OBJECTIVE: To evaluate the effects of madecassoside (MC) on the depression behavior of mice and the activities of monoamine oxidase (MAO) in different rat brain regions. METHODS: Imipramine as the positive contrast medicine, effects of MC on the depression behavior of mice were observed by forced swimming test and reserpine antagonist test. Moclobemide and pargyline as the positive controlled medicines, the activities of monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) in different rat brain regions were determined after intragastric administration of MC in 3 different dosages for 3 days or 21 days. RESULTS: (1) The low, middle and high dosages of MC (i.g.) significantly reduced the immobility time of mice in forced swimming test (P<0.05). (2) MC in dosages of 10 mg/kg and 20 mg/kg prevented the lowering of temperature induced by reserpine (P<0.05), while 40 mg/kg had no significant effects on it (P>0.05). (3) With acute administration (3 days), the low, middle and high dosagey of MC (i.g.) significantly inhibited the activity of MAO-A in hippocampus (P<0.01), and the high dosage significantly inhibited the activity of MAO-A in hypothalamus (P<0.01), while the 3 dosages had no significant effects on the activity of MAO-A in cortex (P>0.05). With chronic administration (21 days), MC in 3 dosages had no significant effects on the activities of MAO-A in cortex and hypothalamus (P>0.05), and the high dosage (40 mg/kg) significantly enhanced the activity of MAO-A in hippocampus (P<0.01). (4) With acute administration, MC in dosages of 10 mg/kg and 20 mg/kg significantly inhibited the activity of MAO-B in cortex (P>0.05), and MC in dosage of 10 mg/kg significantly inhibited the activity of MAO-B in hypothalamus (P<0.05), and MC in dosage of 20 mg/kg significantly enhanced the activity of MAO-B in hippocampus (P<0.01). With chronic administration, MC of 3 dosages produced no significant effects on the activities of MAO-B in 3 different rat brain regions (P>0.05). CONCLUSION: These results support the idea that MC produces antidepressant effects through MAO inhibition in rat brain, which seems stronger with acute administration than chronic administration, while its mechanism remains to be further studied.

Objective To screen the optimal regimen of Chinese medicine combined with hormones for the treatment of premature ovarian failure(POF)using network meta-analysis and to provide an evidence-based basis for the clinical treatment of POF.Methods The randomized controlled trials(RCTs)of Chinese medicine combined with hormones in the treatment of POF were retrieved from thhe domestic and oversea databases of CNKI,VIP,Wanfang,CBM,PubMed,Cochrane,Embase,and Web of Science.The quality of the literature was assessed using the tools for analysis of bias recommended by Cochrane Reviewer's Handbook and by Jadad scale scores.Rstudio and StataSE 15.1 statistical software were used to perform network meta-analysis and graphical presentation of the data.Results A total of 50 RCTs were included,covering 8 intervention methods.The overall risk of bias of the included studies was low,but the quality of the literature was generally low.The results of network meta-analysis showed that,in terms of the effective rate,the intervetion of 7 various Chinese medicines combined with hormone was superior to the conventional treatment(hormone replacement therapy,HRT)in the control group,and Nuangong Qiwei Powder+HRT was superior to the remaining 6 kinds of Chinese medicines combined with HRT;with reference to the values of the surface under the cumulative ranking curve(SUCRA),the efficiencies of the effective rate of the 8 intervention methods in descending order were Nuangong Qiwei Powder+ HRT(SUCRA=81.2),Zishen Yutai Pills + HRT(SUCRA=80.0),modified Zuogui Pills + HRT(SUCRA= 66.1),Ankun Zhongzi Pills + HRT(SUCRA=49.6),Kuntai Capsules + HRT(SUCRA=45.2),modified Erxian Decoction + HRT(SUCRA=39.5),Liuwei Dihuang Pills + HRT(SUCRA=37.4)and HRT(SUCRA=1.0).In terms of improving serum follicle-stimulating hormone(FSH)levels,modified Zuogui Pills + HRT was superior to the remaining 7 intervention methods;with reference to the values of the SUCRA,the efficiencies of the 8 intervention methods in descending order were modified Zuogui Pills + HRT(SUCRA=97.0),HRT(SUCRA= 77.9),Liuwei Dihuang Pills + HRT(SUCRA=76.6),Kuntai Capsules + HRT(SUCRA=46.5),Nuangong Qiwei Powder+HRT(SUCRA=38.9),Ankun Zhongzi Pills + HRT(SUCRA=29.9),modified Erxian Decoction + HRT(SUCRA=18.1),and Zishen Yutai Pills + HRT(SUCRA=15.1).Conclusion All kinds of Chinese medicines combined with HRT exert stronger effect on improving the primary outcome indicators than HRT alone for the treatment of POF.The intervention with Nuangong Qiwei Powder+HRT exerts the highest probability of the optimal regimen for enhancing the efficiency,and the intervention with Zuogui Pills + HRT exerts the highest probability of the optimal regimen for lowering the serum FSH level.However,due to the low quality of the included studies,more rigorously-designed,large sample-size,and high-quality randomized controlled trials need to be conducted in the future to provide conclusive evidence-based evidence.

OBJECTIVETo observe the effect of chronic arsenic exposure on cerebral cortex and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity.

METHODSTwelve 3-week-old male C57BL/6J mice were randomly assigned into exposure group and control group and exposed to sodium arsenite (50 mg/L) via drinking water and deionized water for 12 weeks, respectively. After the exposure, arsenic level in the cerebrum was determined by hydride generation-atomic fluorescence spectrometry. The metabolites in the cerebral cortex and serum were determined using gas chromatography-mass spectrometry (GC/MS) analysis. Principal component analysis (PCA) was used to analyze the difference of the metabolites between the exposure and the control groups. Online tools for analyzing metabolic pathways were used to identify the related metabolites pathways.

RESULTSArsenic content in the brain of exposure group was significantly higher than that in the control group (P<0.05). The mice exposed to arsenic had a higher level of citric acid, phenylalanine, tyrosine, histidine and lysine in the cerebral cortex (P<0.05). Serum levels of serine, glycine, proline, aspartate and glutamate were significantly higher while α-ketoglutaric acid level was significantly lower in the exposure group than in the control group (P<0.05). PCA analysis showed a significant difference in cerebral cortex and serum metabolites between the two groups.

CONCLUSIONChronic arsenic exposure may affect the function of the central nervous system by interfering with amino acid metabolism and tricarboxylic acid cycle, which may be one of the mechanisms of arsenic neurotoxicity.

AIMTo elucidate the molecular mechanism of cell cycle arrest and apoptosis of MCF-7 cells induced by paclitaxel.

METHODSFlow cytometry was used to determine the cell cycle changes of MCF-7 cells upon paclitaxel treatment. Gene expression profiles of MCF-7 cells induced by paclitaxel were obtained by using cDNA microarrays containing 9984 genes and expressed sequence tags (ESTs).

RESULTSCell cycle analysis showed that 77.8% of cells arrested at G2/M phase and 1.3% of cells underwent apoptosis upon 100 nmol x L(-1) paclitaxel treatment for 24 hours; cDNA microarray results revealed that 27 and 77 genes were differentially expressed upon 12.5 nmol x L(-1) (IC50) and 100 nmol x L(-1) paclitaxel treatment, respectively.

CONCLUSIONPaclitaxel stabilized microtubules and caused G2/M cell cycle arrest and apoptotic cell death in a concentration-dependent manner, which is associated with the regulation of selected genes related to microtubule assembly and cytoskeleton, cell cycle regulation, and DNA repair and apoptosis.

Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; genetics ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; DNA Repair ; drug effects ; Dose-Response Relationship, Drug ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Oligonucleotide Array Sequence Analysis ; Paclitaxel ; administration & dosage ; pharmacology

AIM To establish a GC method for the simultaneous determination of β-eudesmol,atractylon,atractylodin,atractylolide Ⅰ,atractylaxanthin Ⅱ and (4E,6E,12E)-tetradecene-8,10-diyne-1,3-diacetate in Atractylodes rhizome,and cluster analysis of A.rhizome according to the content level.METHODS The analysis of A.rhizome solution was performed on an HP-5 capillary column (30 m × 0.32 mm,0.25 μm) with FID as the detector,the initial temperature 100 ℃,with 10 ℃/min to 135 ℃;with 1 ℃/min to 150 ℃;with 50 ℃/min to 200 ℃ (keeping 6 minutes),and with 50 ℃/min to 250 ℃ (keeping 8 minutes).The FID detector temperature was 300 ℃ and the injector temperature was 250 ℃,with the flow rate carrier gas 1.4 L/min;The tail gas was N2 (99.999％),with the ratio of carrier gas Air ∶ H2 ∶ N2 =400 ∶ 30 ∶ 25;The sample volume was 1 μL,and the split ratio was 20 ∶ 1.The results were analyzed by cluster analysis with SPSS 21.0 statistical software.RESULTS Six constituents showed good linear relationships within their own ranges (r ＞ 0.999 6),whose average recoveries were 99.46％-100.95％ with the RSDs of 0.09-0.41.A.rhizome was divided into three categories.CONCLUSION This accurate,stable and reproducible method can be used for the quality control of A.rhizome.

This study aimed to explore the mechanism of Tanreqing Injection in the treatment of acute lung injury(ALI) based on network pharmacology and molecular docking. The active components and action targets of Tanreqing Injection were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), PubChem, and SwissTargetPrediction databases, as well as available literature reports. The ALI-related targets were obtained from the GeneCards database and then mapped with Tanreqing Injection targets. Following the construction of "drug-component-potential target" network with Cytoscape 3.6.1, the potential targets were input into STRING to yield the protein-protein interaction(PPI) network, which was plotted using Cytoscape 3.6.1. Then the screened key targets were subjected to gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis based on DAVID database. The top three key targets RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB) and interleukin-6(IL6) were docked to the top three key compounds by PyMOL and AutoDock vina. A total of 58 active components of Tanreqing Injection, 597 corresponding targets and 503 common targets shared by Tanreqing Injection and ALI were fi-gured out, with the key targets AKT1, ALB and IL6 involved. GO and KEGG enrichment analysis yielded 1 445 biological processes and 148 signaling pathways, respectively. Molecular docking verified a good binding ability of the top three key targets to the top three key compounds. The analysis based on network pharmacology and molecular docking uncovered that Tanreqing Injection directly or indirectly regulated the pulmonary capillary endothelial cells and alveolar epithelial cells via anti-inflammation, thus alleviating ALI.
Acute Lung Injury/genetics* ; Drugs, Chinese Herbal ; Endothelial Cells ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation

To study the effect of Shenqi Dihuang decoction on inflammatory factor, renal function and microcirculation in patients with early diabetic nephropathy. A total of 205 cases of patient with early diabetic nephropathy treated in our hospital from March 2014 to April 2016 were selected and divided into two groups according to the admitted order, with 103 cases in clinical group and 102 in control group. Patients in control group were treated with melbine and captopril, which may be adjusted according to the clinical symptom. The clinical group was given Shenqi Dihuang decoction. Then the clinical efficady, inflammatory factors, renal function, endothelial function and hemorheology index were compared. Compared with 77.45% in the control group, the total effective rate of the clinical group was 92.23%. There was a significant increase (<0.05). The comparison of the values of IL-6, IL-8, TNF-α and CRP between the two groups before and after treatment showed significant differences. The values of inflammatory factors in treatment group were lower than in control group (<0.05). The comparison of the values of β2-MG, Cys-C and urine m-ALB between the two groups before and after treatment showed significant differences. The values of renal function in treatment group were lower than those in control group (<0.05). Compared with before treatment, ET-1 of the two groups after treatment decreased, while NO increased (<0.05). Compared with the control group, the value of ET-1 in patients of the experimental group was lower after treatment, while NO was higher (<0.05). The comparison of the values of whole blood viscosity, plasma viscosity, whole blood reduction viscosity, platelet aggregation rate and fibrinogen between the two groups before and after treatment showed significant differences. The value of hemorheology index in treatment group was lower than that in control group (<0.05). Shenqi Dihuang decoction has a better effect on patients with early diabetic nephropathy. It can significantly intervene with inflammatory response, reduce proteinuria, protect the renal function of patients, and improve the patient's vascular endothelial function and blood rheology, so as to make microcirculation to recover to the normal level.

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; surgery ; Cobalt Radioisotopes ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms ; pathology ; radiotherapy ; surgery ; Laryngectomy ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; Radioisotope Teletherapy ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo analyze the changes in endogenous small molecule metabolites after benzo[a]pyrene (B[a]P) exposure in rat cerebral cortex and explore the mechanism of B[a]P neurotoxicity.

METHODSFive-day-old SD rats were subjected to gavage administration of 2 mg/kg B[a]P for 7 consecutive weeks. After the exposure, the rats were assessed for spatial learning ability using Morris water maze test, ultrastructural changes of the cortical neurons under electron microscope, and metabolite profiles of the cortex using GC/MS. The differential metabolites between the exposed and control rats were identified with partial least squares discriminant analysis (PLS-DA) and the metabolic pathways related with the differential metabolites were analyzed using Cytoscape software.

RESULTSCompared with the control group, the rats exposed to B[a]P showed significantly increased escape latency (P<0.05) and decreased time spent in the target area (P<0.05). The exposed rats exhibited widened synaptic cleft, thickened endplate membrane and swollen cytoplasm compared with the control rats. Eighteen differential metabolites (VIP>1, P<0.05) in the cortex were identified between the two groups, and 9 pathways associated with B[a]P neurotoxicity were identified involving amino acid metabolism, tricarboxylic acid cycle and Vitamin B3 (niacin and nicotinamide) metabolism.

CONCLUSIONB[a]P can cause disturbance in normal metabolisms and its neurotoxicity is possibly related with disorders in amino acid metabolism, tricarboxylic acid cycle and vitamin metabolism.