ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

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, EcNΔ_pMUT1/2-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.

Objective:To revise and enlarge the specification of pharmaceutical excipient denatonium benzoate in the Chinese Pharmacopoeia 2025.Methods:At present,only USP-NF 2023 in domestic and foreign pharmacopoe-ias includes denatonium benzoate.This quality standard is subject to standard research in accordance with USP-NF 2023,the fourth general rules of the Chinese Pharmacopoeia 2020 edition,and other relevant requirements.Results:According to the quality of the product and the actual application in the formulation,the quality standards for the pharmaceutical excipient denatonium benzoate will be studied.At present,the quality standard of denatoni-um benzoate for pharmaceutical excipients has been disclosed.Conclusion:The established standard will fill the domestic gap and provide the quality guarantee for the application of denatonium benzoate in medicines.

Objective:To investigate the value of three-dimensional (3D) T 1WI structural images using different acceleration methods including parallel acquisition technique, joint compressed sensing (uCS) technique, and artificial intelligence-assisted compressed sensing (ACS) technique for brain region segmentation. Methods:In this cross-sectional study, fifty patients (female: n=25, age range: 13 to 87 years old) at Corning Hospital of Ningbo University from July to September 2023 were prospectively and consecutively collected. All the subjects underwent brain MRI. Six groups of 3D T 1WI structural images were obtained using different acceleration technique and parameters, including 3D T 1WI without acceleration factor (3D-T 1WI group), 3D T 1WI with parallel acquisition technique with acceleration factor 3 (3D-T 1WI-PI-3 group), 3D T 1WI with uCS technique with acceleration factor 4.5 and 6.9 (3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group), 3D T 1WI by ACS technique with acceleration factors of 3 and 5 (3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group). T 2WI fluid-attenuated inversion recovery (FLAIR) images were also acquired. Subjective scores (cerebral grey matter and white matter clarity scores, clarity scores of cerebral white matter degeneration lesions in relation to the surrounding white matter, and Gibbs artifact scores) and objective metrics [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), cerebrospinal fluid signal homogeneity, peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and natural image quality evaluator (NIQE)] were used to evaluate image quality in different groups. Totally 109 brain regions were segmented and volumes were measured using the uAI Research Portal image analysis tool. Kappa or intraclass correlation coefficient ( ICC) was used to evaluate the agreement of subjective and objective evaluation indexes between the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group, and 3D-T 1WI group. Kappa or ICC value>0.70 was considered as good agreement. Results:The acquisition time for the 3D-T 1WI group, 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group were 527, 204, 169, 95, 133, 90 s, respectively. Subjective evaluation showed that the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups had excellent agreement with the 3D-T 1WI group in terms of the distribution of cases of cerebral grey matter and white matter clarity scores, respectively (all Kappa value=1.000); The distribution of cases of clarity score of cerebral white matter lesions and surrounding white matter in the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group were in good agreement with that of the 3D-T 1WI group ( Kappa values of 0.775, 0.701, and 0.777, respectively); the distribution of the number of cases of the Gibbs artifact score of the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups was in good agreement with the 3D-T 1WI group (all Kappa value=1.000). Objective evaluation showed the CNR of the images in the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, and 3D-T 1WI-uCS-6.9 groups were in good agreement with those of the 3D-T 1WI group ( ICC of 0.720, 0.759, and 0.752, respectively); PSNR and SSIM were in good agreement among the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group (PSNR: ICC=0.854; SSIM: ICC=0.851). NIQE of 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group images were in good agreement with the 3D-T 1WI group ( ICC value of 0.866, 0.727, 0.753, respectively). The ICC values of the volume of each segmented brain region among the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, 3D-T 1WI-uCS-6.9, 3D-T 1WI-ACS-3, 3D-T 1WI-ACS-5 group and the 3D-T 1WI group images showed decreased in order (all ICC≥0.62). Conclusions:The uCS and ACS techniques used in 3D-T 1WI show high agreement with 3D-T 1WI in terms of brain segmentation. The application of these accelerating techniques can significantly shorten the acquisition time with obtaining images with good image quality, displaying great value.

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.

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.

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.

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.

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.