The effect and mechanism of Xihuang pill inhibits the formation of vasculogenic mimicry in human glioblastoma cells by down-regulating HIF-1α/VEGFA/VEGFR2 signaling pathway / 药学学报

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

Changes of subfoveal choroidal thickness and choroidal volume in different stages of diabetic retinopathy through automated choroid segmentation / 中华实验眼科杂志

Objective:To analyze the changes of subfoveal choroidal thickness (SFCT) and choroidal volume in type 2 diabetes patients with diabetic retinopathy (DR) through automated choroid segmentation.Methods:A cross-sectional study was conducted.Sixty-four patients (88 eyes) with type 2 diabetes diagnosed in The First Affiliated Hospital with Nanjing Medical University from May 2016 to May 2017 were enrolled, including 27 males (32 eyes) and 37 females (56 eyes), with an average age of (62.7±7.4) years and an average diabetes duration of (13.7±7.2) years.Best corrected visual acuity, slit lamp ophthalmoscopy, indirect ophthalmoscopy and spectral domain optical coherence tomography (SD-OCT) examination were carried out among all the patients.The patients were divided into non-DR (NDR) group (28 eyes), nonproliferative DR (NPDR) group (36 eyes) and proliferative DR (PDR) group (24 eyes) according to the Early Treatment Diabetic Retinopathy Study.Nineteen age-matched normal subjects (32 eyes) were enrolled as normal control group.SFCT and choroidal volume were measured through automated choroid segmentation based on SD-OCT with enhanced depth imaging.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of The First Affiliated Hospital with Nanjing Medical University (No.2017-SR-176).Results:Mean SFCT and choroidal volume of normal control group, NDR group, NPDR group and PDR group were (277.8±45.3)μm and (8.8±1.0)mm 3, (220.9±38.7)μm and (7.6±1.3)mm 3, (231.8±26.7)μm and (8.2±0.9)mm 3, (252.0±42.2)μm and (8.7±1.0)mm 3, respectively, with significant overall differences among the groups ( F=14.615, P<0.001; F=7.711, P<0.001). Mean SFCT and choroidal volume were significantly smaller in NDR and NPDR group than those in normal control group (both at P<0.05). Mean SFCT and choroidal volume of PDR group was greater than those of NDR group (both at P<0.05). Conclusions:SFCT and choroidal volume decrease during the early course of diabetes and increase significantly as DR worsens from NDR to PDR.

Detecção de áreas vulneráveis ​​ao escorpionismo e sua associação com fatores ambientais em São Paulo, Brasil / Detection of areas vulnerable to scorpionism and its association with environmental factors in São Paulo, Brazil

Accidents caused by scorpions are considered a neglected condition and represent a major health problem in most tropical countries, especially for children and elderly people. In Brazil, scorpionism is recurrent in the southeast region, mainly in the state of Sao ˜ Paulo, due to the progressive increase in scorpions found in urban habitats. Thus, our study aimed to provide better insights into the geographic and epidemiological characteristics of scorpion envenomation in Sao ˜ Paulo state and identify the environmental factors that are associated with these accidents. This is an ecological and retrospective study with secondary data on scorpion accidents in the state of Sao ˜ Paulo from 2008 to 2018 obtained from the Notifiable Disease Information System. The SatScan software was used to identify the higher- and lower-risk spatiotemporal clusters. A total of 145,464 scorpion sting cases were recorded in the state of Sao Paulo, between 2008 and 2018; there was a four-fold increase in the incidence rate. Accidents occurred more frequently in the spring season, wherein higher-risk clusters were in the north and northwest regions of the state. High temperatures, low precipitation, and poor natural vegetation are associated with higher risk areas. Our study mapped vulnerable areas for scorpion accidents that can aid in the design ofefficient public health policies, which should be intensified during the spring season.

Research progress in ecological prevention of dental caries / 中华口腔医学杂志

Dental caries is one of the most common oral diseases around the world. Dental plaque attached to the surfaces of teeth is the main biological factor leading to caries. Although fluoride is still one of the most commonly used methods to prevent caries, with the change of epidemiological characteristics of caries and the update of the understanding of caries etiology, it is necessary to use other ecological methods such as antimicrobial peptides, arginine, probiotics and natural products, etc. to enhance the effect of fluoride in preventing dental caries. The present article reviews the research progress on the ecological approaches for caries prevention in recent years.

Multimodal deep learning model for staging diabetic retinopathy based on ultra-widefield fluorescence angiography / 中华眼底病杂志

Objective:To apply the multi-modal deep learning model to automatically classify the ultra-widefield fluorescein angiography (UWFA) images of diabetic retinopathy (DR).Methods:A retrospective study. From 2015 to 2020, 798 images of 297 DR patients with 399 eyes who were admitted to Eye Center of Renmin Hospital of Wuhan University and were examined by UWFA were used as the training set and test set of the model. Among them, 119, 171, and 109 eyes had no retinopathy, non-proliferative DR (NPDR), and proliferative DR (PDR), respectively. Localization and assessment of fluorescein leakage and non-perfusion regions in early and late orthotopic images of UWFA in DR-affected eyes by jointly optimizing CycleGAN and a convolutional neural network (CNN) classifier, an image-level supervised deep learning model. The abnormal images with lesions were converted into normal images with lesions removed using the improved CycleGAN, and the difference images containing the lesion areas were obtained; the difference images were classified by the CNN classifier to obtain the prediction results. A five-fold cross-test was used to evaluate the classification accuracy of the model. Quantitative analysis of the marker area displayed by the differential images was performed to observe the correlation between the ischemia index and leakage index and the severity of DR.Results:The generated fake normal image basically removed all the lesion areas while retaining the normal vascular structure; the difference images intuitively revealed the distribution of biomarkers; the heat icon showed the leakage area, and the location was basically the same as the lesion area in the original image. The results of the five-fold cross-check showed that the average classification accuracy of the model was 0.983. Further quantitative analysis of the marker area showed that the ischemia index and leakage index were significantly positively correlated with the severity of DR ( β=6.088, 10.850; P<0.001). Conclusion:The constructed multimodal joint optimization model can accurately classify NPDR and PDR and precisely locate potential biomarkers.

Evolution Characteristics and Clinical Significance of Blood Separation in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis.@*METHODS@#The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed.@*RESULTS@#In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and β2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05).@*CONCLUSION@#Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.

Association between circulating CD39+CD8+ T cells pre-chemoradiotherapy and prognosis in patients with nasopharyngeal carcinoma / 中华医学杂志(英文版)

BACKGROUND@#The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC.@*METHODS@#We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS).@*RESULTS@#The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019).@*CONCLUSIONS@#CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop / 中国天然药物

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

Effect of Kangquan Recipe () on BAMBI Expression in Hypothalamic-Pituitary-Prostate in Rats with Benign Prostatic Hyperplasia / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Kangquan Recipe (, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH).@*METHODS@#Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively.@*RESULTS@#All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01).@*CONCLUSIONS@#KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH.

Protective effect of bisoprolol against hypoxia/reoxygenation injury of cardiac microvascular endothelial cells / 医学研究生学报

Objective　To observe the protective effect of bisoprolol against hypoxia/reoxygenation injury of cardiac microvascular endothelial cells and explore the mechanism.　Methods　Left ventricular of cardiac microvascular endothelial cells (CMECs) were isolated from 8-week-old male C57BL/6N mice. CMECs were randomized into four groups: control group, vehicle group, hypoxia/reoxygenation group (H/R group), hypoxia/reoxygenation + bisoprolol group. The level of cell proliferation, apoptosis, superoxide anion, Cleaved caspase-3 and Nox2 expression were measured in each group.　Results　Compared with control group, H/R group had lower cell proliferation, higher apoptotic level, more superoxide anion level and the expression of Cleaved caspase-3 and Nox2 (P < 0.05). Furthermore, bisoprolol reversed hypoxia/reoxygenation-induced the decreased cell proliferation, the increased apoptosis, superoxide anion level, Cleaved caspase-3 and Nox2 expression (P < 0.05).　Conclusion　Bisoprolol can protect CMECs against hypoxia/reoxygenation injury by reducing the expression of Nox 2 that decreases oxidative stress.

A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function / 世界急诊医学杂志（英文）

BACKGROUND@#Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury (SA-AKI) than among patients with sepsis. However, the pathogenesis underlying SA-AKI remains unclear. We hypothesized that the source of infection affects development of SA-AKI. We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI.@*METHODS@#Between January 2013 and January 2018, 113 patients with SA-AKI admitted to our Emergency Center were identified and divided into two groups: those with pulmonary infections and those with other sources of infection. For each patient, we collected data from admission until either discharge or death. We also recorded the clinical outcome after 90 days for the discharged patients.@*RESULTS@#The most common source of infection was the lung (52/113 cases, 46%), followed by gastrointestinal (GI) (25/113 cases, 22.1%) and urinary (22/113, 19.5%) sources. Our analysis showed that patients with SA-AKI had a significantly worse outcome (30/52 cases, P<0.001) and poorer kidney recovery (P=0.015) with pulmonary sources of infection than those infected by another source. Data also showed that patients not infected by a pulmonary source more likely experienced shock (28/61 cases, P=0.037).@*CONCLUSION@#This study demonstrated that the source of infection influenced the outcome of SA-AKI patients in an independent manner. Lung injury may influence renal function in an as yet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

Characteristics of Electroencephalogram Power Spectrum Network on Uninjured Side of Post-stroke Aphasia / 中国康复理论与实践

Objective:To clarify the characteristics of electroencephalogram (EEG) power spectrum network of right hemisphere in patients with post-stroke aphasia (PSA) after left brain damaged. Methods:From December, 2018 to June, 2019, twelve PSA patients with left hemisphere injury were recruited and twelve healthy adults were matched as control group. China Rehabilitation Research Center aphasia examination (CRRCAE) was used to evaluated the linguistic function, and the EEG was collected. The functional connection characteristics of Alpha and Theta power spectrum were compared, and the correlation with language items was analyzed. Results:In PSA patients, the functional connection enhanced in Alpha and Theta frequency bands of central area, frontal, parietal and frontal-parietal joint areas, and decreased in Theta frequency bands of temporoparietal, parietal-occipital area, frontal, fronta-parietal and frontal central areas. The enhancement of alpha frequency functional connection from the right parietal occipital region to the central region was significantly correlated to the reduction of the expression ability (P < 0.05), while the weakening of theta frequency functional connection between the right parietal occipital region and the forehead and the center of the forehead was significantly correlated to the ability of speaking, reading, copying, dictation and calculation (r = -0.676~-0.717, P < 0.05). Conclusion:EEG power spectrum network can reflect the reorganization of right brain function network, and the change of right frontal parietal central network function connection may be closely related to PSA language injury and recovery.

Stimulation Mode and Model of Word-picture Language Task in Functional Magnetic Resonance Imaging Test for Post-stroke Aphasia (review) / 中国康复理论与实践

The cognitive neuroscience researches about post-stroke aphasia provide the interpretation of all aspects of linguistics. The word-picture research paradigm can be applied to assess different types of aphasia, in various ways of stimulation modes and models. It is more helpful combining functional magenetic resonance imaging to research the mechanism of brain damage and recovery objectively. The interactive application of language task and imaging has also become a new direction in the mechanism study of aphasia.

Functional Connectivities in Right Hemisphere for Post-stroke Aphasia: Based on Dual Stream Model / 中国康复理论与实践

Objective:To study the effect of right brain language network in post-stroke aphasia (PSA) patients with left hemisphere injury. Methods:From December, 2018 to June, 2019, twelve PSA patients with left hemisphere injury, and twelve matched healthy controls were recruited to accept rest-state functional magnetic resonance imaging (f-MRI) scan, and analyzed the characteristics of right brain function network with Dual Stream model. Results:There were two patients lost. Compared with the controls, for dorsolateral lingual pathway, the functional connections increased from superior marginal gyrus to middle frontal gyrus and inferior frontal gyrus of trigone in the patients, while those decreased from posterior central gyrus to inferior frontal gyrus of insula. For ventral lingual pathway, the functional connection increased from angular gyrus to orbital inferior frontal gyrus. For ventral and dorsolateral double-pathway, the functional connections increased from temporal lobe to lenticular pallidum and angular gyrus, from caudate nucleus to inferior frontal gyrus of insula, from lenticular putamen nucleus to middle frontal gyrus and trigonometry, while it decreased from superior marginal gyrus and temporal lobe to inferior frontal gyrus of insula. There was a negative correlation between the functional connection from inferior frontal gyrus to lenticular putamen and repeating (r = -0.720, P < 0.05), between the functional connection from inferior frontal gyrus to the caudate nucleus to speaking and repeating (r < -0.696, P < 0.05). In terms of network index, there were significant differences between the patients and the controls in both local and global indexes for language key brain area in right brain (|t| > 2.143, P < 0.05). Conclusion:The functional network has reorganized in right hemisphere of PSA patients. However, the increase of connection between language critical cortex and subcortical nuclei may play a role in improvement of language function.

Rapid detection of trace Hg~(2+) in animal matrix by specific DNA electrochemical sensor / 中国中药杂志

A highly specific electrochemical biosensor based on T-Hg~(2+)-T structure for fast screening trace Hg~(2+) in complex animal drug matrix was constructed by cyclic voltammetry(CV) and differential pulse voltammetry(DPV). In the presence of Hg~(2+), it can be specifically binded to the T base of DNA sequence on the surface of modified gold electrode, which changes the conformation of DNA molecule and the electrochemical signal. The concentration ratio of EDC/NHS, the concentration ratio of FC-DNA and the reaction time of the biosensor were optimized by the index of sensitivity and reproducibility in CV. The results showed that the stability of the biosensor was good within 3 days(RSD≤1.3%), the difference between batches was low(RSD=4.7%), and the specificity of the biosensor was high in the presence of interfering ions(As~(3+), Cd~(2+), Cu~(2+), Pb~(2+), Zn~(2+) and Fe~(3+)). DPV results showed that the peak current signal value has a linear relationship with the lgC_((Hg)) over a concentration range from 0.1 nmol·L~(-1) to 1.0 μmol·L~(-1) with a detection limit of 0.066 nmol·L~(-1). Finally, the recovery rate tested in the matrix of animal medicine was satisfactory as 99.17%-101.3%, which can meet the needs of the determination of trace Hg~(2+) in the matrix of Bombyx Batryticatus, and provide a new idea for the rapid screening of trace heavy metals in the matrix of other types of complex traditional Chinese medicine.

Effect of Compound Danshen Dropping Pills on Heart of Diabetic Cardiomyopathy Rats by Regulating VEGF/TGF-β1 by miRNA-200b / 中国实验方剂学杂志

Objective: To study the protective effect and mechanism of compound Danshen dropping pills on the heart of rats with type 2 diabetic cardiomyopathy. Method: Seventy-five male SD rats were randomly divided into blank group (15 rats) and model group (60 rats). The model group was fed with high-sugar and high-fat diet, high-sugar and high-fat milk and sucrose water. Six weeks later, rats with foodborne obesity (body mass ≥ the mean body mass of blank control group + 2 times standard deviation) were selected and intraperitoneally injected with 1% streptozotocin (STZ)28 mg·kg-1. After 12 weeks, rats with fasting blood glucose ≥ 11.1 mmol·L-1 and polydipsia, diuresis, polyphagia and weight loss were randomly divided into model group, compound Danshen dropping pills group (0.5 g·kg-1) and metformin group (0.5 g·kg-1) and intervened for 12 weeks. At the end of the experiment, echocardiography was used to evaluate cardiac function. Blood samples were taken to determine the corresponding biochemical indicators of rats. Histopathological changes of myocardium were observed by hematoxylin-eosin (HE) and Masson staining. The ultrastructure of myocardium was observed under electron microscope. Western blot was used to detect the expressions of vascular endothelial growth factor (VEGF), transforming growth factor-beta 1 (TGF-β1) and type Ⅰ collagen (Collagen Ⅰ). Real-time fluorescence quantitative analysis (Real-time PCR) was used to detect the expression of miRNA-200b. Result: Compared with the blank group, the heart weight index (HMI), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterin(LDL-C) levels in the model group were significantly increased (PPPPPβ1 and Collagen I increased (PPPPPPβ1 and Collagen I was decreased (PPConclusion: Compound Danshen dropping pills may play a protective role in the heart of type 2 diabetic cardiomyopathy rats by lowering lipid, up-regulating the expression of miR-200b and inhibiting the expression levels of VEGF, TGF-β1 and Collagen I.

Clinical significance of next-generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia / 白血病·淋巴瘤

Objective@#To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR).@*Methods@#The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring.@*Results@#There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ2 = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2 = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ2 = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05).@*Conclusions@#Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.

Clinical significance of next‐generation sequencing technology for monitoring molecular minimal residual disease in acute myeloid leukemia / 白血病·淋巴瘤

Objective To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR). Methods The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring. Results There were 39 males (57.4% ) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%;χ 2＝ 9.249, P＝ 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2＝ 9.249, P＝ 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ 2 ＝ 4.122, P＝ 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05). Conclusions Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.