Mechanism of Sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation / 中国药理学通报

Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.

Mechanism of Sophora tonkinensis Gagnep regulating leukocyte transendothelial migration pathway in improving acute pharyngitis based on network pharmacology / 中国药理学通报

Aim To elucidate the molecular mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis based on network pharmacology, animal experiments and quantitative real-time PCR.Methods The active components and targets of Sophora tonkinensis Gagnep were collected from the database of traditional Chinese medicinal systems databases and analysis platform(TCMSP). Targets related to acute pharyngitis were acquired through GeneCards, OMIM, DrugBank and Disgenet databases. After the common targets of the two were screened, the STRING database was used to construct the protein interaction network, and the Metascape platform was used for pathway analysis. At the same time, Cytoscape software was used to construct a network of "herbal-disease-component-target" and "herbal-disease-component-target-pathway" network. The acute pharyngitis models in rats were established to study the effect of water extract of Sophora tonkinensis Gagnep on acute pharyngitis in rats. Quantitative real-time PCR technology was used to study the effect of Sophora tonkinensis Gagnep on key gene targets in key pathways of pharyngeal tissues in rats with acute pharyngitis. Results In this experiment, 509 related targets of 21 active components of Sophora tonkinensis Gagnep were obtained, 2 167 related targets of acute pharyngitis were obtained, and 194 common targets of Sophora tonkinensis Gagnep and acute pharyngitis were obtained. KEGG pathway analysis screened 344 related signaling pathways, indicating that IL-17 signaling pathway, NF-kappa B signaling pathway and leukocyte transendothelial migration pathway might play a key role in the improvement of acute pharyngitis by Sophorae tonkinensis Gagnep. Animal experiments showed that the low dose group of Sophora tonkinensis Gagnep water extract had better therapeutic effect on acute pharyngitis. The results of quantitative real-time PCR showed that the low-dose group of Sophora tonkinensis Gagnep significantly down-regulated the expression levels of ITGB2, PIK3CA, PIK3CD and PTPN11 genes in leukocyte transendothelial migration pathway(P<0.05). Conclusions The above results show that Sophora tonkinensis Gagnep has the characteristics of multi-component, multi-target and multi-pathway synergy in improving acute pharyngitis, which provides a theoretical basis for further study on the complex mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis.

A new γ-valerolactone derivative from the roots of Ardisia crispa / 药学学报

Four compounds were isolated from the 70% EtOH extract of Ardisia crispa by using various chromatographic techniques, including silica gel, ODS and semi-preparative HPLC. The structures of 1-4 were elucidated based on physicochemical properties and spectroscopic data. These compounds were defined as crispalactone A (1), (+)-pinoresinol (2), 3,5-dimethoxy-4- hydroxyphenol-1-O-β-D-glucopyranoside (3) and (+)-schizandriside (4). Compound 1 is a new γ-valerolactone derivative, and compounds 2-4 are firstly isolated from Ardisia crispa.

Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

A six-herb Chinese medicine composition ointment as a promising candidate for treatment of hypertrophic scars / 中草药·英文版

Objective: To study the anti-hypertrophic scar effect of the six-herb Chinese medicine composition (SCMC) ointment on the rabbit ear hypertrophic scar models. Methods: The optimal formulation of SCMC ointment matrix was screened by the orthogonal designs and a series of evaluation tests. The SCMC ointment was prepared through emulsifying method. The rabbit ear hypertrophic scar models were established and used to investigate the anti-hypertrophic scar effect of SCMC ointment. Results: Our results demonstrated that all the quality control indications of the SCMC ointment met the requirements. Anti-hypertrophic scar activity results showed that all the rabbit ear scar tissues appeared different degrees of shrink and fading, and took an unobvious but palpable shift from hard to soft texture with the low, middle and high concentration SCMC ointments treatments in vivo. Additionally, on 21st day the scar area and thickness in different concentrations of SCMC ointment groups were significantly reduced than control group, in a concentration-dependent manner. The immunohistochemical results also indicated that the SCMC ointment had good anti-hypertrophic scar properties and could inhibit hypertrophic scar formation. Conclusion: The SCMC ointment could improve the blood circulation condition of hypertrophic scar tissues. Our research has demonstrated the Chinese medicine composition ointment with good anti-hypertrophic scar properties that could be used to treat hypertrophic scars. Meanwhile, it provides a theoretical basis for further clinical application.

Discovery and identification of a tadalafil analogue / 药学学报

A tadalafil analogue was detected during routine screenings from two "fatigue reliever, immunity enhancer" dietary supplements by using UHPLC/Q-TOF HRMS. The MS2 spectrum of this compound was almost identical to that of 2-hydroxypropylnortadalafil. However, the retention time of this analogue was different from that of the 2-hydroxypropylnortadalafil isomers. The analogue was purified by using preparative HPLC and the structure was elucidated by mass spectrometric and NMR spectroscopic experiments. The spectral data suggested that the analogue bore a 3-hydroxypropyl group instead of the N-methyl group in tadalafil. The structure was further confirmed by comparison of the 1H NMR spectra data with those of the reference standard, and thus named as 3-hydroxypropylnortadalafil. The structure is first reported in China.

Differential Proteomics Analysis of Endometriosis in Blood Stasis Syndrome / 中国结合医学杂志

OBJECTIVE@#To investigate the innate characters of 3 endometriosis (EMT) syndromes, blood stasis (BS), qi stagnation and blood stasis (QSBS) as well as Shen (Kidney) deficiency and blood stasis (KDBS) in terms of proteomics, lay a molecular biological basis for the differentiation of various blood stasis syndromes of EMT, establish a EMT microscopic syndrome differentiation and diagnosis system in terms of proteomics, discover the evolution principles and therapeutic targets of these EMT syndromes, and search their signifificant molecular markers and genetic intervention targets.@*METHODS@#Six specimens from the ectopic and entopic endometrium tissues of patients with EMT in each syndrome, BS, QSBS as well as KDBS, in the early proliferative phase of the menstrual cycle, and 6 specimens from normal endometrium tissues in the early proliferative phase of the menstrual cycle were obtained. Three groups were formed in each syndrome by mixing two random specimens in equal amount, and then their respective two-dimensional electrophoresis graphs were obtained after total protein extraction. Finally, the detected differences in protein expression were identifified through matrix-assisted laser desorption Ionization-time of flflight mass spectrometry (MALDI-TOF/MS) and protein database.@*RESULTS@#The results of differential proteins expressed in each syndrome were shown as follows: BS syndrome had 2 differential proteins in entopic endometrium and 1 differential protein in ectopic endometrium; KDBS syndrome had 3 in entopic endometrium and 3 in ectopic endometrium; and QSBS syndrome had 3 in entopic endometrium and 4 in ectopic endometrium. It was found out that annexin was highly expressed in both entopic and ectopic endometrium of KDBS syndrome; and myosin light chain 3 was highly expressed in both entopic and ectopic endometrium of QSBS syndrome.@*CONCLUSION@#There are differential protein expressions among the 3 EMT syndromes, which might be the inner origin of syndrome characters, and these differential proteins might be the candidate biomarkers for the pathogenesis of various EMT syndromes.

Bone Metabolic Markers in Patients with Obstructive Sleep Apnea Syndrome / 中华医学杂志(英文版)

Background@#Obstructive sleep apnea syndrome (OSAS) is prevalent in obesity and is associated with many metabolic abnormalities. The relationship between OSAS and bone metabolism is still unclear. The aim of this study was to investigate the relationship between the severity of OSAS and bone metabolic markers.@*Methods@#A total of 119 obese males were enrolled in this study in spring months from 2015 to 2017. All candidates underwent polysomnography, and their bone mineral density (BMD) and the serum levels of total procollagen type 1 N-terminal propeptide (t-P1NP), N-terminal midfragment of osteocalcin (N-MID), β-C-terminal telopeptide of type 1 collagen (β-CTX), vitamin D (VD), and parathyroid hormone (PTH) were measured. The analysis of variance and Pearson correlation analysis were performed for data analyses.@*Results@#No significant differences in the mean values of BMD were observed among the obesity, mild-to-moderate OSAS, and severe OSAS groups; and the serum levels of t-P1NP and β-CTX in the severe OSAS group were significantly higher than those in the obesity group (48.42 ± 23.78 ng/ml vs. 31.98 ± 9.85 ng/ml, P < 0.001; 0.53 ± 0.24 ng/ml vs. 0.41 ± 0.13 ng/ml, P = 0.011, respectively). The serum level of VD in the obesity group was significantly higher than those in the mild-to-moderate and severe OSAS groups (both P < 0.001), and decreased as the severity of OSAS increased (P < 0.001). The serum level of PTH in the severe OSAS group was significantly higher than those in the obesity and mild-to-moderate OSAS groups (both P < 0.001). The results of correlation analysis indicated that the level of apnea-hypopnea index (AHI) was correlated with the levels of t-P1NP (r = 0.396, P < 0.001), VD (r = -0.404, P < 0.001), and PTH (r = 0.400, P < 0.001), whereas the level of minimum Osaturation (SaOmin) was correlated with the levels of VD (r = 0.258, P = 0.016) and PTH (r = -0.376, P < 0.001).@*Conclusions@#The levels of bone resorption and formation markers in patients with severe OSAS were significantly increased compared to obese men, and the severity of OSAS was correlated with the serum levels of t-P1NP, VD, and PTH.

Clinical observation of percutaneous coblation nucleoplasty for the treatment of cervical spondylotic radiculopathy / 中国骨伤

<p><b>OBJECTIVE</b>To evaluate the clinical effects of percutaneous coblation nucleoplasty in treating cervical spondylotic radiculopathy and investigate its mechanism of action.</p><p><b>METHODS</b>Form January 2015 to January 2017, 21 patients with cervical spondylotic radiculopathy were treated by percutaneous coblation nucleoplasty, including 8 males and 13 females with an average age of 49.6 years old ranging from 43 to 61 years old. The course of disease was for 1 to 6 months with a median age of 4 months. Three cases were single segment, 9 cases were double segments, 7 cases were three-segment, 2 cases were four-segment. Intervertebral disc pressure, VAS were compared before and after operation. Angular displacement(AD) and horizontal displacement(HD) were measured by image data and in order to evaluate the cervical stability. Modified MacNab criteria was used to assess clinical effects.</p><p><b>RESULTS</b>All the patients were followed up from 1 to 12 months with an average of 8.6 months. Preoperative intervertebral disc pressure was (32.0±5.26) cmH2O and immediately after operation was (21.0±7.18) cmH2O, there was statistical significance between before and after operation(=0.003). Preoperative angular displacement and horizontal displacement was (3.85±1.26) ° and (1.23±0.58) mm, six months after operation was (4.18±1.31) ° and (1.69±0.46) mm, respectively. There was no statistical significance before and after operation(>0.05). Preoperative VAS scores were 7.49±0.53, postoperative at 3 days, 3, 6 months were 3.51±0.49, 2.63±0.61, 2.56±0.71, respectively, and postoperative obtained obvious improvement(<0.05). According to modified MacNab criteria, 6 cases obtained excellent results, 7 good, 4 fair 3 poor at 3 days;10 cases obtained excellent results, 5 good, 3 fair, 2 poor at 3 months; 12 cases obtained excellent results, 6 good, 1 fair, 1 poor at 6 months after operation. Postoperative clinical effect at 6 months was better than 3 d, and 3 months(<0.05), and postoperative at 3 months was better than 3 d(<0.05).</p><p><b>CONCLUSIONS</b>Percutaneous coblation nucleoplasty in treating cervical spondylotic radiculopathy can effectively relieve the pain of neck, shoulder and upper limb and can also relieve some associated symptoms such as headache and dizziness.</p>

Preparation of polyclonal antibody and establishment of chemiluminescence immunoassay for aldosterone / 中国免疫学杂志

Objective:The polyclonal antibody of aldosterone (ALD) for immunoassay was developed.And a chemiluminescence immunoassay (CLIA) for the determination of ALD in human blood was established.Methods:Aldosterone oxime was prepared by chemical modification and then conjugated with BSA to prepare immunogen.Rabbit anti ALD polyclonal antibody was prepared by immunizing rabbits with the ALD-BSA.The CLIA of ALD was performed using biotin streptavidin amplification system and competition method.Results:After identification,rabbit No.3 received the highest sensitivity to ALD antibody,and the 50％ binding inhibition (IC50) value for ALD concentration was 268 pg/ml.The measuring range of CLIA method using the antibody was 62.5-2 000 pg/ml.The assay sensitivity was 23.7 pg/ml.The intra-and inter-assay coefficients of variation were 6.9％-9.5％ and 8.5％-12.7％,respectively.Analytical recovery rate was in the range of 93.1％-104.1％.The correlation coefficient between measured and expected values were 0.996 after serial dilution.Compared with radioimmunoassay kit,the correlative equation was y =0.932x+4.596,the correlation coefficient was 0.948 (n =95).Conclusion:The result of methodological identification shows that it was in line with the basic requirements of clinical application.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients

Objective To evaluate the serum Prostaglandin E2 (PGE2) level in Acute-on-chronic liver failure (ACLF) and determine its predicative value for infection. Methods From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values to predict infection. Results Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB (P < 0.000 1). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication (P < 0.000 1). ROC analysis showed that serum PGE2 (area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/mL. Conclusions Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.

Effect of ERK1/2 Signaling Pathway Inhibitor PD98059 on the Expression of Ras, BRaf, MEK, ERK1/2 in Marrow Nucleated Red Blood Cells of CMS Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ERK1 / 2 signaling pathway inhibitor PD98059 on Ras, Raf, MEK, ERK1, ERK2 expression in order to explore a new way for basic research and clinical treatment of the chronic mountain sickness(CMS).</p><p><b>METHODS</b>Sixteen CMS patients were selected, the bone marrow was collected for isolation of monomuclear cells (MNC), the cells were sorted by using CD71 and CD235a antibody magnetic beads, then positive cells were diveded into 5 groups: blank control, DMSO and PD98059 5, 10 and 20 µmol/L, and were cultured in hypoxid condition for 72 hours. The Ras-GTP levels in supernatant was detected by ELISA, the RT-PCR was used to determine the expression of BRaf, MEK, ERK1, ERK2 mRNA in nucleated red blood cells, and the Western blot method was used to detect expression of BRaf, MEK, ERK1, ERK2 protein.</p><p><b>RESULTS</b>PD98059 had no effect on the level of Ras-GTP in each groups. Compared with the blank control group, the expression levels of BRaf, MEK mRNA in DMSO group were not statistically significant (P values were 0.826, 0.298). Compared with the PD98059 20 mol/L group, the expression level of ERK1/2 mRNA was statistically significant (P=0.001, 0.002). Compared with the blank control group, expression levels of p-BRaf, p-MEK protein in DMSO group were not statistically significant (P=0.370, 0.351). Compared with the PD98059 20 mol/L group, the difference of p-ERK1/2 protein level in other 4 groups were statistically significant (P values were <0.001, 0.007).</p><p><b>CONCLUSION</b>PD98059 can up-regulate the expressions of ERK1/2 miRNA and p-ERK1/2 protein in bone marrow nucleated red blood cells, the Ras / Raf / MEK / ERK 1/2 pathway is the main signal transduction pathway in regulating bone marrow nucleated red blood cells, suggesting that Ras/Raf /MEK /ERK 1/2 pathway may be involved in the pathogenesis of chronic mountain sickness process.</p>

Research progress of infection and drug-resistances mechanism of Enterobacter cloacae / 中国人兽共患病学报

Enterobacter cloacae is a facultative anaerobic Gram-negative bacteria,and it mainly causes pulmonary infection.It was one of the most common conditioned pathogens in recent years,and its treatment and drug resistances have attracted more and more attention.Meanwhile,there were many further studies about antimicrobial susceptibility and drug-resistance mechanisms of E.cloacae.E.cloacae shows multi-drug resistance to antibiotics through complex resistant mechanisms.The study gives a brief review on the infection treatments and drug-resistance mechanisms of Enterobacter cloacae.

Elevated serum prostaglandin E2 predicts the risk of infection in hepatitis B virus-related acute-on-chronic liver failure patients

OBJECTIVE@#To evaluate the serum Prostaglandin E2 (PGE2) level in Acute-on-chronic liver failure (ACLF) and determine its predicative value for infection.@*METHODS@#From April 2014 to April 2015, ninety-one patients with hepatitis B virus and ACLF but without infection were enrolled into this prospective study that was carried out at our Hospital. Twenty patients with stable chronic hepatitis B were enrolled from the outpatient department and twenty healthy control subjects without any disease were enrolled from hospital staff. Serum PGE2 levels were determined using ELISA at enrollment. Clinical and laboratory parameters were collected. Receiver operating characteristic (ROC) curves were used to determine optimal cut-off values to predict infection.@*RESULTS@#Significantly higher PGE2 levels were found in patients with ACLF in comparison with healthy controls and patients with stable CHB (P < 0.0001). In ACLF patients, PGE2 levels were significantly higher in patients that eventually developed infection than those without this complication (P < 0.0001). ROC analysis showed that serum PGE2 (area under the ROC curve, 0.83) could predict infection in patients with ACLF with sensitivity of 78.4% and specificity of 81.5% using a threshold of 141 pg/mL.@*CONCLUSIONS@#Serum PGE2 is associated with the susceptibility to secondary infections for patients with ACLF. Increased PGE2 serum levels may serve as a potential biomarker for developing infections in ACLF patients.

Influence of GATA-1 on Expression of EpoR in Bone Marrow CD71+ Cells of Rat Model with High Altitude Polycythemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the influence of GATA-1 on expression of EpoR in bone marrow CD71+ cells of rat model with high altitude polycythemia (HAPC).</p><p><b>METHODS</b>Forty-eight male SD rats were randomly divided into normal control and HAPC model group. HAPC model was established at the altitude of 4 300 meters in the natural environment, and verified by bone marrow cell counts and hematological parameters. Myeloid CD71+ cells were separated by the density gradient centrifugation combined with magnetic activated cell sorting. The expression of EpoR on cell membrane was detected by flow cytometry and cell immunofluorescence. The expression changes of GATA-1 and EpoR mRNA and protein were detected by Q-PCR and Western blot, respectively. CD71+ cells were cultured under normoxia and hypoxia, respectively. After transfection for 96 h, the optimal interference sequence GATA-1 shRNA1 was selected. And the mRNA and protein expression level of GATA-1 and EpoR were detected by Q-PCR and Western blot respectively.</p><p><b>RESULTS</b>The animal model with HAPC was established successfully and comfirmed by the bone marrow cell counting and the hematologic parameters in comparison with that of the normal control. EpoR expression on the myeloid CD71+ cell membrane in HAPC group was significantly higher than that in normal control (P<0.05). The expression of GATA-1 and EpoR in myeloid CD71+ cells of HAPC group was higher than that in control group (P<0.05). The mRNA and protein expression of GATA-1 and EpoR in two groups positively correlated (control group, r=0.929, P<0.01, r=0.802, P<0.05; HAPC group, r=0.822, P<0.05, r=0.839, P<0.01). However, the mRNA and protein expression of EpoR at normoxia and hypoxia was significantly lower than that in negative control group after interfernce with GATA-1 shRNA1 for 96 h (P<0.05). And the expression of GATA-1 and EpoR under hypoxia was higher than that in normoxia.</p><p><b>CONCLUSION</b>The effect of GATA-1 on EpoR expression may be correlated with the pathogenesis of HAPC.</p>

Effect of PD98059 on Proliferation and Apoptosis of CD71(+),CD235a(+) Nucleated Erythrocytes in the Patients with High Altitude Polycythemia / 中国实验血液学杂志

<p><b>UNLABELLED</b>Objective： To study the effect of PD98059, a specific inhibitor of Ras/Raf/MEK/ERK signaling pathway, on the proliferation and apoptisis of bone marrow CD71(+), CD235a(+) nucleated erythrocytes in patients with high altitude polycythemia (HAPC) and the pathogenesis of HAPC.</p><p><b>METHODS</b>The CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients and controls (patients with simple obsolete stracture) were sorted by using the immunemagnetic beads, then were added with 5, 10, 20 µmol/L of PD98059 and DMSO (as control) and were cultured for 72 h under hypoxia. The cell apoptosis was detected by flow cytometry with Annexin V and PI double staining, the cell proliferation was detected by CCK8 method, at same time the erythroid colong-formation ability of bone marrow mononuclear cells (BMMNC) treated with 5, 10, 20 µmol/L of PD98059 and DMSO was observed.</p><p><b>RESULTS</b>With the increase of PD98059 concentration, the apoptosis rate of bone marrow CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients was enhanced (r=0.807,P<0.01), while the proliferation rate of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients dereased (r=0.502,P<0.01). The erythroid colong-formation ability of BMMNC in HAPC patients decreased with the increase of PD98059 concentration (r=0.504,P<0.01). There were statistic differences among different groups at 7 and 14 d.</p><p><b>CONCLUSION</b>The MEK specific inhibitor PD98059 can inhibit the proliferation and promote the apoptosis of CD71(+) and CD235a(+) nucleated erythrocytes in HAPC patients, then inhibit the excessive accumulation of erythrocytes.</p>

Research on effect of Sargentodoxae caulis on activity of osteoclasts and proliferation differentiation of osteoblasts / 中国中药杂志

Through morphological observation, HE staining, TRAP staining and toluidine blue staining of bone resorption pits to identify osteoclasts which obtained by 1α, 25-(OH)2 VitD3 inducing rabbit bone marrow cells. Three indicators-TRAP staining, TRAP enzyme activity detecting and the number and area of bone resorption pits were adapted to detect the effect of Sargentodoxae caulis on the activity of osteoclasts. Culturing MC3T3-E1 Subclong 14 cells and detecting the effect of S. caulis on differentiation and proliferation of them by MTT and detecting the alkaline phosphatase in cells. The results show that all of the low, middle and high doses of water and alcohol extracts of S. caulis have significant inhibition on osteoclast differentiation and bone resorption ability in a dose-dependent manner. The low and middle doses of water and alcohol extracts of S. caulis can stimulate differentiation and proliferation of MC3T3-ElSubclone 14 cells, which indicates S. caulis can prevent osteoporosis and the function could be achieved by inhibiting osteoclast activity and promoting the proliferation and differentiation of osteoblasts.

The in vitro anti-atherosclerotic activity of compound IMB-1680 / 药学学报

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.

Magnetic resonance imaging features of vulnerable plaques in an atherosclerotic rabbit model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Noninvasive detection of vulnerable plaque has a significant implication for prevention and treatment of atherosclerotic diseases. The aim of this study is to investigate the difference between vulnerable plaques and stable plaques in magnetic resonance (MR) images.</p><p><b>METHODS</b>Atherosclerosis was induced in twenty male New Zealand white rabbits by high cholesterol diet and balloon injury of the abdominal aorta. After baseline (pre-triggering) MR imaging (MRI) scan, the rabbits underwent pharmaceutical triggering with Russell's viper venom and histamine to induce atherothrombosis, followed by another MRI scan 48 hours later (post-triggering). Rabbits were euthanized to obtain pathological and histological data. The results of MRI were compared with those of pathology and histology.</p><p><b>RESULTS</b>MRI showed that abdominal aorta of the rabbits had pathological change of atherosclerosis in different degrees. Seventy-five plaques were analysed, among which 14 had vulnerable thrombi and 61 stable. Thrombosis was identified in 7 of 11 rabbits by post-triggering MRI, the sensitivity and K value of MR in detection of vulnerable plaque was 71% and 0.803 (P < 0.05). MRI data significantly correlated with the histopathological data in fibrous cap thickness (r = 0.749) plaque area (r = 0.853), lipid core area (r = 0.900). Compared with stable plaques, vulnerable plaques had a significantly thinner fibrous cap ((0.58 ± 0.27) mm vs. (0.95 ± 0.22) mm), larger lipid core area ((7.56 ± 2.78) mm(2) vs. (3.29 ± 1.75) mm(2)), and a higher ratio of lipid core area/plaque area ((55 ± 16)% vs. (27 ± 17)%), but plaque area was comparable in two groups on MRI. The ratio of lipid core area/plaque area was a strong predictor of vulnerable plaques.</p><p><b>CONCLUSION</b>MRI could distinguish vulnerable plaques from stable plaques in a rabbit model of atherothrombosis and may thus be useful as a noninvasive modality for detection of vulnerable plaques in humans.</p>

Evaluation of medicinal reasonableness and resource utilization of Dida (Zang Yin Cheng) commonly used in Tibetan medicine / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the medicinal reasonableness and resource utilization of Dida from different species.</p><p><b>METHOD</b>With common characteristic absorption peaks of HPLC fingerprints and SPSS cluster, the composition similarity of Dida from different species was evaluated.</p><p><b>RESULT</b>The composition similarity of HPLC fingerprints of 33 Dida samples from 15 species and 1 variety originated from Swertia, Halenia, Gentianopsis, Lomatogonium was difference. The original species can be clustered into four groups by the relative area of 10 common characteristic peaks of HPLC fingerprints. The compositions of four different genera are quite different.</p><p><b>CONCLUSION</b>Because of containing iridoids, xanthones, and triterpenes which have liver protection and cholagogue functions, all of species from Swertia, Halenia, Gentianopsis and Lomatogonium in Gentianaceae are classified as Dida in Tibetan medicine. According to the composition difference among different species, the HPLC fingerprints established for Dida from different source are an effective means to identify nd control the quality of Dida.</p>