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.
7.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
8.Design and Validation of Scoliosis Orthosis Based on Finite Element Model
Jiaxiang LIN ; Yi CHEN ; Guanglin SHI ; Wenfeng WANG ; Kunwu LAN ; Wenjun JIANG ; Zipeng AI ; Weijie PENG
Journal of Medical Biomechanics 2025;40(4):988-995
Objective Based on the finite element simulation analysis of the patient's torso-spine model and combined with theoretical calculation data,an individualized scoliosis orthosis was designed,and the effectiveness of the orthosis was verified through three-dimensional(3D)printing.Methods A patient with idiopathic scoliosis was chosen as the research object.Reverse engineering technology and computer-aided technology were used to establish the torso-spine model of the patient.The finite element method was used to analyze the model,and the optimal position and magnitude of the corrective force were determined by combining literature theory calculation.Based on this,an orthosis was designed.To verify the orthopedic effect,the patient's X-rays before and after wearing the orthosis were compared and evaluated,and the patient was followed up 6 months later.Results The optimal position and magnitude of the initial corrective force were determined through theoretical calculations and finite element simulations.Specifically,a 62.95 N corrective force applied to the L3 vertebral body and the left posterior region corresponding to the upper and lower intervertebral discs in the patient's lateral curvature segment of the spine to achieve the optimal orthopedic effect.On this basis,the orthosis was designed,followed by relevant experimental tests before and after wearing the designed orthosis.By comparing X-ray images of the patient before and after wearing the orthosis and combining them with follow-up data six months later,the optimized design of the orthosis met the expected clinical requirements for orthopedic effects.Conclusions The design of orthosis needs to be personalized according to the specific situation of patients with scoliosis.This study takes a patient with idiopathic scoliosis as the research object,providing new ideas and methods for the design of orthosis for patients with idiopathic scoliosis.
9.Design and Validation of Scoliosis Orthosis Based on Finite Element Model
Jiaxiang LIN ; Yi CHEN ; Guanglin SHI ; Wenfeng WANG ; Kunwu LAN ; Wenjun JIANG ; Zipeng AI ; Weijie PENG
Journal of Medical Biomechanics 2025;40(4):988-995
Objective Based on the finite element simulation analysis of the patient's torso-spine model and combined with theoretical calculation data,an individualized scoliosis orthosis was designed,and the effectiveness of the orthosis was verified through three-dimensional(3D)printing.Methods A patient with idiopathic scoliosis was chosen as the research object.Reverse engineering technology and computer-aided technology were used to establish the torso-spine model of the patient.The finite element method was used to analyze the model,and the optimal position and magnitude of the corrective force were determined by combining literature theory calculation.Based on this,an orthosis was designed.To verify the orthopedic effect,the patient's X-rays before and after wearing the orthosis were compared and evaluated,and the patient was followed up 6 months later.Results The optimal position and magnitude of the initial corrective force were determined through theoretical calculations and finite element simulations.Specifically,a 62.95 N corrective force applied to the L3 vertebral body and the left posterior region corresponding to the upper and lower intervertebral discs in the patient's lateral curvature segment of the spine to achieve the optimal orthopedic effect.On this basis,the orthosis was designed,followed by relevant experimental tests before and after wearing the designed orthosis.By comparing X-ray images of the patient before and after wearing the orthosis and combining them with follow-up data six months later,the optimized design of the orthosis met the expected clinical requirements for orthopedic effects.Conclusions The design of orthosis needs to be personalized according to the specific situation of patients with scoliosis.This study takes a patient with idiopathic scoliosis as the research object,providing new ideas and methods for the design of orthosis for patients with idiopathic scoliosis.
10.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.

Result Analysis
Print
Save
E-mail