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.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.
9.Isolation,identification and treatment effectiveness evaluation of resistant Acinetobacter baumannii phage Abgy202162
Xun TIAN ; Wencai TAN ; Bi YANG ; Xiang LIU ; Wenfeng YU ; Xiaolan QI ; Yinhui JIANG
Acta Universitatis Medicinalis Anhui 2024;59(10):1742-1751
Objective To isolate a Acinetobacter baumannii(Ab)phage from underground sewage,study its prop-erties,and to provide a theoretical basis for phage treatment of Ab infection.Methods Double-layer agar tech-nique was used to isolate phages by using Ab GY-6 as the host strain.Biological characterization and therapeutic effect of the phage was tested.Genetic information of the phage was analyzed.Results Ab phage Abgy202162 was isolated.Transmission electron microscopy(TEM)analysis showed that the morphology of Abgy202162 exhibited an icosahedral structure.Biological characteristic analysis showed that the optimal multiplicity of infection was 1,the latent period was 5 min,and the burst size was approximately 520 PFU per cell.In addition,Abgy202162 re-mained stable at different concentrations of chloroform,pH,and temperatures.Sodium dodecyl sulfate-polyacryl-amide gel electrophoresis(SDS-PAGE)analysis showed that it contained 10 proteins with molecular weights ran-ging from 15 to 100 ku.The double-stranded(ds)DNA genome of Abgy202162 consisted of 40 889 bp and its G+C content was 38.85%.It contained 47 open reading frames(ORFs),of which 26 had specific functions,but no virulence related genes or antibiotic resistance genes were found.Phylogenetic analysis showed that Abgy202162 was a new phage in the Autographiviridae family,Beijerinkvirinae subfamily,and Friunavirus genus.Abgy202162 showed the ability to prevent Ab infection in the Galleria mellonella in vivo model.Conclusion The phage Ab-gy202162 has strong environmental tolerance and high safety,indicating its potential as an antibiotic alternative used in the treatment of infections caused by Ab.
10.Observation on efficacy of temporal straight incision small bone window microscopic craniotomy in treating cerebral hemorrhage in basal ganglia region
Rudan ZHANG ; Wenfeng XIAO ; Min JIANG ; Tingjun TANG ; Jianbo WANG ; Feng WANG ; Xiang ZHANG
Chongqing Medicine 2024;53(15):2349-2352
Objective To study the clinical efficacy of temporal small bone window microscopic craniot-omy in treating cerebral hemorrhage in basal ganglia region.Methods The retrospective analysis was adopt-ed.A total of 130 patients with intracerebral hemorrhage in the basal ganglia region treated in the Department of Neurosurgery of this hospital from January 2020 to January 2023 were selected as the study subjects.The patients treated by traditional frontotemporal large bone flap craniotomy hematoma removal were included in-to the control group (n=82) and the patients adopting temporal straight incision small bone window hemato-ma removal were included into the study group (n=48).The general data,surgical indicators,clinical efficacy,degree of neurological impairment,postoperative complications and postoperative quality of life of the patients were statistically analyzed.Results There were no statistically significant differences in preoperative Glasgow (GCS) score,gender,age and hematoma volume between the two groups (P>0.05);there was no statistically significant difference in the average hematoma clearance rate between the two groups (P>0.05);compared with the control group,the operation time and hospital stay of the study group were shorter,the incidence of severe edema and suboccipital fluid accumulation were lower,and the good prognosis rate was higher,with sta-tistical significance (P<0.05).Conclusion Temporal straight incision small bone window microscopic hema-toma removal in treating cerebral hemorrhage in basal ganglia region has mild edema reaction of brain tissue in operative area,the neurological function obtains the better protection and the good prognostic rate of the pa-tients is significantly increased.


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