1.Protective Effect of Gegen Qianliantang on Intestinal Mucosal Barrier in Ulcerative Colitis Mice via STAT3/NF-κB Axis Regulating Th1/Treg Differentiation
Beilei DENG ; Anan WANG ; Wenya FENG ; Lixin WANG ; Tiansong ZHANG ; Chengyong MA ; Xiutian GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):12-21
ObjectiveTo explore the protective effect and mechanism of Gegen Qianliantang (GQT) on intestinal mucosal barrier function in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model mice. MethodsA UC model was established in C57BL/6 mice using a 2.5% DSS solution. Mice were randomly divided into five groups (n=8 per group): blank group, model group, mesalazine sustained-release granule group (0.52 g·kg-1), high-dose GQT group (2.23 g·kg-1), and low-dose GQT group (1.12 g·kg-1). Fecal characteristics and body weight changes were observed before and after treatment. The body weight loss and disease activity index (DAI) of UC mice were calculated to evaluate symptom severity. Hematoxylin-eosin (HE) staining and Alizarin blue-periodic acid-Schiff (AB-PAS) staining were used to detect histological changes in colon tissue. Immunohistochemistry was used to detect the expression of zonula occludens-1 (ZO-1) and mucin 2 (MUC2). Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of pro-inflammatory cytokines interferon-γ (IFN-γ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-17A, and anti-inflammatory cytokine IL-10. Flow cytometry was used to detect the activation of helper T lymphocyte subsets (Th1, Th17), regulatory T cells (Treg), and regulatory B cells (Breg) in spleen and colon tissues. Western blot was used to detect the expression levels of T-bet, forkhead box protein P3(FoxP3), nuclear transcription factor(NF)-κB p65, phosphorylated NF-κB p65 (p-NF-κB p65), signal transducer and activator of transcription 3(STAT3), and phosphorylated STAT3 (p-STAT3). ResultsCompared with the model group, both high- and low-dose GQT groups significantly improved the body weight loss and DAI scores (P<0.05), alleviated colonic inflammation, and showed optimal efficacy in the high-dose group. AB-PAS staining showed that compared with the model group, both the high- and low-dose GQT groups significantly increased goblet cell proliferation and mucin secretion, indicating improved mucosal barrier function. GQT upregulated the expression of ZO-1 and MUC2 in colon tissue (P<0.05), suppressed IFN-γ, IL-6, and TNF-α secretion (P<0.05), elevated IL-10 secretion (P<0.05), but had no significant effect on IL-17A. At the same time, high- and low-dose GQT intervention increased the activation of CD4+ FoxP3+ Treg cells (P<0.05) and suppressed activation of CD4+ IFN-γ+ Th1 cells (P<0.05). Western blot showed that GQT downregulated T-bet, NF-κB p65, and STAT3 protein expression (P<0.05), upregulated FoxP3 (P<0.05), and also reduced phosphorylation levels of p-NF-κB p65 and p-STAT3 (P<0.05). ConclusionGQT can upregulate the activation of CD4+ FoxP3+ Treg cells, reduce the activation of CD4+ IFN-γ+ Th1 cells, inhibit the secretion of IFN-γ, IL-6, and TNF-α, and increase the secretion of IL-10. It enhances the expression of MUC2 and ZO-1 in colon tissue, thereby alleviating inflammatory damage to the intestinal mucosa and restoring mucosal barrier integrity. These effects may be related to its regulation of NF-κB p65 and STAT3 signaling pathways, ultimately regulating the activation of transcription factors T-bet and FoxP3.
2.Advances in research on biomaterials and stem cell/exosome-based strategies in the treatment of traumatic brain injury.
Wenya CHI ; Yingying HE ; Shuisheng CHEN ; Lingyi GUO ; Yan YUAN ; Rongjie LI ; Ruiyao LIU ; Dairan ZHOU ; Jianzhong DU ; Tao XU ; Yuan YU
Acta Pharmaceutica Sinica B 2025;15(7):3511-3544
Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.
3.Effects and Mechanism of Yuyin Qianyang Tongluo Formula on Cognitive Function in Alzheimer's Disease Mice
Wenya ZENG ; Huicong LI ; Ji'ao ZHAO ; Yifeng GUO ; Shixing HAO ; Peiqi CHEN ; Xiaolu MIAO
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2823-2830
Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P<0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P<0.05 or P<0.01),significantly lower spontaneous alternation percentage in Y-maze test(P<0.05),and significantly elevated hippocampal Aβ1-42 level(P<0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P<0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P<0.05),significantly higher spontaneous alternation percentage in Y-maze test(P<0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P<0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P>0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P>0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.
4.Study on the stability and H+ permeable membrane properties of polymersomes
Kangqing BIAN ; Lingyi GUO ; Wenya CHI ; Yuan YU
Journal of Pharmaceutical Practice and Service 2024;42(1):12-17
Objective To prepare polymersomes (PSs) by block copolymers,evaluate their membrane structural stability,investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.
5.Development of a grading diagnostic model for schistosomiasis-induced liver fibrosis based on radiomics and clinical laboratory indicators
Zhaoyu GUO ; Juping SHAO ; Xiaoqing ZOU ; Qinping ZHAO ; Peijun QIAN ; Wenya WANG ; Lulu HUANG ; Jingbo XUE ; Jing XU ; Kun YANG ; Xiaonong ZHOU ; Shizhu LI
Chinese Journal of Schistosomiasis Control 2024;36(3):251-258
Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.
6.Effect of different fraction of inspiration oxygen on early pulmonary function after laparoscopic rad-ical prostatectomy for prostate cancer in elderly patients
Yang WANG ; Wenya GUO ; Xinjie CAI ; Ye ZHANG ; Yun LI
The Journal of Clinical Anesthesiology 2024;40(5):482-487
Objective To investigate the effects of intraoperative fraction of inspiration oxygen(FiO2)30%and 80%on pulmonary function after laparoscopic radical prostatectomy for prostate cancer in elderly patients.Methods Sixty elderly patients,aged≥65 years,BMI 18-30 kg/m2,ASA physical sta-tus Ⅱ or Ⅲ,underwent elective laparoscopic radical prostatectomy for prostate cancer were selected.The patients were divided into two groups:the FiO2 30%group(group L)and the FiO2 80%group(group H),30 patients in each group.After tracheal intubation,the patients were manoeuvred,and inhaled oxygen con-centration was adjusted by 30%until the removal of the tracheal tube in group L.In group H,inhaled oxy-gen concentration was adjusted by 80%until the removal of the tracheal tube.HR and MAP were recorded 5 minutes after admission(T0),1 hour after the start of surgery(T1),2 hours after the start of surgery(T2),and 30 minutes after extubation(T3),arterial blood gas analysis was performed to record PaO2 and PaCO2,and the oxygenation index(OI)was calculated.Electrical impedance tomography(EIT)monitoring was performed at T0 and T3 to assess the pulmonary ventilation function,and the percentage of the area of the central ventilation zone(CoV),dependent static zone(DSS),and non-dependent static zone(NSS)were recorded.Exertional expiratory volume in the first second(forecd expirtory volume in the first second,FEV1),exertional lung capacity(forecdvital cipitory,FVC),and 1-second rate(FEV1/FVC)were meas-ured on preoperative day 1,postoperative day 1,postoperative day 3 and postoperative day 5.The occur-rence of pulmonary complications such as atelectasis,respiratory infection,and pleural effusion within 5 days postoperatively were recorded.Results Compared with group H,the percentage of DSS area at T3 was significantly decreased(P<0.05),PaO2 and OI were significantly increased(P<0.05),FVC,FEV1,and FEV1/FVC on postoperative day 1 were significantly increased(P<0.05),FEV1/FVC on postopera-tive day 3 was significantly increased(P<0.05),the incidence of cumulative pulmonary atelectasis was significantly decreased in group L within 5 days postoperatively(P<0.05).Conclusion Compared with FiO2 80%,FiO2 30%intraoperatively significantly improves pulmonary ventilation and oxygenation 30 mi-nutes after laparoscopic radical prostatectomy with early postoperative lung function in elderly patients,and reduces postoperative pulmonary atelectasis.
7.Magnetic resonance imaging and clinical manifestations of intraspinal echinococcosis
Yushan CHANG ; Xiong HE ; Tuxunjiang PAHATI· ; Wenya LIU ; Hui GUO
Chinese Journal of Endemiology 2024;43(5):411-415
Objective:To study the magnetic resonance imaging (MRI) and clinical manifestations of intraspinal echinococcosis.Methods:The general conditions, MRI and clinical manifestations of 23 patients with intraspinal echinococcosis diagnosed by pathology at the First Affiliated Hospital of Xinjiang Medical University from September 2011 to May 2023 were retrospectively analyzed.Results:There were 10 males and 13 females of the 23 patients with intraspinal echinococcosis. The age of the patients was (44.1 ± 13.9) years old, with a median age of 41 years old and a range of 25 to 72 years old. Eleven patients (47.8%) had a history of echinococcosis in the spine or other parts of the body. Among the 23 patients with intraspinal echinococcosis, 12 cases (52.2%) involved thoracic segment, 6 cases (26.1%) involved lumbar segment, 1 case (4.3%) involved sacral segment, 1 case (4.3%) involved thoracolumbar segment, 2 cases (8.7%) involved lumbosacral segment, and 1 case (4.3%) involved cervical and lumbar segment. There were 2 cases (8.7%) involving the intramedullary, 9 cases (39.1%) involving the extramedullary subdural, and 12 cases (52.2%) involving the extramedullary epidural. At the same time, 18 cases (78.3%) involved adjacent vertebral bodies, accessories or surrounding soft tissues. Intramedullary cystic echinococcosis was characterized by multiple nodules at the lower end of the spinal cord and the cauda equina nerve on MRI, with equal or low signal on T1WI, slightly high signals on T2WI and short time of inversion recovery (STIR), accompanied by small vesicles with high signal on T2WI. Intramedullary alveolar echinococcosis was characterized by nodular T1WI signals, slightly lower signals on T2WI and STIR, and circular enhancement on enhanced scan. Extramedullary subdural echinococcosis was mostly manifested as oval small vesicles with low signal on T1WI and high signal on T2WI, with a grape string-like appearance, and the capsular wall with low signal on T2WI could be seen at the edge. Extramedullary epidural echinococcosis was manifested as slightly low signal on T1WI, high signals on T2WI and STIR, accompanied by single or multiple small vesicles with high signal on T2WI, and compression of the dural sac. The clinical manifestations were chest and back, lumbosacral pain in 21 cases (91.3%), and lower limb dysfunction in 6 cases (26.1%).Conclusions:Intraspinal echinococcosis is relatively rare compared with other sites. When MRI features are clear, typical clinical manifestations are present, or there is a history of echinococcosis in other sites, intraspinal echinococcosis should be considered.
8.Cross-Sectional Study of Nutritional Service Capacity for Infants and Toddlers in Urban and Rural Medical Facilities in Sichuan Province
Yanxi DING ; Shiyu ZHANG ; Mengtong YANG ; Sijia CHEN ; Ju ZHANG ; Piao ZHANG ; Ming LI ; Danping SU ; Hongli DONG ; Yishan GUO ; Wenya YIN ; Guo ZENG
Journal of Sichuan University (Medical Sciences) 2024;55(4):911-917
Objective To investigate and analyze the current status and challenges of infant and toddler nutritional services in urban and rural medical facilities in Sichuan Province.Methods In 2022,a questionnaire survey was conducted to collect data on infant and toddler nutritional services,including feeding guidance,physical growth assessment,and micronutrient deficiency screening,as well as information on personnel and tools in medical facilities throughout Sichuan Province.The provision of nutritional services was analyzed and the urban-rural disparities were assessed.Results A total of 2206 medical facilities(29.1%from urban areas and 70.9%from rural areas)were investigated.Only 35.8%of medical facilities provided all three types of nutritional services.Specifically,the overall service provision rates were high for feeding guidance(94.6%)and physical growth assessment(85.0%),but lower for micronutrient deficiency screening(37.4%).Rural facilities exhibited significantly lower rates than their urban counterparts for both physical growth assessment and micronutrient deficiency screening(P<0.05).The provision rates of feeding guidance ranged from 70.6%to 93.2%,with responsive feeding guidance being the least implemented(70.6%),particularly in rural areas compared to urban areas(P<0.05).Rates for physical growth assessment and micronutrient deficiency screening ranged from 75.3%to 81.8%and 23.6%to 30.8%,respectively,both showing lower rates in rural settings compared to urban ones(P<0.05).Nutrition service providers were predominantly nurses(52.3%)and clinical practitioners(43.4%).The availability of dietary assessment tools ranged from 7.7%to 15.9%,significantly lower in rural areas compared to urban areas(P<0.001),while physical measurement tools were widely available at rates of 94.6%to 98.5%.Conclusion At present,the infant and toddler nutritional service provisions of medical facilities in Sichuan Province are incomplete,particularly so in the implementation of feeding guidance,physical growth assessment,and micronutrient deficiency screening.There is a notable shortage of personnel and necessary tools,with rural areas facing more significant challenges.Enhancing the overall capacity of infant and toddler nutritional services in Sichuan Province is essential,with specific attention needed for rural healthcare settings.
9.Differential diagnosis of brucellar spondylitis and tuberculous spondylitis based on FS-T2WI sequence combined with machine learning
Tuxunjiang PAHATI ; Laihong YANG ; Xiong HE ; Yushan CHANG ; Wenya LIU ; Yuwei XIA ; Hui GUO
Chinese Journal of Endemiology 2023;42(5):356-362
Objective:To investigate the performance of a predictive model based on fat suppression (FS)-T2WI sequence combined with machine learning in the differential diagnosis of brucellar spondylitis (BS) and tuberculous spondylitis (TS).Methods:The clinical and imaging data of 74 patients with BS and 81 patients with TS diagnosed clinically or pathologically in the First Affiliated Hospital of Xinjiang Medical University from January 2017 to January 2022 were retrospectively analyzed, and all patients underwent spinal magnetic resonance imaging (MRI) examination before treatment. Patients were randomly divided into a training group ( n = 123) and a testing group ( n = 32) in an 8 ∶ 2 allocation ratio, and radiomics feature extraction and dimensionality reduction analysis were performed on FS-T2WI sequence images. Four machine learning algorithms, including K-nearest neighbor (KNN), support vector machine (SVM), random forest (RF) and logistic regression (LR), were used to construct a radiomics model, and receiver operating characteristic (ROC) curve was used to analyze the differential diagnostic performance of each model for BS and TS. Results:A total of 1 409 radiomics features were extracted, and 7 related features were screened and included for identification of BS and TS, among which the Maximum2DDiameterColumn feature value showed a strong correlation, and there was a statistically significant difference between BS and TS patients ( P < 0.001). In the testing group, the area under the ROC curve (AUC) value of the SVM model for identifying BS and TS was 0.886, with a sensitivity of 0.53, a specificity of 0.88, and a diagnostic accuracy of 0.81; in the training group, the AUC value of the SVM model for identifying BS and TS was 0.811, the sensitivity was 0.68, the specificity was 0.72, and the diagnostic accuracy of the model was 0.78. Conclusion:The prediction model based on FS-T2WI sequence combined with machine learning can be used to identify BS and TS, and the diagnostic performance of SVM model is prominent and stable.
10.Construction of albumin nanoparticles loading PROTAC and its inhibition effect on NAD+ in glioma cells
Hongbo WANG ; Lingyi GUO ; Wenya CHI ; Kangqing BIAN ; Wenbo ZHOU ; Yuan YU
Journal of Pharmaceutical Practice 2023;41(10):594-599
Objective To prepare and optimize the formulation of Albumin nanoparticles loading PROTAC molecule and observe the inhibition effect of nanoparticles on the proliferation and NAD+ metabolism of glioma cells. Methods Albumin nanoparticles loading NPT-B2 were prepared and characterized with a thermal driving method, and the prescription was optimized. An HPLC method was established to determine the content of NPT-B2. The proliferation inhibition of NPT-B2 and B2-BSA-NPs on U251 cells were investigated by the CCK8 method, and the degradation effects of NPT-B2 and B2-BSA-NPs on NAMPT in glioma cells were investigated by western blotting. Results The HPLC method was stable, with good linearity, precision, and recovery rate. The nanoparticles had a particle size of about 55.48 nm, a potential of about −12.9 mV, an encapsulation rate of about 94.74%, and a drug loading amount of about 8.61%. The IC50 of NPT-B2 on glioma cells was 61.16 nmol/L, which had a degradation effect on NAMPT. The IC50 of B2-BSA-NPs on glioma was 41.21 nmol/L, which had a very significant degradation effect on NAMPT. Conclusion Albumin nanoparticles loading PROTAC molecules were constructed. The prescription was optimized to improve the drug encapsulation rate, and the low water solubility of PROTAC molecule was improved, which had a significant inhibitory effect on the proliferation and NAD+ energy metabolism of glioma cells.

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