure. A total of 25 patients underwent more than two fat grafting procedures, including 4 who underwent three procedures. Mild local hematoma occurred in 3 patients postoperatively. The intraoperative pain VAS was (1.8±0.5) score. After treatment, the improvement scores for temporal concavity, local pigmentation, and fine lines in the lateral orbital area were (7.4±0.7), (6.8±0.7), and (7.9±0.7) scores, respectively. After one year of follow-up, no complications such as fat embolism, infection, fat liquefaction, or subcutaneous induration were observed in the 157 patients.Conclusion:The modified injection technique for improving temporal concavity deformities is safe and effective, with high patient satisfaction.
9.The effect and mechanism of Panax notoginseng saponins through inhibiting JNK/c-Jun signaling pathway in calcific aortic valve disease
Hongzheng LI ; Tianjiao LIU ; Zucheng SHANG ; Mengfan LI ; Guosheng LIN ; Bin ZHANG ; Zikai YU ; Changgeng FU ; Yongjian WU ; Keji CHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1550-1561
Objective To investigate the effect and mechanism of Panax notoginseng saponins(PNS)in inhibiting c-Jun N-terminal protein kinase(JNK)/c-Jun signaling pathway activation to alleviate calcific aortic valve disease(CAVD)in mice.Methods Twenty-one male ApoE-/-mice aged 6 to 8 weeks were randomly divided into the model,PNS high-dose(60 mg/kg),and PNS low-dose(30 mg/kg)groups using the random number table method,with seven mice per group.Nine male C57BL/6 mice aged 6 to 8 weeks were used as the control group.Mice in the control group were fed a normal diet,whereas ApoE-/-mice were fed a high-fat diet for 12 weeks.After 12 weeks,three C57BL/6 and three ApoE-/-mice(one ApoE-/-mice from each group)were randomly selected to evaluate the CAVD modeling effect.After confirming successful modeling,the PNS high-and low-dose groups received daily intragastric PNS administration.The control and model groups were administered an equal volume of stroke-physiological saline solution by gavage for 4 consecutive weeks.The valve annulus diameter and peak velocity of the mice in each group were then detected using ultrasound.The degree of aortic valve calcification was evaluated using von Kossa and Alizarin Red S staining.The serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Inflammatory factor interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)levels were determined using an enzyme-linked immunosorbent assay.The expressions of calcification markers,runt-related transcription factor 2(RUNX2),and bone morphogenetic protein 2(BMP2)were detected using immunohistochemistry.Aortic valve cell apoptosis was evaluated using TUNEL staining,and JNK/c-Jun signaling pathway-related mRNA and mean fluorescence intensity were detected using quantitative real-time PCR and immunofluorescence,respectively.Results Compared with the control group,the mice in the model group showed an increase in serum TC,TG,LDL-C,TNF-α,and IL-1β levels,a decrease in IL-4 and IL-10 levels,a decrease in annulus diameter,an increase in peak flow velocity,and an increase in von Kossa and Alizarin Red S staining-positive areas.Additionally,the model group showed an increase in aortic valve cell apoptosis rate,an increase in BMP2 and RUNX2-positive rates,and an increase in JNK and c-Jun mRNA expression levels and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Compared to the model group,the PNS low-dose group showed a decrease in serum TC,LDL-C,and TNF-α levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in positive area in Alizarin Red S staining.Furthermore,the PNS low-dose group showed a decrease in BMP2 and RUNX2-positive rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).The PNS high-dose group showed an increase in HDL-C,IL-4 and IL-10 levels,a decrease in serum TC,LDL-C,TNF-α,and IL-1β levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in von Kossa and Alizarin Red S staining-positive areas and cell apoptosis rate.The PNS high-dose group also showed a decrease in BMP2 and RUNX2 positive staining rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Conclusion PNS may reduce valvular cell apoptosis,alleviate inflammation,and protect against aortic valve calcification in mice by inhibiting the activation of JNK/c-Jun signaling pathway.
10.The effect and mechanism of Panax notoginseng saponins through inhibiting JNK/c-Jun signaling pathway in calcific aortic valve disease
Hongzheng LI ; Tianjiao LIU ; Zucheng SHANG ; Mengfan LI ; Guosheng LIN ; Bin ZHANG ; Zikai YU ; Changgeng FU ; Yongjian WU ; Keji CHEN
Journal of Beijing University of Traditional Chinese Medicine 2024;47(11):1550-1561
Objective To investigate the effect and mechanism of Panax notoginseng saponins(PNS)in inhibiting c-Jun N-terminal protein kinase(JNK)/c-Jun signaling pathway activation to alleviate calcific aortic valve disease(CAVD)in mice.Methods Twenty-one male ApoE-/-mice aged 6 to 8 weeks were randomly divided into the model,PNS high-dose(60 mg/kg),and PNS low-dose(30 mg/kg)groups using the random number table method,with seven mice per group.Nine male C57BL/6 mice aged 6 to 8 weeks were used as the control group.Mice in the control group were fed a normal diet,whereas ApoE-/-mice were fed a high-fat diet for 12 weeks.After 12 weeks,three C57BL/6 and three ApoE-/-mice(one ApoE-/-mice from each group)were randomly selected to evaluate the CAVD modeling effect.After confirming successful modeling,the PNS high-and low-dose groups received daily intragastric PNS administration.The control and model groups were administered an equal volume of stroke-physiological saline solution by gavage for 4 consecutive weeks.The valve annulus diameter and peak velocity of the mice in each group were then detected using ultrasound.The degree of aortic valve calcification was evaluated using von Kossa and Alizarin Red S staining.The serum triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical method.Inflammatory factor interleukin-4(IL-4),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-10(IL-10)levels were determined using an enzyme-linked immunosorbent assay.The expressions of calcification markers,runt-related transcription factor 2(RUNX2),and bone morphogenetic protein 2(BMP2)were detected using immunohistochemistry.Aortic valve cell apoptosis was evaluated using TUNEL staining,and JNK/c-Jun signaling pathway-related mRNA and mean fluorescence intensity were detected using quantitative real-time PCR and immunofluorescence,respectively.Results Compared with the control group,the mice in the model group showed an increase in serum TC,TG,LDL-C,TNF-α,and IL-1β levels,a decrease in IL-4 and IL-10 levels,a decrease in annulus diameter,an increase in peak flow velocity,and an increase in von Kossa and Alizarin Red S staining-positive areas.Additionally,the model group showed an increase in aortic valve cell apoptosis rate,an increase in BMP2 and RUNX2-positive rates,and an increase in JNK and c-Jun mRNA expression levels and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Compared to the model group,the PNS low-dose group showed a decrease in serum TC,LDL-C,and TNF-α levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in positive area in Alizarin Red S staining.Furthermore,the PNS low-dose group showed a decrease in BMP2 and RUNX2-positive rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).The PNS high-dose group showed an increase in HDL-C,IL-4 and IL-10 levels,a decrease in serum TC,LDL-C,TNF-α,and IL-1β levels,an increase in annulus diameter,a decrease in peak flow velocity,and a decrease in von Kossa and Alizarin Red S staining-positive areas and cell apoptosis rate.The PNS high-dose group also showed a decrease in BMP2 and RUNX2 positive staining rates,JNK and c-Jun mRNA expression levels,and p-JNK/JNK and p-c-Jun/c-Jun(P<0.05).Conclusion PNS may reduce valvular cell apoptosis,alleviate inflammation,and protect against aortic valve calcification in mice by inhibiting the activation of JNK/c-Jun signaling pathway.

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