1.In Vitro and in vivo Component Identification of Danshenyin Based on UPLC-Q-TOF-MS/MS
Sitong ZHANG ; Xianrun HU ; Wenkang LIU ; Jinchun LEI ; Xuemei CHENG ; Xiaojun WU ; Wansheng CHEN ; Manlin LI ; Changhong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):175-183
ObjectiveTo elucidate the chemical composition of Danshenyin and its blood components in rats after oral administration. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) coupled with PeakView 1.2 software was used to systematically characterize and identify the components of Danshenyin aqueous extract and its migratory components in rat blood after oral administration based on the retention time, quasi-molecular ion peaks, secondary fragmentation ions, and literature reports, and a preliminary compounds identification of Salviae Miltiorrhizae Radix et Rhizoma aqueous extract, the co-decoction of Santali Albi Lignum and Amomi Fructus was carried out to attribute the chemical constituents of the aqueous extract of Danshenyin. ResultsA total of 73 compounds, including 21 phenolic acids, 23 diterpenes, 6 flavonoids, 7 organic acids, 3 volatile oils and 13 others, were identified from the aqueous extract of Danshenyin. And 36 prototypes and 15 metabolites were identified in rat plasma, the major metabolic pathways included reduction, hydration, hydroxylation, demethylation, methylation, sulfation and others, these metabolites were mainly derived from tanshinones and salvianolic acids. ConclusionThe main blood components of the aqueous extract of Danshenyin are salvianolic acids and tanshinones, which may be the material basis of the efficacy. This study can provide reference for pharmacological research, quality control, and clinical application of Danshenyin.
2.Optical Mapping Technology to Evaluate the Dose Relationship of Aconitine Cardiotoxicity
Cuihan ZHANG ; Changhong SHEN ; Qian RAN ; Chen SUN ; Fang CHENG ; Ziqing YAO ; Ruoqi ZHANG
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1631-1637
OBJECTIVE
To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart.
METHODS
By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1.
RESULTS
Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01).
CONCLUSION
Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.To explore the effects of different concentrations of aconitine on the ventricular electrophysiology of the rat heart when applied to the heart.
METHODS
By optical mapping technology, the effects of different concentrations of aconitine on ventricular action potential and calcium signal in rats before and 15 min after administration were observed by in vitro administration of aconitine 0.3, 1, 3 ng·mL−1.
RESULTS
Compared with the blank group, aconitine could be concentration-dependent to delay the conduction of action potentials under both spontaneous and 6 Hz stimulation rhythms, and there was a significant difference at a concentration of 3 ng·mL−1(P<0.05 or P<0.01). Compared with blank group, when the concentration of aconitine was 1 and 3 ng·mL−1, the action potential duration(APD) of the ventricle was significantly prolonged(P<0.01). Aconitine could also increase the dispersion of action potential conduction(P<0.05) and reduce the ratio of effective refractory period(ERP) to APD90(P<0.01). In addition, aconitine could also be concentration-dependent delay of calcium signal conduction, reduce the speed of calcium conduction(P<0.05 or P<0.01), increase the dispersion of calcium conduction and calcium transient duration(P<0.05 or P<0.01), and reduce the amplitude of calcium signal(P<0.01).
CONCLUSION
Using the optical labeling technique, it can be visualized that aconitine induces arrhythmia by concentration-dependent delay of ventricular action potential and calcium signaling in rats.
3.Value of 18F-FDG PET/CT combined with conventional imaging modalities in TNM staging of rectal cancer
Changhong LI ; Zhen LIU ; Cheng GUO ; Huayong GU ; Xipeng ZHAO ; Lin GAO ; Xinglong GUO ; Yue LU ; Yanli WANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(6):349-354
Objective:To investigate the value of 18F-FDG PET/CT combined with conventional imaging modalities in the evaluation of the depth of tumor invasion, regional lymph node metastasis, distant organ and lymph node metastasis (TNM staging), and the adjacent structure invasion of rectal cancer. Methods:Fifty-four patients (28 males, 26 females, age (65.8±11.0) years) with pathologically confirmed rectal cancer admitted to the Affiliated Qingdao Central Hospital of Qingdao University between September 2019 and June 2021 were retrospectively analyzed. 18F-FDG PET/CT examination, conventional imaging modalities including high-resolution MRI (HR-MRI), chest CT plain scan, upper abdominal MRI or CT plain scan+ enhanced examination were performed within 2 weeks before or after the rectal cancer being confirmed. The TNM staging and adjacent structural invasions including circumferential resection margin (CRM), extramural vascular invasion (EMVI), anal sphincter complex involvement were evaluated by 18F-FDG PET/CT and conventional imaging modalities separately or in combination, and those results based on imaging were compared with the pathological results or clinical follow-up results. χ2 test was used to compare the differences of diagnostic sensitivity, specificity and accuracy between the 18F-FDG PET/CT or conventional imaging modalities and combined examination. Results:The accuracy for T staging and the sensitivity and accuracy for N staging of the combined examination were 96.30%(52/54), 98.65%(73/74) and 93.91%(185/197), respectively, which were significantly higher than those of 18F-FDG PET/CT (85.19%(46/54), 66.22%(49/74), 81.73%(161/197); χ2 values: 3.97, 26.88, 13.66, all P<0.05). The specificity (91.06%, 112/123) and accuracy of the combined examination for N staging were higher than those of the conventional imaging modalities (77.24%(95/123), 83.76%(165/197); χ2 values: 8.81, 10.23, both P<0.05). The sensitivity and accuracy of the combined examination for M staging were higher than those of the conventional imaging modalities (97.01%(65/67) vs 73.13%(49/67), 95.95%(71/74) vs 68.92%(51/74); χ2 values: 15.05, 18.66, both P<0.001). The sensitivities of the combined examination in evaluating CRM and EMVI were 100%(22/22) and 95.00%(19/20), and the accuracies were 98.15%(53/54) and 96.30%(52/54), all of which were higher than those of 18F-FDG PET/CT (CRM: 54.55%(12/22), 74.07%(40/54); EVMI: 30.00%(6/20), 74.07%(40/54); χ2 values: 12.94, 13.08, 18.03, 10.56, all P<0.01). The accuracy of the combined examination in evaluating EMVI was higher than that of the conventional imaging modalities (85.19%(46/54); χ2=3.97, P=0.046). Conclusion:18F-FDG PET/CT combined with conventional imaging modalities can improve the diagnostic efficacy for TNM staging and assessment of adjacent structural invasion in rectal cancer.
4.Clinical observation on the overlapping syndrome of myelin oligodendrocyte glycoprotein antibody and anti-N-methyl-D aspartate receptor in children
Shuai GONG ; Weihua ZHANG ; Haitao REN ; Jiuwei LI ; Ji ZHOU ; Hua CHENG ; Xiuwei ZHUO ; Changhong REN ; Tongli HAN ; Junlan LYU ; Changhong DING ; Fang FANG ; Hongzhi GUAN ; Xiaotun REN
Chinese Journal of Pediatrics 2020;58(7):581-585
Objective:To investigate the clinical features, imaging findings and prognosis of children with overlapping syndrome of myelin oligodendrocyte glycoprotein (MOG) antibody disease and anti-N-methyl-D aspartate receptor (NMDAR) encephalitis (MNOS).Methods:The clinical manifestations, immunological antibodies in blood and cerebrospinal fluid, cranial image, treatment and follow-up of 11 patients diagnosed as MNOS in the Department of Neurology, Beijing Children′s Hospital from January 2011 to April 2019 were analyzed retrospectively.Results:A total of 11 patients, including 4 males and 7 females were analyzed, the age of onset was (10.4±2.3) years. A total of 29 episodes occurred in 11 children. At the last follow-up, 8 cases showed relapsed remission course, the interval of recurrence was 3 to 60 months. The onset symptoms of 11 patients included convulsions (10 cases), lethargy (6 cases), psychosis (6 cases). Among 29 episodes, the common symptoms were convulsions (16 episodes), psychosis (13 episodes),and lethargy (10 episodes). According to the diagnostic criteria of anti-NMDAR encephalitis and MOG-antibody disease, 29 episodes were divided into three phenotypes, including anti-NMDAR encephalitis(4 episodes), MOG-antibody diseases (10 episodes) and overlapping types (15 episodes).Twenty-seven times of acute stage cranial magnetic resonance imaging (MRI) were available, common lesions included cortical focus (22 times), subcortical white matter (7 times), brainstem (9 times). All patients were sensitive to first-line immunotherapy. Eight patients had recurrence during glucocorticoid reduction, 6 of them were treated with additional second-line immunosuppressive therapy, including cyclophosphamide (1 case) and mycophenolate mofetil (5 cases). The follow-up time of patients were 5-99 months. At the last follow-up, all patients were in remission, the pediatric cerebral performance category (PCPC) score was 1 (10 cases) and 2 (1 cases).Conclusions:MNOS mainly affects older children. In the period of acute episodes, convulsions and psychosis are common. The cranial MRI showed extensive brain involvement and mainly in the cortex. The recurrence rates of MNOS are relatively high, patients are sensitive to first-line immunotherapy. No significant neurological dysfunction was left in the remission stage.
5. Clinical features of central nerve system inflammatory demyelinating diseases associated with anti-myelin oligodendrocyte glycoprotein antibodies in children
Weihua ZHANG ; Xiaotun REN ; Tongli HAN ; Hua CHENG ; Jiuwei LI ; Shuai GONG ; Weixing FENG ; Xiaoyun ZHU ; Changhong REN ; Ji ZHOU ; Changhong DING ; Haitao REN ; Hongzhi GUAN ; Fang FANG
Chinese Journal of Applied Clinical Pediatrics 2019;34(24):1858-1861
Objective:
To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children.
Methods:
The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared.
Results:
A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(
6.Preoperative evaluation of histologic grade in invasive breast cancer with T2W-MRI based radiomics signature.
Yucun HUANG ; Zixuan CHENG ; Xiaomei HUANG ; Cuishan LIANG ; Changhong LIANG ; Zaiyi LIU
Journal of Central South University(Medical Sciences) 2019;44(3):285-289
To develop and validate a fat-suppressed (T2 weighted-magnetic resonance imaging, T2W-MRI) based radiomics signature to preoperatively evaluate the histologic grade (grade I/II VS. grade III) of invasive breast cancer.
Methods: A total of 202 patients with MRI examination and pathologically confirmed invasive breast cancer from June 2011 to February 2017 were retrospectively enrolled. After retrieving fat-suppressed T2W images and tumor segmentation, radiomics features were extracted and valuable features were selected to build a radiomic signature with the least absolute shrinkage and selection operator (LASSO) method. Mann-Whitney U test was used to explore the correlation between radiomics signature and histologic grade. Receiver operating characteristics (ROC) curve was applied to determine the discriminative performance of the radiomics signature [area under curre (AUC), sensitivity, specificity, and accuracy]. An independent validation dataset was used to confirm the discriminatory power of radiomics signature.
Results: Eight radiomics features were selected to build a radiomics signature, which showed good performance for preoperatively evaluating histologic grade of invasive breast cancer, with an AUC of 0.802 (95% CI 0.729 to 0.875), sensitivity of 78.7%, specificity of 70.3% and accuracy of 73.7% in training dataset and AUC of 0.812 (95% CI 0.686 to 0.938), sensitivity of 80.0%, specificity of 73.3% and accuracy of 76.0% in the validation dataset.
Conclusion: The fat-suppressed T2W-MRI based radiomics signature can be used to preoperatively evaluate the histologic grade of invasive breast cancer, which may assist clinical decision-maker.
Breast Neoplasms
;
diagnostic imaging
;
Humans
;
Magnetic Resonance Imaging
;
Preoperative Care
;
ROC Curve
;
Retrospective Studies
7.CT-based radiomics analysis for evaluating the differentiation degree of esophageal squamous carcinoma.
Leishu CHENG ; Lei WU ; Shuting CHEN ; Weitao YE ; Zaiyi LIU ; Changhong LIANG
Journal of Central South University(Medical Sciences) 2019;44(3):251-256
To build a CT-based radiomics predictive mode to evaluate the differentiation degree of the esophageal squamous carcinoma.
Methods: A total of 160 patients with surgical pathology, complete clinical data and chest CT scanning before operation were retrospectively collected from January 2008 to August 2016. All patients were assigned randomly to a primary data set and an independent validation. Texture analysis was performed on CT images, while the carcinomas were performed by manual segmentation to extract the radiomics features. Radiomics features were extracted and 9 radiomics signatures were finally selected after dimension reduction. Radiomics features were extracted and established via Matlab. Multivariable logistic regression analysis was performed to build the predictive model. A 10-fold cross-validation was used for selecting parameters in the least absolute shrinkage and selection operator (LASSO) model by minimum criteria. The receiver operating characteristic (ROC) curves and areas under ROC curve (AUC) were used to compare the model performance in the primary validation and the independent validation for evaluating the differentiation degree of esophageal squamous carcinoma.
Results: Radiomics signature showed great effect in discriminating primary data set and independent validation. The predictive model had a good performance in primary data set. The AUC was 0.791, the sensitivity was 81.6%, and specificity was 72.3%. In the independent validation, the AUC was 0.757, the sensitivity was 70.0%, and the specificity was 73.0%.
Conclusion: The predictive model can be used for evaluating the differentiation degree of esophageal squamous carcinoma efficiently, which can be helpful to clinicians in diagnosis and choice of treatment for esophageal squamous carcinoma.
Carcinoma, Squamous Cell
;
Esophageal Neoplasms
;
Humans
;
ROC Curve
;
Retrospective Studies
;
Tomography, X-Ray Computed
8.Effects of different wavelet filters on correlation and diagnostic performance of radiomics features.
Zixuan CHENG ; Yanqi HUANG ; Xiaomei HUANG ; Xiaomei WU ; Changhong LIANG ; Zaiyi LIU
Journal of Central South University(Medical Sciences) 2019;44(3):244-250
To investigate the effects of different wavelet filters on correlation and diagnostic performance of radiomics features.
Methods: A total of 143 colorectal cancer (CRC) patients (64 positive in lymph node metastasis and 79 negative) with contrast-enhanced CT examination were recruited. After labeling the tumor area by experienced radiologists, radiomics wavelets features based on 48 different wavelets were extracted using in-house software coded by Matlab. The correlation coefficients of the features with same names between different wavelets were calculated and got the distribution of high-correlation features between each wavelet. The least absolute shrinkage and selection operator (LASSO) was used to build signatures between lymph node metastasis and wavelet features data set based on different wavelets. The numbers of features in signatures and diagnostic performance were compared using Delong's test.
Results: With the difference of wavelet order increased, the number of high-correlation features between two wavelets decreased. Some features were prone to high correlation between different wavelets. When building radiomics signature based on single wavelet, signatures built from 'rbio2.2', 'sym7' and 'db7' did well in predicting lymph node metastasis. The signature based on Daubechies wavelet feature set had the highest performance in predicting lymph node metastasis, while the signature from Biorthogonal wavelet features was worst. Improvement was significant in diagnostic performance after excluding the high-correlation features in the whole features set (P=0.004).
Conclusion: In order to reduce the data redundancy of features, it is recommended to select wavelets with large differences in wavelet orders when calculating radiomics wavelet features. It is necessary to remove high correlation features for improving the diagnostic performance of radiomics signature.
Colorectal Neoplasms
;
Humans
;
Lymphatic Metastasis
;
Retrospective Studies
9.Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.
Dandan LUO ; Weihong GE ; Xiao HU ; Chen LI ; Chia-Ming LEE ; Liqiang ZHOU ; Zhourui WU ; Juehua YU ; Sheng LIN ; Jing YU ; Wei XU ; Lei CHEN ; Chong ZHANG ; Kun JIANG ; Xingfei ZHU ; Haotian LI ; Xinpei GAO ; Yanan GENG ; Bo JING ; Zhen WANG ; Changhong ZHENG ; Rongrong ZHU ; Qiao YAN ; Quan LIN ; Keqiang YE ; Yi E SUN ; Liming CHENG
Protein & Cell 2019;10(8):566-582
The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.
10.The value of cardiac MRI in diagnosis of Ebstein anomaly
Weiqin CHENG ; Jiahua LI ; Meiping HUANG ; Jian ZHUANG ; Xiaomei ZHONG ; Qianjun JIA ; Hui LIU ; Changhong LIANG
Chinese Journal of Radiology 2018;52(3):166-171
Objective To evaluate the value of cardiac MRI in the diagnosis of Ebstein anomaly (EA). Methods Twenty patients from February 2014 to April 2017 with EA confirmed by surgery were enrolled into this study. The analysis in all patients was made according to preoperative cardiac MRI, 2D TTE and surgical data, including the changes of tricuspid valve leaflets, Carpentier classification, the size and function of atrioventricle, late Gadolinium enhancement, the total right/left-volume index and cardiopulmonary bypass time,etc.The numbers of apicaldisplaced leaflets and development condition of all the leaflets were compared using the R×C χ2among the three groups.With surgical results as the reference standard, the diagnostic accuracy of the two groups for the development condition of all the leaflets were evaluated. One-way ANOVA was performed to compare the differences of the apicaldisplaced distance of septal leaflet, using these three methods. Comparisons of the total right/left-volume index, surgery-related data between patients with or without late gadolinium enhancement were performed by independent t test.Results (1) The results in anatomicalstructures, such as distance of apicaldisplacedseptal leaflet,displacement of each leaflet and the Carpentier classification, showed nostatistical difference among MRI,2D TTE and operational findings. The leaflet dysplasia defined by MRI and 2D TTE areequivalent to surgically defined severe dysplasia, and surgically defined mild to moderate dysplasia can't be identified by the former two methods. The overall diagnostic accuracy of MRI and 2D TTE to identify leaflet dysplasia were 41.3%(19/46) and 34.7%(16/46), respectively.(2) Functional right ventricular volume index decreased in 1 case, normal in 8 cases, increased in 11 cases;functional right ventricula rejection fraction decreased in 15 cases. Six patients' left ventricular volume index decreased, 13 remained in normal range, 1 showed increased;left ventricula rejection fraction decreased in 14 cases. (3)LGE was identified in 8 patients and non-LGE in 12. Difference of the total right/left-volume index [(7.12 ± 4.06) vs. (3.84 ± 2.10), P=0.029] between two groups was statistically significant. However, there was no statistical difference in extracorporeal circulation time, aorticcross-clamping time, intubation time, ICU residence time and postoperative hospital staybetween the LGE and non-LGE groups.Conclusions Cardiac MRI can relatively accurately evaluate the apicaldisplacement of leaflets and the morphological changes of the atria and ventricles, as well as quantitatively evaluate the ventricular function, which can rovide references for clinical diagnosis and severity evaluation of EA.


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