1.Effects of increased secretory SERPINE1 expression by dexmedetomidine on the malignant biological behavior of thyroid carcinoma cells
Xueyan TONG ; Wenfeng JIANG ; Liangping ZENG ; Yan LIN
China Pharmacy 2025;36(10):1179-1185
OBJECTIVE To explore the effects of dexmedetomidine (DEX) increasing serpin peptidase inhibitor clade E member 1 (SERPINE1) protein on the malignant biological behavior of thyroid carcinoma (THCA) cells. METHODS THCA cells (KTC-1, TPC-1) were treated with 1, 10 and 100 nmol/L DEX, and their viabilities, clone formation rates, migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected, and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group (0 nmol/L DEX), DEX at 1, 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells (except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h), concentration-dependently elevated the rates of clone formation, migration rates (except for 2 types of THCA cells in 1 nmol/L DEX group), and the number of invasion (P<0.05). A total of 287 differently expressed genes (75 up- tongxueyan180@163.com regulated and 212 down-regulated) were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B, Wnt, and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA, and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients (P<0.05). Compared with the control group, mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1, 10 and 100 nmol/L DEX groups, while the secretion of this protein in conditioned medium was also significantly increased, all of which showed concentration-dependence (P<0.05). After knocking down SERPINE1, the promoting effects of DEX on the proliferation, colony formation, migration and invasion abilities of two types of THCA cells were significantly inhibited (P<0.05). CONCLUSIONS DEX can promote the proliferation, migration and invasion of THCA cell, and the above effects may be associated with the expression of increased secretory SERPINE1 protein.
2.Herbal Textual Research on Tribuli Fructus and Astragali Complanati Semen in Famous Classical Formulas
Jiaqin MOU ; Wenjing LI ; Yanzhu MA ; Yue ZHOU ; Wenfeng YAN ; Shijun YANG ; Ling JIN ; Jing SHAO ; Zhijia CUI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):241-251
By systematically combing ancient and modern literature, this paper examined Tribuli Fructus and Astragali Complanati Semen(ACS) used in the famous classical formulas from the aspects of name, origin, production area, harvesting and processing, clinical efficacy, so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology, and there were nicknames such as Baijili, Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas, and there were nicknames such as Baijili, Shayuan Jili and Tongjili. Because both of them had the name of Baijili, confusion began to appear in the Song dynasty. In ancient and modern times, the main origin of Tribuli Fructus were Tribulus terrestris, and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu, but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part, harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times, and the plump, firm texture, grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing, while modern commonly used is purified, fried and salt-processed. The ancient records of Tribuli Fructus were spicy, bitter, and warm in nature, with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders, improving vision, promoting muscle growth, and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today, the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed, traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter, followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior, while modern standards prioritize plump, uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying, while modern practice commonly employs purification methods. In terms of medicinal properties, the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus, its effects were thus regarded as equivalent to those of Tribuli Fructus, serving as the medicine for treating wind disorders, additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang, solidify sperm and reduce urine, nourish the liver and brighten the eye, etc. Based on the textual research results, it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials, we should pay attention to the specific reference object of Baijili, T. terrestris and A. complanatus should be identified and selected, and the processing method should be in accordance with the requirements of the formulas.
3.Effect of Buyang Huanwutang on Skeletal Muscle Injuries in Mouse Model of Type 2 Diabetes Mellitus
Yang WANG ; Lijuan JIANG ; Wei CUI ; Wenfeng ZHANG ; Yan WEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):10-16
ObjectiveTo study the effects of Buyang Huanwutang on the skeletal muscle injuries in type 2 diabetes mellitus from mitochondrial transport, glucose metabolism, oxidative stress, and inflammation. MethodA total of 60 SPF-grade male C57BL/6J mice were selected in this study. The mouse model of type 2 diabetes mellitus was established with a high-fat diet combined with intraperitoneal injection of streptozotocin. The mice were assigned by the random number table method into blank control, model, high-, medium-, and low-dose (86.5, 43.2, 21.6 g·kg-1, respectively) Buyang Huanwutang, and metformin (150 mg·kg-1) groups, 10 mice in each group. During the experiment period, blood glucose and other indicators of mice were measured regularly. At the end of the experiment, skeletal muscle samples were collected and frozen in 4% paraformaldehyde and -80 ℃, respectively. Blood samples were sent for examination. The skeletal muscle was stained with hematoxylin-eosin. The levels of inflammation indicators and reactive oxygen species (ROS) were determined by enzyme-linked immunosorbent assay. The expression of mitochondrial proteins was determined by Western blot and immunohistochemistry. ResultCompared with the blank control group, the model group showcased increased fasting blood glucose, water intake, and food intake (P<0.01) and decreased body weight (P<0.01). Compared with the model group, metformin and Buyang Huanwutang reduced the fasting blood glucose, water intake, and food intake (P<0.05, P<0.01) and increased the body weight (P<0.01). Compared with the blank control group, the model group showed rising levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and ROS (P<0.01), which were decreased by metformin and Buyang Huanwutang (P<0.05, P<0.01). The skeletal muscle fibers in the model group were generally atrophic and thin, which suggested atrophy and morphological changes of the skeletal muscle, while metformin and Buyang Huanwutang alleviated the pathological changes of the skeletal muscle and restored the morphology of fiber bundles. Compared with the blank control group, the modeling down-regulated the expression of the mitofusin2 (Mfn2) (P<0.01), which was up-regulated by metformin and Buyang Huanwutang (P<0.05, P<0.01). Compared with the blank control group, the modeling up-regulated the expression of the dynamin-related protein (Drp1) (P<0.01), which were down-regulated by metformin and Buyang Huanwutang (P<0.01). ConclusionBuyang Huanwutang can improve the body weight and attenuate the pathological changes of the skeletal muscle, reduce fasting blood glucose, food intake, and water intake, lower the levels of TNF-α, IL-6, and ROS, down-regulate the expression of Drp1, and up-regulate the expression of Mfn2 in the mouse model of type 2 diabetes mellitus.
4.Clinical characteristics and prognosis of male dermatomyositis patients with positive anti-melanoma differentiation associated gene 5 antibody
Yitian SHI ; Fenghong YUAN ; Ting LIU ; Wenfeng TAN ; Ju LI ; Min WU ; Zhanyun DA ; Hua WEI ; Lei ZHOU ; Songlou YIN ; Jian WU ; Yan LU ; Dinglei SU ; Zhichun LIU ; Lin LIU ; Longxin MA ; Xiaoyan XU ; Yinshan ZANG ; Huijie LIU ; Tianli REN
Chinese Journal of Rheumatology 2024;28(1):44-49
Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.
5.Influence of sarcopenia on quality of life in patients with adenocarcinoma of gastroesophageal junction
Ya XIE ; Wenfeng YAN ; Xiaobo XIA ; Yingying LU ; Junwei BAI
Chinese Journal of Digestive Surgery 2023;22(11):1330-1336
Objective:To investigate the influene of sarcopenia on quality of life in patients with adenocarcinoma of gastroesophageal junction (AEG).Methods:The retrospective cohort study was conducted. The clinicopathological data of 109 patients with AEG who were admitted to Henan Provincial People′s Hospital from January 2019 to December 2022 were collected. There were 63 males and 46 females, aged (63±11)years. All patients underwent 3D laparoscopic assisted radical total gastrectomy+D 2 lymph node dissection. The skeletal muscle content of patient was obtained within 3 days before surgery by using a multi-frequency bioelectrical impedance human body composition analyzer. Observation indicators: (1) clinical characteristics of patients with sarco-penia and non sarcopenia; (2) intraoperative and postoperative conditions in patients with sarco-penia and non sarcopenia; (3) analysis of serious postoperative complications in patients with AEG; (4) preoperative and postoperative quality of life score in patients with sarcopenia and non sarco-penia. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Mann-Whitney U non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA, and their variances were tested using a spherical test. Univariate analysis was conducted using the Logistic regression model, and multivariate analysis was conducted using the Logistic stepwise regression model. Results:(1) Clinical characteristics of patients with sarcopenia and non sarcopenia. Of 109 patients with AEG, there were 42 cases with sarcopenia and 67 cases with non sarcopenia. The body mass index (BMI), forced expiratory volume in 1 second (FEV1), rate of FEV1/forced vital capacity were (20.3±2.3)kg/m 2, 92%±9%, 79%±11% in patients with sarcopenia, respectively, versus (24.4±2.7)kg/m 2, 97%±9%, 85%±11% in patients with non sarcopenia, showing significant differences in the above indicators between them ( t=8.07, 2.46, 2.77, P<0.05). (2) Intraoperative and postoperative conditions in patients with sarcopenia and non sarco-penia. The volume of intraoperative blood loss, time to postoperative first flatus, duration of post-operative hospital stay, cases with postoperative complications were 208(192, 231)mL, (3.4±0.9)days, (11.4±3.2)days, 26 in patients with sarcopenia, respectively, versus 195(150,215)mL, (2.8±0.7)days, (9.9±1.6)days, 14 in patients with non sarcopenia, showing significant differences in the above indi-cators between them ( Z=-2.14, t=3.25, 3.38, χ2=18.69, P<0.05). (3) Analysis of serious postoperative complications in patients with AEG. Results of multivariate analysis showed that sarcopenia and BMI reduction were independent risk factors influencing serious postoperative complications in patients with AEG ( odds ratio=2.04, 1.98, 95% confidence interval as 1.24-3.36, 1.09-3.60, P<0.05). (4) Pre-operative and postoperative quality of life score in patients with sarcopenia and non sarcopenia. Results of multivariate test in physical function, role function, social function, overall score of patients with sarcopenia and non sarcopenia before surgery, 2 weeks after surgery, 4 weeks after surgery, and 8 weeks after surgery showed that there were significant differences in the temporal effect, intergroup effect and interaction effect of the above indicators between patients with sarcopenia and non sarcopenia ( P<0.05). Results of individual effects showed that there were significant differences in the intergroup effect of the above indicators between patients with sarcopenia and non sarcopenia ( P<0.05). Conclusion:Preoperative sarcopenia increases the risk of severe postoperative complications and reduces the postoperative quality of life in patients with AEG.
6.An intelligent diagnosis model of osteoporotic vertebral compression fracture based on MRI scans
Han YAN ; Wenfeng LIU ; Menglin WU ; Guangtao ZHANG ; Xiankun LIAN ; Zhuliang YU
Chinese Journal of Orthopaedic Trauma 2023;25(1):64-69
Objective:To develop a deep learning model which can automatically and accurately detect osteoporotic vertebral compression fractures (OVCF) based on artificial intelligence.Methods:MRI images of 500 patients diagnosed with OVCF at The First People's Hospital of Guangzhou from January 2019 to October 2021 were collected retrospectively. There were 396 males and 204 females, with an age of (74.5±6.0) years. The T value of bone mineral density was -2.9±0.8. The fracture segments were L1 in 128 cases, L2 in 113 cases, L3 in 109 cases, L4 in 115 cases, and L5 in 108 cases. The multimodal layered converged network was used to train, test, and verify the robustness and generalization ability of a deep learning model based on MRI images of OVCF. The grad-cam was applied to visualize the results. The diagnostic value of the model for OVCF was assessed by comparing the diagnoses between the artificial intelligence model and 2 senior spinal surgeons on the MRI images of 30 OVCF patients randomized from the 500 ones.Results:Of the precise auxiliary diagnosis model for OVCF based on MRI images, the diagnostic accuracy was 96.7%, the sensitivity 93.5%, the specificity 88.9%, the positive predictive value 100.0%, and the negative predictive value 86.6%, all significantly higher than those of the 2 senior spinal surgeons (70.0%, 72.7%, 28.6%, 82.1%, and 28.6%) ( P<0.05). Conclusion:The present study has successfully established a deep learning model which can automatically and accurately diagnose OVCF based on MRI images, showing a high diagnostic efficiency than human spinal surgeons.
7.Effects of Amarogentin on Residual Liver Cancer Stem Cells After Insufficient Thermal Ablation and Related Mechanism
Yan LIU ; Fanbo QIN ; Jianping GONG ; Wenfeng ZHANG
Cancer Research on Prevention and Treatment 2023;50(8):760-766
Objective To observe the effects of amarogentinon liver cancer stem cells (LCSCs) after insufficient thermal ablation and its mechanism. Methods A insufficient thermal ablation model of HepG2 cells was established by water bath method.The percentage of CD133-positive LCSCs and the mRNA and protein levels of CD133 were detected by flow cytometry, qRT-PCR and Western blot.The insufficient thermal ablation model of HepG2 cells was treated with variable doses of amarogentin for 24 h; the percentage of CD133-positive LCSCs, the proliferation and apoptosis of liver cancer cells, and the mRNA and protein levels of CD133, TBC1D15, and p53were detected by flow cytometry, qRT-PCR and Western blot. Results The percentage of CD133-positive HepG2 cells and the mRNA and protein levels of CD133 and TBC1D15in the insufficient thermal ablation model were significantly higher than those in the normal HepG2 cells.Amarogentin then markedly decreased the percentage of CD133-positive LCSCs, the proliferation rate of HepG2 cells, and the mRNA and protein levels of CD133 and TBC1D15 in the insufficient thermal ablationresidual model (all
8.A multi-center, double-blind, randomized, placebo- and positive-controlled phase II clinical study of benvitimod for the treatment of atopic dermatitis.
Lin CAI ; Yan ZHAO ; Min ZHENG ; Furen ZHANG ; Qing SUN ; Quanzhong LIU ; Jin HU ; Juan SHEN ; Jianzhong ZHANG
Chinese Medical Journal 2023;136(2):251-252
9.A Visual Analysis on Animal Model of Sarcopenia Based on VOSviewer
Lei XIANG ; Jinzhu JING ; Zhen LIANG ; Guoqiang YAN ; Wenfeng GUO ; Meng ZHANG ; Wei ZHANG ; Yajun LIU
Laboratory Animal and Comparative Medicine 2023;43(4):429-439
ObjectiveAnalyze the current situation, hotspots and development trends of sarcopenia animal model to provide research direction and basic information for sarcopenia animal model research. MethodsEnglish literature of research on animal models of sarcopenia was retrieved from the Web of Science core data (WOS) set from 1900-01-01 to 2022-12-31. Chinese literature related to animal models of sarcopenia was retrieved from CNKI database between 1915 and 2022. The bibliometric analysis software VOSviewer was used to explore the countries, orgonizations, authors, hotspots and frontier directions in these studies. ResultsA total of 2 819 articles on animal models of sarcopenia were retrieved from WOS core database. The first paper was published in 1995. The United States has the largest number of animal model studies of sarcopenia with 1 105 articles. The institution with the most published articles is the University of Florida in the United States, with 69 articles. The University of Hong Kong has the highest number of publications in China, with 20 articles. American author Van Remmen H, with 50 publications, is the author of the most articles. The journal with the largest number of articles published on animal models of sarcopenia is the American journal called FASEB Journal, with 196 articles. In total, 423 articles on animal models of sarcopenia were retrieved from the CNKI database. Author LI Zhuyi has published 19 articles, and is the author of the most articles in China. The keyword co-occurrence clustering analysis of WOS literature search found that the research focus on animal model of sarcopenia can be summarized as the correlation between sarcopenia and metabolism, cytology and regenerative medicine of sarcopenia animal models, the study of sarcopenia animal models in bone, muscle, nerve and exercise therapy. The retrieval results of CNKI database revealed that the most extensive research was about on the model of denervated sarcopenia, and researches on the effects of Chinese medicine on sarcopenia were also widely reported. Through reading the full articles or abstracts of the literature, the animal models of sacopenia mainly include natural aging model, genetic modification model, high-fat diet induction model, disuse model, hormone induction model and complex sarcopenia models of other diseases. ConclusionIn recent years, the study on animal model of sarcopenia has become a hotspot at home and abroad.The bibliometric analysis provides a basis for the research of animal models of sarcopenia in terms of research direction, hotspots, model animal selection, animal model making, and domestic and international communication and cooperation.
10.Advances and Applications in Animal Models of Neuroblastoma
Zhigang TAN ; Jinxin LIU ; Chuya ZHENG ; Wenfeng LIAO ; Luping FENG ; Hongli PENG ; Xiu YAN ; Zhenjian ZHUO
Laboratory Animal and Comparative Medicine 2023;43(3):288-296
Neuroblastoma (NB) is one of the most common malignant solid tumors in children, ranks fourth in the incidence of pediatric tumors, and accounts for 15% of pediatric tumor deaths in children in China. Despite the development of new treatment options, the prognosis for high-risk patients is still poor. An animal model that can replicate the tumorigenesis of NB is an important tool for the prevention and treatment of NB. However, there are currently no animal models that can simulate all features of human NB. To provide a reference for the construction of animal models and treatment of NB, this article introduced several animal models of NB that have been extensively researched: the mouse, chick embryo chorioallantoic membrane, and zebrafish models. At the same time, it elaborated on the species, construction methods, characteristics, advantages and disadvantages, and research progress in NB.

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