Xinshubao tablet rescues cognitive dysfunction in a mouse model of vascular dementia: Involvement of neurogenesis and neuroinflammation.

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism.

Jujuboside A inhibits oxidative stress damage and enhances immunomodulatory capacity of human umbilical cord mesenchymal stem cells through up-regulating IDO expression.

Impaired immunomodulatory capacity and oxidative stress are the key factors limiting the effectiveness of mesenchymal stem cell transplantation therapy. The present study was aimed to investigate the effects of jujuboside A (JuA) on the protective effect and immunomodulatory capacity of human umbilical cord mesenchymal stem cells (hUC-MSCs). Hydrogen peroxide was used to establish an oxidative damage model of hUC-MSCs, while PBMCs isolated from rats were used to evaluate the effect of JuA pre-treatment on the immunomodulatory capacity of hUC-MSCs. Furthermore, Hoechst 33258 staining, lactate dehydrogenase test, measurement of malondialdehyde, Western blot, high-performance liquid chromatography; and flow cytometry were performed. Our results indicated that JuA (25 µmol·L-1) promoted the proliferation of hUC-MSCs, but did not affect the differentiating capability of these cells. JuA pre-treatment inhibited apoptosis, prevented oxidative damage, and up-regulated the protein expression of nuclear factor-erythroid factor 2-related factor 2 and heme oxygenase 1 in hUC-MSCs in which oxidative stress was induced with H2O2. In addition, JuA pre-treatment enhanced the inhibitory effect of hUC-MSCs against abnormally activated PBMCs, which was related to stimulation of the expression and activity of indoleamine 2,3-dioxygenase. In conclusion, our results demonstrate that JuA pre-treatment can enhance the survival and immunomodulatory ability through pathways related to oxidative stress, providing a new option for the improvement of hUC-MSCs in the clinical setting.

A strategy to comprehensively analyze the bioactivity of complex herbal prescriptions via peak-by-peak cutting and knock-out chromatography: Qiliqiangxin capsule as an example.

An herbal prescription is usually composed of several herbal medicines. The complex and diverse components bring great challenges to its bioactivity study. To comprehensively analyze the bioactivity of an herbal prescription, a new strategy based on peak-by-peak cutting and knock-out chromatography was proposed. In this strategy, active compounds were screened out via peak-by-peak cutting from an herbal extract, and the influence of a compound on the overall activity of the herbal extract was evaluated by knock-out chromatography. Qiliqiangxin capsule is an herbal prescription composed of 11 herbal medicines for the treatment of chronic heart failure. A total of 71 peaks were collected through peak-by-peak cutting, and each peak was identified by a high-resolution mass spectrum. The bioassay against 1,1-diphenyl-2-picrylhydrazyl showed that two types of compounds namely salvianolic acids and caffeoylquinic acids were potent scavengers. Knock-out chromatography suggested that the removal of one single compound had no obvious influence on the overall activity of the Qiliqiangxin capsule. After all the main peaks in the Qiliqiangxin capsule were knocked out, the remaining part still exhibited a potent activity, indicating high activity stability of the Qiliqiangxin capsule. The proposed strategy is helpful for the comprehensive analysis of the bioactivity of other herbal prescriptions.

Icarisid II rescues cognitive dysfunction via activation of Wnt/ß-catenin signaling pathway promoting hippocampal neurogenesis in APP/PS1 transgenic mice.

Restoring the compromised neurogenesis has been served as a potential strategy to rescue cognitive dysfunction of Alzheimer's disease (AD). In this study, we explored whether icarisid II (ICS II), a natural product possessing powerful neuroprotection, could recover the neurogenesis dysfunction of APP/PS1 mice, and investigated its underlying mechanisms. Our results showed that oral administration of ICS II could alleviate cognitive injuries of APP/PS1 mice, promote hippocampal neurogenesis, as well as stimulate Wnt/ß-catenin signal pathway confirmed by upregulated Wnt-3a, phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß), and ß-catenin. ICS II also depressed mitochondrial fission evidenced by upregulated Mitofusin 1 (Mfn 1) and Mitofusin 2 (Mfn 2), and downregulated mitochondrial fission 1 protein (Fis 1), mitochondrial fission factor (Mff), and phosphorylated dynamin-related protein 1 (p-Drp 1). However, these effects of ICS II were blunted by XAV-939, an inhibitor of Wnt/ß-catenin signaling pathway. In summary, our findings revealed that ICS II could improve neurogenesis and inhibit mitochondrial fission via activation of the Wnt/ß-catenin signaling pathway, which contributed to cognitive function restoration of APP/PS1 mice. This study discovered a novel mechanism involving neurogenesis regulation underlying the therapeutic effects of ICS II against AD.

Jujuboside a promotes proliferation and neuronal differentiation of APPswe-overexpressing neural stem cells by activating Wnt/ß-catenin signaling pathway.

Mobilization of hippocampal neurogenesis has been considered as a potential strategy for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). In present study, we evaluated both the neuroprotective effects and the effects on the proliferation and differentiation of APP-overexpressing neural stem cells (APP-NSCs) by Jujuboside A (JuA) in vitro. Our results demonstrated that JuA (50 µM) decreased apoptosis and suppressed oxidative stress damage of APP-NSCs. JuA (50 µM) upregulated the secretion of brain-derived neurotrophic factor and promoted the proliferation and neuronal differentiation of APP-NSCs. Moreover, JuA (50 µM) upregulated Wnt-3a and ß-catenin protein expression, and enhanced the expression of downstream genes Ccnd1, Neurod1 and Prox1. However, XAV-939, an inhibitor of the Wnt/ß-catenin signaling pathway, inhibited these positive effects of JuA. Taken together, these findings suggest that JuA promote proliferation and neuronal differentiation of APP-NSCs partly by activating the Wnt/ß-catenin signaling pathway. We hope that this study will provide a viable strategy for the treatment of AD.

The Patatin-like Phospholipase Domain Containing Protein 7 (PNPLA7) Facilitates M2 Polarization of Macrophages Through a PPARγ-Dependent Mechanism / 中国生物化学与分子生物学报

Lysophosphatidylcholine (LPC) modulates the dynamic and integral process of macrophage polarization in immune responses, tissue inflammation and remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) was identified as an LPC-preferring lysophospholipase recently. However, the expression and role of PNPLA7 in macrophage polarization remained unknown. In the present study, PNPLA7 was found to be upregulated in the process of macrophage polarization toward an alternatively activated (M2) phenotype stimulated with interleukin 4 (IL-4) (P<0.05). We found that knockdown and overexpression of PNPLA1 decreased and increased the expression of M2 marker genes, including arginase 1 (Argl) and chitinase-like 3 (Ym\ ), respectively (P<0.05). Further studies showed that PNPLA7 regulated the expression of peroxisome proliferator activated receptor-γ (P P A R γ) at the mRNA and protein levels during M2 polarization (P < 0.05). However, the phosphorylation of signal transducer and activator of transcription 6 (STAT6) was not influenced by PNPLA7. These findings suggest that PNPLA7 favors macrophage anti-inflammatory M2 polarization through a PPAR

Active constituent of Polygala tenuifolia attenuates cognitive deficits by rescuing hippocampal neurogenesis in APP/PS1 transgenic mice.

BACKGROUND: Alzheimer's disease (AD) is the most common dementia worldwide, and there is still no satisfactory drug or therapeutic strategy. Polygala tenuifolia is a traditional Chinese medicine with multiple neuroprotective effects. In present study, we investigated the effects of three active constituents [3,6'-disinapoyl sucrose (DISS), onjisaponin B (OB) and tenuifolin (TEN)] of Polygala tenuifolia (PT) on the proliferation and differentiation of neural stem cells (NSCs) to identify the potential active constituent of PT promoting hippocampal neurogenesis. METHODS: NSCs were isolated from hippocampi of newborn C57BL/6 mice, and transfected with mutant amyloid precursor protein (APP) gene to establish an AD cell model (APP-NSCs). 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were performed, and the proliferation and differentiation of NSCs were assessed by neurosphere formation assay, 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and immunofluorescence (IF) staining analysis. APP/PS1 transgenic mice were administrated with the potential active constituent DISS for 4 weeks. Morris water maze (MWM), Nissl staining assay and IF staining assays were carried out to evaluate the cognitive function, neural damages and hippocampal neurogenesis, respectively. RESULTS: DISS exerted the optimal ability to strengthen APP-NSCs proliferation and neuronal differentiation, followed by OB and TEN. Furthermore, DISS treatment for 4 weeks strikingly rescued the cognitive deficits, neuronal injures, and neurogenesis disorder in adult APP/PS1 transgenic mice. CONCLUSIONS: Our findings demonstrated that DISS is the constituent of PT that triggers the most potent increase of hippocampal neurogenesis in our mouse model of AD.

A strategy to discover lead chemome from traditional Chinese medicines based on natural chromatogram-effect correlation (NCEC) and natural structure-effect correlation (NSEC): Mahonia bealei and Mahonia fortunei as a case study.

Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC50 values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC50 values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants.

Tanshinone IIA Combined With Cyclosporine A Alleviates Lung Apoptosis Induced by Renal Ischemia-Reperfusion in Obese Rats.

Acute lung injury (ALI), which is induced by renal ischemia-reperfusion (IR), is one of the leading causes of acute renal IR-related death. Obesity raises the frequency and severity of acute kidney injury (AKI) and ALI. Tanshinone IIA (TIIA) combined with cyclosporine A (CsA) was employed to lessen the lung apoptosis led by renal IR and to evaluate whether TIIA combined with CsA could alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats. Hematoxylin-eosin (HE) staining was used to assess the histology of the lung injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was used to assess apoptosis of the lung. Electron microscopy was used to assess mitochondrial morphology in lung cells. Arterial blood gas and pulmonary function were used to assess the external respiratory function. Mitochondrial function was used to assess the internal respiratory function and mitochondrial dynamics and biogenesis. Western blot (WB) was used to examine the PI3K/Akt/Bad pathway-related proteins. TIIA combined with CsA can alleviate lung apoptosis by regulating mitochondrial function through the PI3K/Akt/Bad pathway in obese rats.

Icarisid II promotes proliferation and neuronal differentiation of neural stem cells via activating Wnt/ß-catenin signaling pathway.

Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)-overexpressing NSCs (APP-NSCs) in vitro. Our results demonstrated that ICS II dose-dependently suppressed apoptosis and elevated viability of APP-NSCs. ICS II (1 µM) potently promoted proliferation and neuronal differentiation of NSCs and APP-NSCs. ICS II (1 µM) significantly upregulated Wnt-3a expression, increased the phosphorylation of glycogen synthase kinase-3ß and enhanced the nuclear transfer of ß-catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt-3a, which positively modulates Wnt/ß-catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/ß-catenin signaling pathway.

Multifunctional osthole liposomes and brain targeting functionality with potential applications in a mouse model of Alzheimer's disease.

Osthole (Ost) is a coumarin compound and a potential drug for Alzheimer's disease (AD). However, the effectiveness of Ost is limited by solubility, bioavailability, and low permeability of the blood-brain barrier. In this study, we constructed Ost liposomes with modified CXCR4 on the surface (CXCR4-Ost-Lips), and investigated the intracellular distribution of liposomes in APP-SH-SY5Y cells. In addition, the neuroprotective effect of CXCR4-Ost-Lips was examined in vitro and in vivo. The results showed that CXCR4-Ost-Lips increased intracellular uptake by APP-SH-SY5Y cells and exerted a cytoprotective effect in vitro. The results of Ost brain distribution showed that CXCR4-Ost-Lips prolonged the cycle time of mice and increased the accumulation of Ost in the brain. In addition, CXCR4-Ost-Lips enhanced the effect of Ost in relieving AD-related pathologies. These results indicate that CXCR4-modified liposomes are a potential Ost carrier to treat AD.

Clinical value of PCR-flow Fluorescence Hybridization in Prenatal Genetic Diagnosis of Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the value of PCR-flow fluorenscence immunmicrobeads assay in prenatal gene diagnosis of thalassemia.@*METHODS@#A total of 1001 pregnant women and their couples checked in the First Affiliated Hospital of Sun Yat-Sen University from January 2016 to August 2019 were selected. Both pregnant women and their spouses were the carriers of thalassemia gene. Samples such as amniotic fluid, were used to extract genomic DNA at the right time. Parallel detection of α- and β- thalassemia genes to samples should be carried out by PCR-flow cytometric fluorescence hybridization and traditional multiple Gap-PCR and PCR-RDB techniques. The consistency of two methods in gene diagnosis of thalassemia was evaluated by analyzing the results of detection.@*RESULTS@#389 normal genotypes (38.86%, 389/1001) and 59 abnormal genotypes (61.14%, 612/1001) was cheked out by the two methods, including 416 cases of α-thalassemia, 162 cases of β-thalassemia and 34 cases of αβ- complex thalassemia. The main genotypes of α-thalassemia were --@*CONCLUSION@#Guangzhou is a area with high incidence of thalassemia, and the genetic types of thalassemia are complex and diverse. Prenatal diagnosis is the final barrier to the prevention of thalassemia. PCR flow-cytometric fluorescence hybridization, as a simple and fast technique, combined with traditional techniques in parallel contributed to the accuracy of prenatal gene diagnosis of thalassemia.

Transferrin-Modified Osthole PEGylated Liposomes Travel the Blood-Brain Barrier and Mitigate Alzheimer's Disease-Related Pathology in APP/PS-1 Mice.

INTRODUCTION: Osthole (Ost) is a coumarin compound that strengthens hippocampal neurons and neural stem cells against Aß oligomer-induced neurotoxicity in mice, and is a potential drug for the treatment of Alzheimer's disease (AD). However, the effectiveness of the drug is limited by its solubility and bioavailability, as well as by the low permeability of the blood-brain barrier (BBB). In this study, a kind of transferrin-modified Ost liposomes (Tf-Ost-Lip) was constructed, which could improve the bioavailability and enhance brain targeting. METHODS: Tf-Ost-Lip was prepared by thin-film hydration method. The ability of liposomal formulations to translocate across BBB was investigated using in vitro BBB model. And the protective effect of Tf-Ost-Lip was evaluated in APP-SH-SY5Y cells. In addition, we performed pharmacokinetics study and brain tissue distribution analysis of liposomal formulations in vivo. We also observed the neuroprotective effect of the varying formulations in APP/PS-1 mice. RESULTS: In vitro studies reveal that Tf-Ost-Lip could increase the intracellular uptake of hCMEC/D3 cells and APP-SH-SY5Y cells, and increase the drug concentration across the BBB. Additionally, Tf-Ost-Lip was found to exert a protective effect on APP-SH-SY5Y cells. In vivo studies of pharmacokinetics and the Ost distribution in brain tissue indicate that Tf-Ost-Lip prolonged the cycle time in mice and increased the accumulation of Ost in the brain. Furthermore, Tf-Ost-Lip was also found to enhance the effect of Ost on the alleviation of Alzheimer's disease-related pathology. CONCLUSION: Transferrin-modified liposomes for delivery of Ost has great potential for AD treatment.

Distribution and antimicrobial resistance of 1 061 pathogenic strains isola-ted from blood specimens / 中国感染控制杂志

Objective To investigate the distribution and antimicrobial resistance of pathogens isolated from blood specimen,and provide laboratory basis for clinical treatment of bloodstream infection. Methods Pathogens isolated from blood specimen in a hospital laboratory from January 1,2015 to December 31,2016 were identified and per-formed antimicrobial susceptibility testing.Results A total of 1 061 pathogenic strains were isolated from blood speci-men,of which gram-negative bacillus,gram-positive coccus,and fungus accounted for 53.35%(n= 566),36.10%(n=383),and 10.55%(n= 112)respectively,the major gram-negative bacillus,gram-positive coccus,and fungus were Escherichia coli(E.coli)and Klebsiella pneumoniae(K.pneumoniae),coagulase-negative Staphylococcus,and Candida parapsilosis respectively. Strains were mainly isolated from intensive care unit(ICU,n= 308,29.03%),followed by hematology department and pediatric internal medicine department. Resistance rates of E.coli and K. pneumoniae to imipenem were 2.65% and 40.12% respectively.Extended-spectrum beta-lactamase(ESBL)-produ-cing E.coli and K.pneumoniae accounted for 62.96% and 33.14% respectively. Linezolid- and vancomycmin-re-sistant Staphylococcusspp. Were not found,isolation rates of methicillin-resistant coagulase-negative Staphylococ-cus and methicillin-resistant Staphylococcus aureus were 83.61% and 45.45% respectively,one vancomycin-resis-tant Enterococcus faeciu m and one linezolid-resistant Enterococcus faecium were isolated respectively.Conclusion There are multiple species of pathogens isolated from blood specimen,distribution and antimicrobial resistance of pathogens casing bloodstream infection should be monitored regularly to guide the empiric antimicrobial therapy.

Simultaneous determination of puerarin, daidzin, daidzein, paeoniflorin, albiflorin, liquiritin and liquiritigenin in rat plasma and its application to a pharmacokinetic study of Ge-Gen Decoction by a liquid chromatography-electrospray ionization-tandem mass spectrometry.

A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for simultaneous determination of seven constituents including puerarin, daidzin, daidzein, paeoniflorin, albiflorin, liquiritin and liquiritigenin in rat plasma using schisandrin as the internal standard (IS). The plasma samples were pretreated by a one-step direct protein precipitation with acetonitrile. The chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and water (containing 0.1% formic acid and 5mM ammonium acetate). All analytes and IS were quantitated through electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. The mass transitions were as follows: m/z 417.5→297.2 for puerarin, m/z 417.1→255.2 for daidzin, m/z 255.2→152.4 for daidzein, m/z 498.1→179.3 for paeoniflorin, m/z 481.1→197.3 for albiflorin, m/z 436.2→257.3 for liquiritin, m/z 257.2→137.3 for liquiritigenin and m/z 415.0→384.2 for IS, respectively. All calibration curves exhibited good linearity (r>0.9979) over a wide concentration range for all components. The intra-day and inter-day precisions (RSD) at three different levels were both less than 14.3% and the accuracies (RE) ranged from -13.2% to 14.8%. The extraction recoveries of the seven compounds ranged from 72.9% to 117.4%. The validated method was successfully applied to pharmacokinetic study of the seven components in female rat plasma after oral administration of Ge-Gen Decoction aqueous extract.

Regulatory roles of compound danshen in the downstream path of cyclooxygenases in rheumatoid arthritis patients' synovium / 中国中西医结合杂志

Rheumatoid arthritis (RA) belongs to Bi syndrome (arthralgia) in Chinese medicine. Till now there lacks effective therapeutic methods. Recently cyclooxygenases (COXs) inhibitors, having regulator roles for many pro-inflammatory cytokines, have been widely used in RA treatment. But due to existing cardiovascular risks, researches on targeting the downstream specific factors of COXs have been under discussion. Considering the key role of blood stasis syndrome (BSS) in the pathology of RA and the fact that thromboxane A2 (TXA2) plays a pivotal role in BSS, we theoretically explored possible regulatory roles of Compound Danshen, a representative therapy in blood activating stasis removing method in the downstream path of COXs in synovial cells of RA. We proposed a brand new research direction of RA researches.

Establishment of anther culture system for Angelica dahurica from Sichuan province / 中国中药杂志

<p><b>OBJECTIVE</b>To research the optimal conditions for the callus induction of anther culture and the plant regeneration of Angelica dahurica var. formosana.</p><p><b>METHOD</b>Callus was induced from the anther of A. dahurica from Sichuan province on a MS medium. The effects of callus induction and plant regeneration of different pretreatment hours under low temperature (4 degrees C), different culturing conditions under darkness and illumination, and different culture with different hormone contents and ratios were studied.</p><p><b>RESULT</b>The results showed that A. dahurica anthers without low temperature pretreatment reached the highest induction rate then under the pretreatment under low temperature (4 degrees C) for two days. The optimal culturing condition was under the darkness. The culturing efficiency reached 38.89% on the medium of MS + 2.0 mg x L(-1) 2,4-D + 1.0 mg x L(-1) 6-BA. The optimum medium for differentiate anther callus was MS + 0.5 mg x L(-1) NAA + 1.5 mg x L(-1) KT + 10 mg x L(-1) AgNO3. 1/2MS medium supplemented with 0.5 mg x L(-1) IBA could well promote seedings to take roots.</p><p><b>CONCLUSION</b>An efficient system for callus induction of anther culture and plant regeneration of A. dahurica was preliminarily established.</p>

Effect of siRNA for mutant p53 gene on biological behavior of gastric cancer cell line SGC7901 / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of silencing the expression of mutant p53 gene with RNA interference technique on biological behavior of gastric cancer SGC7901 cells.</p><p><b>METHODS</b>Recombinant plasmid of mutant p53 gene-targeting siRNA was transfected into gastric cancer SGC7901 cells by Lipofectamine(TM)2000. The expressions of mutant p53 gene mRNA and protein were identified by RT-PCR and Western blot assay. The proliferation of SGC7901 cells and changes of Oxaliplatin (OXA) drug sensitivity were detected by MTT assay. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry. Changes in cell tumorigenicity ability were analyzed by colony formation assay and xenograft tumor formation in nude mice.</p><p><b>RESULTS</b>The expression of mutant p53 in SGC7901 cells was remarkable suppressed by mutant p53-siRNA. The cell growth curve of the transfected group turned to left compared to untransfected group and control group. The cell number of G(0)/G(1) phase of transfected group was decreased by 7.4% and 6.7% respectively, and that of S phase was increased both by 17.2% compared to control group and untransfected group, and the cell apoptosis rate induced by Oxaliplatin was remarkable decreased. The IC(50) of OXA in untransfected group, control group and transfected group were 15.88 μmol/L, 14.32 μmol/L and 20.34 μmol/L respectively. The colony formation rate and tumorigenicity ability in nude mice of transfected group increased remarkably.</p><p><b>CONCLUSION</b>Mutant p53-siRNA can significantly inhibit the expression of mutant p53 in SGC7901 cells, however, the use of RNA interference targeting mutant p53 gene in the treatment of gastric cancer is still uncertain.</p>

The efficacy of 18F-FDG PET/CT, 99Tcm-MDP bone scintigraphy, and combination of the two techniques for detecting malignant bone metastasis / 中华核医学杂志

Objective To compare the efficacy of 18F-FDG PET/CT, 99Tcm-MDP bone scintigraphy (BS), and combination of the two techniques (PET/CT + BS) for detecting bone metastasis by ROC curve analysis. Methods All 296 patients with various cancers, who underwent both 99Tcm-MDP BS and 18F-FDG PET/CT within two months, were retrospectively analyzed. These images were interpreted according to 5-point scale (0: definitely negative, 1: probably negative, 2: equivocal, 3: probably positive, 4:definitely positive for bone metastasis), and the scale of PET/CT + BS was the sum of PET/CT and BS. In light of the confirmed diagnosis derived from pathology or follow-up, ROC curve analysis was performed.The area under the ROC curve (AUC) was compared by z-test. Results Of 296 cases, 61 (20.6%) were confirmed as bone metastases and 235 (79.4%) were negative. The AUC were 0. 919 (95% confidence interval (95% CI) :0. 867 - 0. 971) for BS, 0. 949 (95% CI: 0. 906 - 0. 991) for PET/CT, and 0. 994 (95% CI: 0.988-0.999) for PET/CT + BS, rctrospectively. The AUC of PET/CT + BS was statistically significantly larger than that of BS (z=2. 866, P=0.004) or PET/CT (z =2.027, P=0.043), while the AUC of PET/CT was larger than that of BS, but no statistically significance (z = 0. 881, P = 0. 378) was showed. The optimal sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value(NPV) were 90. 2% (55/61), 85. 1% (200/235), 86. 1% (255/296), 61. 1% (55/90), 97. 1%(200/206) for BS, 88.5% (54/61), 97.0% (228/235), 95.3% (282/296), 88.5% (54/61), 97.0% for PET/CT, and 98.4% (60/61), 95.7% (225/235), 96.3% (285/296), 85.7% (60/70) for PET/CT + BS,respectively. The specificity (χ2 = 19.862, P<0. 001), accuracy (χ2 = 23. 361, P<0.001) and PPV (χ2 =11. 791, P =0.001) of PET/CT + BS were significantly higher than those of BS, the sensitivity of PET/CT +BS was significantly higher than that of PET/CT (χ2 =4.167, P=0.031). Compared with BS, PET/CT had a higher specificity (χ2 = 19.600, P<0. 001), accuracy (χ2 = 13. 755, P <0. 001), PPV (χ2 = 13. 608, P <0. 001), but their sensitivity showed no statistically significant difference (χ2 = 0, P = 1. 000). Conclusions The efficacy of 18F-FDG PET/CT for detecting malignant bone metastasis was superior to that of 99Tcm-MDP BS alone. The detection ability can be obviously improved by combination of the two techniques.

The effect of histotype and histodifferentiation on the standardized uptake value of no-small cell lung cancer ~(18)F-FDG PET/CT imaging / 中华核医学杂志

Objective To determine the effect of histotype and histodifferentiation on the maximum standardized uptake value (SUV_(max)) of non-small cell lung cancer (NSCLC) ~(18)F-fluorodeoxyglucose (FDG) PET/CT imaging.Methods Two hundred and sixty patients with NSCLc underwent ~(18)F-FDG PET/CT imaging.They were classified according to (1) histotype:as adenocarcinoma (AC),squamous cell carcinoma(SQC),adenosquamous carcinoma (ASC) and other type carcinoma (OTC),and (2) histodifferentiation:as grade Ⅰ (well-differentiated),grade Ⅱ (moderate-differentiated) and grade Ⅲ (poor-differentiated).The SUV_(max) and size(long diameter)of the primary lesions were measured.Multivariate regression analysis was used to analyze the relationship between the SUV_(max) and variable factors including histotype,histodifferentiation,lesion size,age,sex,body height,body weight,body mass index (BMI),blood glucose level,dose,and rate of dose.Results Two hundred and sixty patients had 260 primary NSCLC tumors.There were 161 AC(15 grade Ⅰ,88 grade Ⅱ,58 grade Ⅲ),74 SQC(6 grade Ⅰ,39 grade Ⅱ,29 grade Ⅲ),15 ASC(7 grade Ⅱ,8 gradeⅢ)and OTC(8 large cell,2 carcinosarcoma).Only lesion size (F=87.046.P＜0.001),histodifferentiation (F=87.604,P＜0.001) and histotype (F=66.663,P＜0.001) were included for multivariate regression analysis with SUV_(max).After adjustment for lesion size,the SUV_(max)(mean and 95%confidence interval) in ascending order was AC Ⅰ:3.3(2.1-4.5),ACⅡ:6.0(5.5-6.6),SQCⅠ:6.1(4.2-8,0),ASC Ⅱ:6.6(4.8-8.4),SQCⅡ.7.8(7.0-8.6),OTC:8.1(6.6-9.6),AC Ⅲ:8.3(7.6-8.9),ASC Ⅲ:8.7(7.0-10.4),and SQC Ⅲ:8.9(8.0-9.8).11he SUV_(max) of AC Ⅰ was significantly lower than that of SQC Ⅰ(q=-2.786,P=0.017),same for AC Ⅱ and SQC Ⅱ(q=-1.776,P＜0.001),but no statistically significant differences were found among AC Ⅲ,ASC Ⅲ and SQC Ⅲ(q=-0.593,-0.422,0.171,P=0.288,0.642,0.860,respectively).For the same histotype lesions,the difference of SUV_(max) among AC Ⅰ,Ⅱ and Ⅲ was statistically significant(q=-2.720,-4.943,-2.223,all P＜0.001),as also for SQC Ⅰ and Ⅲ(q=-2.751,P=0.012).Conclusion Histotype and histodifferentiation are significant correlative factors for ~(18)F-FDG uptake of NSCLC,with histodifferentiation being the factor with greater impact.