1.Regulation of skin pigmentation by miR-25-5p via targeting RAB11B: a mechanistic study
Wenzhu WANG ; Hedan YANG ; Yunyao LIU ; Xiaojie SUN ; Xiaoli ZHANG ; Xiuzhen LI ; Siqi TAN ; Haoxiang XU ; Yin YANG ; Tong LIN
Chinese Journal of Dermatology 2025;58(9):816-824
Objective:To investigate the role of microRNA-25-5p (miR-25-5p) in melanogenesis, and to explore its underlying mechanisms.Methods:Target genes of miR-25-5p were predicted using the TargetScan database. The interaction between miR-25-5p and the 3' untranslated region (3' UTR) of the RAB11B gene (a member of RAS oncogene family) was validated through a dual-luciferase reporter assay. Post-inflammatory hyperpigmentation (PIH) models were established in female C57BL/6J mice (6 - 8 weeks old) and female brown guinea pigs (4 - 6 weeks old) through daily broadband ultraviolet B (UVB) irradiation on the dorsal skin of the mouse ear or shaved dorsal skin of guinea pigs, while untreated mice and untreated dorsal skin areas of guinea pigs served as control groups. During modeling, these experimental animals received intradermal injections of a miR-25-5p agomir or a miR control agomir. Changes in skin pigmentation were observed, and skin tissue samples were harvested for further analysis after modeling. Melanin content in skin tissues was evaluated using Masson-Fontana staining. Expression of RAB11B and tyrosinase (TYR) in skin tissues was determined using immunohistochemical staining and quantitative real-time PCR (qPCR). Primary human melanocytes were isolated from discarded normal foreskin tissues of healthy males after circumcision. Both primary human melanocytes and human MNT1 melanoma cells were transfected with miR-25-5p mimics or miR control mimics. Relative expression levels of miR-25-5p and RAB11B mRNA were quantified by qPCR using the 2 -ΔΔCt calculation method. In MNT1 cells, miR-25-5p and RAB11B were co-overexpressed to assess their effect on the mRNA expression of RAB11B and TYR. Statistical analysis was conducted using t test or one-way analysis of variance followed by Tukey's post hoc test for multiple comparisons. Results:The bioinformatic prediction and dual-luciferase reporter assay confirmed a binding site for miR-25-5p in the 3′ UTR of the RAB11B gene. In both animal models, the treatment with the miR-25-5p agomir significantly reduced local skin pigmentation compared to the control groups; Masson-Fontana staining showed a marked decrease in the density of melanin granules in the epidermis and dermis in the miR-25-5p agomir groups compared with the miR control agomir groups (mice: 0.050 ± 0.005 vs. 0.087 ± 0.008; guinea pigs: 0.067 ± 0.015 vs. 0.110 ± 0.013; both P < 0.05). Immunohistochemical staining revealed significantly lower expression of RAB11B in mouse skin tissues in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). qPCR revealed significantly lower mRNA expression of RAB11B and TYR in skin tissues of guinea pigs in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). Similarly, RAB11B mRNA expression significantly decreased in the miR-25-5p mimics group compared with the miR control mimics group in primary human melanocytes and MNT1 cells (both P < 0.05). In human MNT1 melanoma cells, miR-25-5p overexpression could suppress TYR mRNA expression, whereas co-overexpression of miR-25-5p and RAB11B could reverse this suppression. Conclusion:Overexpression of miR-25-5p could alleviate UVB-induced post-inflammatory hyperpigmentation and inhibit melanogenesis, likely by targeted suppression of RAB11B expression.
2.Separation,purification and immunomodulatory activity of polysaccharides from Polygonatum filipes
Yunyun SUN ; Ming ZHAO ; Shiyue QIN ; Sichun ZHENG ; Haoxiang ZHANG ; Xiaodan MA ; Xiaoliang LI ; Wei XU
Chinese Journal of Immunology 2025;41(1):182-188,194
Objective:To separate and purify the polysaccharides from Polygonatum filipes,characterize their primary structure and investigate the immunomodulatory effects on RAW264.7 macrophages.Methods:Crude polysaccharides from Polygonatum filipes were extracted by ultrasound assisted method,then Polygonatum filipes polysaccharides(CSPFPs)were obtained after elimination of the proteins with combined papain-Sevag method.The total sugar content was determined by phenol-sulfuric acid method.Structures of CSPFPs were analyzed by fourier transform infrared spectroscopy(FT-IR),high performance gel permeation chromatography(HPGPC)and high performance liquid chromatography(HPLC).Effects of CSPFPs on cell viability,pinocytic activity,TNF-α secretion,MAPK and NF-κB signaling pathways of RAW264.7 cells were explored by MTT,Neutral red,ELISA and Western blot,respectively.Results:Extraction rate of CSPFPs by ultrasound-assisted method was 41.61%,which contained total sugar content of 94.00%.CSPFPs with Mw of 3 125 Da was composed of arabinose(1.85%),galactose(6.14%),glucose(56.41%)and mannose(35.60%).The in vitro experiments showed that CSPFPs were non-cytotoxic and enhanced the pinocytic activity,TNF-α secretion and phosphorylation levels of p38,ERK,JNK,p65,IκB and IKK,indicating the activation of MAPK and NF-κB signaling pathways under the concentra-tion of 2.5~200 μg/ml.Conclusion:The ultrasound-assisted method can efficiently isolate CSPFPs with immunomodulatory activity,which provides basic data for the development and application of CSPFPs as an immunostimulant.
3.Development and validation of a predictive model for postoperative blood pressure outcomes in primary aldosteronism based on CYP11B2 gene polymorphism
Qiangfeng FU ; Yongjia CHEN ; Shengtao ZENG ; Haoxiang XU ; Chenglin YANG ; Yue YANG ; Zhi CAO ; Wei WANG
Chinese Journal of Urology 2025;46(7):529-536
Objective:To construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females,with a body mass index(BMI)of(25.50 ± 2.03)kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery,and polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP)were used to detect CYP11B2(rs1799998)promoter region 344(C > T)base substitution. The follow-up duration was more than 6 months,with the following parameters recorded at the last follow-up:plasma aldosterone,renin,serum potassium,and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score(PASO)for primary aldosteronism,and the specific criteria were as follows. ① Clinical complete remission:the patient's blood pressure returned to normal(< 140/90 mmHg,1 mmHg = 0.133 kPa)and all antihypertensive drugs were discontinued;②Partial clinical remission:blood pressure returns to normal,and the number or dose of antihypertensive drugs is reduced compared with before;③Clinical non-remission:blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis,followed by binary logistic forward conditional regression for multivariate analysis,and a variety of machine learning algorithms such as random forest,logistic regression,support vector machine and gradient lifter were integrated,and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model,and the predictive performance of the model was evaluated by using receiver operating characteristic(ROC)curve,calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2(344C > T)(rs1799998)as follows:CC type in 50 cases(43.1%),CT type in 46 cases(39.7%),and TT type in 20 cases(17.3%). There were 74 cases in the complete remission group and 42 cases in the incomplete remission group,and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index[(24.27 ± 2.90)kg/m 2 vs.(26.98 ± 3.17)kg/m 2, P<0.001],preoperative hypertension grade(grade 1/2/3:29/29/16 cases vs. 9/13/20 cases, P = 0.012),preoperative antihypertensive drugs(0/1/≥ 2:25/32/17 cases vs. 7/15/20 cases, P = 0.016),and CYP11B2(344C > T)(CC/TT + CT:39/35 cases vs. 11/31 cases, P = 0.006)were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs[≥ 2: OR = 5.26(95% CI 1.12?24.61, P = 0.016;1: OR = 4.55(95% CI 1.23?22.47), P = 0.025]was the strongest independent predictor,followed by CYP11B2(344C > T)[ OR = 4.02(95% CI 1.16?13.82), P = 0.028]and BMI[ OR = 3.96(95% CI 2.26?6.92), P < 0.001]. Comparing the receiver operating feature(ROC)curves of the four types of machine learning models,the best model was the support vector machine model with an area under the curve(AUC)of 0.88(95% CI 0.82?0.95),followed by the gradient elevator model of 0.83(95% CI 0.76?0.91),the logistic regression model of 0.78(95% CI 0.68?0.88),and the random forest model of 0.77(95% CI 0.68?0.86). The optimal threshold of the Yoden index of the support vector machine model was 0.588,with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms,BMI,and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients,providing new evidence for personalized treatment strategies
4.Separation,purification and immunomodulatory activity of polysaccharides from Polygonatum filipes
Yunyun SUN ; Ming ZHAO ; Shiyue QIN ; Sichun ZHENG ; Haoxiang ZHANG ; Xiaodan MA ; Xiaoliang LI ; Wei XU
Chinese Journal of Immunology 2025;41(1):182-188,194
Objective:To separate and purify the polysaccharides from Polygonatum filipes,characterize their primary structure and investigate the immunomodulatory effects on RAW264.7 macrophages.Methods:Crude polysaccharides from Polygonatum filipes were extracted by ultrasound assisted method,then Polygonatum filipes polysaccharides(CSPFPs)were obtained after elimination of the proteins with combined papain-Sevag method.The total sugar content was determined by phenol-sulfuric acid method.Structures of CSPFPs were analyzed by fourier transform infrared spectroscopy(FT-IR),high performance gel permeation chromatography(HPGPC)and high performance liquid chromatography(HPLC).Effects of CSPFPs on cell viability,pinocytic activity,TNF-α secretion,MAPK and NF-κB signaling pathways of RAW264.7 cells were explored by MTT,Neutral red,ELISA and Western blot,respectively.Results:Extraction rate of CSPFPs by ultrasound-assisted method was 41.61%,which contained total sugar content of 94.00%.CSPFPs with Mw of 3 125 Da was composed of arabinose(1.85%),galactose(6.14%),glucose(56.41%)and mannose(35.60%).The in vitro experiments showed that CSPFPs were non-cytotoxic and enhanced the pinocytic activity,TNF-α secretion and phosphorylation levels of p38,ERK,JNK,p65,IκB and IKK,indicating the activation of MAPK and NF-κB signaling pathways under the concentra-tion of 2.5~200 μg/ml.Conclusion:The ultrasound-assisted method can efficiently isolate CSPFPs with immunomodulatory activity,which provides basic data for the development and application of CSPFPs as an immunostimulant.
5.Construction of a predictive model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke
Yafeng SHEN ; Deyou XUE ; Haoxiang XU ; Derang JIAO
Chinese Journal of Cerebrovascular Diseases 2025;22(10):690-700
Objective To construct a predictive model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke and evaluate its predictive efficacy.Methods Patients with acute stroke caused by anterior circulation large vessel occlusion who underwent endovascular treatment with successful vascular recanalization(modified thrombolysis in cerebral infarction[mTICI]grade 2b or 3)admitted to the Department of Neurosurgery of Tianjin Union Medical Center(the First Affiliated Hospital of Nankai University)from January 2022 to January 2025 were retrospectively and consecutively included.Patients were divided into effective recanalization group(modified Rankin scale[mRS]score≤2)and futile recanalization group(mRS score>2)according to the mRS score at 90 days after endovascular treatment.Baseline and clinical data were collected,including sex,age,medical history(stroke history,hypertension,diabetes mellitus,atrial fibrillation),personal history(smoking history,alcohol consumption history),and National Institutes of Health stroke scale(NIHSS)score,blood pressure,blood glucose,total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,creatinine,neutrophil-to-lymphocyte ratio,fibrinogen,D-dimer,lymphocyte-to-monocyte ratio,white blood cell count,hemoglobin,albumin,C-reactive protein-to-albumin ratio,platelet-to-lymphocyte ratio at admission.Imaging data including culprit vessel(middle cerebral artery,anterior cerebral artery,internal carotid artery),Alberta stroke program early CT score(ASPECTS),infarct core volume,hypoperfusion area volume,mismatch volume between infarct core and hypoperfusion area,American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR)collateral circulation grading,trial of Org 10172 in acute stroke treatment(TOAST)classification.Surgery-related data including onset-to-puncture time,successful puncture-to-vascular recanalization time,immediate postoperative mTICI grade,complications within 24 hours postoperatively(fever,hemorrhagic transformation,symptomatic intracranial hemorrhage),immediate postoperative mTICI grade.Factors with P<0.05 and without multicollinearity(variance inflation factor≥5)in univariate analysis were included in multivariate Logistic regression model analysis to analyze independent influencing factors for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.A nomogram prediction model was constructed based on statistically significant factors in multivariate Logistic regression analysis,and Hosmer-Lemeshow test was used to assess the goodness of fit of the model.The receiver operating characteristic(ROC)curve of the nomogram prediction model for predicting futile recanalization after endovascular treatment in patients with anterior circulation large vessel occlusion stroke was drawn,and calibration curve was used to evaluate the calibration of the nomogram prediction model.Results A total of 187 patients who met the criteria of this study were included,comprising 101 males and 86 females,aged 42-85 years,with a mean age of(70±6)years.The mRS scores at 90days after treatment were:0points in 21 cases(11.23%),1 point in 37 cases(19.79%),2 points in 28 cases(14.97%),3 points in 46 cases(24.60%),4 points in 31 cases(16.58%),5 points in 24 cases(12.83%),and 6 points in 0case.There were 86cases in the effective recanalization group and 101 cases in the futile recanalization group.(1)Statistically significant differences between the two groups were observed in age,atrial fibrillation,infarct core volume,admission NIHSS score,neutrophil-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and C-reactive protein-to-albumin ratio(all P<0.05).(2)Multicollinearity analysis showed that the variance inflation factors of all independent variables with statistically significant differences in univariate analysis were all<5,indicating no multicollinearity.Multivariate Logistic regression analysis showed that age(OR,1.101,95%CI 1.046-1.158,P=0.037),infarct core volume(OR,1.350,95%CI 1.202-1.517,P<0.01),admission NIHSS score(OR,1.501,95%CI 1.213-1.858,P<0.01),lymphocyte-to-monocyte ratio(OR,0.039,95%CI 0.009-0.179,P<0.01),and C-reactive protein-to-albumin ratio(OR,6.015,95%CI 1.625-22.257,P=0.007)were independent influencing factors for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.(3)The receiver operating characteristic curve of the nomogram prediction model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke was constructed based on statistically significant factors in multivariate analysis showed a specificity of 0.970,sensitivity of 0.895,precision of 0.916,recall of 0.970,and area under the curve of 0.979(95%CI0.962-0.996,P<0.01).The absolute mean error of the calibration curve was 0.008,with predicted values close to actual values.Hosmer-Lemeshow test results showed that the model had good consistency without overfitting(χ2=4.830,P=0.776).Conclusions Age,infarct core volume,admission NIHSS score,lymphocyte-to-monocyte ratio,and C-reactive protein-to-albumin ratio are all independent influencing factors for futile recanalization after endovascular treatment in acute anterior circulation large vessel occlusion stroke.The nomogram prediction model constructed accordingly can predict the risk of futile recanalization after endovascular treatment in patients with anterior circulation large vessel occlusion stroke.
6.Regulation of skin pigmentation by miR-25-5p via targeting RAB11B: a mechanistic study
Wenzhu WANG ; Hedan YANG ; Yunyao LIU ; Xiaojie SUN ; Xiaoli ZHANG ; Xiuzhen LI ; Siqi TAN ; Haoxiang XU ; Yin YANG ; Tong LIN
Chinese Journal of Dermatology 2025;58(9):816-824
Objective:To investigate the role of microRNA-25-5p (miR-25-5p) in melanogenesis, and to explore its underlying mechanisms.Methods:Target genes of miR-25-5p were predicted using the TargetScan database. The interaction between miR-25-5p and the 3' untranslated region (3' UTR) of the RAB11B gene (a member of RAS oncogene family) was validated through a dual-luciferase reporter assay. Post-inflammatory hyperpigmentation (PIH) models were established in female C57BL/6J mice (6 - 8 weeks old) and female brown guinea pigs (4 - 6 weeks old) through daily broadband ultraviolet B (UVB) irradiation on the dorsal skin of the mouse ear or shaved dorsal skin of guinea pigs, while untreated mice and untreated dorsal skin areas of guinea pigs served as control groups. During modeling, these experimental animals received intradermal injections of a miR-25-5p agomir or a miR control agomir. Changes in skin pigmentation were observed, and skin tissue samples were harvested for further analysis after modeling. Melanin content in skin tissues was evaluated using Masson-Fontana staining. Expression of RAB11B and tyrosinase (TYR) in skin tissues was determined using immunohistochemical staining and quantitative real-time PCR (qPCR). Primary human melanocytes were isolated from discarded normal foreskin tissues of healthy males after circumcision. Both primary human melanocytes and human MNT1 melanoma cells were transfected with miR-25-5p mimics or miR control mimics. Relative expression levels of miR-25-5p and RAB11B mRNA were quantified by qPCR using the 2 -ΔΔCt calculation method. In MNT1 cells, miR-25-5p and RAB11B were co-overexpressed to assess their effect on the mRNA expression of RAB11B and TYR. Statistical analysis was conducted using t test or one-way analysis of variance followed by Tukey's post hoc test for multiple comparisons. Results:The bioinformatic prediction and dual-luciferase reporter assay confirmed a binding site for miR-25-5p in the 3′ UTR of the RAB11B gene. In both animal models, the treatment with the miR-25-5p agomir significantly reduced local skin pigmentation compared to the control groups; Masson-Fontana staining showed a marked decrease in the density of melanin granules in the epidermis and dermis in the miR-25-5p agomir groups compared with the miR control agomir groups (mice: 0.050 ± 0.005 vs. 0.087 ± 0.008; guinea pigs: 0.067 ± 0.015 vs. 0.110 ± 0.013; both P < 0.05). Immunohistochemical staining revealed significantly lower expression of RAB11B in mouse skin tissues in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). qPCR revealed significantly lower mRNA expression of RAB11B and TYR in skin tissues of guinea pigs in the miR-25-5p agomir group than in those in the miR control agomir group (both P < 0.05). Similarly, RAB11B mRNA expression significantly decreased in the miR-25-5p mimics group compared with the miR control mimics group in primary human melanocytes and MNT1 cells (both P < 0.05). In human MNT1 melanoma cells, miR-25-5p overexpression could suppress TYR mRNA expression, whereas co-overexpression of miR-25-5p and RAB11B could reverse this suppression. Conclusion:Overexpression of miR-25-5p could alleviate UVB-induced post-inflammatory hyperpigmentation and inhibit melanogenesis, likely by targeted suppression of RAB11B expression.
7.Construction of a predictive model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke
Yafeng SHEN ; Deyou XUE ; Haoxiang XU ; Derang JIAO
Chinese Journal of Cerebrovascular Diseases 2025;22(10):690-700
Objective To construct a predictive model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke and evaluate its predictive efficacy.Methods Patients with acute stroke caused by anterior circulation large vessel occlusion who underwent endovascular treatment with successful vascular recanalization(modified thrombolysis in cerebral infarction[mTICI]grade 2b or 3)admitted to the Department of Neurosurgery of Tianjin Union Medical Center(the First Affiliated Hospital of Nankai University)from January 2022 to January 2025 were retrospectively and consecutively included.Patients were divided into effective recanalization group(modified Rankin scale[mRS]score≤2)and futile recanalization group(mRS score>2)according to the mRS score at 90 days after endovascular treatment.Baseline and clinical data were collected,including sex,age,medical history(stroke history,hypertension,diabetes mellitus,atrial fibrillation),personal history(smoking history,alcohol consumption history),and National Institutes of Health stroke scale(NIHSS)score,blood pressure,blood glucose,total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,creatinine,neutrophil-to-lymphocyte ratio,fibrinogen,D-dimer,lymphocyte-to-monocyte ratio,white blood cell count,hemoglobin,albumin,C-reactive protein-to-albumin ratio,platelet-to-lymphocyte ratio at admission.Imaging data including culprit vessel(middle cerebral artery,anterior cerebral artery,internal carotid artery),Alberta stroke program early CT score(ASPECTS),infarct core volume,hypoperfusion area volume,mismatch volume between infarct core and hypoperfusion area,American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology(ASITN/SIR)collateral circulation grading,trial of Org 10172 in acute stroke treatment(TOAST)classification.Surgery-related data including onset-to-puncture time,successful puncture-to-vascular recanalization time,immediate postoperative mTICI grade,complications within 24 hours postoperatively(fever,hemorrhagic transformation,symptomatic intracranial hemorrhage),immediate postoperative mTICI grade.Factors with P<0.05 and without multicollinearity(variance inflation factor≥5)in univariate analysis were included in multivariate Logistic regression model analysis to analyze independent influencing factors for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.A nomogram prediction model was constructed based on statistically significant factors in multivariate Logistic regression analysis,and Hosmer-Lemeshow test was used to assess the goodness of fit of the model.The receiver operating characteristic(ROC)curve of the nomogram prediction model for predicting futile recanalization after endovascular treatment in patients with anterior circulation large vessel occlusion stroke was drawn,and calibration curve was used to evaluate the calibration of the nomogram prediction model.Results A total of 187 patients who met the criteria of this study were included,comprising 101 males and 86 females,aged 42-85 years,with a mean age of(70±6)years.The mRS scores at 90days after treatment were:0points in 21 cases(11.23%),1 point in 37 cases(19.79%),2 points in 28 cases(14.97%),3 points in 46 cases(24.60%),4 points in 31 cases(16.58%),5 points in 24 cases(12.83%),and 6 points in 0case.There were 86cases in the effective recanalization group and 101 cases in the futile recanalization group.(1)Statistically significant differences between the two groups were observed in age,atrial fibrillation,infarct core volume,admission NIHSS score,neutrophil-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and C-reactive protein-to-albumin ratio(all P<0.05).(2)Multicollinearity analysis showed that the variance inflation factors of all independent variables with statistically significant differences in univariate analysis were all<5,indicating no multicollinearity.Multivariate Logistic regression analysis showed that age(OR,1.101,95%CI 1.046-1.158,P=0.037),infarct core volume(OR,1.350,95%CI 1.202-1.517,P<0.01),admission NIHSS score(OR,1.501,95%CI 1.213-1.858,P<0.01),lymphocyte-to-monocyte ratio(OR,0.039,95%CI 0.009-0.179,P<0.01),and C-reactive protein-to-albumin ratio(OR,6.015,95%CI 1.625-22.257,P=0.007)were independent influencing factors for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke.(3)The receiver operating characteristic curve of the nomogram prediction model for futile recanalization after endovascular treatment in patients with acute anterior circulation large vessel occlusion stroke was constructed based on statistically significant factors in multivariate analysis showed a specificity of 0.970,sensitivity of 0.895,precision of 0.916,recall of 0.970,and area under the curve of 0.979(95%CI0.962-0.996,P<0.01).The absolute mean error of the calibration curve was 0.008,with predicted values close to actual values.Hosmer-Lemeshow test results showed that the model had good consistency without overfitting(χ2=4.830,P=0.776).Conclusions Age,infarct core volume,admission NIHSS score,lymphocyte-to-monocyte ratio,and C-reactive protein-to-albumin ratio are all independent influencing factors for futile recanalization after endovascular treatment in acute anterior circulation large vessel occlusion stroke.The nomogram prediction model constructed accordingly can predict the risk of futile recanalization after endovascular treatment in patients with anterior circulation large vessel occlusion stroke.
8.Development and validation of a predictive model for postoperative blood pressure outcomes in primary aldosteronism based on CYP11B2 gene polymorphism
Qiangfeng FU ; Yongjia CHEN ; Shengtao ZENG ; Haoxiang XU ; Chenglin YANG ; Yue YANG ; Zhi CAO ; Wei WANG
Chinese Journal of Urology 2025;46(7):529-536
Objective:To construct and validate a clinical model combining CYP11B2 gene polymorphisms with clinical parameters to predict complete postoperative hypertension remission in primary aldosteronism patients.Methods:The clinical data of a total of 116 patients with primary aldosteronism who underwent unilateral adrenalectomy from April 2018 to August 2024 were retrospectively included. There were 63 males and 53 females,with a body mass index(BMI)of(25.50 ± 2.03)kg/m 2. Genomic DNA was extracted from venous blood leukocytes before surgery,and polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP)were used to detect CYP11B2(rs1799998)promoter region 344(C > T)base substitution. The follow-up duration was more than 6 months,with the following parameters recorded at the last follow-up:plasma aldosterone,renin,serum potassium,and sodium levels. Blood pressure progression and antihypertensive medication usage were also assessed. The postoperative outcome was determined according to the Primary Aldosteronism Surgical Outcome score(PASO)for primary aldosteronism,and the specific criteria were as follows. ① Clinical complete remission:the patient's blood pressure returned to normal(< 140/90 mmHg,1 mmHg = 0.133 kPa)and all antihypertensive drugs were discontinued;②Partial clinical remission:blood pressure returns to normal,and the number or dose of antihypertensive drugs is reduced compared with before;③Clinical non-remission:blood pressure does not drop and antihypertensive drugs do not change or increase compared with before surgery. Patients were divided into complete and incomplete remission groups. The chi-square test was used for univariate analysis,followed by binary logistic forward conditional regression for multivariate analysis,and a variety of machine learning algorithms such as random forest,logistic regression,support vector machine and gradient lifter were integrated,and the results of multivariate analysis were included to construct a postoperative blood pressure outcome model,and the predictive performance of the model was evaluated by using receiver operating characteristic(ROC)curve,calibration curve and clinical decision curve. Results:The PCR-RFLP detection results of 116 cases showed the genotype distribution of CYP11B2(344C > T)(rs1799998)as follows:CC type in 50 cases(43.1%),CT type in 46 cases(39.7%),and TT type in 20 cases(17.3%). There were 74 cases in the complete remission group and 42 cases in the incomplete remission group,and the rate of complete remission with hypertension at the end of the operation was 63.8%. Univariate analysis showed that the the differences between complete remission group and incomplete remission group in body mass index[(24.27 ± 2.90)kg/m 2 vs.(26.98 ± 3.17)kg/m 2, P<0.001],preoperative hypertension grade(grade 1/2/3:29/29/16 cases vs. 9/13/20 cases, P = 0.012),preoperative antihypertensive drugs(0/1/≥ 2:25/32/17 cases vs. 7/15/20 cases, P = 0.016),and CYP11B2(344C > T)(CC/TT + CT:39/35 cases vs. 11/31 cases, P = 0.006)were statistically significant. Multivariate analysis showed that the type of preoperative antihypertensive drugs[≥ 2: OR = 5.26(95% CI 1.12?24.61, P = 0.016;1: OR = 4.55(95% CI 1.23?22.47), P = 0.025]was the strongest independent predictor,followed by CYP11B2(344C > T)[ OR = 4.02(95% CI 1.16?13.82), P = 0.028]and BMI[ OR = 3.96(95% CI 2.26?6.92), P < 0.001]. Comparing the receiver operating feature(ROC)curves of the four types of machine learning models,the best model was the support vector machine model with an area under the curve(AUC)of 0.88(95% CI 0.82?0.95),followed by the gradient elevator model of 0.83(95% CI 0.76?0.91),the logistic regression model of 0.78(95% CI 0.68?0.88),and the random forest model of 0.77(95% CI 0.68?0.86). The optimal threshold of the Yoden index of the support vector machine model was 0.588,with a sensitivity of 78.5% and a specificity of 86.5%. The clinical decision curve and calibration curve show that the support vector machine model has a higher net benefit and acceptable stability and reliability. Conclusions:The support vector machine model incorporating CYP11B2 gene polymorphisms,BMI,and types of preoperative antihypertensive medications could effectively predict postoperative hypertension remission in primary aldosteronism patients,providing new evidence for personalized treatment strategies
9.Impacts of sevoflurane combined with lung protective ventilation strategy on pulmonary ventilation function and lung compliance in obese patients undergoing laparoscopic weight loss surgery
Haoxiang HU ; Qianlin YE ; Zehua TU ; Jinxiong XU ; Zengting LU
China Journal of Endoscopy 2024;30(5):16-22
Objective To investigate the impacts of sevoflurane combined with lung protective ventilation strategy on pulmonary ventilation function and lung compliance in obese patients undergoing laparoscopic weight loss surgery.Methods 60 obese patients underwent laparoscopic weight loss surgery were randomly divided into two groups.The control group was given lung protective ventilation intervention alone during anesthesia,and the study group was given sevoflurane inhalation anesthesia combined with lung protective ventilation intervention.Arterial blood was collected before tracheal intubation(T0),5 min after tracheal intubation(T1),40 min after tracheal intubation(T2)and 5 min after tracheal extubation(T3)for blood gas analysis.The pulmonary ventilation function and lung compliance of patients in the two groups were compared.Results Peak airway pressure(Ppeak)and plateau airway pressure(Pplat)at T2 were lower in the study group than those in the control group,and the differences were statistically significant(P<0.05);At T2 and T3 time points,the dynamic lung compliance(Cldyn)of the study group was higher than that of the control group,and the differences were statistically significant(P<0.05);7 days after surgery,the forced vital capacity(FVC)and forced expiratory volume in one second(FEV1)in the study group were higher than those in the control group,and the differences were statistically significant(P<0.05);At time points T1,T2 and T3,the levels of serum transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in the study group were lower than those in the control group(P<0.05);After surgery,the awakening time,spontaneous breathing recovery time,and extubation time in the study group were shorter than those in the control group,the number of adverse events during the recovery period was less than that in the control group,after awakening,the Ramsay score was lower than that in the control group(P<0.05).Conclusion The combination of sevoflurane and lung protective ventilation strategy can reduce inflammatory response,improve pulmonary ventilation function,and improve lung compliance in obese patients undergoing laparoscopic weight loss surgery,with good safety and fast postoperative recovery.
10.Effect of pressure controlled ventilation-volume guaranteed mode on respiratory mechanics and gas exchange function in pediatric patients undergoing laparoscopic herniorrhaphy
Jinxiong XU ; Qianlin YE ; Haoxiang HU
China Journal of Endoscopy 2024;30(11):24-30
Objective To investigate the effects of pressure controlled ventilation-volume guaranteed(PCV-VG)mode on respiratory mechanics and gas exchange index in pediatric patients underwent laparoscopic herniorrhaphy.Methods 90 patients,scheduled for elective laparoscopic herniorrhaphy under general anesthesia of tracheal intubation,were randomly divided into 3 groups(n=30 each)using a random number table method:PCV-VG group,pressure controlled ventilation(PCV)group and volume controlled ventilation(VCV)group.At 5 min before pneumoperitoneum(T1),10 min after pneumoperitoneum(T2)and 5 min after release of pneumoperitoneum pressure(T3),respiratory mechanical indexes[inspiratory tidal volume(VTinsp),peak airway pressure(Ppeak),mean airway pressure(Pmean),dynamic lung compliance(Cldyn)]were recorded and gas exchange index[alveolar-artery oxygen partial pressure gradient(PA-aO2),respiratory index(RI)and oxygenation index(OI)]were recorded in three groups.The occurrence of pulmonary complications were recorded within 7 d after operation in three groups.Results Compared with the VCV group,Ppeak was significantly decreased and Cldyn was significantly increased at T2 and T3 time points in PCV-VG group and PCV group,the differences were statistically significant(P<0.05);Compared with PCV group,Ppeak was decreased at T2 and T3 time points in PCV-VG group,the difference was statistically significant(P<0.05).Compared with T1 time points,Ppeak and Pmean were increased and Cldyn was decreased at T2 and T3 time points in VCV group,Ppeak and Pmean were increased and Cldyn was decreased at T2 in PCV-VG group and PCV group,the differences were statistically significant(P<0.05).There were no significant differences in PA-aO2,RI and OI among three groups at T1,T2 and T3 time points(P>0.05).Compared with T1 time point,PA-aO2 and RI were increased and OI was decreased at T2 and T3 time points in three groups,the differences were statistically significant(P<0.05).There was no significant difference in the incidence of postoperative complications among the three groups(P>0.05).Conclusion PCV-VG mode can effectively reduce Ppeak and improve lung compliance,which is suitable for laparoscopic herniorrhaphy in pediatric patients.

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