1.Engineered Escherichia coli Nissle 1917 targeted delivery of extracellular PD-L1-mFc fragment for treating inflammatory bowel disease.
Yuhong WANG ; Lin HU ; Lei WANG ; Chonghai ZHANG ; Wenhao SHEN ; Hongli YANG ; Min LI ; Xin ZHANG ; Mengmeng XU ; Muxing ZHANG ; Kai YANG ; Xiaopeng TIAN
Acta Pharmaceutica Sinica B 2025;15(11):6019-6033
Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔpMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.
2.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
3.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
4.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
5.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
6.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
7.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
8.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
9.Construction and Validation of the Prediction Model for the First Cesarean Section Delivery in Multiparas
Xiaopeng XU ; Yawen ZHANG ; Minhong SHEN ; Qin HUANG
Journal of Practical Obstetrics and Gynecology 2024;40(8):657-663
Objective:To establish a predictive model of the first cesarean delivery in multiparous women based on the situation of two consecutive pregnancies.Methods:The data of patients with two consecutive deliv-eries of single live birth and the previous delivery was vaginal delivery in the First Affiliated Hospital of Soochow U-niversity during the second delivery time range from January 1,2018 to December 31,2021 were retrospectively analyzed.According to whether the second pregnancy occurred cesarean section,the patients were divided into two groups(vaginal delivery group and cesarean section group).Univariate,stepwise,and multiple Logistic re-gression analyses were used to screen the influencing factors of multipara's first cesarean section delivery,and the prediction model was established.R language was used to build the model's nomogram and calibration curve.The bootstrap resampling method was used for internal verification.After establishing the model,clinical data of patients with two consecutive births of single live birth between January 1,2022 and April 1,2023 were retrospec-tively collected for external verification of the model.Results:①A total of 2709 patients were included in this study for modeling,of which 6.31%(171/2709)underwent cesarean section for the first time.603 cases were included for external verification.②According to univariate,stepwise and multivariate Logistic regression analysis,all the variables affecting the first delivery by cesarean section were screened out,including:abnormal labor in previous labor,age of current delivery,assisted reproductive technology,hypertension disorder complicating pregnancy,pregnancy with thrombocytopenia,oligohydramnios,excessive amniotic fluid,macrosomia,fetal growth restriction,abnormal fetal position,fetal distress,all of the above variables P<0.05 and incorporated into the final prediction model.③The AUC of this model was 0.949(95%CI 0.928-0.969),and the calibration curve showed that the model intercept was 0 and the slope was 1.Hosmer-Lemeshow test had a P>0.05,indicating that the model had a high accuracy.④The AUC of external validation was 0.958,the slope of the calibration curve was 0.972,and the Hosmer-Lemeshow test had a P of 0.49.Conclusions:The prediction model of the first delivery by cesarean section during the second pregnancy has been established.The prediction efficiency of the model is good,and it can provide a tool for the individualized evaluation of menstrual women in clinical work.
10.Investigating efficacy mechanism of electroacupuncture in treating Parkinson disease through TMT proteomics
Lu ZHU ; Guona LI ; Pin WU ; Luyi WU ; Lin SHEN ; Yu QIAO ; Jing LI ; Lingjie LI ; Zhaoqin WANG ; Yiyi CHEN ; Xiaopeng MA ; Kunshan LI ; Huangan WU ; Yanping YANG
Journal of Acupuncture and Tuina Science 2024;22(6):470-481
Objective:To explore the therapeutic mechanism of electroacupuncture(EA)in treating Parkinson disease(PD)using Tandem mass tag(TMT)quantitative proteomics technology. Methods:Forty-eight PD patients were randomly divided into a control group and an observation group,with 24 patients in each group.The control group received routine drug treatment,while the observation group received EA in addition to the routine drug treatment.EA was administered for 30 min per session,3 times a week,for a total of 12 weeks.Nine patients from each group were randomly selected to provide peripheral blood serum samples before and after treatment for TMT quantitative proteomics analysis.Differentially expressed proteins between the two groups were compared,and bioinformatics analysis was performed.The screened differentially expressed proteins were validated using enzyme-linked immunosorbent assay(ELISA). Results:In the observation group,scores on the unified Parkinson disease rating scale(UPDRS),UPDRS Ⅱ,and UPDRS Ⅲ were significantly reduced after treatment(P<0.05).In the control group,these scores tended to increase,but the changes were not statistically significant(P>0.05).After treatment,the UPDRS and UPDRS Ⅲ scores in the observation group were significantly lower than those in the control group(P<0.05).The observation group showed 62 differentially expressed proteins,while the control group had 36.Compared to the control group,the observation group had 142 differentially expressed proteins.These proteins were primarily involved in the cyclic adenosine monophosphate(cAMP)signaling pathway,T helper(Th)1 and Th2 cell differentiation,ATP-binding cassette transporter,vascular endothelial growth factor signaling pathway,and high-affinity immunoglobulin E receptor(FcεRI)signaling pathway.ELISA verification indicated that after EA treatment,the levels of α-Synuclein(αSyn)and heat shock protein beta 1(HSPB1)in the observation group were significantly lower than those in the control group(P<0.05),while the regulator of G-protein signaling 10(RGS10)level was significantly higher(P<0.05). Conclusion:EA,combined with routine drug therapy,can significantly improve clinical symptoms of PD,potentially through the regulation of the cAMP signaling pathway and the contents of differentially expressed proteins of αSyn,HSPB1,and RGS10.

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