1.Diterpenoids and lignans from fossil Chinese medicinal succinum and their activity against renal fibrosis.
Yefei CHEN ; Yunfei WANG ; Yunyun LIU ; Yongming YAN ; Yongxian CHENG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):888-896
Five previously undescribed diterpenoids, named succipenoids D‒H (1‒5), along with four undescribed lignans, named succignans A‒D (6‒9), were isolated from the dichloromethane extract of Chinese medicinal succinum. Compounds 1‒5 were characterized as nor-abietane diterpenoids, while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units. The structures of these novel compounds, including their absolute configurations, were determined through spectroscopic and computational methods. Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis, including α-smooth muscle actin (α-SMA), collagen I, and fibronectin in transforming growth factor-β1 (TGF-β1) induced normal rat kidney proximal tubular epithelial cells (NRK-52e).
Animals
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Rats
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Lignans/isolation & purification*
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Diterpenes/isolation & purification*
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Fibrosis/drug therapy*
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Drugs, Chinese Herbal/pharmacology*
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Molecular Structure
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Cell Line
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Kidney Diseases/pathology*
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Transforming Growth Factor beta1/genetics*
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Kidney/metabolism*
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Actins/genetics*
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Fibronectins/genetics*
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Collagen Type I/genetics*
;
Epithelial Cells/metabolism*
2.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
3.Using diffusion-relaxation correlation spectroscopic imaging to assess the heterogeneity of head and neck tumors and identify occult lymph node metastasis
Siyu LI ; Ya CHEN ; Wentao HU ; Yongming DAI ; Yingwei WU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(9):1202-1213
Objective·To evaluate the feasibility and diagnostic performance of diffusion-relaxation correlation spectroscopic imaging(DR-CSI)in assessing the heterogeneity of benign and malignant head and neck tumors,as well as in identifying occult lymph node metastasis(OLNM).Methods·A prospective study was conducted from January to December 2024 at Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,enrolling patients with suspected head and neck tumors who were scheduled for surgery and had a confirmed pathological diagnosis.All patients underwent preoperative routine head and neck plain and contrast-enhanced magnetic resonance imaging(MRI)examinations,including DR-CSI sequence.Conventional imaging parameters,including maximal diameter(MD),depth of invasion(DOI)for tumors,and MD and short diameter(SD)for lymph nodes,were obtained.Post-processing was performed to obtain apparent diffusion coefficient(ADC),T2 value,and D-T2 spectra for all lesions.The compartment segmentation strategy was optimized based on the spectral peak distribution characteristics of different diseases,and the volume fraction(Vi)of each compartment was obtained.Independent sample t-tests,Mann-Whitney U tests,chi-square tests,or Fisher's exact tests were used to compare intergroup differences in clinical data and imaging metrics.Principal component analysis(PCA)and Adonis analysis were employed to evaluate the discriminative ability of imaging metrics among different subtypes of benign tumors.Receiver operating characteristic(ROC)analysis was used to evaluate the ability of univariate and multivariable models to characterize the malignancy of head and neck squamous cell carcinoma(HNSCC)and identify OLNM.Results·A total of 97 cases were collected,including 28 benign tumors and 69 HNSCCs.Fifteen pathologically confirmed OLNMs and 20 benign lymph nodes(BLNs)were also enrolled.Among the 28 benign tumors,there were 6 cases of pleomorphic adenoma stroma-rich(PA stroma-rich),9 cases of pleomorphic adenoma stroma-poor(PA stroma-poor),9 cases of Warthin's tumor(WT),and 4 cases of basal cell adenoma(BCA).Statistically significant differences were observed in certain imaging parameters(ADC,T2,and DR-CSI Vi)among benign tumor subtypes.PCA analysis demonstrated a strong discriminative ability of imaging parameters in distinguishing pathological subtypes of benign tumors(R2=0.64,P<0.001).Among the 69 HNSCCs,47 were classified as Grade 1(well/moderately well-differentiated)and 22 as Grade 2(moderately/poorly differentiated).Compared to Grade 1,Grade 2 showed lower ADC and higher T2 values,though differences were not statistically significant.As HNSCC malignancy increased,VA4 decreased and VB4 increased significantly.OLNM showed a significant increase in SD and VA4 compared to BLNs.The combination of SD and VA4 for preoperative OLNM identification achieved a diagnostic efficiency of 0.843.Conclusion·DR-CSI can analyze diffusion and relaxation characteristics at the sub-voxel level,offering valuable insights for characterizing benign head and neck tumor subtypes,assessing HNSCC malignancy,and identifying OLNMs.Compared to traditional parameters like ADC or T2,DR-CSI provides enhanced tissue microstructure analysis.
4.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
5.Combination of the LPS/TLR4 Pathway and Fecal Metabolomics Analysis Reveals the Chronic Inflammatory Mechanism of Early Atherosclerosis in Tibetan Miniature Pigs
Qinqin YANG ; Songtao XU ; Yueqin CAI ; Yongming PAN ; Junjie HUANG ; Keyan ZHU ; Minli CHEN ; Xiaoping XU
Cardiology Discovery 2025;05(2):121-132
Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.
6.Predictive Value of apoB and apoB/A1 in Acute Myocardial Infarction of Phlegm Blended with Blood Stasis Syndrome
Guangmei CHEN ; Kang YUAN ; Jingli CHEN ; Dandan ZHAO ; Na HUANG ; Yongming YANG ; Ying BI
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(3):546-551
Objective To analyze the predictive value of apolipoprotein B(apoB)and apoB to apolipoprotein A1(apoA1)ratio(apoB/A1)in acute myocardial infarction(AMI)of phlegm blended with blood stasis syndrome.Methods A total of 200 patients with AMI confirmed by coronary angiography in Foshan Hospital of Traditional Chinese Medicine during the trial period were collected.Data collection covered the basic information of gender,age,medical history of hypertension,coronary heart disease and diabetes mellitus,and smoking history,the information of four diagnostic methods of traditional Chinese medicine(TCM),and relevant indicators of blood lipids,the number of lesioned branches of coronary arteries and the Gensini scores.The predictive value of apoB and apoB/A1 for AMI of phlegm blended with blood stasis syndrome was explored by univariate Logistic regression analysis and multivariate Logistic regression analysis as well as by plotting the Receiver Operating Characteristic(ROC)curves.Results(1)Among the 200 AMI patients,41 cases were differentiated as qi deficiency and blood stasis syndrome,36 cases as qi stagnation and blood stasis syndrome,74 cases as phlegm blended with blood stasis syndrome,and 49 cases as other syndromes(including 16 cases of cold accumulation in heart vessels syndrome,22 cases of qi and yin deficiency syndrome,and 11 cases of healthy-qi deficiency and yang collapse syndrome).(2)The difference of Gensini scores among the patients with various TCM syndrome types were statistically significant(H=43.735,P=0.000<0.001).And the Gensini scores in the patients with syndromes of qi deficiency and blood stasis,qi stagnation and blood stasis,and phlegm blended with blood stasis were relatively high,being 60.0(43.0,87.0),70.0(48.5,84.0)and 65.0(40.0,95.0)points,respectively,which were higher than that of the other TCM syndrome types[44.0(32.0,64.0)points].The pairwise comparison between various TCM syndrome types showed that the differences were statistically significant(P<0.05).However,there was no statistically significant difference in the number of lesioned branches of coronary arteries among the patients with various TCM syndrome types(H=1.180,P=0.758>0.05).(3)The results of correlation analysis showed that the number of lesioned branches of coronary arteries,Gensini score and apoB/A1 were significantly and positively correlated(r=0.140,P=0.049<0.05;r=0.205,P=0.004<0.01).(4)The results of univariate Logistic regression analysis and multivariate Logistic regression analysis showed that apoB and apoB/A1 were the independent risk factors for phlegm blended with blood stasis syndrome(P<0.01).ROC curve analysis showed that apoB/A-1 exerted a high predictive value for AMI of phlegm blended with blood stasis syndrome,with high sensitivity and specificity.Conclusion It is indicated that ApoB/A1 can be used as an objective indicator for predicting AMI of phlegm blended with blood stasis syndrome in clinical practice.
7.Combination of the LPS/TLR4 Pathway and Fecal Metabolomics Analysis Reveals the Chronic Inflammatory Mechanism of Early Atherosclerosis in Tibetan Miniature Pigs
Qinqin YANG ; Songtao XU ; Yueqin CAI ; Yongming PAN ; Junjie HUANG ; Keyan ZHU ; Minli CHEN ; Xiaoping XU
Cardiology Discovery 2025;05(2):121-132
Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.
8.Using diffusion-relaxation correlation spectroscopic imaging to assess the heterogeneity of head and neck tumors and identify occult lymph node metastasis
Siyu LI ; Ya CHEN ; Wentao HU ; Yongming DAI ; Yingwei WU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(9):1202-1213
Objective·To evaluate the feasibility and diagnostic performance of diffusion-relaxation correlation spectroscopic imaging(DR-CSI)in assessing the heterogeneity of benign and malignant head and neck tumors,as well as in identifying occult lymph node metastasis(OLNM).Methods·A prospective study was conducted from January to December 2024 at Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,enrolling patients with suspected head and neck tumors who were scheduled for surgery and had a confirmed pathological diagnosis.All patients underwent preoperative routine head and neck plain and contrast-enhanced magnetic resonance imaging(MRI)examinations,including DR-CSI sequence.Conventional imaging parameters,including maximal diameter(MD),depth of invasion(DOI)for tumors,and MD and short diameter(SD)for lymph nodes,were obtained.Post-processing was performed to obtain apparent diffusion coefficient(ADC),T2 value,and D-T2 spectra for all lesions.The compartment segmentation strategy was optimized based on the spectral peak distribution characteristics of different diseases,and the volume fraction(Vi)of each compartment was obtained.Independent sample t-tests,Mann-Whitney U tests,chi-square tests,or Fisher's exact tests were used to compare intergroup differences in clinical data and imaging metrics.Principal component analysis(PCA)and Adonis analysis were employed to evaluate the discriminative ability of imaging metrics among different subtypes of benign tumors.Receiver operating characteristic(ROC)analysis was used to evaluate the ability of univariate and multivariable models to characterize the malignancy of head and neck squamous cell carcinoma(HNSCC)and identify OLNM.Results·A total of 97 cases were collected,including 28 benign tumors and 69 HNSCCs.Fifteen pathologically confirmed OLNMs and 20 benign lymph nodes(BLNs)were also enrolled.Among the 28 benign tumors,there were 6 cases of pleomorphic adenoma stroma-rich(PA stroma-rich),9 cases of pleomorphic adenoma stroma-poor(PA stroma-poor),9 cases of Warthin's tumor(WT),and 4 cases of basal cell adenoma(BCA).Statistically significant differences were observed in certain imaging parameters(ADC,T2,and DR-CSI Vi)among benign tumor subtypes.PCA analysis demonstrated a strong discriminative ability of imaging parameters in distinguishing pathological subtypes of benign tumors(R2=0.64,P<0.001).Among the 69 HNSCCs,47 were classified as Grade 1(well/moderately well-differentiated)and 22 as Grade 2(moderately/poorly differentiated).Compared to Grade 1,Grade 2 showed lower ADC and higher T2 values,though differences were not statistically significant.As HNSCC malignancy increased,VA4 decreased and VB4 increased significantly.OLNM showed a significant increase in SD and VA4 compared to BLNs.The combination of SD and VA4 for preoperative OLNM identification achieved a diagnostic efficiency of 0.843.Conclusion·DR-CSI can analyze diffusion and relaxation characteristics at the sub-voxel level,offering valuable insights for characterizing benign head and neck tumor subtypes,assessing HNSCC malignancy,and identifying OLNMs.Compared to traditional parameters like ADC or T2,DR-CSI provides enhanced tissue microstructure analysis.
9.Clinical study on the treatment of 2-3cm renal stones with intelligent pressure controlled retrograde nephrolithotomy
Zhongsheng YANG ; Junjing WU ; Hua CHEN ; Yongming HUANG ; Leming SONG
China Modern Doctor 2024;62(14):15-18
Objective To investigate the clinical efficacy and safety of intelligent pressure controlled retrograde renal surgery(IRIRS)for the treatment of 2-3cm kidney stones.Methods Totally 110 patients with renal stones with a diameter of 2-3cm admitted to Ganzhou People's Hospital from January 2019 to December 2021 were randomly divided into IRIRS group and control group(microchannel percutaneous nephrolithotomy with vacuum aspiration),with 55 cases in each group.The surgical time,rate of stone clearance,hemoglobin decrease,scores for postoperative pain,hospital stay and incidence of complications were systematically compared between the two groups.Results The surgical time and stone clearance rates at four weeks post-operation did not exhibit any statistically significant differences between the IRIRS group and the control group(P>0.05).The hospitalization time,hemoglobin decrease,and scores for postoperative pain in the IRIRS group were notably lower compared to the control group,with these differences being statistically significant(P<0.05).The difference in total postoperative complication rates between the IRIRS and control groups was not statistically significant(P>0.05).Conclusion IRIRS is an effective and safe method for treating renal stones with a diameter of 2-3 cm,meriting broader clinical adoption and application.
10.Effects of stimulator of interferon gene on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 in mouse dendritic cells under sepsis
Mengyao WU ; Pengyi HE ; Yu DUAN ; Liyu ZHENG ; Renqi YAO ; Qiyuan ZHOU ; Yu CHEN ; Ning DONG ; Yao WU ; Yongming YAO
Chinese Journal of Burns 2024;40(10):920-929
Objective:To investigate the effects of stimulator of interferon gene (STING) on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 (ACSL4) in mouse dendritic cells (DCs) under sepsis, providing a basis for improving the dysregulation of immune response in sepsis caused by factors such as wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) were divided into lipopolysaccharide (LPS) stimulation 0 h (unstimulated) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 18 h group, and LPS stimulation 24 h group according to the random number table (the same grouping method below), which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of phosphorylated STING (p-STING), STING, and ACSL4 in cells were determined by Western blotting. DC2.4 successfully transfected with lentivirus containing STING gene small interfering RNA (hereinafter referred to as siSTING) were divided into siSTING+phosphate buffer solution (PBS) group and siSTING+LPS group. DC2.4 successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After being stimulated with PBS or LPS and cultured for 24 hours, the protein expressions of p-STING, STING, and ACSL4 in cells were determined as above. Cell lipid peroxidation degrees were observed using the lipid peroxidation assay kit, and cell apoptosis rates were detected using flow cytometry. The sample numbers in the above cell experiments were all 3. Eighty male C57BL/6J mice aged 6 to 8 weeks were divided into sham surgery+normal saline (NS) group, cecal ligation and puncture (CLP)+NS group, sham surgery+C-176 group, and CLP+C-176 group, with 20 mice in each group. Mice in the two C-176 groups were intraperitoneally injected with C-176, while mice in the two NS groups were intraperitoneally injected with an equivalent volume of NS. One hour later, sham surgery was performed on the mice in the two sham surgery groups, and CLP surgery was performed on the mice in the two CLP groups to establish a sepsis model. At 24 h post-surgery, 10 mice from each group were sacrificed to extract spleen DCs, and protein expression, lipid peroxidation, and apoptosis rates were detected as above ( n=3). Hematoxylin-eosin staining was performed to observe pathological damage in the heart, liver, lung, and kidney tissue. The remaining 10 mice in each group were observed for survival within 7 days after surgery. Results:The protein expressions of p-STING, STING, and ACSL4, as well as the p-STING/STING ratio in DC2.4 in LPS stimulation 24 h group were significantly higher than those in LPS stimulation 0 h group ( P<0.05). After 24 h of culture, the protein expressions of p-STING, STING, and ACSL4 in DC2.4 in siSTING+LPS group and empty vector+PBS group were significantly lower than those in empty vector+LPS group ( P<0.05); the lipid peroxidation degrees of DC2.4 in siSTING+LPS group and empty vector+PBS group were weaker than those in empty vector+LPS group. The apoptosis rates of DC2.4 in empty vector+PBS group, empty vector+LPS group, siSTING+PBS group, and siSTING+LPS group were (15.7±3.0)%, (37.8±2.9)%, (13.1±2.1)%, and (20.6±1.8)%, respectively. The apoptosis rates of DC2.4 in empty vector+PBS group and siSTING+LPS group were significantly lower than that in empty vector+LPS group ( P<0.05). At 24 h post-surgery, the protein expressions of p-STING and ACSL4, and the p-STING/STING ratio in spleen DCs of mice in CLP+NS group were significantly higher than those in sham surgery+NS group and CLP+C-176 group ( P<0.05); the protein expression of STING in spleen DCs of mice in CLP+NS group was significantly higher than that in sham surgery+NS group ( P<0.05); the lipid peroxidation degrees of spleen DCs of mice in CLP+C-176 group and sham surgery+NS group were weaker than that in CLP+NS group. The apoptosis rates of spleen DCs of mice in sham surgery+NS group and CLP+C-176 group were significantly lower than that in CLP+NS group ( P<0.05), and the apoptosis rate of spleen DCs of mice in CLP+C-176 group was significantly higher than that in sham surgery+C-176 group ( P<0.05). Pathological tissue damage in the heart, liver, lung, and kidney of mice in CLP+NS group was significantly worse than that in sham surgery+NS group, while such damage in the above organs of mice in CLP+C-176 group was significantly alleviated compared with that in CLP+NS group. The survival ratio of mice in CLP+NS group within 7 days after surgery was significantly lower than that in sham surgery+NS group ( χ2=8.30, P<0.05). Conclusions:Under sepsis, STING activation in mouse DCs is significant, which enhances ACSL4-mediated ferroptosis. Inhibiting STING activation can significantly reduce ACSL4-mediated ferroptosis level in mouse DCs under sepsis, thereby improving the survival rate of septic mice.

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