Objective: Based on the tumor-bearing rat model, using rutin, quercitrin, and isoquercitrin from Hedyotis diffusa as the research object, the pharmacokinetics of those three flavonoid glycosides in the pathological state was studied. Methods: Establishing a method for the comparison of the pharmacokinetics of flavonoid extracts in normal rats and tumor-bearing rats, which was analyzed by HPLC-MS/MS in subcutaneous tumor models of SD rat made with tumour cell of Walker-256. Results: Compared with the pharmacokinetics parameters of flavonoid glycosides in normal rats, the Cmax and AUC0-∞ of rutin, quercetin, and isoquercitrin in the tumor-bearing rats were significantly decreased, t1/2z was prolonged, and the metabolic time of three components was prolonged to 24 h, which revealed the effect of pathological condition on the pharmacokinetic characteristics of flavonoid glycosides. Conclusion: The method established in this study is simple, fast, sensitive, and suitable for the pharmacokinetic study of flavonoid glycosides in rats in vivo. The pharmacokinetic characteristics of flavonoids in normal and tumor-bearing rats are different.

Objective: To screen the material basis of Huopu Xialing Decoction in the treatment of damp pathogen stagnation of lung syndrome of early COVID-19 and predict its mechanism. Methods: Literatures and clinical reports were reviewed to analyze the relationship between Huopu Xialing Decoction and damp pathogen stagnation of lung syndrome of early stage of COVID-19. TCMSP database was used to screen the potential active components in Huopo Xialing Decoction. Molecular docking of the active components with SARS-CoV-2 hydrolase and ACE2 was also carried out. According to the binding ability, the core components with both were screened. The interaction network of key components target proteins was constructed by using the software of Cytoscape to screen the main targets; The GO analysis of the main targets was carried out by using the STRING database, and the Pathway and KEGG enrichment analysis was carried out by using the plug-in of the software ClueGO of Cytoscape. Results: The Huopo Xialing Decoction was used to treat the early coronavirus pneumonia with damp pathogen and lung depression syndrome in the relationship analysis between prescriptions and syndrome, and the potential components of the 12 ingredients in Huopo Xialing Decoction were selected, with 67 core targets. Among them, paryriogenin I from Tetrapanax papyrifer, ergosterol peroxide from Poria cocos and Polyporus umbellatus, baicalin from Pinellia ternata had good binding activity with SARS-CoV-2 3CL hydrolase and ACE2. The results of enrichment analysis of GO, Pathway and KEGG showed that 12 potential components in Huopo Xialing Decoction were involved in regulating the biological processes such as stimulation response, signal transduction, cell death and the related signaling pathways including interleukins, EGFR in cancer, tyrosine kinases, programmed cell death and MAPK signaling pathways. Conclusion: For the early COVID-19 patients with the syndrome of damp pathogen stagnation of lung, Huopo Xialing Decoction was used to resolve dampness and detoxification, and ventilate lung and promote pathogenic penetration. Phenanthrone, baicalin, jujuboside_qt, cerevisterol, hederagenin, ergosterol peroxide, citrostadienol, ergosterol-7,22-diene-3-one, paryriogenin I, alisol B,23-acetate, alisol B, neohesperidin may be the main material basis, and play a role by blocking the protein synthesis of SARS-CoV-2 virus, preventing the virus from entering the host cells, regulating the IL signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, T cell receptor signaling pathway, C-type lectin receptor signaling pathway and inhibiting the expression of related inflammatory factors.

OBJECTIVE: To observe the effect of Biochanin A (Bio A) on rat hippocampal neurons injuries impaired by H2O2 and Bcl-2, Bax and caspase-3 protein expression. METHODS: Hippocampal neurons of newly born rat were cultured in vivo and were injured by H2O2. Different concentration of Bio A on cell viability was measured by CCK-8; cell apoptosis rate was tested by flow cytometry analysis; Bcl-2, Bax and caspase-3 protein expression were tested by Western blot method. RESULTS: Compared with the model group, Bio A significantly improved hippocampal neurons cell viability and inhibited cell apoptosis and necrosis. In addition, Bio A clearly enhanced the protein expression of Bcl-2 and decrease the protein expression of Bax and caspase-3. CONCLUSION: The protective effect of Bio A on rat hippocampal neurons injuries impaired by H2O2 may be related to the inhibition of hippocampal neurons apoptosis. The mechanism of Bio A against cell apoptosis may involve the increased Bcl-2 protein expression and reduced Bax, caspase-3 protein expression.

Human respiratory syncytial virus (hRSV) was considered to be the leading cause of lower respiratory tract disease in infants and young children. So far, there was a lack of effective anti-hRSV drugs and vaccines. In this paper, the latest research progress on anti hRSV infection drugs was reviewed from three aspects of effective constituents of Chinese materia medica, Chinese materia medica, and Chinese medicine compound antiviral inhibitor research and development, which would lay a theoretical foundation for the research and development of anti-hRSV drugs and the anti hRSV infection treatment strategy.

Objective: To observe the effect and explore the mechanism of Tribulus terrestris (TT) on kidney of rats with obesity-related hypertension through leptin mediated JAK2/STAT3 pathway. Methods: To establish the model of rats with obesity-related hypertension by high-fat diet. The model rats were randomly divided into three groups: TT group (eight rats, 17.2 g/kg), Telmisartan group (eight rats, 3.4 mg/kg), and model group (eight rats, normal saline 2 mL/d). Rats were ig given drugs or saline for 12 weeks. The body weights and blood pressure were measured regularly. At the end of the study, the rats were sacrificed and the levels of serum lipid and angiotensinII (AngII) and β2-microglobulin (β2-MG) were determined by ELISA. Morphological changes of adipose tissue and kidney were observed by HE staining. The density of LepR in kidney was observed by immunohistochemical staining. Levels of mRNA and protein expression of JAK2 and STAT3 in kidney were determined by quantitive real-time PCR (qRT-PCR) and Western blotting. Results: Both body weights and blood pressure of TT group were decreased (P < 0.05). The levels of serum TG, TC, and LDL-C of TT group were decreased significantly (P < 0.05). Kidney morphology of TT group was improved obviously and the size of lipocyte decreased. The levels of serum Ang II, Lep, and β2-MG of TT group decreased significantly (P < 0.05). The density of LepR in kidney of TT group decreased significantly (P < 0.05). The mRNA and protein expression of JAK2 and STAT3 in kidney of TT group was decreased significantly (P < 0.05). Conclusion: TT improves the leptin resistance of the obesity-related hypertensive rats mainly through JAK2/STAT3 pathway.

China ; Humans ; Neoplasms ; radiotherapy ; Positron-Emission Tomography ; Radiation Oncology ; methods ; Radiotherapy, Intensity-Modulated ; Tomography, X-Ray Computed

OBJECTIVEThis study was aimed to investigate the risk factors of renal impairment and the predictive factors of renal function recovery so as to provide basis for its prevention and treatment.

METHODSMedical records of 161 patients with MM firstly diagnosed from January 2007 to April 2013 were analyzed retrospectively. Among them 58 cases accompanied with renal insufficiency (group A, others belong to group B) and 39 of them regain normal renal function after some treatment. The possible related renal impairment risk factors and reversible predictors were analyzed with chi-square test for significance firstly, then factors that have significant difference were entered into multivariate logistic regression analysis.

RESULTSSystolic blood pressure (SBP), hemoglobin, uric acid, blood calcium, phosphorus, serum β2-microglobulin, urine β2-microglobulin levels, M-component type, light chain type, nephrotoxic drug use, infection in group A had significant difference (P<0.05) compared with those in group B; the systolic blood pressure, diastolic blood pressure, platelet, globulin, blood calcium, and urine β2-microglobulin levels, the chemotherapy applied and the response to chemotherapy in reversed group were significantly different from no-reversed group (P<0.05). Multivariate logistic regression showed that light chain type, Hb, uric acid, Ca were the independent risk factors for the development of renal failure in MM, and Ca, chemotherapy and the response to chemotherapy were the predictors of renal function recovery.

CONCLUSIONHigh blood calcium, severe anemia, λ light chain, high uric acid are the independent risk factors of renal impairment in MM patients. Patients with high blood calcium before treatment easily regain normal renal function after effective chemotherapy. Bortezomib-based chemotherapy has higher response rate and higher reversal rate, and it may be related with its unique mechanism.

OBJECTIVE: To observe the levels of four hydroxylated metabolites of polycyclic aromatic hydrocarbons(PAHs)in the urine of coke workers and its influencing factors.To explore the feasibility of using PAHs as biomarkers for exposure of coke oven emissions(COEs).METHODS: A cross-sectional survey was used to compare 261 coke oven workers in a coke oven plant as exposure group with 111 workers without COEs exposure in an oxygen making plant as control group.Ultra high liquid chromatography-mass spectrometry was used to detect four hydroxylated metabolites of PAHs,including1-hydroxypyrene(OHP),1-hydroxynaphthalene(OHN),2-OHN and 3-hydroxyphenanthrene,in urine of these two groups.RESULTS: The levels of four hydroxylated metabolites of PAHs in urine in exposure group were higher than that of the control group(P<0.01).The levels of urinary 1-OHP,1-OHN,2-OHN were followed by the sequence of bottomoven,side-oven,and top-oven subgroups among the exposure group(P<0.05).The multiple linear regression results indicated that the levels of urinary 1-OHP,1-OHN,2-OHN were correlated with COEs exposure(P<0.05),after adjusting the confounding factors of gender,age,length of service,smoking status and alcohol drinking status.The levels of urinary 1-OHP,1-OHN,2-OHN of the exposure group increased with the increase of COEs exposure levels showing a dose-effect relationship(P<0.01).The levels of 1-OHN and 2-OHN were associated with smoking apart from COEs exposure(P<0.01).CONCLUSION: The urinary 1-OHP can be used as a reliable biomarker for the evaluation of internal exposure to COEs.The 1-OHN and 2-OHN can be used as adjuvant biomarkers.

OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating (LSMAR) needling on the expression of receptor activity-modifying protein 1 (RAMP 1, receptor of calcitonin gene-related peptide), 5-hydroxytryptamine 1 D receptor(5-HT 1 DR) in the spinal trigeminal nucleus (STN) and midbrain in migraine rats, so as to explore its underlying mechanism in relieving migraine. METHODS: A total of 40 male Wistar rats were randomly divided into control, model, LSMAR and conventional needling groups (n=10 rats in each). The migraine model was established by subcutaneous injection of nitroglycerin at the posterior neck. LSMAR was applied to "Baihui" (GV 20), bilateral "Fengchi" (GB 20), "Neiguan" (PC 6) and "Taichong" (LR 3) in the LSMAR group and conventional needling was applied to "Baihui" (GV 20) and bilateral "Fengchi" (GB 20) in the conventional acupuncture group for 30 min, once a day for 8 days before modeling. The expression levels of RAMP 1 and 5-HT 1 DR proteins and mRNAs in the STN and mesencephalon were detected by real-time fluorescent quantitative PCR and Western blot, separately. RESULTS: Compared with the control group, the expression levels of RAMP 1 protein and mRNA in STN and mesencephalon were significantly increased (P<0.05) and those of 5-HT 1 DR protein and mRNA considerably decreased (P<0.05) in the model group. After the acupuncture treatment, the increased levels of RAMP 1 protein and mRNA and the decreased levels of 5-HT 1 DR protein and mRNA in the STN and midbrain were obviously reversed in the LSMAR and conventional needling groups relevant to the model group (P<0.05). The effect of LSMAR needling was significantly superior to that of conventional needling in down-regulating the expression levels of RAMP 1 mRNA and protein in the STN and mesencephalon (P<0.05) and in up-regulating the expression levels of 5-HT 1 DR mRNA and protein in the two brain regions (P<0.05). CONCLUSION: Manual acupuncture stimulation of GV 20, GB 20, etc. can inhibit the expression of RAMP 1 protein and mRNA in the STN and midbrain, and up-regulate the expression of 5-HT 1 DR in the two brain regions of migraine rats, which may be related to its effect in relieving migraine.

OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating (LSMAR) needling on behavior reactions and contents of serum calcitonin gene-related peptide (CGRP), substance P (SP), interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in migraine rats, so as to explore its mechanism underlying relief of migraine. METHODS: Thirty-two male Wistar rats were randomly divided into control, model, LSMAR needling and conventional needling groups (n=8 rats in each). The migraine model was established by hypodermic injection of glyceryl trinitrate (5 mg/kg) at the napex. Acupuncture preconditioning was conducted once daily for 8 days before modeling. Acupuncture needles were inserted into "Baihui" (GV 20), and bilateral "Fengchi" (GB 20), "Neiguan" (PC 6) and "Taichong" (LR 3), manipulated for a while and retained for 30 min. The rats' behavioral changes (times of head scratching, tail-biting, cage-crawling, and to- and fro-movement in 30 min) were scored (one symptom = one point) before modeling, after modeling, and after intervention. The concentrations of CGRP, SP, IL-1 β, TNF-α in serum were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After modeling, the behavioral scores were significantly increased in the migraine model rats relevant to the control group (P<0.05). Whereas after the treatment, the behavior scores were considerably decreased during 60-90 min and 120-150 min of the measuring period in both LSMAR and conventional needling groups compared with the model group (P<0.05). The concentrations of CGRP, SP, IL-1 β and TNF-α were significantly higher in the model group than in the control group (P<0.05), and notably lower in both LSMAR and conventional needling groups than in the model group (P<0.05). The therapeutic effect of LSMAR was markedly superior to that of conventional needling in down-regulating the concentrations of CGRP, SP, IL-1 β and TNF-α (P<0.05). CONCLUSION: Acupuncture preconditioning can effectively relieve pain in migraine rats possibly by decreasing the concentrations of CGRP, SP, IL-1 β and TNF-α in the peripheral blood, and the therapeutic effect of LSMAR is evidently superior to that of conventional needling.