Objective: To investigate the value of MDM2 RNA in situ hybridization (RNA-ISH) in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and dedifferentiated liposarcoma (DDL). Methods: A total of 26 ALT/WDL/DDLs diagnosed from March 2017 to May 2019 in West China Hospital, Sichuan University, Chengdu, China and 18 control cases were included. MDM2 RNA-ISH was performed on all samples and compared with the fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) regarding their performance in detecting MDM2. Results: All samples were detected successfully using the three methods. Among 26 ALT/WDL/DDLs, all cases showed MDM2 amplification and positivity for MDM2 RNA-ISH (26/26, 100%). Twenty-four (24/26, 92.3%) of the 26 tested cases were positive for MDM2 IHC while two of them were negative. Eighteen control cases were all negative for MDM2 FISH and RNA-ISH, and 15 (15/18) cases were negative for MDM2 IHC. The sensitivity and specificity of RNA-ISH were both 100%, and those of MDM2 IHC were 92.3% and 83.3%, respectively. Diffuse staining was identified in all MDM2 RNA-ISH positive ALT/WDL/DDLs, but identified in only 8/24 (33.3%) of the MDM2 IHC positive cases. Among the 11 ALT/WDL/DDL samples evaluated on tissue microarray, the positive rate of MDM2 RNA-ISH was 100% with diffuse staining in all cases. The positive rate of MDM2 IHC was 9/11 while only 1 of the 9 cases showed diffuse staining. The result of MDM2 RNA-ISH was identical to that of MDM2 FISH and was overall consistent with that of MDM2 IHC (Kappa=0.763, P<0.001). Conclusions: In ALT/WDL/DDLs, results of MDM2 RNA-ISH are highly consistent with those of FISH. MDM2 RNA-ISH is more sensitive and more specific and has more diffuse positive signals than the IHC. The findings indicate that MDM2 RNA-ISH is highly valuable for the diagnosis and differential diagnosis of ALT/WDL/DDLs.
Biomarkers, Tumor/genetics* ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Liposarcoma/genetics* ; Proto-Oncogene Proteins c-mdm2/genetics* ; RNA

Objective:To explore the antidepressant mechanism of Yinxing Mihuan oral solution （YMO） by investigating its effect on depression model rats. Method:The depression rats were induced by isolation combined with chronic unpredictable mild stress （CUMS） and then randomly divided into model group， fluoxetine group （10 mg·kg^-1） and high-dose （618 mg·kg^-1） and low-dose （309 mg·kg^-1） YMO groups. A blank control group was also set up and ten rats were included in each group. Modeling lasted for 21 consecutive days， and rats were administered the 8th day after stimulation at a dose of 10 mL·kg^-1 for 14 days， except those in the blank control and model groups which were given distilled water. Afterward， the sucrose preference test， open field test， tail suspension test were carried out. The pathological changes of hippocampus in depression rats were observed after hematoxylin-eosin （HE） staining. The content of interleukin-1β （IL-1β）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats in each group and the expression of NOD-like receptor 3 （NLRP3） and other proteins in its related activation signaling pathways were detected with multi-factor detection （Luminex） and Western blot. Result:After 14 days of continuous administration， compared with the blank control group， the model group witnessed significantly reduced sugar water consumption rate and the times of rearing and significantly prolonged cumulative time of immobility during tail suspension （P<0.05， P<0.01）. Compared with the model group， the fluoxetine group and the high-dose YMO group saw increases in the times of rearing， times of crossing and sugar water consumption rate and a significant decrease in the cumulative time of immobility during tail suspension （P<0.05， P<0.01）. The results of HE staining showed that the neurons in the hippocampus of rats in the high-dose YMO group were arranged in order and slightly loosened， without obvious microglia infiltration observed. The levels of IL-1β， IL-6 and TNF-α in the hippocampus of the model group increased significantly as compared with the blank control group （P<0.05， P<0.01）， and their content in the high-dose YMO group was significantly lowered in the comparison with the model group （P<0.05， P<0.01）. Molecular biology experiments demonstrated that compared with the results of blank group， the expression of purinergic receptor P2X7 （P2RX7）， NLRP3， apoptosis-associated speck-like protein （ASC）， Caspase-1 and IL-1β remarkably increased in the model group （P<0.05， P<0.01）. Additionally， the expression of P2RX7， NLRP3， ASC， Caspase-1 and IL-1β was significantly inhibited in the fluoxetine group and the high-dose YMO group compared with the model group （P<0.05， P<0.01）. Conclusion:YMO can improve the depression-like behaviors of rats induced by isolation combined with CUMS， and its mechanism of action is related to the regulation of the P2RX7/NLRP3 signaling pathway.

Objective To explore the correlation of progesterone and expression of extrasynaptic δ-subunits containing γ-aminobutyric acid type A receptors (δGABA

Drainage ; Humans ; Pancreas ; surgery ; Pancreaticoduodenectomy ; Stents

The Concurrent treatment of the brain and heart (CTBH) theory is proposed based on traditional Chinese medical theory and clinical practice. In this study, a framework for the pharmacological research platform was established to investigate the principles of concurrent treatment of the brain and heart. The platform for CTBH includes several key techniques for network modeling, discovery of active substances, dissecting mechanism of action and investigation of pharmacokinetic property of TCM. Taking network modeling of CTBH as an example, using database search, literature mining, network construction and module analysis, the that network modules closely associated with the pathological progress of cardiovascular and cerebrovascular diseases were identified, while further functional enrichment analysis of these modules indicated that the key biological processes included oxidative stress, metabolism and inflammation. GSK3B, NOTCH1, CDK4 were identified as key nodes in these network modules. The above-mentioned platform was applied to construct component-biomolecules network of Danhong injection for the identification of common targets and pathways. Among them, GSK3B had the highest correlation with the composition of Danhong injection in the network, and the biological function of whose cluster was related to cell oxidative stress. Based upon results of network analysis, validation experiments suggested that Danhong injection significantly improved the survival rate of oxidative injured myocardial cells and nerve cells, and the protective effect was related to the increase of phosphorylated GSK3β protein expression. Moreover, extracts of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos exerted the synergisticcytoprotective effect. The results indicated that the mechanism of treatment of cardiovascular and cerebrovascular diseases of Danhong injection could be studied through network modeling and other methods. In summary, the proposed pharmacological platform provided a feasible way for revealing the mechanism of CTBH by using modern scientific methods.

OBJECTIVETo analyze serum levels of non-esterified fatty acids (NEFA) and albumin (ALB) in children with nephrotic syndrome (NS) and investigate the clinical significance of altered serum NEFA to ALB ratio in children with NS in acute and remission phases.

METHODSSerum levels of NEFA and ALB were measured in 55 NS children in acute phase, in 33 NS children in remission and in 122 healthy control children, and the ratio of NEFA to ALB was calculated. The other lipid/lipoprotein and renal function parameters were also analyzed in these children.

RESULTSCompared with the healthy control children, children with NS had a significantly decreased serum ALB level (t=11.152, P<0.001) and a significantly increased NEFA to ALB ratio (t=4.991, P<0.001). Compared with NS children in remission, those in acute phase showed a significantly decreased ALB (Z=7.822, P<0.001) and an increased NEFA to ALB ratio (t=4.991, P<0.001). In all the NS children, NEFA to ALB ratio was positively correlated with the levels of TC (r=0.564, P<0.001), TG (r=0.444, P<0.001), LDL-C (r=0.625, P<0.001), urea (r=0.437, P<0.001), creatinine (r=0.278, P=0.013), and uric acid (r=0.397, P<0.001), while negatively correlated with the level of total protein (r=-0.461, P<0.001). Multiple linear regression analyses showed that NEFA to ALB ratio was independently associated with serum urea levels (β=0.703, P=0.001; adjusted R=0.494) after adjustment of other related factors.

CONCLUSIONSerum NEFA to ALB ratio is significantly increased in NS children in close association with impaired kidney function, and may function as a novel parameter for assessing the development of NS.

Case-Control Studies ; Child ; Fatty Acids, Nonesterified ; blood ; Humans ; Nephrotic Syndrome ; blood ; Regression Analysis ; Serum Albumin, Human ; analysis

Naoxintong capsule has beneficial effects for activating blood circulation, dispersing blood stasis and dredging collateral. It is widely used in the treatment of coronary heart disease, angina pectoris, stroke and cardiovascular disease. However, the pharmacodynamic basis and possible mechanism of its preventive effects are not clear. In this study, 10 male and 10 female C57BL/6 mice were used, and were randomly divided into the control group (saline) and Naoxintong group. Adaptively fed for 7 days in common conditions, mice were given Naoxintong capsule or saline for 3 days via intragastric administration. Serum was collected from 6 mice in each group 1 h after the last administration. Serum proteins were prepared to do two-dimensional gel electrophoresis. Then image analysis and mass spectrometry detection were carried out to screen and identify the differentially expressed proteins and make bioinformatics analysis. It was found that 24 differentially expressed proteins between Naoxintong group and control group. Compared with the control group, 12 proteins were increased, and 12 were decreased. The proteins were involved in apoptosis signal pathway and vascular endothelial growth factor signal transduction pathway, in which vasohibin-1 is a negative feedback regulation factor in angiogenesis. Western blot showed that the expression of vasohibin-1 in Naoxintong group was reduced, which is consistent with the result in two-dimensional electrophoresis. Serum proteins expression is different between Naoxintong and control groups. The targets of these differentially expressed proteins include endothelial cells, inflammatory cells and platelets. The changes on proteins showed that Naoxintong capsule may ameliorate coronary heart disease and ischemic cerebrovascular disease, and provide potential biological markers to prevent ischemic disease.

Objective To investigate suitable points and approach for the clinical pharmacists to carry out pharmaceutical care for an intensive care unit( ICU) heart failure patient with amyloid cardiomyopathy caused by myeloma.Methods The clinical pharmacists take part in clinical rounds, give suggestions on treatment and carry out pharmaceutical care.For the complex treatment cases, the clinical pharmacists find useful in-formation from the literature and provide professional medicine support for the clinical treatment.Results and Conclusion The clinical pharma-cists take part in the clinical work and give professional suggestions,which can improve the treatment effect and decrease the adverse reactions.

AIM: To establish the Spectrum-Effect integrated fingerprint of Polygonum cuspidatum to evaluate the quality of P. cuspidatum. METHODS: An on-line HPLC-DAD-flow injection chemiluminescence (FICL) method was developed to investigate the quality of P. cuspidatum from different habitats based on the established Spectrum-Effect integrated fingerprint. RESULTS: Nineteen batches of samples of P. cuspidatum were evaluated for the similarity of their chromatographic and free radical scavenging fingerprints, and the results compared. Main antioxidants were estimated by regression analysis between peak areas of thirteen compounds and their activities. Some active compounds were identified by HPLC-ESI-MS. CONSULSIONS The results indicated that main antioxidants in P. cuspidatum could be rapidly screened by the established Spectrum-Effect integrated fingerprint based on on-line HPLC-DAD-FICL, and would be more efficient and objective method to evaluate the quality of P. cuspidatum.
Antioxidants ; analysis ; Chromatography, High Pressure Liquid ; instrumentation ; methods ; Drugs, Chinese Herbal ; analysis ; Fallopia japonica ; chemistry ; Flow Injection Analysis ; Luminescence ; Quality Control

The microbial transformation of buflomedil by Cunninghamella blakesleana AS 3.153 was studied, as well as a microbial model which can be used to mimic metabolism of buflomedil in mammal was established. Experiments were conducted to screen the capabilities of four strains of Cunninghamella species to transform buflomedil, in which C. blakesleana AS 3.153 was selected for a preparative biotransformation. Furthermore, the microbial model was established based on the transformation condition optimization. The parent drug and its metabolites produced by C. blakesleana AS 3.153 were detected by liquid chromatography-mass spectrometry method and three metabolites were identified while two of them were new found metabolites. Two major metabolites, para-O-desmethyl buflomedil and 12-C-oxidated buflomedil, were isolated by semi-preparative HPLC. Based on the comparison between different species, the microbial transformation of buflomedil by C. blakesleana AS 3.153 is more similar to the metabolism of buflomedil in human and Beagle dog than that in rat.
Adult ; Animals ; Biotransformation ; Chromatography, High Pressure Liquid ; Cunninghamella ; metabolism ; Dogs ; Female ; Humans ; Male ; Molecular Structure ; Pyrrolidines ; chemistry ; pharmacokinetics ; Rats ; Rats, Wistar ; Spectrometry, Mass, Electrospray Ionization ; Young Adult