1.Mechanism of Icariin in Regulating TGF-β1/Smad Pathway to Induce Autophagy in Human Bone Microvascular Endothelial Cells
Yaqi ZHANG ; Yankun JIANG ; Guoyuan SUN ; Bo LI ; Ran DING ; Cheng HUANG ; Weiguo WANG ; Qidong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):123-130
ObjectiveTo investigate the regulatory effect of icariin (ICA) on transforming growth factor-β1 (TGF-β1)/Smad pathway in bone microvascular endothelial cells (BMECs) and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured, and the cell types were identified by immunofluorescence. Cells were divided into the control group, model group (0.1 g·L-1 methyl prednisolone), ICA group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA), and TGF-β inhibitor group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA +1×10-5 mol·L-1 LY2157299). Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β1/ Smad pathway. ResultsAfter cell separation culture, platelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged, and the nucleus was pyknotic and broken in the model group. Compared with the model group, the ICA group had complete cell membranes, clear structures, with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes, and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group, in the model group and the LY2157299 group, autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group, the mRNA and protein expressions of autophagy effector protein 1 (Beclin1) and microtubule-associated protein 1 light chain 3B (LC3B) in the model group were significantly decreased (P<0.01), and those of ubiquitin-binding protein (p62) were significantly increased (P<0.01). The mRNA expression of TGF-β1, Smad homolog 2 (Smad2), and Smad homolog 3 (Smad3) decreased (P<0.05, P<0.01). The protein expressions of TGF-β1, p-Smad2, and p-Smad3 were significantly decreased (P<0.01). Compared with those of the model group, the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased (P<0.01), and those of p62 significantly reduced (P<0.01). The mRNA expression of TGF-β1, Smad2, and Smad3 increased significantly (P<0.01). The protein expression of TGF-β1, p-Smad2, and p-Smad3 increased significantly (P<0.01). Compared with those in the model group, the mRNA and protein expressions of Beclin1, LC3B, and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β1 pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs, and its mechanism may be related to activating the TGF-β1/Smad signaling pathway.
2.Mechanism of Traditional Chinese Medicine in Treating Steroid-Induced Osteonecrosis of Femoral Head via Regulating PI3K/Akt Pathway: A Review
Yaqi ZHANG ; Bo LI ; Jiancheng TANG ; Ran DING ; Cheng HUANG ; Yaping XU ; Qidong ZHANG ; Weiguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):141-149
Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells, necrosis, and trabecular fractures, SONFH is accompanied by pain, femoral head collapse, and joint dysfunction, which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis, bone microvascular endothelial cell (BMEC) apoptosis, oxidative stress, and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation, thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts, promoting angiogenesis in BMECs, and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine (TCM) has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway, as well as its regulatory effects on osteoblasts, mesenchymal stem cells, osteoclasts, BMECs, and other cells. Additionally, the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings, this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM, it is expected to bring safer and more effective treatment options for patients with SONFH.
3.Construction of a therapeutic effect prediction model for bronchial asthma
Qidong HUANG ; Minxi LI ; Yilong LI ; Wanqi SHAO ; Shumei ZHAO ; Xiaoyan GONG ; Lindu ZHAO ; Lanying LIU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):729-740
Objective We aimed to investigate the feasibility and method of constructing a traditional Chinese medicine(TCM)curative effect prediction model based on the data of Kechuanting acupoint plastering therapy in the treatment of bronchial asthma(asthma).Methods Data from the Chronic Disease Management Research Platform of 303 patients with asthma who were treated with Kechuanting acupoint plastering therapy for 6 weeks in the Department of Acupuncture and Rehabilitation of Jiangsu Hospital of Traditional Chinese Medicine from June to August 2018 to 2021 were selected.We used Phyton 3.10 for statistical analysis.After data preprocessing,the influencing factors were used to build models by Logistic regression,support vector machine,K-means clustering algorithm,Bayes algorithm,random forest method and Light gradient boosting machine(LightGBM)respectively,with the improvement of asthma control test score(ACT),forced expiratory volume in one second(FEV1)and exhaled nitric oxide(FeNO)as the outcome indicators.Then,the models were compared and analyzed.Subsequently,the superior model was used to establish the efficacy prediction model and verify its stability to obtain the accuracy rate and eliminate the relatively important factors.Results The accuracy rate of the Kechuanting acupoint plastering therapy curative effect prediction model established by the LightGBM model was more than 70%.Five important factors were selected,including allergic history,tabacco and alcohol abuse,plastering duration,ACT before treatment,and FeNO before treatment.According to the classification analysis and the relationship between the important factors and the outcome indicators,Kechuanting acupoint plastering therapy significantly improved the ACT of patients with no history of allergy,no tabacco and alcohol abuse,and poor ACT:5-15 points(P<0.05).Furthermore,Kechuanting acupoint plastering therapy improved FeNO more significantly in patients with more than 3 years of treatment than those with no more than 3 years(P<0.05).However,Kechuanting acupoint plastering therapy only improved FeNO in a few patients with poor asthma control levels(P<0.05)and severe airway inflammation(FeNO>50×10-9)(P>0.05).Conclusion Acupoint plastering application has a significant effect on improving the control level of asthma,but its effect on improving airway inflammation is limited.It is feasible to use data from the chronic disease management research platform to construct the prediction model.After optimization and testing,the predictive model established based on the data of this study may provide an effective evaluation tool for targeted clinical treatment.
4.Comparison of Jinzhen oral liquid and ambroxol hydrochloride and clenbuterol hydrochloride oral solution in the treatment of acute bronchitis in children: A multicenter, non-inferiority, prospective, randomized controlled trial.
Qinhua FAN ; Chongming WU ; Yawei DU ; Boyang WANG ; Yanming XIE ; Zeling ZHANG ; Wenquan SU ; Zizhuo WANG ; Changchang XU ; Xueke LI ; Ying DING ; Xinjiang AN ; Jing CHEN ; Yunying XIAO ; Rong YU ; Nan LI ; Juan WANG ; Yiqun TENG ; Hongfen LV ; Nian YANG ; Yuling WEN ; Xiaoli HUANG ; Wei PAN ; Yufeng LIU ; Xueqin XI ; Qianye ZHAO ; Changshan LIU ; Jian XU ; Haitao ZHANG ; Lie ZHUO ; Qiangquan RONG ; Yu XIA ; Qin SHEN ; Shao LI ; Junhong WANG ; Shengxian WU
Acta Pharmaceutica Sinica B 2024;14(12):5186-5200
The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.
5.Construction of a competing risk model for disease-free survival of patients with non-muscle invasive bladder cancer
Li WANG ; Zihe PENG ; Qidong LUO ; Shanlong HUANG ; Yun SUN ; Min ZHANG ; Luan JIA ; Le ZHAO ; Hongliang LI
Journal of Modern Urology 2023;28(6):487-492
【Objective】 To construct an easy-to-use individual survival prognostic tool based on competing risk analyses to predict the risk of 1-, 2- and 3- year recurrence for patients with non-muscle invasive bladder cancer (NMIBC). 【Methods】 The follow-up data of 419 NMIBC patients were obtained. The patients were randomly divided into training cohort (n=293) and validation cohort (n=126). The variables included age at diagnosis, sex, history of smoking, tumor number, tumor size, histolo-gic grade, pathological stage, and bladder perfusion drug. The cumulative incidence function (CIF) of recurrence was estimated using all variables in the training cohort and potential prognostic variables were determined with Gray’s test. The Fine-Gray subdistribution proportional hazard approach was used as a multivariate competitive risk analysis to identify independent pro-gnostic variables. A competing risk nomogram was developed to predict the recurrence. The performance of the competing risk model was evaluated with the area under the receiver operating characteristic curve (AUC), calibration curve, and Brier score. 【Results】 Five independent prognostic factors including age, number of tumors, tumor size, histologic grade and pathological stage were used to construct the competing risk model. In the validation cohort, the AUC of 1-, 2- and 3- year recurrence were 0.895 (95%CI: 0.831-0.959), 0.861(95%CI: 0.774-0.948) and 0.827(95%CI: 0.721-0.934), respectively, indicating that the model had a high predictive performance. 【Conclusion】 We successfully constructed a competing risk model to predict the risk of 1-, 2- and 3-year recurrence for NMIBC patients. It may help clinicians to improve the postoperative management of patients.
6.Characteristics and influencing factors of cognitive impairment in children with attention deficit hyperactivity disorder
Yuanyuan Huang ; Qidong Zhu ; Fengchen Wang ; Feng Geng ; Yulong Zhang ; Ling Zhang ; Huanzhong Liu
Acta Universitatis Medicinalis Anhui 2023;58(8):1387-1392
Objective :
The differences of cognitive impairment between children with attention deficit hyperactivity
disorder (ADHD) and normal children were compared , the influencing factors of cognitive impairment of children with ADHD were analyzed .
Methods :
A total of 133 children with ADHD were selected as the ADHD group , and 117 normal children were recruited as the control group . The severity of the subjects ′ clinical symptoms was assessed using the Swanson , Nolan , & Pelham Rating Scale⁃Fourth Edition ( SNAP⁃IV) and the Weiss Functional Impairment Rating Scale . The degree of cognitive functional impairment of subjects was assessed using the MATRICS cognitive suite (MCBB) , and the executive function impairment of the subjects was assessed by the Behavior Rating Inventory of Executive Function ( BRIEF) . The differences in cognitive functional impairment of the two groups were compared . The children with ADHD were further divided into three groups according to their clinical phenotype and age , respectively , and the differences of cognitive impairment among the three groups were compared . The influencing factors of the degree of cognitive impairment in children with ADHD were analyzed by multiple linear regression . The improvement of methylphenidate sustained⁃release tablets on cognitive and executive functional impairment in children with ADHD was observed .
Results :
The scores of SNAP⁃IV , Weiss Functional Impairment Rating Scale , connection test and BRIEF of ADHD patients were significantly higher than those of normal controls (P < 0. 05) . The scores of symbol coding test and maze test of ADHD patients were significantly lower than those of normal controls (P < 0. 05) . The score of symbol encoding test in children with ADHD⁃HI was significantly higher than that in ADHD⁃I and ADHD⁃C groups (P < 0. 05) , and the total BRIEF score of ADHD⁃C was significantly higher than that in ADHD⁃I and ADHD⁃HI groups (P < 0. 05) . With the increase of age , the score of connection test of ADHD children gradually decreased , while the scores of symbol coding test and maze test gradually increased (P < 0. 05) . The results of multiple linear regression analysis showed that age was the influencing factor of ADHD children ′s score in the connection test , symbol coding test and maze test (P < 0. 05) ; the scores of SNAP⁃IV and Weiss Functional Impairment Rating Scale were the influencing factors of BRIEF score of ADHD children (P < 0. 05) . After methylphenidate treatment , the scores of connection testand BRIEF significantly decreased (P < 0. 001) , while the scores of symbol coding test and maze test significantly increased (P < 0. 001) .
Conclusion
The younger the age and the more serious the clinical symptoms related to ADHD suggest that the cognitive impairment of children with ADHD is more serious . After methylphenidate treatment , the degree of cognitive and executive impairment in children with ADHD are improved .
7.Pathological analysis of 4 652 cases of renal biopsy: a multicentral study in Beijing from 2008 to 2020
Zongli DIAO ; Zengyu GUO ; Huamin WANG ; Qidong ZHANG ; Qun JIANG ; Gang WANG ; Weikang GUO ; Hongdong HUANG ; Wenhu LIU
Chinese Journal of General Practitioners 2021;20(12):1282-1287
Objective:To analyze characteristics and trends of histopathological diagnosis of adult renal biopsy in Beijing from 2008 to 2020.Methods:A total of 4 652 cases of adult renal biopsy were collected from three hospitals in Beijing between 2008 and 2020. The patients were divided into three age groups: 18-40 years, 40-65 years and≥ 65 years; and also divided into three period: 2008-2011, 2012-2015, and 2016-2020. The pathological characteristics and changes of renal biopsy were analyzed in three age groups at different periods.Results:Among 4 652 cases primary glomerular disease accounted for 81.8%, the membranous nephropathy (MN, 32.4%, 1 509/4 652), IgA nephropathy (IgAN, 29.2%, 1 356/4 652) and minor glomerular abnormalities (MGA, 11.3%, 526/4 652) were the top three pathological types. The overall proportion of MN and diabetic nephropathy (DN) increased from 20.3% and 2.3% in 2008-2011 to 37.3% and 10.1% in 2016-2020) (χ2=99.9 and 96.1, both P<0.01), respectively. For age group 18-40 years, the MN and DN increased from 11.2% and 1.6% in 2008-2011 to 24.7% and 5.5% in 2016-2020 (χ2=32.7 and 20.7, both P<0.01), respectively. For age group 40-65 years the MN and DN increased from 26.6% and 3.2% in 2008-2011 to 41.5% and 13.1% in 2016-2020 (χ2=39.1 and 57.3, both P<0.01), respectively. For age group≥65 years the MN was the most common pathological type in the three periods, fluctuating between 41.3% and 55.0% (χ2=5.2, P=0.08); and DN increased from 0(0/63) in 2008-2011 to 7.5%(22/292) in 2016-2020 (χ2=8.1, P=0.02). Conclusion:The renal biopsy data show that membranous nephropathy and diabetic nephropathy are the most common primary and secondary adult glomerular diseases in Beijing recently.
8.Combined application of low kV,low mAs, and iterative model reconstruction (IMR) in carotid CT angiography
Guo SA ; Qidong WANG ; Shuangzhi LYU ; Jianjun YAO ; Genren YANG ; Qiang HUANG ; Zhan FENG
Chinese Journal of Radiological Medicine and Protection 2017;37(6):471-475
Objective To evaluate the application value of combination of low kV,low mAs,and iterative model reconstruction (IMR) in carotid CT angiography.Methods Forty patients (BMI 20-25 kg/m2) were enrolled and randomly divided into routine dose group(20) and low dose group(20),The parameters in routine dose group were 120 kV,automatic mAs,and filter back projection(FBP);and that in low dose group were 80 kV,automatic mAs but upper limit 150 mAs,and FBP or IMR.All patients received the injection of 32 ml of iopamidol(370 mg I/100 ml) at a flow rate of 4 ml/s,followed by 50 ml normal saline at the same rate.The CT value and image noise(SD)of the aortic arch,left carotid artery bifurcation,and right carotid artery of rock bone were measured with region of interest(ROI) method,and then signal to noise ratios (SNR) and contrast to noise ratio (CNR)of image were calculated.The image quality was evaluated by two radiologists using a subjective four points scale on multiplanar reformated (MPR),maximum density projected (MIP) and volume rendered (VR) images.Volume CT dose index (CTDIvol),dose length product (DLP),and the effective dose (E) of each patient were recorded.Results CT values of carotid artery[(479.87 ± 70.28),(514.78 ± 82.69),(436.50 ± 89.87) HU] in low dose group were significantly higher than those in routine dose group [(295.63 ± 34.75),(325.09 ± 37.81),(286.93±36.46)HU](t =-6.47,-5.76,-3.66,P<0.05).The SNR and CNR of IMR reconstructed image in low dose group were significantly higher than those of FBP reconstructed image in routine dose group (t =-7.54,-3.55,-5.31,-7.13,-5.28,-8.35,P<0.05).The image quality of FBP reconstructed images in routine dose group and IMR reconstructed images in low dose group were all enough for diagnosis.The image quality of FBP reconstructed images in low dose group was significantly poorer than that in routine dose group and IMR reconstructed images in low dose group (Z =-2.87,-3.69,P <0.05).The effective dose in low dose group (0.57 ±0.13) mSv was 73% less than that in routine dose group (2.22 ± 0.36) mSv.Conclusions Using low kV,low mAs,and IMR would help to obtain good carotid CT angiographic images and low radiation dose.
9.Long-term efficacy of neonatal hepatitis B vaccination against chronic hepatitis B virus infection and chronic liver disease: a cross-sectional study based on Qidong Hepatitis B Intervention Study.
Taoyang CHEN ; Chunfeng QU ; Hongyu YAO ; Lingling LU ; Jian FAN ; Yuting WANG ; Fei HUANG ; Jianhua LU ; Zhengping NI ; Chunsun FAN ; Yawei ZHANG ;
Chinese Journal of Epidemiology 2016;37(1):64-67
OBJECTIVETo evaluate the long-term protection efficacy of neonatal hepatitis B vaccination on chronic hepatitis B (CHB) and liver fibrosis and cirrhosis in adults.
METHODSFrom January to October, 2013, a cross-sectional study was conducted among the participants from Qidong Hepatitis B Intervention Study (QHBIS), who were selected through stratified random sampling. The detections of serum alanine aminotransferase (ALT), HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe were conducted and ultrasonography on liver, gallbladder and spleen was performed for them. The positive rates of each serologic markers, the prevalence of active CHB and liver fibrosis and cirrhosis were calculated, the gender specific differences between vaccination group and control group were compared with Chi-square test.
RESULTSA total of 4 421 participants aged (25.59±1.84) years in vaccination group and 3 880 participants aged (26.61±2.24) years in control group were surveyed. The positive rates of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 2.38%, 37.73%, 3.78%, 0.57% and 2.15% in vaccination group, and 9.02%, 29.41%, 16.83%, 2.73% and 8.87% in control group, respectively, the differences between two groups were statistically significant (all P<0.05). The prevalence of active CHB and liver fibrosis and cirrhosis were 0.45% and 0.16% in vaccination group, 1.29% and 0.39% in control group, the differences between two groups were statistically significant (P<0.05). The active CHB prevalence was lower in females than in males in both vaccination group and control group (P<0.05). The liver fibrosis and cirrhosis prevalence was lower in females than in males in control group (P<0.05); whereas, no statistical significant difference in liver fibrosis & cirrhosis prevalence between males and females was found in vaccination group (P>0.05).
CONCLUSIONSProtection conferred by neonatal hepatitis B vaccination could last to marrying age. The gender specific difference in protection efficacy needs further study.
Adult ; China ; Cross-Sectional Studies ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Hepatitis B, Chronic ; prevention & control ; Humans ; Liver Cirrhosis ; Male ; Prevalence ; Vaccination ; statistics & numerical data


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