1.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
2.Update of molecular diagnostic methods in invasive Aspergillosis
Shuangshuang YANG ; Shifeng HUANG ; Chuanming ZHANG ; Linbo ZHANG ; Ju CAO
Chinese Journal of Laboratory Medicine 2025;48(2):297-302
Invasive Aspergillosis (IA) is a severe filamentous fungal infection caused by opportunistic pathogenic Aspergillus. Due to its insidious incidence and high mortality rate, accurate diagnosis of IA is in urgent need. Recent advances in molecular diagnostic techniques have enabled novel approaches for Aspergillus detection in clinical fungal laboratory. To this end, this paper summarizes recent progress in molecular detection of Aspergillus nucleic acids and discusses its value in IA diagnosis. The findings provide guidance for both current diagnostic approaches and the development of new in vitro diagnostic technologies for IA.
3.Update of molecular diagnostic methods in invasive Aspergillosis
Shuangshuang YANG ; Shifeng HUANG ; Chuanming ZHANG ; Linbo ZHANG ; Ju CAO
Chinese Journal of Laboratory Medicine 2025;48(2):297-302
Invasive Aspergillosis (IA) is a severe filamentous fungal infection caused by opportunistic pathogenic Aspergillus. Due to its insidious incidence and high mortality rate, accurate diagnosis of IA is in urgent need. Recent advances in molecular diagnostic techniques have enabled novel approaches for Aspergillus detection in clinical fungal laboratory. To this end, this paper summarizes recent progress in molecular detection of Aspergillus nucleic acids and discusses its value in IA diagnosis. The findings provide guidance for both current diagnostic approaches and the development of new in vitro diagnostic technologies for IA.
4.Establishment and evaluation of a disease-syndrome combined rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome
Zhuoxiu LIU ; Yangjing HAO ; Hao FU ; Qinqing LI ; Jianjun ZHANG ; Shifeng CHU ; Zhao ZHANG ; Zhuoqing CAO ; Wenbin HE
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1091-1104
Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.
5.Establishment and evaluation of a disease-syndrome combined rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome
Zhuoxiu LIU ; Yangjing HAO ; Hao FU ; Qinqing LI ; Jianjun ZHANG ; Shifeng CHU ; Zhao ZHANG ; Zhuoqing CAO ; Wenbin HE
Acta Laboratorium Animalis Scientia Sinica 2025;33(8):1091-1104
Objective To establish and evaluate an integrated disease-syndrome rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Methods Thirty male Wistar rats were allocated randomly into three groups(n=10 per group):sham operation(sham),2-vessel occlusion(2-VO)group,and sleep deprivation combined with 2-VO(SD+2-VO)group.We comprehensively assessed Qi deficiency and blood stasis syndrome manifestations in the rats using a dual evaluation approach,combining exhaustive swimming tests with quantitative tongue chroma analysis.Cognitive function was evaluated using the Barnes maze,and cerebral blood flow was compared using laser speckle contrast imaging.The histopathology of the hippocampal cytoarchitecture and white matter were examined using hematoxylin-eosin(HE)and Luxol fast blue(LFB)staining,respectively,and ultrastructural alterations of neurons in the hippocampal CA1 region were observed by transmission electron microscopy(TEM).Protein expression levels of NeuN,vascular endothelial growth factor A(VEGFA)and CD31 were detected by Western Blot and immunofluorescence.Results Cerebral blood flow was significantly reduced in rats in the 2-VO group compared with the sham group,but they failed to recapitulate the key clinical hallmarks of Qi deficiency and blood stasis syndrome.In contrast,rats in the SD+2-VO group exhibited significantly reduced locomotor activity,exacerbated cerebral hypoperfusion,shortened swimming duration,and darkened tongue color compared with 2-VO rats.Rats in the SD+2-VO group demonstrated significantly impaired learning and memory abilities in the Barnes maze test.Consistent with these observations,HE staining,TEM,and LFB staining revealed substantial neuronal and white matter damage in the SD+2-VO group.NeuN expression was decreased and VEGFA and CD31 expression levels were increased in the 2-VO and SD+2-VO groups,as shown by Western Blot.Taken together,these findings indicated that the SD+2-VO model effectively recapitulated the clinical features of chronic cerebral ischemia with Qi deficiency and blood stasis pattern.Conclusions The combination of sleep deprivation and bilateral carotid artery occlusion successfully established a rat model of chronic cerebral ischemia with Qi deficiency and blood stasis syndrome.Compared with the 2-VO model,SD+2-VO model demonstrates more pronounced syndrome manifestations and better clinical relevance,thus providing a valuable animal model for traditional Chinese medicine research on chronic cerebral ischemia.
6.Classification research of TCM pulse conditions based on multi-label voice analysis
Haoran Shen ; Junjie Cao ; Lin Zhang ; Jing Li ; Jianghong Liu ; Zhiyuan Chu ; Shifeng Wang ; Yanjiang Qiao
Journal of Traditional Chinese Medical Sciences 2024;11(2):172-179
Objective:
To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals.
Methods:
We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets.
Results:
The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%.
Conclusion
Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.
7.The novel anthraquinone compound Kanglexin prevents endothelial-to-mesenchymal transition in atherosclerosis by activating FGFR1 and suppressing integrin β1/TGFβ signaling.
Yixiu ZHAO ; Zhiqi WANG ; Jing REN ; Huan CHEN ; Jia ZHU ; Yue ZHANG ; Jiangfei ZHENG ; Shifeng CAO ; Yanxi LI ; Xue LIU ; Na AN ; Tao BAN ; Baofeng YANG ; Yan ZHANG
Frontiers of Medicine 2024;18(6):1068-1086
Endothelial-mesenchymal transition (EndMT) disrupts vascular endothelial integrity and induces atherosclerosis. Active integrin β1 plays a pivotal role in promoting EndMT by facilitating TGFβ/Smad signaling in endothelial cells. Here, we report a novel anthraquinone compound, Kanglexin (KLX), which prevented EndMT and atherosclerosis by activating MAP4K4 and suppressing integrin β1/TGFβ signaling. First, KLX effectively counteracted the EndMT phenotype and mitigated the dysregulation of endothelial and mesenchymal markers induced by TGFβ1. Second, KLX suppressed TGFβ/Smad signaling by inactivating integrin β1 and inhibiting the polymerization of TGFβR1/2. The underlying mechanism involved the activation of FGFR1 by KLX, resulting in the phosphorylation of MAP4K4 and Moesin, which led to integrin β1 inactivation by displacing Talin from its β-tail. Oral administration of KLX effectively stimulated endothelial FGFR1 and inhibited integrin β1, thereby preventing vascular EndMT and attenuating plaque formation and progression in the aorta of atherosclerotic Apoe-/- mice. Notably, KLX (20 mg/kg) exhibited superior efficacy compared with atorvastatin, a clinically approved lipid-regulating drug. In conclusion, KLX exhibited potential in ameliorating EndMT and retarding the formation and progression of atherosclerosis through direct activation of FGFR1. Therefore, KLX is a promising candidate for the treatment of atherosclerosis to mitigate vascular endothelial injury.
Animals
;
Atherosclerosis/prevention & control*
;
Mice
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Receptor, Fibroblast Growth Factor, Type 1/metabolism*
;
Signal Transduction/drug effects*
;
Anthraquinones/pharmacology*
;
Humans
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Integrin beta1/metabolism*
;
Epithelial-Mesenchymal Transition/drug effects*
;
Male
;
Transforming Growth Factor beta/metabolism*
;
Disease Models, Animal
;
Mice, Inbred C57BL
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Human Umbilical Vein Endothelial Cells/drug effects*
8.Identification of laccase gene family members in peach and its relationship with chilling induced browning.
Kang WANG ; Minjie YANG ; Siyi WU ; Qingli LIU ; Shifeng CAO ; Wei CHEN ; Liyu SHI
Chinese Journal of Biotechnology 2022;38(1):264-274
The laccase (PpLAC) gene family members in peach fruit were identified and the relationship between their expression pattern and chilling induced browning were investigated. The study was performed using two varieties of peaches with different chilling tolerance, treated with or without exogenous γ-aminobutyric acid (GABA) during cold storage. Twenty-six genes were screened from the peach fruit genome. These genes were distributed on 6 chromosomes and each contained 5-7 exons. The PpLAC gene family members shared relatively similar gene structure and conserved motifs, and they were classified into 7 subgroups based on the cluster analysis. Transcriptome sequencing revealed that the expression levels of PpLAC7 and PpLAC9 exhibited an increasing pattern under low temperature storage, and displayed a similar trend with the browning index of peach fruit. Notably, GABA treatment reduced the degree of browning and inhibited the expression of PpLAC7 and PpLAC9. These results suggested that PpLAC7 and PpLAC9 might be involved in the browning of peach fruit during cold storage.
Food Storage
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Fruit/genetics*
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Laccase/genetics*
;
Prunus persica/genetics*
9.Association of nutritional risk screening and nutritional support with postoperative complications and length of hospital stay in surgery patients
Jin ZHOU ; Wenwen CAO ; Junmei SHI ; Yuxia MA ; Shifeng BAO ; Shurong DING ; Dandan CAO
Chinese Journal of Clinical Nutrition 2015;23(6):368-372
Objective To investigate the status of nutritional risk and nutritional support in general surgery patients, and to explore their association with postoperative complications and length of hospital stay.Methods From January 2014 to February 2015, 853 inpatients in general surgical wards in the Second Hospital of Hebei Medical University were enrolled.Nutritional Risk Screening 2002 (NRS 2002) was used to estimate nutritional status of patients.The patients were divided into 2 groups based on whether they received nutritional support.The length of hospital stay in days and postoperative complications were recorded.The association of nutritional risk and nutritional support with complications and length of hospital stay were analyzed.Results In the 853 surgery patients, the prevalence of nutritional risk was 31.1% (265/853) and that of malnutrition was 5.4% (46/853).The incidence of postoperative complications was 14.2% (121/853).The patients with nutritional risk had a significantly higher incidence of postoperative complications compared to those without nutritional risk [29.8% (79/265) vs.7.1% (42/588) , P < 0.000] , and a longer hospital stay [(12.5 ±6.4) days vs.(4.2 ±3.9) days, P <0.001].In the 853 patients, 27.3% (233/853) received nutrition support.In the patients with nutritional risk, those on nutritional support had a significantly lower incidence of complications compared with those not on nutritional support [16.7% (32/192) vs.64.4% (47/73), P<0.05] and shorter hospital stay [(7.5±4.6) days vs.(16.3±8.5)days, P < 0.05].Conclusions According to NRS 2002 result, a fairly high percentage of general surgery patients may have nutritional risk.Patients with decreased body mass, less dietary intake, and at higher age may be more likely to have nutritional risk.Nutritional risk may be associated with a higher incidence of postoperative complications and longer hospital stay.Patients at nutritional risk appear to be more likely to benefit from nutritional support.
10.Surveillance of antimicrobial resistance in clinical isolates from intensive care units during 2012
Li YAN ; Siqiang NIU ; He CAO ; Ping YANG ; Xiaobing ZHANG ; Shifeng HUANG ; Xiaoheng ZHANG ; Shan SUN ; Xiuli HE
Chongqing Medicine 2013;(25):3022-3023,3025
Objective To investigate the antimicrobial resistance of main clinical isolates from ICU during 2012 .Methods Auto-matic microbiology analysis system and the disk diffusion method were performed to determine the antimicrobial susceptibility .All the data were analyzed by WHONET5 .6 software according to the breakpoints of The American Association of Clinical Laboratory Standardization Institute (CLSI) 2012 .Results A total of non-repeated 1 374 clinical isolates were collected in ICU during 2012 , including 1 089 strains (79 .3% ) of Gram-negative bacilli and 285 strains (20 .7% )of Gram-positive cocci ;The top five pathogens were Acinetobacter baumannii ,Pseudomonas aeruginosa ,Escherichia coli ,Klebsiella pneumoniae and Staphylococcus aureus ;Some Enterobacteriaceae strains were resistant to imipenem or ertapenem .2 strains of Enterococcus faecium were found resistant to van-comycin .Conclusion Non-fermenting bacteria ,Enterobacteriaceae and Staphylococci remain the predominant pathogens isolated from the patients in ICU ,their drug resistance is serious ,it is important to use antibacterial agents rationally and strengthen the sur-veillance of bacterial drug resistance .


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