1.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
2.Investigation of oligomeric proanthocyanidins extracted from Rhodiolae Crenulatae Radix et Rhizomes using deep eutectic solvents and identified via data-dependent acquisition mass-spectroscopy.
Li JIA ; Liming WANG ; Xiaoxiao ZHANG ; Qingrui ZHANG ; Peng LEI ; Yanxu CHANG ; Lifeng HAN ; Xin CHAI ; Wenzhi YANG ; Yuefei WANG ; Miaomiao JIANG
Journal of Pharmaceutical Analysis 2024;14(11):101002-101002
In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS2 scan mode that turns on the "if idle pick others" function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.
3.A novel biological sources consistency evaluation method reveals high level of biodiversity within wild natural medicine: A case study of Amynthas earthworms as "Guang Dilong".
Zhimei XING ; Han GAO ; Dan WANG ; Ye SHANG ; Tenukeguli TULIEBIEKE ; Jibao JIANG ; Chunxiao LI ; Hong WANG ; Zhenguo LI ; Lifu JIA ; Yongsheng WU ; Dandan WANG ; Wenzhi YANG ; Yanxu CHANG ; Xiaoying ZHANG ; Liuwei XU ; Chao JIANG ; Luqi HUANG ; Xiaoxuan TIAN
Acta Pharmaceutica Sinica B 2023;13(4):1755-1770
For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.
4.Predictive value of 18F-FDG PET/CT for anti-MDA5 antibody and prognosis of dermatomyositis
Jiajin LI ; Yumei CHEN ; Xuesong LIU ; Wenzhi JIA ; Ruixue ZHANG ; Shuxian AN ; Cheng WANG ; Liangrong WAN ; Haiqin BAO ; Yi XIONG ; Gang HUANG ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(1):17-21
Objective:To assess the imaging characteristics of muscle FDG metabolism, tumor incidence, and pulmonary interstitial changes in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody positivity in 18F-FDG PET/CT imaging, and the value of 18F-FDG PET/CT in differentiating anti-MDA5 antibody positive dermatomyositis. Methods:From June 2016 to July 2019, the PET/CT images of 75 patients with dermatomyositis (21 males, 54 females, age (52.3±14.3) years; 34 anti-MDA5 antibody positive and 41 anti-MDA5 antibody negative) and 30 healthy controls (10 males, 20 females; age (53.5±11.8) years) were retrospectively analyzed in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The SUV max of muscle was measured and the mean of SUV max (mSUV max) was calculated. Statistics of patients with dermatomyositis complicated with neoplastic lesions and the SUV max of pneumonia lesions in patients with dermatomyositis complicated with interstitial pneumonia was determined. Independent sample t test, one-way analysis of variance, Student-Newman-Keuls (SNK) test and χ2 test were used to analyze data. The ROC curve analysis was used to analyze the diagnostic efficacy of mSUV max for the differential diagnosis of anti-MDA5 antibody positive dermatomyositis. Results:The muscle mSUV max of the control group, anti-MDA5 antibody positive and negative groups were 0.39±0.05, 0.66±0.21 and 0.87±0.29 ( F=39.93, P<0.001), respectively. The muscle mSUV max of dermatomyositis patients was increased compared with healthy controls ( q values: 6.76, 12.63, both P<0.001), and the muscle mSUV max of anti-MDA5 antibody negative was higher than positive ( q=5.79, P<0.001). The AUC was 0.74, and the cut-off value of muscle mSUV max was 0.75 with the accuracy of 74.7%(56/75). Of 41 patients with negative anti-MDA5 antibody, there were 6 (14.6%) had malignant tumor, while there was no malignant tumor in patients with positive anti-MDA5 antibody (0/34; χ2=5.41, P=0.020). There were 11 patients (26.8%, 11/41) with anti-MDA5 antibody negative dermatomyositis complicated with interstitial pneumonia and 33 patients (97.1%, 33/34) with anti-MDA5 antibody positive dermatomyositis complicated with interstitial pneumonia ( χ2=37.81, P<0.001). FDG metabolism in anti-MDA5 antibody positive patients was higher than that in anti-MDA5 antibody negative patients (lesion SUV max: 3.65±1.83 and 2.38±1.27; t=2.13, P=0.039). Conclusions:The muscle FDG metabolism of anti-MDA5 antibody positive dermatomyositis patients is higher than that of healthy controls, but lower than that of anti-MDA5 antibody negative patients. The incidence of neoplastic lesions in patients with positive anti-MDA5 antibody is lower than that in patients with negative anti-MDA5 antibody. The proportion and severity of interstitial pneumonia are higher in patients with positive anti-MDA5 antibody than in those with negative anti-MDA5 antibody. 18F-FDG PET/CT has certain value on identifying anti-MDA5 antibody positive dermatomyositis.
5.Feasibility of a Clinical-Radiomics Model to Predict the Outcomes of Acute Ischemic Stroke
Yiran ZHOU ; Di WU ; Su YAN ; Yan XIE ; Shun ZHANG ; Wenzhi LV ; Yuanyuan QIN ; Yufei LIU ; Chengxia LIU ; Jun LU ; Jia LI ; Hongquan ZHU ; Weiyin Vivian LIU ; Huan LIU ; Guiling ZHANG ; Wenzhen ZHU
Korean Journal of Radiology 2022;23(8):811-820
Objective:
To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes.
Materials and Methods:
Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses.
Results:
Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness.
Conclusion
The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.
6.Applications of stable isotope metabolic flux analysis in tumor metabolic reprogramming
Qianyun WU ; Wenzhi JIA ; Yumei CHEN ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(9):563-567
Metabolic reprogramming is a hallmark of tumors. Tumors own unique metabolic patterns in different stages of their occurrence and development. The stable isotope metabolic flux analysis technology uses stable isotope to trace the metabolites in tumors and crystallize tumor metabolism network. Stable isotope metabolic flux analysis is a useful tool for studying tumor metabolism, which can determine the nutritional sources, find the metabolic liabilities, confirm the metabolic pattern of tumors, and discover new mechanisms of tumor metabolic reprogramming, thus providing theoretical bases for imaging, diagnosis, treatment and evaluation of tumor. This article reviews the applications of stable isotope flux analysis in tumor metabolic reprogramming.
7.Offline two-dimensional liquid chromatography coupled with ion mobility-quadrupole time-of-flight mass spectrometry enabling four-dimensional separation and characterization of the multicomponents from white ginseng and red ginseng
Tiantian ZUO ; Chunxia ZHANG ; Weiwei LI ; Hongda WANG ; Ying HU ; Wenzhi YANG ; Li JIA ; Xiaoyan WANG ; Xiumei GAO ; Dean GUO
Journal of Pharmaceutical Analysis 2020;10(6):597-609
Inherent complexity of plant metabolites necessitates the use of multi-dimensional information to accomplish comprehensive profiling and confirmative identification. A dimension-enhanced strategy, by offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spec-trometry (2D-LC/IM-QTOF-MS) enabling four-dimensional separations (2D-LC, IM, and MS), is proposed. In combination with in-house database-driven automated peak annotation, this strategy was utilized to characterize ginsenosides simultaneously from white ginseng (WG) and red ginseng (RG). An offline 2D-LC system configuring an Xbridge Amide column and an HSS T3 column showed orthogonality 0.76 in the resolution of ginsenosides. Ginsenoside analysis was performed by data-independent high-definition MSE (HDMSE) in the negative ESI mode on a Vion TM IMS-QTOF hybrid high-resolution mass spectrometer, which could better resolve ginsenosides than MSE and directly give the CCS information. An in-house ginsenoside database recording 504 known ginsenosides and 58 reference compounds, was estab-lished to assist the identification of ginsenosides. Streamlined workflows, by applying UNIFI TM to auto-matedly annotate the HDMSE data, were proposed. We could separate and characterize 323 ginsenosides (including 286 from WG and 306 from RG), and 125 thereof may have not been isolated from the Panax genus. The established 2D-LC/IM-QTOF-HDMSE approach could also act as a magnifier to probe differ-entiated components between WG and RG. Compared with conventional approaches, this dimension-enhanced strategy could better resolve coeluting herbal components and more efficiently, more reli-ably identify the multicomponents, which, we believe, offers more possibilities for the systematic exposure and confirmative identification of plant metabolites.
8.Relationship between 18F-FDG PET/CT metabolic parameters and liver metastasis from colorectal cancer
Hui YAN ; Yumei CHEN ; Wenzhi JIA ; Gang HUANG ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2018;38(7):485-488
Objective To investigate the relationship between 18F-fluorodeoxyglucose (FDG) PET/CT metabolic parameters of colorectal cancer (CRC) and liver metastasis.Methods A total of 98 CRC patients (66 nales,32 females,average age:(64+13) years) from January 2012 to October 2016 in Shanghai Renji Hospital were enrolled in this retrospective study.All patients underwent 18F-FDG PET/CT and had not received any treatment before surgery.The relationships between clinical pathological results,metabolic parameters and liver metastasis were analyzed.Data were analyzed usingx2 test and logistic regression analysis.Results Patients were divided into two groups,78 without liver metastasis,20 with liver metastasis.Univariate analysis showed that the tumor primary location(x2=5.983),T stage(x2=6.447),serum carcinoembryonic antigen (CEA) levels(x2 =5.501),metabolic tumor volume (MTV;x2 =6.282) and total lesion glycolysis (TLG;x2=9.046) were significantly different between the two groups (all P<0.05).Multiple factor analysis showed that the tumor primary location,T stage,serum CEA levels,MTV and TLG (odds ratio (OR):0.059-7.575)were independent risk factors of CRC liver metastasis,and MTV and TLG were negatively correlated with liver metastasis.Conclusions Tumor primary location,T stage,serum CEA levels,MTV and TLG are independent risk factors of CRC liver metastasis.MTV and TLG are negatively correlated with liver metastasis.
9.Differential regulation of H3S10 phosphorylation, mitosis progression and cell fate by Aurora Kinase B and C in mouse preimplantation embryos.
Wenzhi LI ; Peizhe WANG ; Bingjie ZHANG ; Jing ZHANG ; Jia MING ; Wei XIE ; Jie NA
Protein & Cell 2017;8(9):662-674
Coordination of cell division and cell fate is crucial for the successful development of mammalian early embryos. Aurora kinases are evolutionarily conserved serine/threonine kinases and key regulators of mitosis. Aurora kinase B (AurkB) is ubiquitously expressed while Aurora kinase C (AurkC) is specifically expressed in gametes and preimplantation embryos. We found that increasing AurkC level in one blastomere of the 2-cell embryo accelerated cell division and decreasing AurkC level slowed down mitosis. Changing AurkB level had the opposite effect. The kinase domains of AurkB and AurkC were responsible for their different ability to phosphorylate Histone H3 Serine 10 (H3S10P) and regulate metaphase timing. Using an Oct4-photoactivatable GFP fusion protein (Oct4-paGFP) and fluorescence decay after photoactivation assay, we found that AurkB overexpression reduced Oct4 retention in the nucleus. Finally, we show that blastomeres with higher AurkC level elevated pluripotency gene expression, which were inclined to enter the inner cell mass lineage and subsequently contributed to the embryo proper. Collectively, our results are the first demonstration that the activity of mitotic kinases can influence cell fate decisions in mammalian preimplantation embryos and have important implications to assisted reproduction.
Animals
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Aurora Kinase B
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metabolism
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Aurora Kinase C
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metabolism
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Blastocyst
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metabolism
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Gene Expression Regulation, Developmental
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physiology
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Histones
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metabolism
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Mice
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Phosphorylation
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physiology
10.Predictive value of tumor metabolic indexes measured by 18F-FDG PET/CT in recurrence of resected stage Ⅰ non-small cell lung cancer
Wenzhi JIA ; Zongping ZHU ; Yumei CHEN ; Liangrong WAN ; Yiping SHI ; Gang HUANG ; Jianjun LIU
Chinese Journal of Nuclear Medicine and Molecular Imaging 2016;36(6):486-489
Objective To evaluate the predictive value of tumor metabolic indexes measured by 18F-FDG PET/CT in recurrence of stage Ⅰ NSCLC after surgery.Methods A total of 85 patients (44 males,41 females,age (62.46± 10.38) years) in Shanghai Renji Hospital with stage Ⅰ NSCLC,who underwent 18F-FDG PET/CT and subsequent surgical resection,were retrospectively enrolled from April 2006 to December 2011.Gender,age,tumor size,pathology,SUVmax,MTV and TLG of the primary tumor were selected as variables.ROC curve analysis was used to analyze the cut off value.The prognostic significance of parameters for recurrence-free survival (RFS) was evaluated by univariate and multivariate analyses.Survival analysis was analyzed by Kaplan-Meier method.Results During follow-up period,tumor recurrence occurred in 21 patients (24.7%,21/85) and 11 patients (12.9%,11/85) died.The median follow-up period was 44 months.The median values of SUVmax,MTV and TLG were 4.100,3.048 cm3 and 7.970,respectively.Cut off values of SUVmax,MTV and TLG were 7.115,4.701 cm3 and 12.015 according to ROC curve analysis.Univariate Cox analysis showed that SUVmax(x2 =22.091),MTV (x2 =4.941) and TLG(x2 =10.488) were associated with RFS(all P<0.05).But gender,age,tumor size,and pathology were not independent risk factors of recurrence (x2=0.248-3.888,all P>0.05).Multivariate Cox analysis revealed that SUVmax(=16.902,HR=15.426,P<0.05) and TLG (x2=6.029,HR=4.054,P<0.05) were independent prognostic factors for recurrence.Kaplan-Meier survival analysis showed that the period of RFS in high SUVmax (> 7.115) group (x2=32.545,P<0.05) and in high TLG (>12.015) group (x2=12.665,P<0.05) were lower than those in low SUVmax group and low TLG group.Conclusion The SUVmax and TLG measured by 18F-FDG PET/CT have significant value for predicting the recurrence of stage Ⅰ NSCLC.

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