1.Optimization of extraction technology,evaluation of hypoglycemic activity and component analysis of total flavonoids from Hypericum japonicum
Zhihong ZHOU ; Qin HU ; Mingming XIAO
China Pharmacy 2024;35(16):1972-1978
OBJECTIVE To optimize the ultrasound-assisted extraction-deep eutectic solvents technology of total flavonoids from Hypericum japonicum, evaluate its hypoglycemic activity in vitro, and analyze its chemical compositions preliminarily. METHODS The most suitable deep eutectic solvent for total flavonoids from H. japonicum was screened using the composition of hydrogen bond acceptor and donor, molar ratio, water content as factors, and the total flavonoid yield as the response value. Using liquid-solid ratio, ultrasonic power, ultrasonic temperature and ultrasonic time as factors, the yield of total flavonoids as response value, the extraction technology of total flavonoids from H. japonicum was optimized by single-factor experiments combined with Box-Behnken response surface method, and the optimum extraction technology was validated. Taking acarbose as the positive control, the inhibitory activities of total flavonoids from H. japonicum on α-amylase and α-glucosidase in vitro were determined. The chemical constituents of total flavonoids from H. japonicum were analyzed by UPLC combined with comparing the reference substances. RESULTS The most suitable deep eutectic solvent was choline chloride-oxalic acid (the molar ratio of 1∶1, the water content of 30%). The optimum extraction technology was as follows: the ratio of liquid-solid was 52∶1 (mL/g), the ultrasonic temperature was 54 ℃ , the ultrasonic power was 240 W, and the ultrasonic time was 42 min; the total extraction yield of total flavonoids from H. japonicum in 3 validation tests was (73.26±2.48) mg/g, the relative error of which with the theoretical value (73.48 mg/g) was -0.30%. The total flavonoids from H. japonicum could inhibit α-amylase and α-glucosidase with IC50 values of 0.73 and 0.44 mg/mL, respectively, which were higher than those of acarbose (0.23 and 0.15 mg/mL). UPLC analysis showed that the total flavonoids from H. japonicum contained isoquercetin, quercitrin, quercetin-7-O-α-L-rhamnoside and quercetin. CONCLUSIONS The optimized extraction technology of total flavonoids from H. japonicum is stable and feasible, and the extract has certain hypoglycemic activity in vitro and contains isoquercetin, quercitrin and quercetin-7-O-α-L-rhamnoside, etc.
2.Cytoplasmatic Localization of Six1 in Male Testis and Spermatogonial Stem Cells
Mingming QIN ; Linzi MA ; Wenjing DU ; Dingyao CHEN ; Guoqun LUO ; Zhaoting LIU
International Journal of Stem Cells 2024;17(3):298-308
Sine oculis homeobox 1 (Six1) is an important factor for embryonic development and carcinoma malignancy. However, the localization of Six1 varies due to protein size and cell types in different organs. In this study, we focus on the expression and localization of Six1 in male reproductive organ via bioinformatics analysis and immunofluorescent detection. The potential interacted proteins with Six1 were also predicted by protein-protein interactions (PPIs) and Enrichr analysis. Bioinformatic data from The Cancer Genome Atlas and Genotype-Tissue Expression project databases showed that SIX1 was highly expressed in normal human testis, but low expressed in the testicular germ cell tumor sample. Human Protein Atlas examination verified that SIX1 level was higher in normal than that in cancer samples.The sub-localization of SIX1 in different reproductive tissues varies but specifically in the cytoplasm and membrane in testicular cells. In mouse cells, single cell RNA-sequencing data analysis indicated that Six1 expression level was higher in mouse spermatogonial stem cells (mSSCs) and differentiating spermatogonial than in other somatic cells.Immunofluorescence staining showed the cytoplasmic localization of Six1 in mouse testis and mSSCs. Further PPIs and Enrichr examination showed the potential interaction of Six1 with bone morphogenetic protein 4 (Bmp4) and catenin Beta-1 (CtnnB1) and stem cell signal pathways. Cytoplasmic localization of Six1 in male testis and mSSCs was probably associated with stem cell related proteins Bmp4 and CtnnB1 for stem cell development.
3.Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, and Their Combination Treat Colonic Motility Disorders in Rats with Slow Transit Constipation via PINK1/Parkin Signaling Pathway-mediated Mitophagy
Xiaopeng WANG ; Huiju YANG ; Mingming SUN ; Jing LIU ; Bensheng WU ; Yinzi YUE ; Yuanyuan QIN ; Yinghui CHEN ; Lie TIAN ; Yan LI ; Yahui WANG ; Shuai YAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):45-53
ObjectiveTo observe the effects of Aurantii Fructus Immaturus, Atractylodis Macrocephalae Rhizoma, and their combination on slow transit constipation via PTEN-induced putative kinase 1 (PINK1)/Parkin pathway-mediated mitophagy. MethodFifty-six male SD rats were randomly assigned into normal group, model group, natural recovery group, Aurantii Fructus Immaturus group, Atractylodis Macrocephalae Rhizoma group, Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group, and mosapride group, with 8 rats in each group. Slow transit constipation model was established by gavage with loperamide (3 mg·kg-1·d-1) for 14 days in other groups except the normal group. After successful modeling, except that the model group was continuously induced by loperamide, the normal group and the natural recovery group were administrated with 0.9% normal saline by gavage, and the rats in the Aurantii Fructus Immaturus (1.35 g·kg-1·d-1) group, the Atractylodis Macrocephalae Rhizoma (2.7 g·kg-1·d-1) group, the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma (4.05 g·kg-1·d-1) group, and the mosapride (1.56 mg·kg-1·d-1) group were administrated with corresponding drugs by gavage for 7 days. The amount of feces, fecal water content, and intestinal propulsion rate of rats were determined. The pathological changes of the colon were evaluated by hematoxylin-eosin (HE) staining and Alcian blue-periodic acid-Schiff (AB-PAS) staining. The activity of respiratory chain complex and the ultrastructure of the colon tissue were determined by ultraviolet spectrophotometry and observed by transmission electron microscopy, respectively. Real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was employed to determine the mRNA levels of PINK1, Parkin, and p62, and Western blot to determine the protein levels of microtubule-associated protein 1 light chain 3 (LC3), PINK1, and Parkin. ResultCompared with the normal group, the model group and the natural recovery group showed decreases in the amount of feces, fecal water content, intestinal propulsion rate (P<0.05,P<0.01), and activities of mitochondrial respiratory chain complexes Ⅱ, Ⅲ, and Ⅳ in the colon tissue (P<0.05,P<0.01). Further, the mRNA levels of PINK1 and Parkin and the protein levels of PINK1, Parkin, and LC3 were up-regulated (P<0.01) and the mRNA level of p62 was down-regulated in the model group (P<0.05) and the natural recovery group. Compared with the model group and the natural recovery group, the Aurantii Fructus Immaturus combined with Atractylodis Macrocephalae Rhizoma group showed increased amount of feces, fecal water content, intestinal propulsion rate, and activities of mitochondrial respiratory chain complexes Ⅱ, Ⅲ, and Ⅳ (P<0.05,P<0.01). Moreover, the combination meliorated the degree of mitochondrial swelling in the colon tissue, down-regulated the mRNA levels of PINK1 and Parkin and the protein levels of PINK1, Parkin, and LC3 (P<0.05,P<0.01), and up-regulated the mRNA level of p62 (P<0.05). ConclusionAurantii Fructus Immaturus and Atractylodis Macrocephalae Rhizoma, and their combination may remedy the colonic motility disorders in rats with slow transit constipation by blocking PINK1/Parkin signaling pathway to inhibit the excessive mitophagy in interstitial cells of Cajal in the colon tissue.
4.Prognostic prediction value of quantitative digital subtraction angiography parameters after mechanical thrombectomy in patients with acute ischemic stroke with large vessel occlusion in the anterior circulation of different etiology
Kangmo HUANG ; Rui LIU ; Juan DU ; Weihe YAO ; Mingming ZHA ; Shanmei QIN ; Yan XU ; Wusheng ZHU ; Qingshi ZHAO ; Xinfeng LIU
Chinese Journal of Neurology 2023;56(6):637-645
Objective:To explore the prognostic prediction value of quantitative digital subtraction angiography (DSA) parameters in patients with acute anterior circulation ischemic stroke undergoing mechanical thrombectomy, and whether the clinical values vary by stroke etiology.Methods:This study was a post hoc analysis of the Multicenter Prospective Captor Trial. Patients with acute anterior circulation large-vessel occlusion and successful recanalization from April 2018 to July 2019 were screened. Post-processing analysis was performed on the DSA imaging sequence after recanalization, and 4 regions of interest (ROI) were selected in the target vessel: ROI1 (the proximal of the internal carotid artery-C2 segment), ROI2 (the starting point of the internal carotid artery-C7 segment), ROI3 (the end of the middle cerebral artery-M1 segment), and ROI4 (the end of the middle cerebral artery-M2 segment). Time to peak (TTP) was defined as the time at contrast concentration of selected ROI reached its maximum. Relative TTP (rTTP) was calculated by subtracting the TTP of ROI1 from the TTP of distalis ROIs. Successful recanalization was defined as modified Thrombolysis In Cerebral Infarction (mTICI) grade≥2b. Favorable outcomes at 3 months were defined as the modified Rankin Scale score≤2. According to the modified Rankin Scale score, the patients were divided into good prognosis group and poor prognosis group. The differences in clinical characteristics, postoperative hemodynamic parameters, and other data were compared between patients with good and poor prognoses. Univariate and multivariate Logistic regression was used to analyze factors related to a good prognosis. Finally, the prognostic prediction value of hemodynamic parameters was analyzed in patients with different Trial of Org10172 in Acute Stroke Treatment etiological classifications.Results:A total of 245 patients were collected, of which 161 patients [age 69 (60, 76) years, 92 (57.1%) male] were finally included in the analysis, including 36 cases of large artery atherosclerosis (LAA) stroke, 76 cases of cardiogenic embolism (CE), and 49 cases of other causes of stroke. Seventy-one (44.1%) patients had favorable outcomes at 3 months. The post-operative hemodynamic analysis indicated that patients with favorable outcomes ( n=71) had a higher proportion of mTICI grade 3 [54/71 (76.1%) vs 41/90 (45.6%),χ 2=15.26, P<0.001] and lower rTTP 31 [means TTP ROI3-TTP ROI1;0.33 (0.23, 0.54) s vs 0.47 (0.31, 0.65) s, Z=-2.71, P=0.007] than patients with unfavorable outcomes ( n=90). The mTICI score and rTTP 31 were respectively included in multivariate Logistic regression models. It was shown that mTICI grade 3 (adjusted OR=5.97, 95% CI 2.49-14.27, P<0.001) and rTTP 31 (adjusted OR=0.24, 95% CI 0.06-0.99, P=0.048) were significantly associated with favorable outcomes, and the area under the receiver operating characteristic curve of the models had no statistically significant difference ( P=0.170). Subgroup analysis showed that rTTP 31 was significantly associated with the prognosis of patients with LAA stroke ( OR=0, 95% CI 0-0.25, P=0.014), while mTICI grade was associated with the prognosis of patients with CE ( OR=3.91, 95% CI 1.40-10.91, P=0.009) and other etiologies ( OR=7.35, 95% CI 1.92-28.14, P=0.004). Conclusions:In patients with acute anterior circulation ischemic stroke and successful recanalization, both mTICI score and rTTP 31 had significant predictive value for favorable outcomes at 3 months. Moreover, rTTP 31 was significantly associated with the prognosis of patients with LAA stroke, while mTICI score was significantly related to the prognosis of patients with CE and other causes of stroke.
5.A software for blood product information management: development and application
En DONG ; Senyu YU ; Rongrong ZHU ; Mingming QIN ; Shengying PENG ; Wei WU ; Longfeng SUN ; Gefei LIU
Chinese Journal of Blood Transfusion 2023;36(12):1159-1162
【Objective】 To develop a mobile software application named " Component Assistant" and test for its performance in practical work, so as to address the difficulties and problems encountered during the management process of blood component preparation, such as communication and coordination in the workflow, personnel scheduling and workload arrangements. 【Methods】 The software was developed based on the daily work requirements and processes using Java language, and foreground-background separation technologies were employed to provide secure and reliable data support. 【Results】 The results of practical work verification showed that through this software, component preparation managers were able to real-time monitor blood collection situations, blood transfusion details, manage inventory levels, and summarize and review the details of the preparation process. Comparison of the usage sequence of this software, the average amount of blood prepared of employees has increased(198 bloodbag,
6.Role of cardiopulmonary ultrasound in predicting the occurrence of heart failure with preserved ejection fraction in patients with acute myocardial infarction
Runyu TIAN ; Weiwei ZHU ; Qizhe CAI ; Yunyun QIN ; Mingming LIN ; Shan JIN ; Wanwei ZHANG ; Xiuzhang LYU
Chinese Journal of Ultrasonography 2023;32(2):111-116
Objective:To evaluate the left ventricular diastolic function and pulmonary congestion in patients with acute myocardial infarction (AMI) with preserved left ventricular ejection fraction (LVEF) by cardiopulmonary ultrasound (CPUS), and to explore the value of CPUS in predicting the occurrence of heart failure with preserved ejection fraction (HFpEF) in AMI patients with preserved LVEF during hospitalization.Methods:A total of eighty-four patients with AMI with preserved LVEF (≥50%) who received optimal emergency reperfusion therapy on admission at Beijing Chaoyang Hospital Affiliated to Capital Medical University from August 2021 to March 2022 were enrolled. All patients completed comprehensive cardiopulmonary ultrasonography within 12 hours after reperfusion therapy and LVEF, left atrial maximum volume(LAV), peak flow velocity of tricuspid valve regurgitation (V TR), peak flow velocity of mitral valve in early diastole (E), peak velocity of mitral valve annulus on septal side and left ventricular lateral side in early diastole and other conventional echocardiography parameters were obtained, and then the left atrial volume index (LAVI), the mean peak velocity of the mitral valve annulus on the septal side and left ventricular lateral side in early diastole (e′) and E/e′ were calculated; lung ultrasound parameters(the number of B lines) were obtained; the left ventricular global long-axis strain (GLS) was obtained using speckle tracking imaging (STE). The predictive power of CPUS parameters for HFpEF during hospitalization in AMI patients with preserved LVEF were analyzed. Results:①The incidence of HFpEF during hospitalization was 40.4% (34/84). ②The number of B lines and LAVI were independently correlated with the occurrence of HFpEF during hospitalization( P<0.05). ③The ROC curve analysis showed that the area under the curve (AUC) of the number of B lines and LAVI for predicting the occurrence of HFpEF during hospitalization were 0.766 and 0.690, respectively. The number of B lines combined with LAVI had the best predictive performance in predicting the occurrence of HFpEF during hospitalization, with the largest AUC of 0.903, which was significantly better than the number of B lines and LAVI ( P<0.05). Conclusions:The number of B lines combined with LAVI can effectively predict the occurrence of HFpEF during hospitalization in AMI patients with preserved LVEF, which is helpful to further improve the clinical management of AMI patients at risk of HFpEF.
7.An overview of clinical studies on SARS-CoV-2 infection in dialysis patients
Zuolin LI ; Mingming PAN ; Guihua WANG ; Qing YIN ; Anran SHEN ; Qin YANG ; Bicheng LIU
Chinese Journal of Nephrology 2023;39(11):860-866
The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a catastrophic impact on human life and economic life. Due to the combination of multiple underlying diseases and low vaccination rates, dialysis patients are susceptible to SARS-CoV-2 infection and are likely to have more severe illness and even death. Moreover, dialysis patients with SARS-CoV-2 infection may initially present as asymptomatic or with mild symptoms, which makes it very difficult to identify severe patients at an early stage. Here, the epidemiology, clinical characteristics, risk factors for prognosis, vaccination and therapeutic strategies of dialysis patients with SARS-CoV-2 infection were summarized and analyzed, and it is hoped to provide a reference for the diagnosis and treatment of SARS-CoV-2 infection in this special group of patients.
8.A feasibility study of classification between breast carcinoma in situ and invasive carcinoma using intratumoral and peritumoral radiomics based on dynamic contrast-enhanced MRI
Yuan JIANG ; Yuanjia CHENG ; Li GUO ; Mingming MA ; Yaofeng ZHANG ; Xiaodong ZHANG ; Xiaoying WANG ; Naishan QIN
Chinese Journal of Radiology 2022;56(9):976-981
Objective:To explore the feasibility of classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study included consecutive invasive breast carcinoma pathological diagnosed by core needle biopsy or surgery from January 2013 to December 2013 and carcinoma in situ of breast diagnosed by surgery from January 2013 to December 2015 in Peking University First Hospital. All patients had pretreatment breast MRI images. A total of 251 cases (251 lesions) were included, with 208 invasive breast carcinoma and 43 carcinoma in situ of breast. They were all females and median age was 53 (23-82) years old. Patients were randomly divided into the training ( n=176) and testing dataset ( n=75) in a 7∶3 ratio. In the training dataset, combined with DCE mask and early enhancement images, intratumoral and peritumoral area were semi-automatic segmentation, and radiomics features were extracted and dimension reduction, finally a prediction model was established. Model performance was tested in the testing dataset. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the model prediction performance. Results:The prediction models established by intratumoral, peritumoral and intratumoral combined with peritumoral radiomics had good performance. The AUC of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models in differentiating breast carcinoma in situ and invasive carcinoma were 0.865, 0.896 and 0.922 in the testing dataset, there was no significant difference in pairwise comparisons ( P>0.05). The sensitivity of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models were 77.4%, 87.1%, 83.9%, the specificity were 92.3%, 84.6%, 100%, and the accuracy were 80.0%, 85.3%, 86.7%. Conclusion:It is potential feasible for classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast DCE MRI.
9.Imaging features of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusions: comparison with chromophobe renal cell carcinoma
Jianxing QIU ; Yi LIU ; Mingming MA ; Xiaoying WANG ; Naishan QIN
Chinese Journal of Radiology 2022;56(9):1015-1020
Objective:To compare the imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion (Xp11.2 RCC) with chromophobe RCC.Methods:From November 2016 to January 2020, 28 patients with Xp11.2 RCC and 28 patients with chromophobe RCC confirmed by pathology were retrospectively analyzed in Peking University First Hospital. All 23 patients underwent preoperative CT examination, and 5 patients underwent routine MRI in each group. The clinical and imaging features were observed and recorded. The CT features including side, location, size, boundary, shape, uniform density, composition (solid, cystic-solid, cystic), hemorrhage, calcification, lymph node metastasis of the lesions and distant metastasis were observed, and the CT value of the solid part of the tumor at each stage was measured. On MRI images, the signal of the lesion in each sequence and enhancement mode were observed. The differences in clinical and imaging characteristics between the 2 groups were compared using independent samples t test or χ 2 test. Results:The Xp11.2 RCC more frequently affected young [(27±10) years] patients, while chromophobe RCC more frequently involved middle-aged [(37±7) years] patients asymptomatically, and the difference was statistically significant ( t=-4.99, P<0.001). The lesion size of Xp11.2 RCC [(5.4±2.2) cm] were significantly smaller than that of chromophobe RCC [(6.9±1.8) cm] ( t=-2.93, P=0.005). There were significant differences in the density and composition of lesions between Xp11.2 RCC and chromophobe RCC (χ 2=4.60, 18.67, P=0.032,<0.001). There were no significant differences in the side, location, boundary, shape, hemorrhage, calcification, fat, lymph node metastasis and distant metastasis between the 2 kind of lesions (all P>0.05). The CT values of solid components in Xp11.2 RCC in cortico-medullary phase and delayed phase were higher than those in chromophobe RCC, and the difference were statistically significant ( t=11.80, 20.15, both P<0.001). Five cases of Xp11.2 RCC showed iso- or slightly hyperintense signal on T 1WI and slightly hypointense signal on T 2WI. Two cases showed delayed enhancement after enhancement, and 3 cases showed a slight decrease in delayed phase enhancement. Conclusion:Compared with chromophobe RCC, Xp11.2 RCC has certain characteristics in imaging manifestations (lesion size, density uniformity, composition, CT value of post-enhanced cortico-medullary phase and delayed phase). Imaging manifestations combining the clinical manifestations (age of onset) are helpful for preoperative diagnosis of Xp11.2 RCC.
10.The SACT Template: A Human Brain Diffusion Tensor Template for School-age Children.
Congying CHU ; Haoran GUAN ; Sangma XIE ; Yanpei WANG ; Jie LUO ; Gai ZHAO ; Zhiying PAN ; Mingming HU ; Weiwei MEN ; Shuping TAN ; Jia-Hong GAO ; Shaozheng QIN ; Yong HE ; Lingzhong FAN ; Qi DONG ; Sha TAO
Neuroscience Bulletin 2022;38(6):607-621
School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).

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