Effective substances and mechanism of Yishen Guluo Mixture in treatment of chronic glomerulonephritis based on metabolomics and serum pharmacochemistry / 中国中药杂志

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children / 中华儿科杂志

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

Efficacy of intravascular ultrasound versus coronary angiographic guided drug-eluting stent implantation in the treatment of left main coronary artery disease: a meta-analysis / 中华心血管病杂志

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.

Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Radiomics based on biparametric MRI for the detection of significant residual prostate cancer after androgen deprivation therapy: using whole-mount histopathology as reference standard / 亚洲男科学杂志(英文版)

We aimed to study radiomics approach based on biparametric magnetic resonance imaging (MRI) for determining significant residual cancer after androgen deprivation therapy (ADT). Ninety-two post-ADT prostate cancer patients underwent MRI before prostatectomy (62 with significant residual disease and 30 with complete response or minimum residual disease [CR/MRD]). Totally, 100 significant residual, 52 CR/MRD lesions, and 70 benign tissues were selected according to pathology. First, 381 radiomics features were extracted from T2-weighted imaging, diffusion-weighted imaging, and apparent diffusion coefficient (ADC) maps. Optimal features were selected using a support vector machine with a recursive feature elimination algorithm (SVM-RFE). Then, ADC values of significant residual, CR/MRD lesions, and benign tissues were compared by one-way analysis of variance. Logistic regression was used to construct models with SVM features to differentiate between each pair of tissues. Third, the efficiencies of ADC value and radiomics models for differentiating the three tissues were assessed by area under receiver operating characteristic curve (AUC). The ADC value (mean ± standard deviation [s.d.]) of significant residual lesions ([1.10 ± 0.02] × 10-3 mm2 s-1) was significantly lower than that of CR/MRD ([1.17 ± 0.02] × 10-3 mm2 s-1), which was significantly lower than that of benign tissues ([1.30 ± 0.02] × 10-3 mm2 s-1; both P < 0.05). The SVM feature models were comparable to ADC value in distinguishing CR/MRD from benign tissue (AUC: 0.766 vs 0.792) and distinguishing residual from benign tissue (AUC: 0.825 vs 0.835) (both P > 0.05), but superior to ADC value in differentiating significant residual from CR/MRD (AUC: 0.748 vs 0.558; P = 0.041). Radiomics approach with biparametric MRI could promote the detection of significant residual prostate cancer after ADT.

Selection of statistical methods for estimating the association between exposure factors and rare outcomes based on cohort studies / 中华流行病学杂志

Odds ratio (OR) and relative risk (RR) are the most commonly used statistical indicators for the estimation of the association between exposure and outcome. In the cohort study with rare outcomes, the estimated OR approximately equals RR, but RR seems more interpretable. The study aims to explore the difference between OR and RR estimated by different multivariate analyses to provide reference for the selection of more appropriate multivariate regression methods and reporting indicators for estimating the association between exposure and rare outcome in cohort studies. This case study used the data from China birth cohort study. Modes of conception and congenital disabilities were regarded as exposure and outcome, respectively. Maternal age, family history of congenital disabilities with clear evidence were included as covariates. Logistic regression, log-binomial regression, and Poisson regression were used to estimate the OR and RR, respectively. Then, OR, RR, and their 95%CI estimated by three regression models were compared. The OR estimated by logistic regression was approximately equal to the RR estimated by log-binomial regression or Poisson regression. However, the RR estimated by log-binomial regression or Poisson regression was closer to 1.00, with a narrower 95%CI. Log-binomial regression or Poisson regression might have non convergence or over dispersion problems. It is recommended to report the RR obtained by log-binomial regression or Poisson regression in the cohort study with rare outcomes if applicable.

Urine metabolomics study of hepatocellular carcinoma / 中华肿瘤杂志

Objective: To investigate the urinary small molecular metabolites and their metabolic characteristics of patients with hepatocellular carcinoma (HCC). Methods: High throughput ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to detect the small molecular metabolites in urine of healthy control (n=10), patients with hepatic hemangioma (n=10) and patients with HCC (n=10). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA), hierarchical cluster analysis of multivariate analysis and univariate analysis were used to analyze the differential metabolites of the three groups. Results: The metabolic profiles of the three groups showed that the total of 381 differential metabolites were identified and divided into 96 up-regulated metabolites and 285 down-regulated metabolites. There were 55 urinary metabolites specifically related to HCC. Twenty-one of them were significantly up-regulated, including Acetyl-DL-Leucine, Ala Asp, HoPhe-Gly-OH, while 34 were significantly down-regulated, including Selenocystathionine, Met Trp Met Cys, Valsartan acid and so on. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the differential metabolites were mainly enriched in glutamine/glutamate metabolism, lysine biosynthesis, tricarboxylic acid cycle and purine metabolism. Conclusions: The occurrence of HCC is accompanied by the abnormalities of multiple metabolites and metabolic pathways. The analysis of the characteristic metabolic profile of urine in patients with HCC is helpful to find metabolic markers and potential therapeutic targets for liver cancer.

Predictive value of left ventricular ejection fraction for the occurrence of postoperative myocardial infarction after coronary endarterectomy in patients with diffuse coronary artery disease / 中华心血管病杂志

Objective: To investigate the predictive value of ejection fraction for the postoperative myocardial infarction after coronary endarterectomy (CE) in patients with diffuse coronary artery disease (DCAD). Methods: Patients who underwent cardiac artery bypass graft (CABG) surgery and CE in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2020 were enrolled in this prospective observational study. Baseline features including age, sex and echocardiography parameters were obtained. Left ventricular ejection fraction(EF) was measured by echocardiography. The patients were divided into postoperative myocardial infarction (PMI) group and non-PMI group according to PMI occurrence. Linear regression analysis, logistic regression model, and receiver operating characteristic(ROC) curve were used to analyze the correlation between left ventricular ejection fraction and PMI and the influencing factors. Results: A total of 120 patients were enrolled in the study. There were 32 patients (27%) in the PMI group (male 27(84%), age (62±8)), inferior myocardial infarction occurred in 24 (75%) patients. There were 88 patients (73%) in the non-PMI group (male 70(80%), age (62±8)). EF (55% (49%, 64%) vs. 62% (55%, 67%), P=0.01) was significantly lower in the PMI group than in the non-PMI group. Perioperative TNI, IABP use and length of hospitalization were significantly higher in the PMI group than in the non-PMI group. Multivariate logistic regression showed that lower EF was an independent risk factor of PMI (OR=0.93, 95%CI: 0.89-0.98, P=0.01) after adjusting age, sex and body mass index. ROC curve analysis showed that EF<60% could sufficiently predict the occurrence of PMI (AUC= 0.67, sensitivity 64%, specificity 69%, P=0.01). Linear regression analysis showed that left ventricular end-diastolic diameter (OR=-0.52, 95%CI:-1.13-0.60, P<0.001), graft flow in left anterior descending (OR=-0.20, 95%CI:-0.15-0.01, P=0.02) and history of diabetes (OR=-0.28, 95%CI:-8.25-1.85, P=0.002) were negatively correlated with preoperative EF value. Conclusion: Lower preoperative EF is an independent risk factor for PMI after CABG and CE in DCAD patients, closely related to the left ventricular end-diastolic diameter, graft flow in left anterior descending artery and diabetes mellitus.

Effective substance and mechanism of Ziziphi Spinosae Semen extract in treatment of insomnia based on serum metabolomics and network pharmacology / 中国中药杂志

This study aims to study the effective substance and mechanism of Ziziphi Spinosae Semen extract in the treatment of insomnia based on serum metabolomics and network pharmacology. The rat insomnia model induced by p-chlorophenylalanine(PCPA) was established. After oral administration of Ziziphi Spinosae Semen extract, the general morphological observation, pentobarbital sodium-induced sleep test, and histopathological evaluation were carried out. The potential biomarkers of the extract in the treatment of insomnia were screened by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS) combined with multivariate analysis, and the related metabolic pathways were further analyzed. The "component-target-pathway" network was constructed by ultra-high performance liquid chromatography coupled with quadrupole-Exactive mass spectrometry(UHPLC-Q-Exactive-MS/MS) combined with network pharmacology to explore the effective substances and mechanism of Ziziphi Spinosae Semen in the treatment of insomnia. The results of pentobarbital sodium-induced sleep test and histopathological evaluation(hematoxylin and eosin staining) showed that Ziziphi Spinosae Semen extract had good theraputic effect on insomnia. A total of 21 endogenous biomarkers of Ziziphi Spinosae Semen extract in the treatment of insomnia were screened out by serum metabolomics, and the metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and nicotinate and nicotinamide metabolism were obtained. A total of 34 chemical constituents were identified by UHPLC-Q-Exactive-MS/MS, including 24 flavonoids, 2 triterpenoid saponins, 4 alkaloids, 2 triterpenoid acids, and 2 fatty acids. The network pharmacological analysis showed that Ziziphi Spinosae Semen mainly acted on target proteins such as dopamine D2 receptor(DRD2), 5-hydroxytryptamine receptor 1 A(HTR1 A), and alpha-2 A adrenergic receptor(ADRA2 A) in the treatment of insomnia. It was closely related to neuroactive ligand-receptor interaction, serotonergic synapse, and calcium signaling pathway. Magnoflorine, N-nornuciferine, caaverine, oleic acid, palmitic acid, coclaurine, betulinic acid, and ceanothic acid in Ziziphi Spinosae Semen may be potential effective compounds in the treatment of insomnia. This study revealed that Ziziphi Spinosae Semen extract treated insomnia through multiple metabolic pathways and the overall correction of metabolic disorder profile in a multi-component, multi-target, and multi-channel manner. Briefly, this study lays a foundation for further research on the mechanism of Ziziphi Spinosae Semen in treating insomnia and provides support for the development of innovative Chinese drugs for the treatment of insomnia.

Determination of orcinol glucoside by LC-MS in Curculigo orchioides and its application to a pharmacokinetic study

ABSTRACT This study was designed to explore the pharmacokinetic regularity of the plasma concentration, tissue distribution and excretion of orcinol glucoside from aqueous extracts of raw and processed Curculigo orchioides Gaertn., Hypoxidaceae. The experiment first used an ultrahigh-performance liquid chromatography-tandem mass spectrometry approach with multiple reaction monitoring and a positive mode to separate orcinol glucoside from naringin to obtain the plasma concentration curves, bar graph of tissue distribution and excretion curves. These results might be beneficial for reasonable clinical application of C. orchioides and for further development of its wine and salt-processing mechanism.

Differences of brain pathological changes and cognitive function after bilateral common carotid artery occlusion between Sprague-Dawley and Wistar rats / 生理学报

The aim of the present study was to investigate the differences of the pathological changes and cognitive function after bilateral common carotid artery occlusion (BCCAO) between Sprague-Dawley (SD) and Wistar rats. Male SD and Wistar rats were randomly divided into 2 groups, respectively: sham operated (S-sham and W-sham) and operated (S-BCCAO and W-BCCAO) groups. The survival rate and the rate of loss of pupillary light reflex (PLR) were observed on day 1, 3, 7, 14 and 28 after the operation, and the light-dark box, Y-maze and odor recognition tests were performed to detect cognitive function on day 28 after the operation. HE and Luxol fast blue staining were used to observe the pathological changes of gray matter (hippocampus), white matter (optical tract), optic nerve, and retina. The results showed that the survival rate of the W-BCCAO group was 62.5%, and PLR loss rate was 100%; whereas the survival rate of the S-BCCAO group was 100%, and PLR loss rate was 58.3%. In the W-BCCAO group, percentages of time spent and distance traveled in the light box were more than those in the W-sham group, but there was no statistical significance between the S-BCCAO and S-sham groups. In the S-BCCAO group, the percentages of time spent and distance traveled in the III arm (labyrinth arm) of the Y-maze were less than those in the S-sham group, but no statistical significance was found between the W-BCCAO group and W-sham group. In the S-BCCAO group, the discrimination ratio of the odor recognition task was less than that in the S-sham group, but no statistical significance could be seen between the W-BCCAO and W-sham groups. Ischemic injury was observed in the CA1 area of the hippocampus in the S-BCCAO group, but no readily visible damage was observed in the W-BCCAO group. Ischemic injury of the visual beam and optic nerve was observed in both the S-BCCAO and W-BCCAO groups. Compared with the corresponding sham groups, the S-BCCAO and W-BCCAO groups showed serious retinal damage with significant thinner retina. The ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer (OPL) were thinner in the S-BCCAO group, but no statistical significances were shown in the other layers. All the layers, except the outer nuclear layer (ONL), were significantly thinner in the W-BCCAO group. The results indicate that there are differences of the pathological changes in the hippocampus and visual conduction pathway after BCCAO between SD and Wistar rats, and the degree of learning and memory injury was also different, which suggests that the vascular dementia model of different rat strains should be selected according to research purpose.

Modern research on detection technology of exogenous pollutants in Chinese materia medica / 中草药

The residues of exogenous pollutants in Chinese materia medica (CMM) have become an important cause of adverse reactions of CMM, including agricultural/veterinary drug residues, heavy metal contamination, mycotoxin residues, pathogenic microbial contamination and other organic pollutant residues according to their sources. This paper reviews the modern research on inspection objects and detection methods of main exogenous pollutants in CMM, with view to providing reference and basis for supplementing, perfecting and improving the quality and safety system of CMM.

In vitro study of genistein inducing apoptosis in MDA-MB-231 breast cancer cells via NF-κB and MAPK signaling pathways / 中国药理学通报

Aim To study the effect of genistein on apoptosis in human breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MTT as-say was used to observe the inhibitory rate on human breast cancer MDA-MB-231 cells treated with genistein. Colony assay was used to determine the cell colony formation rate on human breast cancer MDA-MB-231 cells treated with genistein. Western blot was used to detect the expression of Bcl-2, Bax, caspase-3,NF-κB, ERK, p-ERK, JNK and p-JNK in human breast cancer MDA-MB-231 cells treated with genistein. Results The results of MTT assay showed that genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time- and concentration-de-pendent manner. Colony assay suggested that genistein had an antiproliferative effect on MDA-MB-231 cells. The expression levels of Bcl-2, NF-κB and p-ERK were significantly down-regulated compared with con-trol(P < 0.01). However, the expression of Bax, caspase-3 and p-JNK was significantly up-regulated(P<0.01). Conclusions Genistein could inhibit the growth of human breast cancer MDA-MB-231 cells and induce apoptosis,and the mechanism may be related to the inhibition of NF-κB, ERK/MAPK signaling path-ways and the activation of JNK/MAPK signaling path-way.

Rosmarinic acid derivative RAD-9 induces apoptosis in gastric cancer MGC-803 cells via PI3K/Akt and p38 MAPK signaling pathway / 中国药理学通报

Aim To study the apoptosis-inducing effect of rosmarinic acid derivative RAD-9 on gastric cancer MGC-803 cells and the underlying mechanisms.Methods MTT assay was taken to detect the survival of gastric cancer MGC-803 cells effected by RAD-9.Cell apoptosis was detected by flow cytometry.The apoptotic morphology of MGC-803 cells was observed by Hoechst 33258 staining.The protein expression levels of Bcl-2,Bax,caspase-3,Akt,p-Akt,p38 MAPK and p-p38 MAPK were measured by Western blot.Results The results of MTT assay showed that RAD-9 inhibited the viability of gastric cancer MGC-803 cells in a time and concentration-dependent manner.Flow cytometry showed that RAD-9 significantly promoted apoptotic cell percentage in gastric cancer MGC-803 cells (P ＜ 0.01).Hoechst 33258 staining showed that the nucleus of MGC-803 cells could be observed with typical apoptotic morphological changes after RAD-9 administration.Compared with the control group,the protein expression levels of Bcl-2,Akt,p-Akt were significantly down-regulated (P ＜ 0.01),while those of Bax,caspase-3,p38 MAPK,p-p38 MAPK were significantly up-regulated (P ＜ 0.01).Conclusion RAD-9 can inhibit the growth and further induce apoptosis in gastric cancer MGC-803 cells,which may involve inhibiting PI3K/Akt and activating p38 MAPK signaling pathway.

Are medical undergraduate really unwilling to apply for clinic medicine speciality? Based on the quality of 5-year medical undergraduates / 中国卫生政策研究

Objective:To investigate the quality of 5-year medical undergraduates in China,analyze the influ-ence factors and put forward relevant policy suggestions. Method:By stratified random sampling,there are 24 medi-cal colleges or universities in northeastern, eastern, central, southern and southwestern China were included. Ac-cording to access the official websites,the enrollment data of 5-year medical undergraduates were collected. Result:The percentile of medical students'average score in entrance examination was around 33.46% ~56.32% in the first batch. There are significant difference among areas about the quality of medical undergradnates. Conclusion:At pres-ent,the quality of the 5-year medical undergraduates is good. Because high quality students unwilling to apply for clinical medicine,the quality of students declined. For this question,the suggestions are to improve enrollment sta-tus,school finical support,medical environment and doctors' welfare.

Correlation between the expression of aryl hydrocarbon receptor mRNA and tryptophan dioxygenase mRNA in patients with acute leukemia / 新乡医学院学报

Objective To investigate the correlation between the expression of aryl hydrocarbon receptor(AHR) mR-NA and tryptophan dioxygenase (TDO) mRNA in bone marrow mononuclear cells of patients with acute leukemia.Methods Sixty-five patients with newly diagnosed acute leukemia in Henan Provincial People's Hospital from August 2013 to August 2014 were selected as observation group,and there were 50 patients with acute myeloid leukaemia(AML) and 15 patients with acute lymphoblastic leukaemia(ALL).Fifteen patients with anemia were selected as control group in the same period(excluding the malignant disease of blood system).The expression of AHR mRNA and TDO mRNA in bone marrow mononuclear cells of patients in the groups was detected by real time fluorescence quantitative reverse transcription polymerase chain reaction.The correlation between AHR mRNA and TDO mRNA was analyzed.Results The expression of TDO mRNA and AHR mRNA in bone marrow mononuclear cells of AML and ALL patients in the observation group was significantly higher than that in the control group(P ＜0.05).There was no significant difference in the expression of TDO mRNA and AHR mRNA in bone marrow mononuclear cells between AML and ALL patients (P ＜ 0.05).There was significantly positive correlation between the expression of TDO mRNA and AHR mRNA in bone marrow mononuclear cells of AML and ALL patients(r =0.801,0.922;P ＜ 0.05).The levels of white blood cell,hemoglobin,platelet and lactate dehydrogenase were not related to the expression of TDO mRNA and AHR mRNA in AML and ALL patients(P ＜ 0.05).Conclusion The expression of TDO and AHR in bone marrow mononuclear cells of acute leukemia patients is high,and the TDO-KYN-AHR pathway promotes the development of acute leukemia.

MiT family translocation renal cell carcinoma:imaging findings in 15 patients / 复旦学报（医学版）

Objective To analyze the imaging findings in MiT family translocation renal cell carcinoma (RCC) for the better understanding on the rare tumor combined with its clinicopathological features.Methods Fifteen patients with MiT family translocation RCC were analyzed retrospectively including 14 cases of Xp11.2 RCC and 1 case of t(6;11) RCC.Tumor location,size,capsule sign,hemorrhage,cystic change,calcification,density,signal features and enhancement pattern were evaluated.Results Four men and ten women aged from 14 to 42 years old (mean age of 26 years old) were diagnosed as Xp1 1.2 RCC.Most of the tumors (n =12) were located in renal medulla and most of the tumors (n =11) were 4 cm or more in diameter.There were 8 cases with hemorrhage.They were always well-defined (n =11) and all heterogeneous.Additionally,we could find calcification (a half of the number) typically distributed on CT.The tumor density was grater on plain CT (n =8) and the signal intensive was slightly high on T1WI (n-6) and low or slightly low on T2WI (n =9) than renal cortex.All of the cases were slightly or moderately persistent enhancement on DCE CT and MRI.The imaging features of the male patient with t(6;11)RCC was similar with Xp11.2 RCC apart from the diameter of 16 cm.Conclusions MiT family translocation RCC should be considered when a young patient presents with a relatively huge and well-defined renal tumor with an obviously heterogeneous features,annular calcification and persistent enhancement.It is difficult to distinguish Xp11.2 RCC and t(6,11) RCC,but size maybe play a hinting role in discriminate them.

Research progress on the pathogenesis of microvascular neuropathy in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is one of the common and serious microvascular complications of diabetes. In foreign countries, DR is the leading cause of blindness in the working age group (20 - 64 years). In China, the incidence of DR and the rate of blindness increase year by year, which seriously affects the patients' quality of life. Previous studies on the pathogenesis and treatment of diabetic retinopathy were mainly focused on the microvascular; in recent years, with the deepening of researches, more and more scholars believe that DR is no longer simply a kind of microangiopathy, but is also accompanied by retinal neurodegeneration. However, studies on the pathogenesis of microvascular disease and neurodegenerative changes of diabetic retinopathy in the literature domestic and abroad are mostly single. This article reviews the relationship between microvascular disease and neurodegenerative changes in diabetic retinopathy.

Identification of Newly Diagnosed Diabetes and Prediabetes Using Fasting Plasma Glucose and Urinary Glucose in a Chinese Population: A Multicenter Cross-Sectional Study / 中华医学杂志(英文版)

<p><b>Background</b>Although fasting plasma glucose (FPG) has been highly recommended as the sole test for diabetes screening, the efficacy of FPG alone for diabetes screening is potentially limited due to its low sensitivity. The aim of this study was to improve the efficacy of FPG for diabetes screening using urinary glucose (UG).</p><p><b>Methods</b>This study was initiated on November 12, 2015, and ended on June 28, 2016. A representative sample of individuals aged between 18 and 65 years, with no history of diabetes, from 6 cities in Jiangsu Province participated in this study. A 75-g oral glucose tolerance test was used to diagnose diabetes. All urine samples were collected within 2 h of oral glucose loading to measure UG. Partial correlation analyses were used to evaluate the associations between UG and other glycemic variables, including FPG, 2-h plasma glucose (2h-PG), and glycated hemoglobin A1c, after adjustment for age. The performance of UG was evaluated using a receiver operating characteristic (ROC) curve analysis.</p><p><b>Results</b>Of the 7485 individuals included, 8% were newly diagnosed with diabetes and 48.7% had prediabetes. The areas under the ROC curves for UG were 0.75 for estimation of 2h-PG ≥7.8 mmol/L and 0.90 for 2h-PG ≥11.1 mmol/L, respectively. The sensitivity and specificity of UG were 52.3% and 87.8%, respectively, for 2h-PG ≥7.8 mmol/L (cutoff point ≥130 mg), and 83.5% and 87.5%, respectively, for 2h-PG ≥11.1 mmol/L (cutoff point ≥178.5 mg). The combination of FPG and UG demonstrated a significantly higher sensitivity than that of FPG alone for the identification of diabetes ([483/597] 80.9% vs. [335/597] 56.1%, χ = 85.0, P < 0.001) and glucose abnormalities ([2643/4242] 62.3% vs. [2365/4242] 55.8%, χ = 37.7, P < 0.001).</p><p><b>Conclusions</b>The combination of UG and FPG substantially improves the efficacy of using FPG alone for diabetes screening; this combination might be a practical screening tool and is worth being recommended in the future.</p>

The application of piezoelectric gait analysis system in plantar pressure monitoring / 医用生物力学

Objective To provide references for human gait analysis and its application in clinical medicine and rehabilitation through research on practical application of piezoelectric gait analysis system in plantar pressure monitoring.Methods Piezoelectric gait analysis system was designed to collect pressure signals of six acquisition points in insole.The signals were transferred by bluetooth,and then analyzed and handled by APP and MATLAB.Results The plantar pressure cloud chart,center of pressure (COP) butterfly diagram were obtained by interpolation and color mapping in MATLAB,the walk cycle was calculated by measuring swing phase of both feet,and real time pressure monitoring was realized by mobile APP to give an accidental fall alarm.Conclusions The system can achieve monitoring of standing posture,state of equilibrium,walk cycle and accidental fall,and the experimental results are coincident with clinical research conclusions.Meanwhile,the wearable structure is more suitable in real walking scene.