Effect of acetylalkannin from Arnebia euchroma on proliferation, migration, and invasion of human melanoma A375 cells / 中国中药杂志

This study aimed to explore the effect and mechanism of acetylalkannin from Arnebia euchroma on the proliferation, migration, and invasion of human melanoma A375 cells. A375 cells were divided into a blank group, and low-, medium-, and high-dose acetylalkannin groups(0.5, 1.0, and 2.0 μmol·L~(-1)). The MTT assay was used to detect cell proliferation. Cell scratch and transwell migration assays were used to detect cell migration ability, and the transwell invasion assay was used to detect cell invasion ability. Western blot was used to detect the protein expression of migration and invasion-related N-cadherin, vimentin, matrix metalloproteina-se-9(MMP-9), and Wnt/β-catenin pathway-related Wnt1, Axin2, glycogen synthase kinase-3β(GSK-3β), phosphorylated GSK-3β(p-GSK-3β), β-catenin, cell cycle protein D_1(cyclin D_1), and p21. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) was used to detect the mRNA expression of E-cadherin, matrix metalloproteinase-2(MMP-2), N-cadherin, vimentin, β-catenin, snail-1, and CD44. MTT results showed that the cell inhibition rates in the acetylalkannin groups significantly increased as compared with that in the blank group(P<0.01). The results of cell scratch and transwell assays showed that compared with the blank group, the acetylalkannin groups showed reduced cell migration and invasion, and migration and invasion rates(P<0.05, P<0.01) and weakened horizontal and vertical migration and invasion abilities. Western blot results showed that compared with the blank group, the high-dose acetylalkannin group showed increased expression of Axin2 protein(P<0.05), and decreased expression of N-cadherin, vimentin, MMP-9, Wnt1, p-GSK-3β, β-catenin, cyclin D_1, and p21 proteins(P<0.05, P<0.01). The expression of GSK-3β protein did not change significantly. PCR results showed that the overall trend of MMP-2, N-cadherin, vimentin, β-catenin, snail-1, and CD44 mRNA expression was down-regulated(P<0.01), and the expression of E-cadherin mRNA increased(P<0.01). Acetylalkannin can inhibit the proliferation, migration, and invasion of human melanoma A375 cells, and its mechanism of action may be related to the regulation of Wnt/β-catenin signaling pathway.

Mechanism of Berberis atrocarpa anthocyanin against Alzheimer's disease based on network pharmacology and experimental verification / 中国中药杂志

This study aimed to explore the potential mechanism of Berberis atrocarpa Schneid. anthocyanin against Alzheimer's disease(AD) based on network pharmacology, molecular docking technology, and in vitro experiments. Databases were used to screen out the potential targets of the active components of B. atrocarpa and the targets related to AD. STRING database and Cytoscape 3.9.0 were adopted to construct a protein-protein interaction(PPI) network and carry out topological analysis of the common targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed on the target using the DAVID 6.8 database. Molecular docking was conducted to the active components and targets related to the nuclear factor kappa B(NF-κB)/Toll-like receptor 4(TLR4) pathway. Finally, lipopolysaccharide(LPS) was used to induce BV2 cells to establish the model of AD neuroinflammation for in vitro experimental validation. In this study, 426 potential targets of active components of B. atrocarpa and 329 drug-disease common targets were obtained, and 14 key targets were screened out by PPI network. A total of 623 items and 112 items were obtained by GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking results showed that NF-κB, NF-κB inhibitor(IκB), TLR4, and myeloid differentiation primary response 88(MyD88) had good binding abilities to the active components, and malvidin-3-O-glucoside had the strongest binding ability. Compared with the model group, the concentration of nitric oxide(NO) decreased at different doses of malvidin-3-O-glucoside without affecting the cell survival rate. Meanwhile, malvidin-3-O-glucoside down-regulated the protein expressions of NF-κB, IκB, TLR4, and MyD88. This study uses network pharmacology and experimental verification to preliminarily reveal that B. atrocarpa anthocyanin can inhibit LPS-induced neuroinflammation by regulating the NF-κB/TLR4 signaling pathway, thereby achieving the effect against AD, which provides a theoretical basis for the study of its pharmacodynamic material basis and mechanism.

Risk factors associated with malignant vasovagal syncope in children / 中华儿科杂志

Objective: To analyze the clinical characteristics and risk factors of malignant vasovagal syncope (VVS) in children. Methods: This was a case-control study. The data of 368 VVS patients who were treated in the Department of Cardiology, Children's Hospital, Capital Institute of Pediatrics from June 2017 to December 2021 was collected and analyzed. They were divided into malignant VVS group and non-malignant VVS group according to the presence of sinus arrest, and then their demographic characteristics were compared. The children with malignant VVS and complete clinical information were recruited into the case group and were matched by age and sex (1∶4 ratio) with non-malignant VVS patients during the same period.Their clinical characteristics and lab tests were compared. Independent sample t test, Mann Whitney U or χ2 test was used for comparison between groups.Logistic regression was used to analyze the risk factors for malignant VVS in children. Results: Eleven malignant VVS and 342 non-malignant VVS met the inclusion and exclusion critera. Eleven malignant VVS and 44 non-malignant children were recruited in the case-control study. Ten patients of the 11 malignant VVS had a cardiac arrest occurring at 35 (28, 35) minutes of the head-up tilt test, and the duration of sinus arrest was (9±5) s. One patient had syncope occurring while waiting for drawing blood, and the duration of sinus arrest was 3.4 s. The children with malignant vasovagal syncope were younger than non-malignant VVS patients (9 (7, 10) vs. 12 (10, 14) years old, P<0.05), and had higher mean corpuscular hemoglobin concentration (MCHC) and standard deviation of the mean cardiac cycle over 5-minute period within 24 hours ((347±9) vs. (340±8) g/L, (124±9) vs. (113±28) ms, both P<0.05). Logistic regression analysis showed that MCHC was an independent risk factor for malignant VVS in pediatric patients (OR=1.13, 95%CI 1.02-1.26, P=0.024). Conclusions: The onset age of malignant VVS was younger, with no other special clinical manifestations. MCHC was an independent risk factor for malignant VVS.

A Campylobacteriosis Outbreak Caused by One Asymptomatic Food Handler Carrier / 生物医学与环境科学（英文）

In August 2021, three students with diarrhea from the same school visited a local hospital in the S district of Beijing. An epidemic investigation showed that there were more students with diarrhea in the same school and they had one meal together. Campylobacter jejuni was isolated from both patients with diarrhea and asymptomatic food handlers; however, the latter also carried Campylobacter coli. Phylogenomic analysis showed that there was a campylobacteriosis outbreak among the students, and the asymptomatic food handler may have been the source of the infection. Routine inspection and surveillance for Campylobacter is needed for the food producing staff, particularly those cooking in the cafeteria in schools or other public food services.

Protective Mechanism of Lavender Against Skin Photodamage Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo predict the active ingredients and mechanism of action of lavender in protecting skin photodamage based on network pharmacology and molecular docking technology，and further verify possible signal pathways via animal experiments. MethodThe active ingredients and potential targets of lavender were obtained by SwissTargetPrediction，PharmMapper， and literature. Skin photodamage-related targets were searched from GeneCards，Online Mendelian Inheritance in Man （OMIM），DrugBank and DisGeNET databases. After common targets of the two were screened out，STRING was adopted to analyze the protein-protein interaction （PPI） network，where topological analysis and core target screening were performed by CytoNCA plug-in of Cytoscape 3.8.2. Based on DAVID， gene ontology （GO） annotations and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were carried out among the intersection targets， and the active ingredients of lavender and the signal pathway proteins were selected and verified via molecular docking with AutoDock vina 1.1.2. Finally， mouse photodamage model was established by UVB irradiating the bare skin of mouse back， and the skin condition was observed by naked eyes. Hematoxylin-eosin （HE） and picric acid-acid fuchsin staining （Van Gieson， VG） were used to observe the pathological changes of mouse skin tissues. Western blot was employed to detect the protein expression in mouse skin tissues to further validate the key signal pathways. ResultIn this study，6 active ingredients of lavender，526 potential targets，2 688 disease-related targets，and 258 intersection targets were screened out， and 16 core targets were obtained by PPI network. Additionally， 113 related signal pathways were obtained by KEGG pathway analysis，among which phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） pathway and nuclear transcription factor-κB （NF-κB） signal pathway might play a key role in skin photodamage protection by lavender. Molecular docking showed that the active ingredients and the signal pathway proteins were well docked. Animal experiments indicated that the total flavonoids of lavender improved the appearance and histopathological condition of mouse skin， reduced the relative expression levels of phosphorylated（p）-PI3K，p-Akt，and B cell lymphoma 2 （Bcl-2） proteins （P<0.05，P<0.01）， and increased relative expression level of Bcl-2-associated X protein（Bax） （P<0.05）. ConclusionLavender exerts synergistic effect in resisting skin photodamage，with the characteristics of multi-components，multi-targets，and multi-pathways， which provides a basis for subsequent in-depth research on the complex mechanism of lavender against skin photodamage.

Mechanism of Arnebia euchroma Against Melanoma： An Exploration Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo preliminarily predict the active components， action targets， and signaling pathways of Arnebia euchroma in the treatment of melanoma based on network pharmacology and molecular docking， and to verify its possible mechanism of action in in vitro experiments. MethodThe active components and related targets of A. euchroma were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）SwissTargetPrediction and literature， and the targets related to melanoma from the GeneCards， Online Mendelian Inheritance in Man （OMIM）， and Comparative Toxicogenomics Database （CTD）. Following the construction of the protein-protein interaction （PPI） network of active components and related targets of A. euchroma and melanoma-related targets using STRING， Cytoscape 3.8.2 was used for screening and analyzing the nodes in the network of A. euchroma against melanoma. The intersections were subjected to gene ontology （GO） and Kyoto encyclopedia of genes and genomes （KEGG） enrichment analysis using DAVID 6.8. Acetyl alkannin， the active component in A. euchroma， was docked to the target by AutoDock Vina 1.1.2. The in vitro experiments were then carried out to verify the anti-melanoma effect of A. euchroma. ResultA total of 271 common targets of A. euchroma and melanoma were harvested， among which 23 were key targets， including matrix metalloproteinase-9 （MMP-9） and Janus kinase 2 （JAK2）. As revealed by KEGG enrichment analysis， A. euchroma mainly acted on Janus kinase/signal transduction and activator of transcription （JAK/STAT）， tyrosine kinase receptor （ErbB）， and vascular endothelial growth factor （VEGF） signaling pathways to resist melanoma. According to molecular docking， acetyl alkannin exhibited a good docking activity with JAK2， STAT3， VEGF， MMP-9， and E-cadherin receptors. The results of Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） showed that acetyl alkannin at different doses inhibited the protein and gene expression of JAK2， STAT3， VEGF， MMP-9， and E-cadherin in A375 cells （P<0.05）. ConclusionA. euchroma alleviates melanoma via multiple targets and multiple pathways， and it may exert the therapeutic effects by affecting the expression of such key target proteins as JAK2， STAT3， VEGF， MMP-9， and E-cadherin and inhibiting the invasion and metastasis of melanoma cells. This study has provided an experimental basis for the treatment of tumor with A. euchroma.

Overview of systematic reviews on Shenmai Injection in prevention and treatment of diseases / 中国中药杂志

To summarize and evaluate the efficacy and safety of Shenmai Injection in the treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy, so as to provide supportive evidences for clinical rational use of Shenmai Injection. By searching literatures about studies on the systematic reviews on Shenmai Injection in treatment of viral myocarditis, shock, pulmonary heart disease, coronary heart disease, neutropenia and tumor chemotherapy from the main Chinese and English databases. Primary efficacy and safety outcome measures were selected for comparative analysis and summary, and the appraisal tool of AMSTAR 2 was used to evaluate the included studies.A total of 36 systematic reviews(published from 2005 to 2020) were included, involving viral myocarditis, shock, pulmonary heart disease, malignant tumor and coronary heart disease. The number of cases included in each type of the above diseases was 3 840, 2 484, 12 702, 28 036 and 27 082, respectively. The comparison results showed that, Shenmai Injection combined with conventional/western medicine treatment groups had better efficacy than conventional/western medicine groups alone in the prevention and treatment of the above five diseases. The main adverse reactions of Shenmai Injection reported in the included studies were facial flushing, rash, palpitation, etc., but the incidence was low and the general symptoms were mild, so no special treatment was needed. Therefore, the application of Shenmai Injection on the basis of conventional treatment or western medicine treatment had better prevention and treatment efficacy of the diseases. It was suggested that more multi-center and larger sample-size randomized controlled trials should be carried out in the future, and the relevant reporting standards should be strictly followed in systematic reviews, so as to improve the scientificity and transparency of the study.

Investigation and validation of magnetic resonance white matter atlas for 0 to 2 years old infants / 北京大学学报(医学版)

OBJECTIVE@#To construct and verify a standard template of white matter based on Chinese normal 0 to 2 years old infants by using nonlinear high registration accuracy of non-rigid diffeomorphism paradigm (large deformation diffeomorphic metric mapping, LDDMM).@*METHODS@#Full-term spontaneous labor children without maternal pregnancy disease (hypertension, diabetes, etc.), intrauterine hypoxia and ischemia, head trauma, intracranial infection, intracranial surgery history, family history of mental disorders were selected. Diffusion tensor imaging (DTI) data from the 120 normal Chinese infants under 2 years old were acquired after excluding the existence of neurological diseases revealed by neurologists, radiologists and Gesell Developmental Scale. All the data were divided into six groups including group A: 1 day to 1.5 months, group B: 1.5 to 4.5 months, group C: 4.5 to 9.0 months, group D: 9 to 15 months, group E: 15 to 21 months, and group F: 21 to 24 months. Data pre-processing, normalizing, tensor fitting and calculation of all the images were performed by using MRlcron, DtiStudio, DiffeoMap and SPM software package combined with LDDMM image registration method based on the selected single template of each group. And the average templates of each group were constructed by MATLAB software platform. The set of templates included fractional anisotropy figure (FA), color map, T1 weighted image, b0 image and the mean of all DWfs figures.@*RESULTS@#The templates of FA, T1, b0, DWfs and color map for the normal brain magnetic resonance white matter development of the Chinese infants aged 0 to 2 years were successfully established with the subjective scores exceeding 2 points. The objective evaluation root mean squared error was controlled below 0.19, and the cubic chart of brain alternation trend for the children aged 0 to 2 years was consistent with previous literature.@*CONCLUSION@#Constructing a standard template of white matter based on Chinese normal infants, by using nonlinear high registration accuracy of non-rigid diffeomorphism paradigm provides not only a foundation of further research on brain development, mechanism and treatment of pediatric diseases associated with brain, but also objective and fair imaging information for medical education and research.

Effects of video teaching combined with empowerment theory on rehabilitation training in elderly patients undergoing total knee arthroplasty / 中国实用护理杂志

Objective:To investigate the effects of video teaching combined with empowerment theory on activation of rehabilitation training and prognosis in elderly patients undergoing total knee arthroplasty (TKA).Methods:A total of 174 elderly TKA patients from September 2017 to September 2018 were selected and assigned into 2 groups (87 cases each group) by random number table, the control group was given routine nursing, on the basis of the control group, the observation group was given rehabilitation training instruction based on video teaching and empowerment theory. The time of intervention was 3 months. Patient Activation Measure(PAM) was used to assess the activation of rehabilitation training of patients in the 2 groups, Hospital for Special Surgery knee Score (HSS) was used to assess the patients′ prognosis.Results:After intervention, the scores of cognitive, skill, action, belief dimensions and the total score of the observation group were (11.24±1.49), (31.94±3.59), (22.59±3.02), (16.82±2.34), (82.59±6.29) significantly higher than (9.42±1.47), (29.48±4.29), (20.24±3.31), (14.29±2.57), (73.43±5.63) of the control group, the difference was significant ( t value was 4.102-10.121, all P <0.01). After intervention, the HSS scores of the observation group was (79.24±3.78), which was significantly higher than (72.45±3.13) of the control group ( t value was 12.905, P<0.01). Conclusions:The rehabilitation training instruction based on video teaching combined with empowerment theory can improve activation of rehabilitation training and function recovery of knee joint in elderly TKA patients.

Intermedin in Paraventricular Nucleus Attenuates Sympathoexcitation and Decreases TLR4-Mediated Sympathetic Activation via Adrenomedullin Receptors in Rats with Obesity-Related Hypertension / 神经科学通报·英文版

Intermedin/adrenomedullin-2 (IMD/AM2), a member of the calcitonin gene-related peptide/AM family, plays an important role in protecting the cardiovascular system. However, its role in the enhanced sympathoexcitation in obesity-related hypertension is unknown. In this study, we investigated the effects of IMD in the paraventricular nucleus (PVN) of the hypothalamus on sympathetic nerve activity (SNA), and lipopolysaccharide (LPS)-induced sympathetic activation in obesity-related hypertensive (OH) rats induced by a high-fat diet for 12 weeks. Acute experiments were performed under anesthesia. The dynamic alterations of sympathetic outflow were evaluated as changes in renal SNA and mean arterial pressure (MAP) in response to specific drugs. Male rats were fed a control diet (12% kcal as fat) or a high-fat diet (42% kcal as fat) for 12 weeks to induce OH. The results showed that IMD protein in the PVN was downregulated, but Toll-like receptor 4 (TLR4) and plasma norepinephrine (NE, indicating sympathetic hyperactivity) levels, and systolic blood pressure were increased in OH rats. LPS (0.5 µg/50 nL)-induced enhancement of renal SNA and MAP was greater in OH rats than in obese or control rats. Bilateral PVN microinjection of IMD (50 pmol) caused greater decreases in renal SNA and MAP in OH rats than in control rats, and inhibited LPS-induced sympathetic activation, and these were effectively prevented in OH rats by pretreatment with the AM receptor antagonist AM22-52. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) inhibitor U0126 in the PVN partially reversed the LPS-induced enhancement of SNA. However, IMD in the PVN decreased the LPS-induced ERK activation, which was also effectively prevented by AM22-52. Chronic IMD administration resulted in significant reductions in the plasma NE level and blood pressure in OH rats. Moreover, IMD lowered the TLR4 protein expression and ERK activation in the PVN, and decreased the LPS-induced sympathetic overactivity. These results indicate that IMD in the PVN attenuates SNA and hypertension, and decreases the ERK activation implicated in the LPS-induced enhancement of SNA in OH rats, and this is mediated by AM receptors.

Effect of acetaminophen on thyroxine relative genes of zebrafish embryos / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of N-acetyl-p-aminophenol (APAP) on zebrafish pigments and thyroxine related genes. METHODS Well-developed zebrafish embryos were exposed to APAP 0, 2, 4 and 8 mmohL-1 from 4 h post fertilization (hpf) and observed at 24, 48, 72 and 96 hpf, respectively, each with 3 replicates. Image J was used to detect the change of pericardial edema of zebrafish. The conentrations of triiodothyronine and tetraiodothyronine were determined by ELISA. mRNA of thyroxine relative genes TPO, Trh, Dio2, Dio3, Thru and Thrf} was detected by fluorescent quantitative PCR. RESULTS At 72 hpf, compared with control group, the hatching rate and pigmentation accumulation decreased in APAP 8 mmol • L-1 group (FcO.OI), but the pericardial area was increased (P<0.01). The conentrations of tetraiodothyronine and triiodothyronine were decreased in APAP 8 mmol • L-1 group (P<0.05). Quantitative PCR results showed that APAP down-regulated mRNA levels of TPO, Trh and Thrfi in APAP 8 mmol-L-1 exposure group (P<0.05). There was no statistically significant difference in the expression of other genes. CONCLUSION The decrease in pigmentation and hatching rate caused by APAP may be related to the decreased expressions of thyroid hormone-related genes.

Early cardiac injury in patients with obstructive sleep apnea / 中国应用生理学杂志

OBJECTIVE@#To evaluate the early cardiac injury caused by obstructive sleep apnea (OSA) before the development of cardiovascular symptoms of OSA.@*METHODS@#Ninety-two patients without any known cardiovascular disorders who underwent polysomnography (PSG) were enrolled in the study. Subjects were divided into mild, moderate, and severe OSA groups by their apnea hypopnea index (AHI), and 25 healthy individuals were identified as controls. After PSG examination, fasting blood samples for the evaluation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and heart-type fatty acid binding protein (h-FABP) were collected in the morning, and left ventricular(LV) functions were assessed by using echocardiographic methods. Thirty moderate and severe OSA patients were treated with continuous positive airway pressure respectively (CPAP).@*RESULTS@#The levels of h-FABP and NT-proBNP were obviously higher in all OSA groups than those in the control group (<0.01), and were positively correlated with AHI (<0.01). The Em/Am values of all OSA groups and E/A values of the moderate and severe OSA groups were significantly reduced (<0.01). The difference in Em/Am values among the groups was statistically significant (<0.01). Compared with those before treatment, h-FABP and NT-BNP levels in serum of OSA patients after CPAP treatment were significantly reduced (<0.01), and Em/Am and E/A values were significantly increased (<0.01).@*CONCLUSIONS@#Left ventricular diastolic dysfunction and early myocardial microtrauma are major manifestations of early heart damage in patients with OSA. CPAP therapy could significantly improve early cardiac damage in OSA patients.

Rapid analysis of chemical components in Zizyphi Spinosae Semen by UHPLC-LTQ-Orbitrap-MS / 中国中药杂志

This study aimed to analyze the chemical components of Zizyphi Spinosae Semen by using ultra high performance liquid chromatography-linear ion trap/orbitrap high resolution mass spectrometry (UHPLC-LTQ-Orbitrap-MS). The chromatographic separation of the components was achieved on a Waters Acquity UPLC BEH-C₁₈ column (2.1 mm×50 mm, 1.7 μm), with acetonitrile-water (0.1% formic acid) as mobile phase at a flow rate of 0.3 mL·min⁻¹. Electrospray ionization-(ESI) source was applied and operated in negative ion mode. The parent ion list (PIL)-MS₂ and high energy collision dissociation (HCD) techniques were used to identify triterpene saponins in Zizyphi Spinosae Semen. Through analysis of the mass spectrometry data and literature data, 24 compounds and 4 unknown compounds were identified and inferred, including 21 flavonoids, 5 saponins and 2 triterpenoids. The use of UHPLC-LTQ-Orbitrap-MS technology provide an efficient and rapid analytical method for the qualitative analysis and quality control of the chemical components in Zizyphi Spinosae Semen. It can also provide reference data for the research on the material basis of pharmacodynamics and the resources development and utilization.

Cloning and functional identification of a new NADPH-cytochrome P450 reductase in Andrographis paniculata / 中国中药杂志

Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculata，with a variety of pharmacological activity，widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this study，the coding sequence of A. paniculata CPR was screened and cloned by homologous alignment，named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression. After isolation and purification，the enzyme activity was identified . The results showed that ApCPR4 could reduce the cytochrome c and ferricyanide in NADPH-dependent manner. In order to verify its function，ApCPR4 and CYP76AH1 were co-transformed into yeast engineering bacteria. The results showed that ApCPR4 could help CYP76AH1 catalyze the formation of rustols in yeast. Real-time quantitative PCR results showed that the expression of ApCPR4 increased gradually in leaves treated with methyl jasmonate (MeJA). The expression pattern was consistent with the trend of induction and accumulation of andrographolide by MeJA，suggesting that ApCPR4 was associated with biosynthesis of andrographolide.

Therapeutic effects of number of BCD (bortezomib, cyclophosphamide, dexametha-sone) chemotherapy courses on newly diagnosed multiple myeloma / 中国肿瘤临床

Objective: To analyze the treatment effect of the number of bortezomib, cyclophosphamide, and dexamethasone (BCD) chemotherapy courses for newly diagnosed multiple myeloma. Methods: We retrospectively analyzed data of patients with newly diagnosed multiple myeloma from January 2014 to July 2016 in Peking University People's Hospital. All 70 patients received two or more courses of BCD chemotherapy. Patients with extramedullary disease or amyloidosis were excluded. Patients completed their follow-up, and the treatment effects were studied in those who only received two, four, and six chemotherapy courses. Results: Among the 70 patients, the ratio of male to female was 36 :34, the median age of disease onset was 58.4 y (range: 33-81 y), and the number of patients with ISS stagesⅠ,Ⅱ, and Ⅲ was 16, 18, and 36, respectively. The number of patients who received two, four, and six chemotherapy courses was 14, 20, and 36, respectively. The percentages of complete remission, equal or more than very good partial remission, equal or more than partial remission for patients who received two courses were 14.28%, 42.86%, and 71.42%, those for four courses were 30.00%, 60.00%, 80.00%, and those for six courses were 38.89%, 75.00%, 83.33%, respectively. During the median 15.37 (range: 2-32) months follow up, the estimated progression free survival (PFS) was 21.96 months (95% CI: 19.26-24.70). No statistically significant difference for PFS was observed among the three groups (P=0.700). Conclusions: For the BCD chemotherapy regimen, the maximum therapeutic effect occurred after four or more courses. As the number of induction courses after four chemotherapies increased, the depth of disease relief increased but overall remission did not show substantial improvement. Therefore, four or more BCD chemotherapies can be used for the first line of induction therapy.

The value of fecal calprotectin in predicting endoscopic activity and severity of ulcerative colitis / 医学研究生学报

Objective The invasive colonoscopy is an important method for evaluating the severity of intestine and the muco-sal healing in ulcerative colitis(UC)patients. The aim of this study was to investigate the advantage of fecal calprotectin(FC)in diagnosing UC endoscopic activity and severity and analyze the FC correlation with endoscopic scores. Methods A total of 70 UC in-patients in our hospital from January 2016 to September 2017 were retrospectively analyzed and categorized into endoscopic remission UC [mucosal healing(n=12),mucosal lesion(n=10)]and endoscopic active UC[mild-moderate(n=30)and severe(n=18)]according to UC Endoscopic Index of Severity(UCEIS).The ROC curve was used to analyze the predictive efficacy of each laboratory indicator to identify endoscopically active UC and severe UC and evaluate the correlation of UCEIS with all these indicators. Results In UC pa-tients,the levels of FC[828.5(416.6,1079.7)μg/g],PCT[0.03(0.02,0.06)μg/L]and IL-6[13.4(7.32,21.45)ng/L]were sig-nificantly higher in endoscopically active UC than those[43.4(9.4,91.4)μg/g、0.02(0.02,0.03)μg/L、5.82(5.14,6.73)ng/L]in remission and the levels of CRP,ESR,WBC count and PLT count also increased significantly,while HB and ALB levels were signifi-cantly lower than those in remission(all P value<0.001).In endoscopically active UC patients,the levels of FC[1117.1(916.5,1492. 4)μg/g]and IL-6[18.18(12.72,33.25)ng/L]were significantly higher than those of mild-moderate UC[622.4(218.7,924.2)μg/g,8.27(7.08,16.60)ng/L](P<0.05)and the levels of CRP,ESR and WBC also increased significantly(P<0.05),while the ALB showed a significant lower level(P=0.002). When FC>175.6 μg/g,it was of higher accuracy in diagnosing UC endoscopic activity and the sensitivity,specificity,positive predictive value and negative predictive value were respectively 87.50%,90.91%,95.45%and 76.92%;When FC>781.1 μg/g,it was of higher accuracy in diagnosing severe UC and the sensitivity,specificity,positive predic-tive value and negative predictive value were respectively 88.89%,73.33%,66.66% and 91.66%. The levels of FC,PCT,IL-6, CRP,ESR,WBC and PLT all presented positive correlation with UCEIS(P<0.001),while the HB and ALB levels showed a negative correlation with UCEIS(P<0.001). Conclusion FC is a good indicator to judge UC endoscopic activity and severe UC. FC can be used as a non-invasive and surrogate marker for endoscopy to monitor UC disease activity in clinical practice.

miR-548a-3p targeting MMP-2 inhibits the metastasis and invasion of gastric cancer cells / 实用医学杂志

Objective To study the mechanism of miR-548a-3p targeting MMP-2 inhibits the metastasis and invasion of gastric cancer cells.Methods Bioinformatics were used to search those miRNAs targeting MMP-2.The level of miR-548a-3p in gastric cancer tissues were detected by qRT-PCR and the expression of MMP-2 were detected by Western blot.The level of miR-548a-3p in three reconstructed gastric cancer cell lines were detected by qRT-PCR and the expression of MMP-2 were detected by Western blot.miR-548a-3p targeting the 3'-UTR of MMP-2 were detected by Luciferase reporter assay detected.And the changes of ability of metastasis and invasion were examined by Transwell experiment before and after transfection.Results There were high expression of miR217 and low expression of MMP-2 in human poorly differentiated gastric cancer cell line BGC-823.There were low expression of miR-548a-3p and high expression of MMP-2 in human middle and high differentiated gastric cancer cell line MKN-28 and SGC-7901 (P ＜ 0.05).The result of Luciferase reporter assay showed that miR-548a-3p can targeting the 3’-UTR of MMP-2.There were high expression of miR-548a-3p and low expression of MMP-2 in MKN28-miR-548a-3p mimics.There were low expression of miR-548a-3p and high expression of MMP-2 in others reconstructed three cell lines.There were smaller invaded cells in SGC-7901-miR-217 mimics than in others three cell lines (P ＜ 0.05).Conclusions miR-548a-3p can target the 3'-UTR of MMP-2 and down regulate its expression and inhibit the ability of invasion of gastric cancer cells.

Study on the peripheral blood T lymphocyte subsets and natural killer cell in children with asthmatic pneumonia / 国际检验医学杂志

Objective To explore the expression and significance of peripheral blood T lymphocyte subgroups and natural killer cell in children with asthmatic pneumonia.Methods From 2013 to 2016,asthmatic children with pneumonia were erolled in the study as asthmatic pneumonia group(36 cases) and 36 cases medical health children as control group at the same time in Zhongshan City people′s hospital.Flow cytometry was used to test analysis of two groups of T lymphocyte subsets and natural killer cell in serum and the expression of CD28,CD56,using ROC curve analysis results.Results Asthmatic pneumonia group compared with control group,the difference of CD3+ and CD3+CD8+,CD28+,CD8+CD28+,CD8+CD28-,CD3-CD16+CD56+ and CD3+CD16+CD56+,CD3+CD4+/CD3+ CD8+ was statistically significant(P<0.05).According to the results of flow parameters have higher sensitivity by the ROC curve statistics.Conclusion Asthmatic pneumonia children have immune dysfunction,immune function changes associate with asthmatic,which is of great clinical significance to carry out immune function detection for children with asthmatic pneumonia.

Overexpression and isolation of CYP76AH1 in Salvia miltiorrhiza hairy roots / 中国中药杂志

Protein complexes are involved in the synthesis of multiple secondary metabolites in plants, and their separation is essential to elucidate plant secondary metabolism and improve in vitro catalytic efficiency. In this study, the transgenic hairy roots of CYP76AH1, a key enzyme of tanshinone synthesis pathway, was constructed and the transgenic hairy roots of Danshen overexpressing CYP76AH1 protein were screened by Western blotting and used as a tissue culture material for the subsequent extraction of protein complex in tanshinone synthesis pathway. By optimizing the type and concentration of the detergent in the protein extraction buffer, the buffer containing 0.5% Triton X-100 was selected as the best extraction buffer, and a relatively large amount of soluble CYP76AH1 protein was isolated. This study lays the foundation for the further separation and purification of protein complexes interacting with CYP76AH1, and provides the idea for deep analysis of tanshinone metabolic pathway.

Correlation between Simplified Endoscopic Score for Crohn's Disease (SES-CD) and Clinical and Laboratory Markers in Patients with Crohn's Disease / 胃肠病学

Endoscopic activity has been used as an endpoint in treatment of Crohn's disease (CD).Simplified Endoscopic Score for Crohn's Disease (SES-CD) is a simple and easy-to-use endoscopic scoring system for CD, however, studies evaluating the correlation between SES-CD and noninvasive inflammatory markers are scarce.Aims: To investigate the correlation between SES-CD and clinical and laboratory inflammatory markers for identifying a noninvasive surrogate marker for endoscopic activity of CD.Methods: Forty-two patients with CD were enrolled for detecting laboratory inflammatory markers including leukocyte and platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin (Alb) and fecal calprotectin (FC);SES-CD and Crohn' disease activity index (CDAI) were assessed.Predictive performance of these markers for endoscopic activity of CD was analyzed by ROC curve, and the correlation of SES-CD with all these markers was evaluated.Results: The platelet count, CRP, ESR, FC and SES-CD were significantly higher in active CD than in inactive CD, while Hb and Alb were significantly lower in active CD (P all <0.05).In all the noninvasive markers, only CDAI and FC had an area under the curve (AUC) greater than 0.9 for predicting CD endoscopic activity.Taken 150 as the cut-off value of CDAI and 50 μg/g (the upper limit of normal, ULN) as the cut-off value of FC, the sensitivity of CDAI and FC were 58.8% and 100%, and the specificity were 100% and 60.0%, respectively.SES-CD had moderate correlation with CDAI, platelet count, CRP, ESR, Alb and FC, respectively (P all <0.05).Conclusions: SES-CD is correlated moderately with the clinical and laboratory inflammatory markers, however, when taken the ULN as cut-off value the conventional inflammatory markers such as CDAI, CRP and ESR are hard to predict sensitively and accurately the endoscopic activity of CD;while FC has fairly high accuracy and sensitivity and can be used as a noninvasive surrogate marker for evaluating endoscopic activity of CD.