Experimental study of curcumol inhibiting vascular endothelial growth factor-induced neovascularization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the role and mechanism of curcumol in neovascularization induced by vascular endothelial growth factor(VEGF).METHODS: Human umbilical vein endothelial cells were cultured in vitro and treated with 50ng/mL VEGF and curcumol at different concentrations. Cell proliferation was detected by CCK-8 and EdU assay, the migration ability of cells was analyzed by Transwell assay, the angiogenesis ability of endothelial cells was analyzed by tube formation assay, and the change of Akt/mTORC1 signal pathway was detected by Western blot.RESULTS: CCK-8 results showed that the OD450 value of cells in 400 and 800 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(all P<0.01). EdU results showed that the rate of cell proliferation in 400 μmol/L curcumol+VEGF group was significantly lower than that in VEGF group(P<0.001). Transwell assay and the formation assay results showed that the number of migratory cells in 400 μmol/L curcumol+VEGF group was decreased, and the number and length of tube branches were also reduced compared with VEGF group(all P<0.001). Western blot results showed that curcumol significantly inhibited the expression of p-Akt and p-S6, which were downstream targets of Akt/mTORC1 pathway in cells.CONCLUSION: Curcumol can inhibit VEGF-induced cell proliferation, migration and tube formation of vein endothelial cells, and has a strong inhibitory effect on angiogenesis, which can be further studied in the treatment of ocular fundus neovascularization.

Prognostic significance of systemic immune inflammation index in patients with pancreatic cancer based on propensity score matching analysis / 中华胰腺病杂志

Objective:To investigate the predictive value of systemic immune inflammation index (SII) for the overall survival of patients with pancreatic cancer by propensity score matching analysis.Methods:The clinical data of 457 patients with pancreatic cancer admitted to the Affiliated Hospital of Qingdao University from August 2000 to December 2019 were retrospectively analyzed. The age, gender, presence of jaundice, pancreatitis and diabetes, serum CA19-9, total bilirubin level, neutrophil count, platelet count, lymphocyte count in blood, presence of radical surgery, tumor TNM stage, tumor location and the like were recorded. The cut-off value of SII was determined by Youden index. The patients were divided into high and low SII groups accroding to the cut-off value. The propensity score matching was applied to reduce the selection bias of patients. Patients were 1∶2 matched and the caliper value was 0.1. The difference on overall survival between the two groups was compared. The prognostic factors were analyzed by univariate and multivariate Cox regression analysis. Kaplan-Meier was used to draw the overall survival curve to calculate the cumulative survival rate, and the differences between the curves were analyzed by Log-Rank test.Results:The cut-off value of SII was 765. There were statistically significant differences between the high SII group ( n=125) and the low SII group ( n=332) on the presence or absence of pancreatitis, the level of total bilirubin in blood, radical surgery, and TNM stage before the propensity score matching (all P value <0.05). After propensity score matching, there was no statistically significant difference between the high SII group ( n=113) and the low SII group ( n=182) on all the clinical parameters mentioned above except for CA19-9, indicating that the two groups were comparable. Univariate analysis showed that the level of CA19-9, SII, radical surgery and different TNM stage were all related to the overall survival of pancreatic cancer patients. Multivariate analysis showed that high CA19-9 level, high SII, no radical surgery, and worse TNM stage were independent risk factors for short overall survival, and high SII ( HR=1.882, 95% CI 1.446-2.450, P<0.001) was significantly associated with poor prognosis. The overall survival of patients with high SII was obviously shorter than the low SII group ( P<0.001), and the average survival time of patients with high and low SII were 8.86 and 11.38 months, respectively. Conclusions:SII is of great value in evaluating the overall survival of pancreatic cancer patients. Higher SII is associated with shorter overall survival.

Synthesis, and anti-inflammatory activities of gentiopicroside derivatives / 中国天然药物

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Characteristics of fusion gene expression in acute lymphoblastic leukemia / 中华病理学杂志

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.

Effects of Angong Niuhuang Pills against heart failure based on cross-scale polypharmacological study / 中国中药杂志

Angong Niuhuang Pills(AGNHP) are effective in clearing heat, removing the toxin, and eliminating phlegm for resuscitation. Clinically, it is widely used to treat various diseases such as febrile convulsion due to heat attacking pericardium, but its therapeutic effects on heart failure(HF) have not been well recognized. In this study, the profiles of differential metabolites regulated by AGNHP were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS). The underlying mechanism of AGNHP against HF was illustrated based on the integrated analysis of pharmacological data and metabolic molecular network. The HF model was induced by isoproterenol in mice. After oral administration of AGNHP for one week, cardiac functions in HF mice were evaluated by echocardiography, and serum samples of mice were collected for metabolomics analysis. Eight differential metabolites of AGNHP against HF were screened out through partial least square discriminant analysis(PLS-DA) and input into MetaboAnalyst for the analysis of metabolic pathways. Moreover, the critical metabolic pathways regulated by AGNHP were enriched according to the potential targets of major compounds in AGNHP. After AGNHP treatment, the recovered index of relative content of some metabolites underwent cross-scale fusion analysis with therapeutic efficacy data, followed by "compound-reaction-enzyme-gene" network analysis. It is inferred that the anti-HF effects of AGNHP may be attributed to the metabolism of arachidonic acid, amino acid, glycerophospholipid, and linoleic acid. The cross-scale polypharmacological analysis method developed in this study provides a new method to interpret scientific principles of AGNHP against HF with modern technologies.

New tirucallane-type triterpenoids from the resin of Boswellia carteriiand their NO inhibitory activities / 中国天然药物

Six new tirucallane-type triterpenoids (1-6), along with ten known triterpenoids, were isolated from methylene chloride extract of the resin of Boswellia carterii Birdw. By the application of the comprehensive spectroscopic data, the structures of the compounds were clarified. The experimental electronic circular dichroism spectra were compared with those calculated, which allowed to assign the absolute configurations. Compounds 5 and 6 possesed a 2, 3-seco tirucallane-type triterpenoid skeleton, which were first reported. Their inhibitory activity against NO formation in LPS-activated BV-2 cells were evaluated. Compound 9 showed appreciable inhibitory effect, with an IC

Progress of Tumor Infiltrating Lymphocytes in Immunotherapy of Triple Negative Breast Cancer / 中国医学科学院学报

Breast cancer has become the most common cancer for women in China.Lack of effective therapeutic targets,triple negative breast cancer(TNBC)has poorer prognosis compared with other subtypes of breast cancer.Tumor infiltrating lymphocytes(TILs)are a group of heterogeneous lymphocytes around the tumor,which are believed as immunoreactive products of host immune response to tumor antigens.At present,there have been reports on the predictive effect of TILs on the prognosis of breast cancer,and the available studies focus mainly on TNBC.This article briefly reviews the recent progress of tumor infiltrating lymphocytes in immunotherapy of TNBC.

Non-invasive electrical neuromodulation techniques: analgesic effects and neural mechanisms / 生理学报

As non-pharmaceutical interventions, non-invasive electrical neuromodulation techniques are promising in pain management. With many advantages, such as low costs, high usability, and non-invasiveness, they have been exploited to treat multiple types of clinical pain. Proper use of these techniques requires a comprehensive understanding of how they work. In this article, we reviewed recent studies concerning non-invasive electrical peripheral nerve stimulation (transcutaneous electrical nerve stimulation and transcutaneous vagus/vagal nerve stimulation) as well as electrical central nerve stimulation (transcranial direct current stimulation and transcranial alternating current stimulation). Specifically, we discussed their analgesic effects on acute and chronic pain, and the neural mechanisms thereof. We then contrasted the four kinds of nerve stimulation techniques, pointing out limitations of existing studies and proposing directions for future research. With more extensive and in-depth research to overcome these limitations, we shall witness more clinical applications of non-invasive electrical nerve stimulations to alleviate patients' pain and ease the crippling medical and economic burden imposed on patients, their families, and the entire society.

Chinese Medicine Prevention and Treatment of Tumor Based on Ferroptosis： A Review / 中国实验方剂学杂志

Ferroptosis is a new type of cell death caused by abnormal accumulation of iron-dependent reactive oxygen species （ROS） and imbalance of redox with the participation of iron ions. In recent years， studies have found that ferroptosis is associated with various diseases and can especially regulate the development of tumors. Chinese medicine has unique advantages in tumor prevention and treatment. How to use ferroptosis theory to guide the prevention and treatment of cancer and other tumor diseases by Chinese medicine is a new research hotspot. This paper summarizes the proposal， action mechanism， and signaling pathway of ferroptosis， its application in tumor therapy， and the research on the activity of Chinese medicine based on ferroptosis. Results found that the occurrence of ferroptosis is related to iron metabolism， lipid ROS metabolism， and other signaling pathways and gene expressions. Ferroptosis can regulate tumor initiation and development， treatment， and tumor immunity， which provides strategies for tumor treatment and anti-tumor drug development. By analyzing the biological activity of Chinese medicine against ferroptosis， we found that Chinese medicines （Scutellariae Radix， Puerariae Lobatae Radix， Astragali Radix， Ginkgo， Epimedii Folium， Artemisiae Annuae Herba， and Salviae Miltiorrhizae Radix et Rhizoma）， Chinese herbal compounds （ Naotaifang， Si Junzitang， and Shenmai injection）， and Chinese medicine effective components （baicalein， dihydroartemisinin， puerarin， piperlongumine， luteolin， and quercetin） can exert antitumor and other biological activities by regulating ferroptosis. Therefore， Chinese medicine has great potential in preventing and controlling tumors and other diseases by regulating ferroptosis. This paper provides theoretical basis and research ideas for the in-depth study of ferroptosis theory and guides the prevention and treatment of tumor diseases by Chinese medicine.

Advance in Application of Functional Reach Test (review) / 中国康复理论与实践

The evaluation of balance includes clinical observation, scales and instrumental measures. Functional Reach Test is simple and can be carried out in both standing and sitting, but the error of reading the measuring ruler is large, which results in new moving rulers and inertial sensors. The factors influencing the results of Functional Reach Test are moving strategy, age, moving efficiency, goal orientation, single or double arms, human characteristics, number of experiments and others. In the future, combination of electromyogram and inertia sensor can be used to discuss the variety of muscles and the changes of muscle strength, and more influence factors for the test are needed to research.

Effects of Kinesio Taping on Lower Limb Function for Stroke Patients at Different Recovery Stages / 中国康复理论与实践

Objective:To observe the effect of Kinesio taping on lower limb motor function in patients with hemiplegia at different stages of stroke. Methods:From August, 2015 to August, 2017, 60 patients at stages of Brunnstrom III (n = 30) and Brunnstrom IV (n = 30) were randomly divided into control group (n = 15) and treatment group (n = 15). All the patients received comprehensive rehabilitation training, while the treatment group taped Kinesio taping in the lower extremities, for four weeks. They were assessed with Fugl-Meyer Assessment-Lower Extremity (FMA-LE), Time 'Up & Go' Test (TUGT) and gait analysis before and after treatment. Results:The results of all the measurements improved after treatment in all the groups (P < 0.001). For the patients at Brunnstrom IV, FMA-LE score and walking speed improved more in the treatment group than in the control group after treatment (P < 0.01); for those at Brunnstrom III, FMA-LE score, walking speed, TUGT time, hip extension angle and gait symmetry improved more in the treatment group than in the control group after treatment (P < 0.05). Conclusion:Kinesio taping is effective on the lower limb motor function for patients with hemiplegia after stroke, especially for patients at Brunnstrom III.

Tetrahydroxystilbene glucoside protects against sodium azide-induced mitochondrial dysfunction in human neuroblastoma cells / 中草药·英文版

Objective: Mitochondrial dysfunction is evident in the early stage of Alzheimer's disease (AD). Therefore development of drugs that protect mitochondrial function is a promising strategy for AD. The present work was to investigate the effects of 2, 3, 5, 4′-Tetrahydroxystilbene-2-O-β-d-glucosides (TSG) on a mitochondrial dysfunction cell model induced by sodium azide and elucidate the underlying mechanisms. Methods: Mitochondrial membrane potential (MMP) was detected by a fluorescence method. Cellular adenosine triphosphate (ATP) level was measured using a firefly luciferase-based kit. Reactive oxygen species (ROS) was detected using dichlorofluorescin diacetate (DCFH-DA). The expression levels of Bcl-2 and Bax were measured by Western blotting assay. Flow cytometry was utilized to measure apoptosis. Results: Pretreatment of TSG (25–200 μmol/L) for 24 h significantly elevated MMP and ATP content, reduced ROS level and Bax/Bcl-2 ratio, and inhibited apoptosis in SH-SY5Y cells exposed to sodium azide. Conclusion: These results suggest that TSG protects SH-SY5Y cells against sodium azide-induced mitochondrial dysfunction and apoptosis. These findings are helpful to understand the protective effect of TSG on mitochondria, which are involved in the early stage of AD.

Application of Cell Membrane Chromatography Coupled with Mass Spectrometry in Screening of Active Ingredients of Traditional Chinese Medicines / 中国实验方剂学杂志

The chemical components (groups) contained in traditional Chinese medicine(TCM) and its compound preparations are the material basis for its curative effect, because of the integrity of the action of TCM and the complexity of its compositions and mechanism. The separation and analysis of chemical constituents in TCM and its compound prescriptions by various methods is always a key problem to be solved in the research of disease prevention and treatment of TCM. The binding of drug molecules to receptors at the cellular level was explored to provide a new idea for the screening of active components of TCM or its compound preparations. Traditional methods have some drawbacks, such as cumbersome operation, time-consuming, waste of solvents and irreversible adsorption of samples. The basic information of pharmacological parameters cannot be given in the separation process, and the active ingredients cannot be efficiently and accurately located. At present, cell membrane chromatography (CMC), one of the methods, is used to study the interaction between drug molecules and receptors, and can combine the existing chromatography and mass spectrometry technology, cell biology and receptor pharmacology, and correctly reflect the interaction between active parts, active components and cell membrane and membrane receptors, so it has unique advantages in screening effective parts, separation of active components and high-throughput screening from complex TCM system. The principles and characteristics of CMC, the cell membrane model in the field of active ingredient selection of TCM and its research status in combination with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were reviewed, and its development prospects and future research methods were discussed, which provides theoretical basis and practical guidance for the research and utilization of CMC in the field of TCM.

Feasibility of expanded indication for endoscopic submucosal dissection in undifferentiated early gastric cancer / 中华消化杂志

Objective:To evaluate the feasibility of expanded indication for endoscopic submucosal dissection (ESD) in undifferentiated early gastric cancer, to investigate the risk factors of lymph node metastasis (LNM), so as to provide the theoretical evidence for the choice of treatment.Methods:From June 2007 to December 2018, at the Affiliated Hospital of Qingdao University, the clinical and pathological data of 807 patients with undifferentiated early gastric cancer and undergoing gastrectomy plus lymphadenectomy were retrospectively analyzed. Chi-square test was performed to analyze the correlation between clinicopathologic characteristics of early gastric cancer and LNM. Multivariate logistic regression model was used to analyze the independent risk factor of LNM.Results:LNM was found in 17.2% (139/807) patients with undifferentiated early gastric cancer. And no LNM was detected in 110 patients who met the expanded indication of ESD. The results of univariate analysis indicated that LNM was significantly associated with increased carcinoembryonic antigen (CEA), tumour size, gross type, ulcer, invasion depth, lymphovascular invasion and perineural invasion ( χ2=4.500, 13.332, 16.611, 6.083, 51.064, 0.564 and 17.006, all P<0.05). The results of multivariate analysis demonstrated that the maximum diameter of tumor over 20 mm (odds ratio ( OR)=1.606, 95% confidence interval ( CI) 1.021 to 2.526, P=0.040), lymphovascular invasion ( OR=16.835, 95% CI 10.510 to 26.966, P<0.01), the depth of submucosal superficial invasion (≤500 μm ; OR=1.962, 95% CI 1.022 to 3.765, P=0.043) and the depth of submucosal deep invasion (>500 μm ; OR=3.014, 95% CI 1.753 to 5.181, P<0.01) were independent risk factors of LNM in early gastric cancer. Conclusions:The expanded ESD indication of undifferentiated early gastric cancer is applicable for endoscopic treatment considering the low risk of LNM. In early undifferentiated gastric cancer, maximum diameter of tumor over 20 mm, lymphovascular invasion, submucosal superficial and deep invasion are the independent risk factors of LNM.

Feasibility of expanded indication for endoscopic submucosal dissection in undifferentiated early gastric cancer / 中华消化杂志

Objective@#To evaluate the feasibility of expanded indication for endoscopic submucosal dissection (ESD) in undifferentiated early gastric cancer, to investigate the risk factors of lymph node metastasis (LNM), so as to provide the theoretical evidence for the choice of treatment.@*Methods@#From June 2007 to December 2018, at the Affiliated Hospital of Qingdao University, the clinical and pathological data of 807 patients with undifferentiated early gastric cancer and undergoing gastrectomy plus lymphadenectomy were retrospectively analyzed. Chi-square test was performed to analyze the correlation between clinicopathologic characteristics of early gastric cancer and LNM. Multivariate logistic regression model was used to analyze the independent risk factor of LNM.@*Results@#LNM was found in 17.2% (139/807) patients with undifferentiated early gastric cancer. And no LNM was detected in 110 patients who met the expanded indication of ESD. The results of univariate analysis indicated that LNM was significantly associated with increased carcinoembryonic antigen (CEA), tumour size, gross type, ulcer, invasion depth, lymphovascular invasion and perineural invasion (χ2=4.500, 13.332, 16.611, 6.083, 51.064, 0.564 and 17.006, all P<0.05). The results of multivariate analysis demonstrated that the maximum diameter of tumor over 20 mm (odds ratio (OR)=1.606, 95% confidence interval (CI) 1.021 to 2.526, P=0.040), lymphovascular invasion (OR=16.835, 95%CI 10.510 to 26.966, P<0.01), the depth of submucosal superficial invasion (≤500 μm ; OR=1.962, 95%CI 1.022 to 3.765, P=0.043) and the depth of submucosal deep invasion (>500 μm ; OR=3.014, 95%CI 1.753 to 5.181, P<0.01) were independent risk factors of LNM in early gastric cancer.@*Conclusions@#The expanded ESD indication of undifferentiated early gastric cancer is applicable for endoscopic treatment considering the low risk of LNM. In early undifferentiated gastric cancer, maximum diameter of tumor over 20 mm, lymphovascular invasion, submucosal superficial and deep invasion are the independent risk factors of LNM.

Modulation of Wnt/ß-catenin signaling in IL-17A-mediated macrophage polarization of RAW264. 7 cells

Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.

Regulatory Effect of Guben Fangxiao Decoction on Expression of TLR4 and TLR7 in Mice with Asthma Remission / 中国实验方剂学杂志

Objective:To observe the regulatory effect of Guben Fangxiao decoction on Toll-like receptor (TLR)4, TLR7, nuclear factor-kappa B p65 (NF-κB p65) and NF-κB inhibitor protein alpha (IκBα) in mice with asthma remission, in order to explore the mechanism of Guben Fangxiao decoction in treating asthma remission. Method:Respiratory syncytial virus (RSV) combined with chicken ovalbumin (OVA) was used to build asthma remission model in 3-week-old BALB/c mice. Sixty mice were divided into blank group, model group, dexamethasone group (0.001 g·kg-1), low,medium and high-dose Guben Fangxiao decoction group (6.5,13,26 g·kg-1), respectively. Intervention was given once a day for 28 days. After administration, the mice were put to death. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue and score the pulmonary inflammation. Western blot was used to detect the expressions of TLR4, TLR7, IκBα and nuclear NF-κB p65 in lung tissue of mice. Immunofluorescence was used to observe the expression of NF-κB p65 in cellnucleuses. Result:Compared with blank group, the lung tissue of model group showed obvious inflammatory cell infiltration (PκB p65 increased significantly (PκBα proteins increased significantly (PPκB p65 (PκB p65 (PκBα proteins (PConclusion:Guben Fangxiao decoction can alleviate airway inflammation, and its therapeutic effect may be achieved by regulating TLR4, TLR7, NF-κB p65 and IκBα.

Pharmacokinetics of Achyranthes bidentata on adjuvant arthritis rats by microdialysis and UHPLC-MS/MS / 中国中药杂志

To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 μg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg~(-1)+60 mg·kg~(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.

Effect of long non-coding RNAs on glycolytic pathway in primary liver cancer and related mechanisms / 临床肝胆病杂志

Primary liver cancer is a common malignant tumor with complex pathogeneses and has the features of insidious onset, high degree of malignancy, and poor prognosis. The change in glycolytic pathway is one of the most important differences between tumor cells and normal cells, and tumor cells prefer to generate energy from glycolysis. Aerobic glycolysis is often associated with the progression and poor prognosis of primary liver cancer. Long non-coding RNAs (lncRNAs) can influence the glycolysis pathway in many tumors by regulating glucose uptake and the expression and activation of glycolytic enzymes and thus play an important role in the development and progression of primary liver cancer, which suggests that lncRNAs can be used as a therapeutic target for liver cancer. This article summarizes the influence of lncRNAs on primary liver cancer and glucose metabolism and related mechanisms, so as to find potential and effective targeted therapies for primary liver cancer.

Slit/Robo pathway participates in luteal cells apoptosis / 生理学报

This study was aimed to examine the expression and function of Slit/Robo family members in mouse ovary. Real-time PCR was used to assess the mRNA expression levels of Slit/Robo family members, and immunohistochemistry was used to examine the location of Slit2 and Robo1 in the ovary. The mRNA and protein expression levels of Slit2 and Robo1 in early-, middle- and late-phase corpus luteum (CL) were examined by real-time PCR and immunohistochemistry, respectively. Blocking agent ROBO1/Fc chimera was used in the luteal cells in vitro to examine the function of Slit/Robo signaling pathway in mouse CL. The results showed that, among the Slit/Robo family members, the expression levels of ligand Slit2 and receptor Robo1 were the highest in mouse ovarian tissue. Moreover, both of them were specifically expressed in mouse luteal cells. Compared with proestrus ovaries, the expression levels of Slit2 and Robo1 mRNA in the ovaries during diestrus were significantly up-regulated (P < 0.01, P < 0.001). The mRNA expression levels of Slit2 and Robo1 in late-phase CL were significantly increased when compared with pregnant CL. Furthermore, blocking Slit/Robo signaling pathway with ROBO1/Fc chimera in the luteal cells in vitro significantly decreased the apoptotic rate of late luteal cells. These results suggest that Slit/Robo family members are mainly expressed in the late-phase CL of ovary and participate in luteal cells apoptosis.