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.Xp11 translocation neoplasms with melanotic differentiation/melanotic TFE3-rearrangement soft tissue neoplasms:a clinicopathological analysis of five cases
Diwei ZHOU ; Ping LEI ; Lingling XIE ; Qin ZHENG ; Danju LUO ; Mixia WENG ; Xuefei LI ; Qin CAO ; Xiu NIE ; Ming YANG
Chinese Journal of Clinical and Experimental Pathology 2024;40(8):812-817
Purpose To investigate the clinicopathologic,immunophenotypic features,genetic alterations and prognosis of melanotic Xp11 neoplasms/melanotic TFE3-rearrangement neo-plasms.Methods Five cases were selected from the Depart-ment of Pathology,Union Hospital,Huazhong University of Sci-ence and Technology from November 2018 to July 2023.The clinicopathologic,immunohistochemical,FISH assays,next-generation sequencing(NGS)and follow-up details were collect-ed.Results There were 1 male and 4 females,with their ages ranging from 16 to 59 years(mean 28.2 years).The maximum diameters of the masses were 3-6 cm(average 4.7 cm).The tumors located in right kidneys(3 cases),tubal interstitium(1 case)and pelvis(1 case).Microscopically,most tumors shared similar morphology such as nested,acinar structures sep-arated by a delicate vascular network.Epithelioid tumor cells presented with clear to granular eosinophilic cytoplasm.Lym-phocytic infiltration was seen in the background;melanin depo-sition was noted in the cases;neoplastic necrosis was detected in 4 cases.Mitotic activity was low with 5 cases showing<3/10 HPF.Intravascular tumor thrombus was detected in 2 cases,no lymphovascular and nerve invasions were detected in other 3 ca-ses.Immunohistochemically,all 5 cases expressed TFE3 dif-fusely,and expressed HMB45,Melan A to varying degrees,CK(AE1/AE3),CK7,EMA,PAX8,TFEB,S-100,SOX10,SMA,desmin were all non-reactive in the 5 cases.The Ki67-la-beling index was<20%.TFE3 separation signal in 4 cases were detected by FISH,1 case was interpreted as negative due to atypical signal which was confirmed by next-generation se-quencing(NGS)assay as RBM10-TFE3.Clinical follow-up was available for five patients for 2-60 months,in which four pa-tients were alive with no evidence of disease after initial resec-tion,and one patient with thoracic spine metastasis was currently in stable condition.Conclusion Melanotic Xp1 1 neoplasms/melanotic TFE3-rearrangement neoplasms has unique morpholog-ic,immunophenotypic and genetic characteristics.It might be reclassified into a distinctive malignant mesenchymal tumor enti-ty.
3.BRICS report of 2021: The distribution and antimicrobial resistance profile of clinical bacterial isolates from blood stream infections in China
Yunbo CHEN ; Jinru JI ; Zhiying LIU ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Jiliang WANG ; Hui DING ; Haifeng MAO ; Yizheng ZHOU ; Yan JIN ; Yongyun LIU ; Yan GENG ; Yuanyuan DAI ; Hong LU ; Peng ZHANG ; Ying HUANG ; Donghong HUANG ; Xinhua QIANG ; Jilu SHEN ; Hongyun XU ; Fenghong CHEN ; Guolin LIAO ; Dan LIU ; Haixin DONG ; Jiangqin SONG ; Lu WANG ; Junmin CAO ; Lixia ZHANG ; Yanhong LI ; Dijing SONG ; Zhuo LI ; Youdong YIN ; Donghua LIU ; Liang GUO ; Qiang LIU ; Baohua ZHANG ; Rong XU ; Yinqiao DONG ; Shuyan HU ; Kunpeng LIANG ; Bo QUAN ; Lin ZHENG ; Ling MENG ; Liang LUAN ; Jinhua LIANG ; Weiping LIU ; Xuefei HU ; Pengpeng TIAN ; Xiaoping YAN ; Aiyun LI ; Jian LI ; Xiusan XIA ; Xiaoyan QI ; Dengyan QIAO ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2023;16(1):33-47
Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.
4.BRICS report of 2020: The bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China
Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Yuanyuan DAI ; Jiliang WANG ; Haifeng MAO ; Hui DING ; Yongyun LIU ; Yizheng ZHOU ; Hong LU ; Youdong YIN ; Yan JIN ; Hongyun XU ; Lixia ZHANG ; Lu WANG ; Haixin DONG ; Zhenghai YANG ; Fenghong CHEN ; Donghong HUANG ; Guolin LIAO ; Pengpeng TIAN ; Dan LIU ; Yan GENG ; Sijin MAN ; Baohua ZHANG ; Ying HUANG ; Liang GUO ; Junmin CAO ; Beiqing GU ; Yanhong LI ; Hongxia HU ; Liang LUAN ; Shuyan HU ; Lin ZHENG ; Aiyun LI ; Rong XU ; Kunpeng LIANG ; Zhuo LI ; Donghua LIU ; Bo QUAN ; Qiang LIU ; Jilu SHEN ; Yiqun LIAO ; Hai CHEN ; Qingqing BAI ; Xiusan XIA ; Shifu WANG ; Jinhua LIANG ; Liping ZHANG ; Yinqiao DONG ; Xiaoyan QI ; Jianzhong WANG ; Xuefei HU ; Xiaoping YAN ; Dengyan QIAO ; Ling MENG ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2021;14(6):413-426
Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.
5.Functional bone tissue engineering scaffold used to repair tuberculosis bone defect
Xiaohu SUN ; Jing YUAN ; Yu ZHANG ; Yongjie QIAO ; Xuefei CAO ; Lei MENG ; Zhanwang GAO ; Ping ZHEN
Chinese Journal of Tissue Engineering Research 2016;20(30):4539-4546
BACKGROUND:Repairing tuberculosis bone defect has become a research focus with the development of anti-tuberculosis functional bone tissue engineering scaffold. OBJECTIVE:To evaluate the preparation, drug release performance and osteogenic properties of the anti-tuberculosis functional bone tissue engineering scaffold. METHODS:PubMed, Chinese Journal Ful-text Database, Wanfang databases were searched by computer for articles addressing functional bone tissue engineering scaffold for repair of tuberculosis bone defect. The keywords were“bone tissue engineering scaffold;tuberculosis;bone defect”in English and Chinese. RESULTS AND CONCLUSION:The anti-tuberculosis functional bone tissue engineering scaffold has good drug delivery, biocompatibility, osteogenic properties and anti-tuberculosis properties. As a good choice to avert bone defect relapse, the scaffold enables a long and stable drug release into bone defects to enhance the therapeutic efficacy of anti-tuberculosis drugs topical y. Given the technical deficiencies, we can only combine two drugs with the anti-tuberculosis bone tissue engineering scaffold, although the combined use of three or four anti-tuberculosis drugs is preferred. Additional y, a complete course of anti-tuberculosis treatment often lasts for 6-12 months, which cannot be achieved by the existing anti-tuberculosis bone tissue engineering scaffold. Up to now, the effect of this scaffold has not yet been confirmed in animal models, although how to prepare this scaffold has been reported.
6.3D printing of bone tissue engineering scaffolds
Xuefei CAO ; Pengjie SONG ; Yongjie QIAO ; Ping ZHEN
Chinese Journal of Tissue Engineering Research 2015;(25):4076-4080
BACKGROUND:Although bone tissue engineering scaffolds made of traditional methods have made certain achievements, the three-dimensional structure, mechanical strength and personalized property of the scaffolds are unsatisfied. 3D printing technology is expected to change these shortcomings. OBJECTIVE:To review the 3D printing of bone tissue engineering scaffolds and to prospect the optimization of the scaffolds. METHODS:A computer-based search of PubMed and Google academic database was performed for articles addressing the 3D printing of bone tissue engineering scaffolds published from 2008 to 2015. Articles concerning the structure design and materials of bone tissue engineering scaffolds and different 3D printing technologies for scaffold preparation were included, and repetitive and old articles were excluded. Final y, 37 articles were summarized. RESULTS AND CONCLUSION:Currently, 3D printing technologies used for preparation of bone tissue engineering scaffolds include melt laminated molding, stereolithography, selective laser sintering and 3DP technology. 3D printing technologies have unique advantages in mechanics, structure and personalized aspects, but there are stil many problems to be solved, such as raw materials, insufficiency of different 3D technologies, and improvement of 3D printer. Under the multi-disciplinary co-operation, 3D printing technology is expected to prepare suitable bone tissue engineering scaffolds and bring benefit to the mankind.
7.A meta-analysis of proximal femoral nail anti-rotation, dynamic hip screw and total hip arthroplasty for intertrochanteric fractures in the elderly
Yongjie QIAO ; Xuefei CAO ; Lvdan ZHANG ; Qinpeng WANG ; Ping ZHEN
Chinese Journal of Tissue Engineering Research 2015;(31):5057-5064
BACKGROUND:The methods to treat intertrochanteric fracture are controversial. A large number of clinical studies concern the therapeutic effects of several popular methods to repair intertrochanteric fracture, but these results lack of independence, and may have bias that cannot be measured in the variable and observational studies. Thus, relevant studies have been limited. OBJECTIVE:To compare the repair effects of proximal femoral nail anti-rotation, dynamic hip screw and total hip arthroplasty on intertrochanteric fracture in aged patients by meta-analysis. METHODS: Four electronic databases were searched, including Cochrane library, PubMed, Web of Science and Chinese BioMedical Literature Database, to colect al randomized controled trials concerning the treatment of intertrochanteric fractures in the elderly with proximal femoral nail anti-rotation, dynamic hip screw and total hip arthroplasty. Using meta-analysis of evidence-based medicine, X-ray exposure time, postoperative complication rate, postoperative bed time, postoperative wound infection rate, Harris hip scores, mean operation time, intraoperative blood loss, length of hospital stays and length of the incision were compared and evaluated. Standard and methodology quality of the trials were criticaly assessed and relative data were extracted. This study used the Review Manager 5.0 software provided by Cochrane colaboration network. RESULTS AND CONCLUSION:Twelve randomized controled trials with 1 454 patients were included. Significant differences in mean operation time, intraoperative blood loss, X-ray exposure time, postoperative complication rate, and postoperative bed time were detected between the proximal femoral nail anti-rotation and dynamic hip screw groups (P < 0.05). Significant differences in length of hospital stays, postoperative complication rate, and postoperative bed time were observed between the proximal femoral nail anti-rotation and total hip arthroplasty groups (P < 0.05). Significant differences in postoperative complication rate, postoperative bed time, and Harris hip scores were detectable between the dynamic hip screw and total hip arthroplasty groups (P < 0.05). These data confirm that proximal femoral nail anti-rotation was apparently better than dynamic hip screw and total hip arthroplasty in operation time, intraoperative blood loss, length of hospital stays, postoperative complication rate, and postoperative bed time. Dynamic hip screw was better than proximal femoral nail anti-rotation in X-ray exposure time. Total hip arthroplasty was better than dynamic hip screw and proximal femoral nail anti-rotation in length of hospital stays, postoperative complication rate and postoperative bed time.
8.Structural properties influence the osteoinduction of calcium phosphate ceramics
Lei MENG ; Ping ZHEN ; Xiaoyan LIANG ; Xuefei CAO
Chinese Journal of Tissue Engineering Research 2015;(43):7010-7016
BACKGROUND:Currently, the mechanism by which calcium phosphate ceramics induces osteogenesis is not fuly understood, and many scholars have tried to expound the mechanism from the perspective of the structural properties. OBJECTIVE:To review how the structural properties of calcium phosphate ceramics affect their osteoinductive activity. METHODS: The PubMed database and Google academic database (1997-01/2015-03) were searched to retrieve the related articles about the structural properties of calcium phosphate ceramics affecting their osteoinductive activity. After the articles with outdated reviews or repetitive contents were ruled out, 60 articles were suitable for further analysis and review. RESULTS AND CONCLUSION:The structural properties of calcium phosphate ceramics are displayed by macrostructure, such as macropores, holes, pipes and space between particles, and microstructure, such as micropore, particle size, surface roughness, specific surface area. Each parameter of the structural properties affects the bioactivities of calcium phosphate ceramics in some way, which renders their abilities of inducing osteogenesis to arise from nothing or change from weakly to strongly. Apart from structure design, physical and chemical properties of calcium phosphate ceramics wil also affect its biological activityin vivo. Therefore, the physicochemical properties of calcium phosphate ceramics should be considered in the structure design in order to achieve an optimal osteoinductive activity.
9.Experience on the Treatment of Postpartum Body Pain by Herbal Paste from the Centralizer Exorcism
Xuefei YUAN ; Yang CAO ; Tingting ZHNAG
Journal of Zhejiang Chinese Medical University 2014;(8):959-961
Purpose]To explore the paste treated postpartum body pain in curative effect. [Methods]By fol owing professor Zhang diagnosis ,the paper summarized with herbal paste for gynecology as the methods of treatment of postpartum body pain, and listed 2 proven cases.[Result]Postpartum woman is weak in both qi and blood, paste has an advantage in taking the fast-rising tonifying deficiency and curing correction,and it is superior to the liquid form, convenient for long-term use, paste treating pantalgia after childbirth in the disease has a unique advantage, and because of its smal side effects, especial y suitable for women. [Conclusion]Herbal paste in chronic disease of department of gynaecology modulation has a unique advantage due to the efficacy of comprehensive,and takes into consideration the physiological and pathological features of menstruation,leucorrhea,pregnancy and delivery. She focuses on the individual syndrome differentiation,and attaches great importance to the balances of relationship between pathogenic factors and healthy qi,yin yang heat cold,viscera and meridians qi blood,to achieve the aim of preventing and treating diseases,regulating the body ,and is worth promoting.
10.Immune effectiveness of A/H1N1 influenza vaccine immunization in 505 health care workers within three months after vaccination
Xingan LIU ; Yanming GUO ; Xiaoguang ZHANG ; Jinyan Lü ; Guixia YANG ; Qingxiang XU ; Mingjuan YANG ; Yandan DU ; Bin GUO ; Qin CAO ; Yingzhi LI ; Xuefei CHEN
Chinese Journal of Infectious Diseases 2010;28(11):677-680
Objective To investigate the immunization effect of influenza A/H1N1 vaccine in health care workers (HCW) in Inner Mongolia Greater Khingan Mountains area. Methods Five hundred and five HCW who received A/H1N1 influenza vaccination (immunized group) and 129 staffs who didn't receive the vaccination (unimmunized group) were randomly sampled for semiquantitative testing of serum H1N1 antibody (IgG) levels by enzyme-linked immunosorbent assay (ELISA).Results were analyzed and stratified by age, sex, occupation and the time interval between the time of vaccination and serum sample collection. The antibody positive rates of the two groups were compared by x2test. Results There were 401 (79. 4%) HCW whose H1N1 antibody were positive and 50 (9.9%) whose antibody were weak positive among 505 immunized HCW. While among 129 unimmunized HCW, there were 59 (45.7%) whose antibody were positive and 15 (11.6%) whose antibody were weak positive. The seroconversion rates of specific antibody were not significantly different among the different age groups after receiving A/H1N1 influenza vaccine (P> 0.05).However, there were statistical differences of the seroconversion rates among different sex groups (men 95.7% vs women 87.4% in immunized group, x2=6.40, P<0.05; and men 73.3% vs women 52.5% in unimmunized group, x2 =4.07, P<0.05) and different occupation groups (doctor 86.0% vs nurse 94.5% in immunized group, x2 = 9. 16, P<0.01; and doctor 43. 8% vs nurse 75.0% in unimmunized group, x2=12.61, P<0.01 ). The seroconversion rate was 81.5% after 80 to 89 days of vaccination, which was significantly lower than those after 30 to 39, 50 to 59 days and 60 to 69 days of vaccination, which was 100.0%, 94.7% and 93.6%, respectively (x2 =3.96, P <0.05; x2=7.15, P <0. 01; x2 = 9. 98, P<0. 01). Conclusions A/H1N1 influenza vaccination can induce effective immune response in HCW in Greater Khingan Mountains area of Inner Mongolia. However,the level of specific antibody significantly reduces after 80 to 89 days of vaccination.

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