1.Huangqi Jianzhongtang Regulates Polarization of Macrophages M1/M2 and Improves Fat Consumption in Cancer Cachexia Mice
Zhiyan FANG ; Haiyan ZHU ; Wenying HUAI ; Cong HUANG ; Ruocong YANG ; Haiyan YU ; Tiane ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):61-69
ObjectiveTo investigate the effects of Huangqi Jianzhongtang (HQJZ) on macrophage polarization and fat consumption in cancer cachexia (CC) mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap HRMS) was used to control the quality of HQJZ. (1) In vitro experiment: HQJZ-containing serum was prepared, and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages (RAW264.7) were cultured and randomly divided into six groups, including a blank group, a classically activated macrophages (M1) group, an alternatively activated macrophages (M2) group, a HQJZ + blank group, a HQJZ+M1 group, and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86, inducible nitric oxide synthase (iNOS), CD206, and arginase-1 (Arg1) was detected by real-time quantitative polymerase chain reaction (Real-time PCR ). (2) In vivo experiment: Thirty-two BALB/c mice were randomly divided into a control group, a model group, a medroxyprogesterone acetate (MPA) group, and a HQJZ group. Except for the control group, the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA (0.13 g·kg-1·d-1) or HQJZ (13.13 g·kg-1·d-1) by gavage, respectively, while mice in the control and model groups were given an equal volume of saline by gavage, with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers (iNOS, Arg1, CD86, CD206) and fat browning-related genes uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor γ (PPARγ) in epididymal adipose tissue. Western blot (WB) was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography (micro-CT) was used to measure residual fat volume, and hematoxylin-eosin (HE) staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro, the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that, compared with the blank group, Arg1 expression decreased in the HQJZ+blank group (P<0.05), CD206 showed a downward trend without statistical significance, while iNOS and CD86 expression were significantly increased (P<0.05). Compared with the M1 group, Arg1 and CD206 expression decreased in the HQJZ+M1 group (P<0.05). Compared with the M2 group, CD206 expression decreased in the HQJZ+M2 group (P<0.05), CD86 expression increased significantly (P<0.01). In vivo, Real-time PCR results showed that, compared with the control group, CD86 and CD206 expression levels were significantly increased in the model group (P<0.01). Compared with the model group, CD206 expression in the MPA group was significantly decreased (P<0.01). In the HQJZ group, CD206 was significantly decreased (P<0.01). WB results showed that, compared with the model group, protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group (P<0.05, P<0.01). micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group (P<0.05). HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group (P<0.05). ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization, thereby delaying fat consumption in CC mice.
2.ALKBH3-regulated m1A of ALDOA potentiates glycolysis and doxorubicin resistance of triple negative breast cancer cells.
Yuhua DENG ; Zhiyan CHEN ; Peixian CHEN ; Yaming XIONG ; Chuling ZHANG ; Qiuyuan WU ; Huiqi HUANG ; Shuqing YANG ; Kun ZHANG ; Tiancheng HE ; Wei LI ; Guolin YE ; Wei LUO ; Hongsheng WANG ; Dan ZHOU
Acta Pharmaceutica Sinica B 2025;15(6):3092-3106
Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m1A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m1A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.
3.Effects of SIRT2 regulation on migration and proliferation of cardiac fibroblasts in Ang Ⅱ-induced mice
Lichan Lin ; Zhiyan Liu ; Zhenyu Liu ; Peng Liu ; Sui Sui ; Yunsen Zhang ; Xianwen Hu ; Rui Li ; Hui Tao
Acta Universitatis Medicinalis Anhui 2025;60(4):589-595, 603
Objective:
To investigate the effect of sirtuin 2(SIRT2) on the proliferation and migration of cardiac fibroblasts(CFs)in C57BL/6 mice under angiotensin II(Ang Ⅱ) stimulation.
Methods :
The hearts were taken from 1 to 2 days C57BL/6 milk mice. After cutting and digesting, CFs were extracted by different adhesion centrifugation. After CFs attachment, the cells were cultured under control medium and Ang Ⅱ(100 nmol/L) medium and treated using OE-SIRT2 plasmid to overexpression the SIRT2 gene. RT-qPCR was used to detect mRNA expression of SIRT2 proliferating cell nuclear antigen(PCNA), periostin(POSTN)and type Ⅰ collagen procollagen A1(Col1A1), Western blot assay was used to measure the protein expression levels of SIRT2, PCNA, POSTN and Col1A1, CCK-8 assay and EdU assay were used to evaluate CFs proliferation rate, Transwell experiment was used to assess CFs migration activity.
Results:
Compared with control group, Ang Ⅱ stimulation led to down-regulation of SIRT2 expression in CFs, increased collagen expression, and promoted CFs proliferation and migration. The expression of SIRT2 was up regulated in CFs treated with OE-SIRT2 plasmid under Ang Ⅱ stimulation, Col1A1, POSTN and PCNA expression was down regulated, and CFs proliferation and migration ability decreased.
Conclusion
Overexpression of SIRT2 can inhibit the proliferation and migration of CFs under Ang Ⅱ stimulation, indicating that SIRT2 may be a key regulatory point in the onset and progression of cardiac fibrosis.
4.Diagnosis of Two-Dimensional Speckle Tracking Automatic Functional Imaging of Postsystolic Shortening in Ischemia with Non-Obstructive Coronary Arteries
Ying LI ; Dandan SUN ; Zhiyan QIN ; Yuhui YANG ; Huihui ZHANG ; Mingyan DING ; Hanzhang ZHAO
Chinese Journal of Medical Imaging 2024;32(10):1000-1004,1006
Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.
5.Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy
Bin YUAN ; Zhiyan JIANG ; Huaan MA ; Mei HAN ; Zhuyun LIU ; Xianzhi REN ; Weiwei LI ; Sumei WANG ; Xueqing ZHANG ; Xiaohui ZHU ; Lei WANG ; Chanchan HU ; Jun MA ; Tianhan WANG ; Shuo LI
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(2):184-189
Literature related to children's adenoid hypertrophy was retrieved to form an expert questionnaire.According to the group standard writing rules of the China Association of Chinese Medicine,the peer consultation,quality evaluation and suitability eval-uation were completed through three rounds of Delphi expert questionnaire surveys and expert discussion meetings,and the Clinical Practice Guidelines for TCM in Children with Adenoidal Hypertrophy was finally formed.The guidelines have been formulated to clarify the scope of application of the guidelines,normative reference documents,terms and definitions,diagnosis,syndrome differentiation,treatment,prevention and care,and to provide an important reference for the clinical practice and diagnosis and treatment norms of tra-ditional Chinese medicine for children with adenoid hypertrophy.
6.A proton birdcage coil integrated with interchangeable single loops for multi-nuclear MRI/MRS
ZHANG YI ; QUAN ZHIYAN ; LOU FEIYANG ; FANG YUJIAO ; J.THOMPSON GARTH ; CHEN GAO ; ZHANG XIAOTONG
Journal of Zhejiang University. Science. B 2024;25(2):168-180,后插1-后插4
Energy metabolism is fundamental for life.It encompasses the utilization of carbohydrates,lipids,and proteins for internal processes,while aberrant energy metabolism is implicated in many diseases.In the present study,using three-dimensional(3D)printing from polycarbonate via fused deposition modeling,we propose a multi-nuclear radiofrequency(RF)coil design with integrated 1H birdcage and interchangeable X-nuclei(2H,13C,23Na,and 31P)single-loop coils for magnetic resonance imaging(MRI)/magnetic resonance spectroscopy(MRS).The single-loop coil for each nucleus attaches to an arc bracket that slides unrestrictedly along the birdcage coil inner surface,enabling convenient switching among various nuclei and animal handling.Compared to a commercial 1H birdcage coil,the proposed 1H birdcage coil exhibited superior signal-excitation homogeneity and imaging signal-to-noise ratio(SNR).For X-nuclei study,prominent peaks in spectroscopy for phantom solutions showed excellent SNR,and the static and dynamic peaks of in vivo spectroscopy validated the efficacy of the coil design in structural imaging and energy metabolism detection simultaneously.
7.Analysis factors influencing left ventricular thrombus in patients with non-ischemic heart failure
Zhiyan WANG ; Hao ZHANG ; Wenjie LI ; Chang HUA ; Yangyang TANG ; Xinru LIU ; Yuling XIONG ; Qiang LYU ; Jianzeng DONG ; Xin DU
Chinese Journal of Cardiology 2024;52(10):1155-1161
Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.
8.Comprehensive imaging diagnosis and comparative study of breast architectural distortion lesions
Yuhan BAI ; Jian YANG ; Zhiyan SONG ; Lin ZHANG ; Haifeng LIU ; Hongfen PENG ; Dongyou ZHANG
Journal of Practical Radiology 2024;40(6):913-916,930
Objective To analyze the characteristics of breast architectural distortion(AD)in mammography,MRI,and ultrasound,and to explore the value of each imaging examination in the diagnosis of AD lesions.Methods The mammography,ultrasound,and MRI data of 46 patients(48 lesions)with AD detected by mammography were analyzed retrospectively.Based on the pathological results,the imaging characteristics of benign and malignant AD were compared.Results The morphological and central density differences between benign and malignant lesions were statistically significant.There was no significant difference in microcalcification between benign and malignant AD.On 48 breast MRI,26 lesions showed mass enhancement,17 lesions showed non-mass enhancement,3 lesions showed punctate enhancement and 2 lesions showed no enhancement.There was no statistical significance in the distribution of enhancement types.The difference in time-signal intensity curve(TIC)types between benign and malignant AD was statistically significant.There was no statistical significance in ultrasound manifestation between benign and malignant AD.Using imaging findings greater than those in the breast imaging reporting and data system(BI-RADS)4 categories as a suspected malignant diagnosis,based on pathological examination results.The area under the curve(AUC)by mammography,ultrasound,and MRI was 0.582,0.426,and 0.764,respectively,showed significant differences in diagnostic efficiency.Conclusion MRI has higher sensitivity and specificity in detecting breast AD,which significantly improves the diagnosis coincidence rate of lesions,and can provide an important basis for clinicians to make decisions on surgical treatment.
9.Yunpi Huatan Tongqiao Prescription Regulates Microglial Cell Polarization Phenotype to Improve Inflammation and Cognitive Impairment in OSA Mice by Down-regulating Glycolysis
Wenyan PU ; Anqi LIU ; Yan LIN ; Xuejun LI ; Hongyu ZHANG ; Zhiyan JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):35-42
ObjectiveTo validate the efficacy of Yunpi Huatan Tongqiao prescription (YHTP) in down-regulating glycolysis to modulate microglia phenotype and improve inflammation and cognitive memory deficits in obstructive sleep apnea (OSA) mice. MethodForty-eight male Balb/C mice were randomly divided into a normal group, a model group, a montelukast sodium group (30 mg·kg-1), and low, medium, and high dose groups of YHTP (8.28, 16.56, and 33.12 g·kg-1), with 8 mice in each group. All groups, except the normal group, received intraperitoneal injections of lipopolysaccharide (LPS) and underwent chronic intermittent hypoxia (CIH) modeling for 4 weeks. Subsequently, the mice were treated with medications for 4 weeks and then sampled. Animal behavioral tests assessed memory impairment due to hypoxia. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to measure mRNA expression levels of M1-associated inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and markers such as T lymphocyte activation antigen (CD86) and inducible nitric oxide synthase (iNOS), as well as M2-associated inflammatory factors interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and the marker mannose receptor (CD206) in hippocampal tissue. Western blot was employed to detect differences in the expression of M1 and M2 microglia phenotypic markers (CD86, CD206) and glycolysis-related proteins glucose transporter type 1 (GLUT1), hexokinase 2 (HK2), phosphofructokinase (PFKM), pyruvate kinase 2 (PKM2), and monocarboxylic acid transporter 1 (MCT1). ResultBehavioral tests showed that compared to the results in the normal group, the Y-maze autonomous alternation rate was significantly reduced in the model group (P<0.01). The latency time for the target hole in the Barnes' maze during the training period (days 2, 3, 4) and testing period (days 5, 12) was significantly increased (P<0.05, P<0.01). M1 glial cell markers CD86 and iNOS, as well as inflammatory factors IL-1β and TNF-α mRNA, were significantly elevated (P<0.01). In contrast, the mRNA expression of M2 glial cell markers IL-10, CD206, and TGF-β was significantly reduced (P<0.01). The protein expression of glycolytic proteins HK2, PFKM, PKM2, MCT1, and the M1 marker CD86 was significantly increased (P<0.05, P<0.01), while M2 marker CD206 protein expression was significantly decreased (P<0.01). Compared to the results in the model group, the Y-maze autonomous alternation rate was significantly increased in the medium and high dose groups of YHTP (P<0.05, P<0.01). The latency time for the target hole during the training (day 4) and testing periods (days 5, 12) was significantly reduced (P<0.01). Real-time PCR results indicated that mRNA expression levels of M1-related pro-inflammatory factors in the hippocampal tissue were significantly reduced in the low, medium, and high dose groups of YHTP (P<0.01), while M2-related inflammatory factors' mRNA expression was significantly increased (P<0.01). Western blot results showed that in the medium and high dose groups of YHTP, the expression of the M1 marker CD86 in the hippocampus was reduced, whereas the expression of the M2 marker CD206 was significantly increased (P<0.01), with a significant decrease in the expression of glycolysis-related proteins (P<0.01). ConclusionYHTP can improve inflammation and cognitive impairment induced by hypoxia in OSA model mice. This is achieved by downregulating glycolysis in brain microglia, inhibiting M1 activation, reducing pro-inflammatory factor release, and promoting M2 activation, thereby exerting a therapeutic effect on inflammation and cognitive impairment caused by OSA.
10.Association of polycyclic aromatic hydrocarbon metabolite concentration with sleep quality in workers
Qin REN ; Xin LI ; Zhiyan ZHANG ; Xin WANG ; Zhanfei SONG ; Hongmei ZHANG
Journal of Environmental and Occupational Medicine 2024;41(3):303-310
Background Sleep is a crucial physiological activity for the human body, and research has shown that air pollution can affect sleep quality. However, the association between polycyclic aromatic hydrocarbons (PAHs) exposure, neurotoxic compounds in air pollutants, and sleep quality remains uncertain. Objective To evaluate the association of PAHs exposure with sleep quality, and to provide evidence for improving sleep quality. Methods This study used a cross-sectional design. We selected 632 workers from a coking plant of a large state-owned enterprise as the exposure group, and 477 workers from the energy and power plant of the same enterprise as the control group. All workers worked in three shifts. A questionnaire survey was conducted to collect basic information including gender, years of service, age, educational level, smoking, alcohol consumption, consumption of fried foods, cooking frequency, types of cooking fuels. Worker's post-shift morning midstream urine was sampled to determine the concentrations of eight PAHs metabolites (OH-PAHs) using gas chromatography-tandem mass spectrometry (GC-MS). Worker's sleep quality was assessed using Pittsburgh Sleep Quality Index (PSQI). A higher PSQI score indicated a lower sleep quality. Associations of urinary OH-PAHs levels with sleep quality in the workers were analyzed using linear regression, Bayesian kernel-machine regression (BKMR), and quantile g-computation. Results The median (P25, P75) concentration of total OH-PAHs in the exposure group [88.84 (46.27, 151.96) μg·L−1] was higher than that in the control group [54.33 (24.86, 97.97) μg·L−1]. Additionally, the PSQI score (


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