1.Exploring Therapeutic Effect of Yuejuwan on Depressed Mice Based on Lipidomics
Zhentao ZHANG ; Dan SU ; Huizhen LI ; Yonggui SONG ; Huanhua XU ; Meixizi LAI ; Zhifu AI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):85-94
ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice based on lipidomics, and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group, model group, Yuejuwan group(3.6 g·kg-1) and fluoxetine group(10 mg·kg-1), and chronic unpredictable mild stress(CUMS) was used to establish the depression model. After 3 weeks of modeling, each administration group was gavaged with the corresponding drug solution according to the dose, and mice in the blank and model groups were given an equal volume of deionised water by gavage, one time/d for 2 weeks. After administration, the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test, open field test, tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in mouse serum. Lipidomic analysis of mouse serum, prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS), and the expression of mammalian target of rapamycin(mTOR), ribosomal protein S6 kinase(S6K), phosphorylation(p)-mTOR, p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group, mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly increased(P<0.01), and serum levels of TC, TG, LDL-C, HDL-C, AST and ALT were significantly elevated(P<0.05, P<0.01). Compared with the model group, the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test(P<0.01), the immobility times in the tail suspension test and forced swimming test were significantly reduced(P<0.01), and the serum levels of TC, TG, LDL-C, AST and ALT were significantly decreased(P<0.05, P<0.01). Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum, prefrontal cortex and hippocampus of depressed mice, and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism, sphingolipid signaling, and glycosylphosphatidylinositol-anchored protein biosynthesis, among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased(P<0.01). In comparison with the model group, the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased(P<0.01). ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect, which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.
2.Progress in the diagnosis and treatment of reactive arthritis in children
Huizhen LI ; Jinping XU ; Lanfang CAO
Chinese Journal of Applied Clinical Pediatrics 2024;39(6):469-472
Reactive arthritis(ReA) is a kind of sterile, non-purulent arthritis that occurs after microbial infections far from the joints.The disease has a broad spectrum, and it can be classified into three categories based on clinical characteristics: human leukocyte antigen B27(HLA-B27)-associated ReA, acute rheumatic fever(ARF), and post-streptococcal reactive arthritis(PSRA).In addition to joints, it may also involve the gastrointestinal tract, skin, eyes, and heart.Unlike adults, the pathogenesis of ReA in children is more complex.HLA-B27-associated ReA is more common after gastrointestinal and respiratory infections, with less involvement of the central axis and sacroiliac joints and more involvement of the hip and peripheral joints and attachment point inflammation.ARF is most common in children aged 5 to 15 years, characterized by migratory and multiple arthritis.The duration of onset of PSRA in children is shorter than that in adults.This article reviews the epidemiology, clinical manifestations, diagnosis and treatment of ReA in children to improve clinicians′ understanding of ReA in children.
3.Polydatin protects vascular endothelial cells by modifying the JAK2/STAT3 signaling pathway
Wenwen KONG ; Huizhen WEI ; Yuanying XU ; Wenjun SHA ; Jun LU ; Tao LEI
Acta Universitatis Medicinalis Anhui 2024;59(7):1201-1205,1212
Objective To study the protective effect of polydatin on lipopolysaccharide-induced injury of human umbilical vein vascular endothelial cells(HUVECs)through the protein Janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)signaling pathway.Methods HUVECs were cultured in vitro,and 500 ng/ml LPS induced their injury and set as a model group;based on the model group,endothelial cells were inter-vened with different concentrations(10,20,and 40 μmol/L)of polydatin for 24 h,and set as polydatin low concentration group,polydatin medium concentration group,and polydatin high concentration group,respectively;a control group was set as another group.CCK-8,monocyte-endothelial cell adhesion,scratch and Transwell assays were used to detect cell viability,adhesion,migration and invasive ability;ELISA was used to detect interleukin-6(IL-6)and tumor necrosis factor-alpha(TNF-α)levels in the cell supernatant;Western blot was used to detect the expression of proteins related to the JAK2/STAT3 signaling pathway levels of JAK2/STAT3 signaling pathway relat-ed proteins.Results Compared with the control group,the model group showed decreased cell survival(P<0.01),increased cell adhesion,migration and invasion(P<0.001,P<0.05,P<0.01),increased levels of IL-6 and TNF-α in the cell supernatant(P<0.001),and increased levels of phosphorylation of JAK2 and STAT3 pro-teins in the cells(P<0.05).Compared with the model group,LPS damage to cells was attenuated after polydatin intervention,cell survival was increased in polydatin low-,medium-and high-concentration groups(P<0.05),cell adhesion,migration,and invasion decreased(P<0.05,P<0.05,P<0.001),IL-6 and TNF-α levels in cell supernatants decreased(P<0.05),and the levels of cellular JAK2 and STAT3 protein phosphorylation lev-els decreased(P<0.05).Conclusion Polydatin seems to reduce the inflammatory injury of human umbilical vein endothelial cells induced by LPS,reducing the secretion of inflammatory factors,and inhibiting the ability of cell ad-hesion,migration and invasion,which may be related to the down-regulation of JAK2/STAT3 signal pathway by polydatin.
4.Effect of Stemona tuberosa Alkaloids on Apoptosis and PI3K/Akt and JNK/MAPK Signaling Pathways of Human Lung Cancer A549 Cells
Si LIN ; Huizhen QIN ; Zeyu LI ; Liba XU ; Lingyu DENG ; Jing LUO ; Fengfeng XIE ; Miao ZHANG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(4):69-76
ObjectiveTo investigate the effect of Stemona tuberosa alkaloids (STA) on apoptosis and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (JNK/p38 MAPK) signaling pathways in human lung cancer A549 cells. MethodA549 cells were classified into blank group and STA groups (100, 150, 200, 250, 300 mg⋅L-1). Thiazole blue (MTT) assay and colony formation assay were used to evaluate the proliferation of A549 cells. Apoptosis was observed based on Hoechst 33258 staining, flow cytometry, and Annexin V-FITC/PI staining. Western blot was employed to detect the expression of apoptosis-related proteins cysteine-aspartic acid protease-3 (Caspase-3), B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and Bcl-2, and the expression of PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, JNK, p-JNK, p38 MAPK, and p-p38 MAPK. ResultCompared with the blank group, STA groups (150, 200, 250, 300 mg⋅L-1) demonstrated the increase in inhibition rate of cell proliferation (P<0.01) and cell clone inhibition rate, and decrease in cell clone formation rate (P<0.01). In comparison with the blank group, STA groups showed typical characteristics of apoptosis, such as chromatin condensation and enhanced fluorescence reaction. The apoptosis rate of STA groups was significantly higher than that of the blank group (P<0.01). Compared with the blank group, STA (150, 200, 250, 300 mg⋅L-1) significantly up-regulated the protein expression of Caspase-3 and Bax (P<0.05, P<0.01) and down-regulated the expression of Bcl-2 protein (P<0.01). Compared with the blank group, STA had no significant influence on the total protein expression of PI3K, Akt, JNK, and p38 MAPK. However, STA (150, 200, 250, 300 mg⋅L-1) significantly decreased the levels of p-PI3K and p-Akt (P<0.05, P<0.01) and increased the level of p-p38 MAPK (P<0.05, P<0.01). Compared with the blank group, STA (200, 250, 300 mg⋅L-1) significantly raised the level of p-JNK (P<0.05, P<0.01). ConclusionSTA can inhibit the proliferation and induce the apoptosis of A549 cells by inhibiting PI3K/Akt signaling pathway and activating JNK/p38 MAPK signaling pathway.
5.Screening and identification of a polyurethane-degrading bacterium G-11 and its plastic degradation characteristics.
Zhitong JIANG ; Xue CHEN ; Jinhui LEI ; Huizhen XUE ; Bo ZHANG ; Xiaofan XU ; Huijing GENG ; Zhoukun LI ; Xin YAN ; Weiliang DONG ; Hui CAO ; Zhongli CUI
Chinese Journal of Biotechnology 2023;39(5):1963-1975
Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism*
;
Polyurethanes/chemistry*
;
RNA, Ribosomal, 16S
;
Bacteria/genetics*
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Biodegradation, Environmental
6.Mechanism of Stemona tuberosa Alkaloids in Inhibiting Proliferation and Inducing Apoptosis of Non-small Cell Lung Cancer NCI-H460 Cells
Si LIN ; Huizhen QIN ; Liba XU ; Li LONG ; Hua ZHU ; Xiaoxun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(22):71-78
ObjectiveTo study the effect and underlying mechanism of Stemona tuberosa alkaloids on the proliferation and apoptosis of human non-small cell lung cancer NCI-H460 cells. MethodNon-small cell lung cancer NCI-H460 cells were divided into a blank group and S. tuberosa alkaloids groups (50, 100, 150, 200, and 250 mg·L-1). The effect of S. tuberosa alkaloids on the proliferation of human NCI-H460 cells was observed by thiazolyl blue tetrazolium bromide (MTT) assay and colony formation assay. Cell apoptosis was observed by Hoechst 33258 staining and flow cytometry. Real-time fluorescence-based polymerase chain reaction (Real-time PCR) was used to detect the effect of S. tuberosa alkaloids on the mRNA expression of cysteinyl aspartate-specific protease 3 (Caspase-3), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and epidermal growth factor receptor (EGFR). The protein expression levels of Caspase-3, Bax, Bcl-2, protein kinase B (Akt), phosphorylated (p-)Akt, EGFR, c-Jun N-terminal kinase (JNK), p-JNK, p38 mitogen-activated protein kinase (p38 MAPK), and p-p38 MAPK were measured by Western blot. ResultCompared with the blank group, the S. tuberosa alkaloids groups showed increased inhibition rate on cell proliferation (P<0.01), reduced number of cell clones formed and the rate of cell clonal formation (P<0.05, P<0.01), and increased karyopyknosis, cytoplasmic aggregation, and cell apoptosis rate (P<0.01). The S. tuberosa alkaloids groups at 100, 150, 200, and 250 mg·L-1 showed increased Caspase-3 mRNA expression (P<0.05), decreased EGFR mRNA expression (P<0.05, P<0.01), up-regulated protein expression of Caspase-3 and p-JNK (P<0.01), and down-regulated protein expression of EGFR and p-Akt (P<0.05, P<0.01). Additionally, compared with the blank group, the S. tuberosa alkaloids groups showed increased expression of Bax mRNA (P<0.01), decreased expression of Bcl-2 mRNA (P<0.01), up-regulated protein expression of Bax and p-p38 MAPK (P<0.01), and down-regulated protein expression of Bcl-2 (P<0.01). ConclusionsS. tuberosa alkaloids can inhibit proliferation and induce apoptosis of human non-small cell lung cancer NCI-H460 cells, and the mechanism may be related to the inhibition of EGFR protein expression and phosphorylation of Akt protein, as well as the activation of the JNK/p38 MAPK signaling pathway.
7.Umbrella trial for clinical trial design of oncology drugs
Xiaoqin ZHOU ; Huizhen LIU ; Ting WANG ; Xu LI ; Fanfan SHI ; Deying KANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(09):1228-1234
The umbrella trial has received increasing attention in the design of clinical trials for oncology drugs in recent years. This trial design categorizes a single disease into multiple sub-types based on predictive biomarkers or other predictive factors, and simultaneously evaluates the efficacy of multiple targeted therapies. When compared with the traditional drug development model of phase Ⅰ, phaseⅡ, and phase Ⅲ randomized controlled trials, umbrella trials are a more scientifically rigorous trial design that can speed up drug evaluation to address the conflict between numerous untested drugs and diseases with a lack of effective treatment options. This article will focus on the concept, main characteristics, eligibility criteria, design and statistical considerations, ethical considerations, and future directions of umbrella trials, with the aim of providing methodological guidance for the design of clinical trials for oncology drugs.
8.Treatment of acromioclavicular joint dislocation with double Endobutton internal fixation assisted by orthopaedic robot
Chengzhi YANG ; Renchong WANG ; Huizhen ZENG ; Xiangtao XIE ; Jian XU ; Jingli TANG ; Hao WU ; Bing LI ; Juzheng HU
Chinese Journal of Orthopaedics 2022;42(21):1423-1432
Objective:To investigate the early clinical effects of orthopedic surgery robot-assisted double Endobutton titanium plate internal fixation in the treatment of fresh acromioclavicular joint dislocation.Methods:Thirty-nine patients with fresh acromioclavicular joint dislocation were included from January 2020 to January 2022. A total of 19 patients were treated with double Endobutton suspension internal fixation assisted by the domestic third-generation orthopaedic surgical robot (TiRobot ? 2.0) Dimensity system. There were Rockwood type III in 11 cases, type IV in 8 cases. Twenty cases were treated with conventional incision double Endobutton internal fixation, with Rockwood type III in 13 cases, type V in 7 cases. The operation duration, blood loss volume, incision length and hospitalization time were compared between the two groups. The following CT parameters of acromioclavicular joint at 2 days and 1 year after operation, distance between distal inferior cortex of clavicle and subacromial cortex, distance between upper and lower endobuttons, horizontal distance between anterior edge of distal clavicle and anterior edge of acromion and diameter of coracoid process and diameter of clavicular tunnel were measured. The visual analogue score (VAS), Constant-Murley shoulder function score and shoulder abduction activity were also evaluated before and at 12 months after operation. Results:The follow-up duration was 10.8±2.4 months in the robot group and 11.5±3.1 months in the routine group. The VAS score of the robot group decreased from 5.3±2.1 to 0.3±0.2 at 12 months after operation ( t=10.46, P=0.014). The Constant-Murley score increased from 55.6±6.4 to 92.0±4.2. The range of shoulder abduction increased from 42.2°±5.4° to 172.6°±6.1° ( t=17.24, P<0.001). The operation duation of the robot group was 74.4±6.6 min, which was longer than that of the conventional group 61.7±7.2 min ( t=5.43, P=0.037). There was no significant difference in VAS score, Constant-Murley score, shoulder abduction activity or CT measurement between the two groups ( P>0.05). During the follow-up, two cases in the robot group had cortical osteolysis on the supraclavicular surface, one case in the conventional group had loss of reduction, one case in the supraclavicular cortical osteolysis, and 4 cases in the cortical defect on the side of the coracoid process tunnel. Conclusion:Orthopedic robot-assisted and conventional incision with double Endobutton titanium plate internal fixation in treating fresh acromioclavicular joint dislocation can achieve satisfied early clinical effects. Accurate establishment of clavicle and coracoid bone tunnel assisted by robot can overcome the defects of bone tunnel deviation in conventional incision operation and can prevent reduction and bone loss. However, robot-assisted and conventional incision Endobutton internal fixation could enlarge bone tunnel.
9.Clinical significance of suction blister transplantation in improving efficacy of ReCell technique in treatment of vitiligo
Fei LONG ; Wenchao ZHANG ; Zhifei LIU ; Yong TAO ; Chunyu XU ; Huizhen XU ; Mingzi ZHANG ; Zenan XIA ; Bin LIU ; Nanze YU
Chinese Journal of Medical Aesthetics and Cosmetology 2021;27(3):218-221
Objective:To investigate the clinical significance of suction blister transplantation in improving the efficacy of ReCell technique in the treatment of vitiligo.Methods:Patients were divided into three groups, namely, vitiligo patients without history of suction blister therapy, patients with ineffective suction blister therapy and patients with effective suction blister therapy. There were 30 patients in each group. All patients were treated with standard procedure of ReCell technique. The color recovery effect of leukoplakia was observed 3 and 6 months after operation, and the incidence of complications was also observed.Results:The effective rate of color recovery 3 and 6 months after operation were as follow: in patients without history of suction blister group, the effective rate of three months was 53.3%, and that of six months was 63.3%; in patients with ineffective suction blister group, the effective rate was 43.3% in three months and 50.0% in six months, and in patients with effective suction blister group, the effective rate was 76.7% in three months and 90.0% in six months. No obvious complications were observed in the three groups.Conclusions:For the treatment of stable vitiligo with ReCell technique, suction blister method is a simple and effective method for screening patients.
10.Erythropoietin-Modified Mesenchymal Stem Cells Enhance Antifibrosis Efficacy in Mouse Liver Fibrosis Model
Xianyao WANG ; Huizhen WANG ; Junhou LU ; Zhanhui FENG ; Zhongshan LIU ; Hailiang SONG ; Heng WANG ; Yanhua ZHOU ; Jianwei XU
Tissue Engineering and Regenerative Medicine 2020;17(5):683-693
BACKGROUND:
Mesenchymal stem cell (MSC)-based cell transplantation is an effective means of treating chronic liver injury, fibrosis and end-stage liver disease. However, extensive studies have found that only a small number of transplanted cells migrate to the site of injury or lesion, and repair efficacy is very limited.
METHODS:
Bone marrow-derived MSCs (BM-MSCs) were generated that overexpressed the erythropoietin (EPO) gene using a lentivirus. Cell Counting Kit-8 was used to detect the viability of BM-MSCs after overexpressing EPO. Cell migration and apoptosis were verified using Boyden chamber and flow cytometry, respectively. Finally, the anti-fibrosis efficacy of EPO-MSCs was evaluated in vivo using immunohistochemical analysis.
RESULTS:
EPO overexpression promoted cell viability and migration of BM-MSCs without inducing apoptosis, and EPO-MSC treatment significantly alleviated liver fibrosis in a carbon tetrachloride (CCl4 ) induced mouse liver fibrosis model.
CONCLUSION
EPO-MSCs enhance anti-fibrotic efficacy, with higher cell viability and stronger migration ability compared with treatment with BM-MSCs only. These findings support improving the efficiency of MSCs transplantation as a potential therapeutic strategy for liver fibrosis.


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