Objective: To explore the potential mechanism of Shema Zhichuan liquid in treatment of asthma by network pharmacology. Method: Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (TCM), systematic pharmacological database and analysis platform of TCM were employed to find the components in Shema Zhichuan liquid and their targets, and asthma-related genes were obtained from the comparative toxicogenomics database (CTD). The data set of Shema Zhichuan liquid-gene and asthma-gene were imported into the Draw Venn Diagram for intersection analysis. The obtained data set of Shema Zhichuan liquid-asthma-gene was imported into String 11.0 for protein-protein interaction (PPI) analysis, and was visualized by Cytoscape 3.6.1, and further important modules were analyzed with MCODE. DAVID 6.8 was used to analyze pathway enrichment and biological process of Shema Zhichuan liquid-asthma-gene. Result: A total of 399 components and 2 099 potential targets were obtained from Shema Zhichuan liquid, 98 asthma-related targets were retrieved, 45 common genes and 16 hub genes were screened, including transforming growth factor-β₁(TGF-β₁), heme oxygenase-1 (HMOX1), interleukin-4 (IL-4), etc. Enrichment analysis showed that the common biological processes of Shema Zhichuan liquid and asthma were related to inflammation, contraction and remodeling of airway, cell proliferation and apoptosis, etc. The common biological pathways mainly included tumor necrosis factor (TNF) signaling pathway, receptor with high affinity for immunoglobulin E (Fc epsilon RI) signaling pathway, nuclear transcription factor-kappa B (NF-κB) signaling pathway, nucleotide binding oligomerization domain (NOD)-like receptor signaling pathway and so on. Conclusion: Shema Zhichuan liquid serves as a multi-target, multi-pathway treatment for asthma, which can provide a reference for the further research and clinical application of this preparation.

OBJECTIVETo evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine (TET) in female BALB/c mice.

METHODSThe median lethal dose (LD) of intravenously administered TET was calculated in mice using Dixon's up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET (30, 90 and 150 mg/kg) each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period.

RESULTLDwas found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically signifificant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET (P >0.05). In the sub-acute toxicity study, no signifificant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group (P >0.05), however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions.

CONCLUSIONSThe overall fifindings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.

Administration, Intravenous ; Animals ; Benzylisoquinolines ; administration & dosage ; toxicity ; Body Weight ; drug effects ; Female ; Mice, Inbred BALB C ; Organ Specificity ; drug effects ; Toxicity Tests, Acute ; Toxicity Tests, Chronic

BACKGROUNDThe most critical mechanism governing drug resistance in Candida albicans (C. albicans) involves efflux pumps, the functionality of which largely depends on energy metabolism. Alcohol dehydrogenase I (ADH1) plays an important role in intracellular energy metabolism. The aim of this study was to explore the relationship between ADH1 and drug resistance in C. albicans.

METHODSTwenty clinical C. albicans samples isolated from individual patients diagnosed with vulvovaginal candidiasis, and two C. albicans strains obtained from a single parental source (the fuconazole (FLC)-sensitive strain CA-1S and the FLC-resistant strain CA-16(R)) were included in our study. In accordance with the Clinical and Laboratory Standards Institute (CLSI) M27-A3 guidelines, we used the microdilution method to examine the FLC minimum inhibitory concentrations (MICs) and real-time reverse transcription polymerase chain reaction (RT-PCR) to measure the mRNA expression levels of ADH1 and the azole resistance genes CDR1, CDR2, MDR1, FLU1 and ERG11 in all the isolates.

RESULTSA highly significant positive correlation between the mRNA levels of ADH1 and the MICs (rs = 0.921, P = 0.000), as well as positive correlations between the mRNA level of ADH1 and those of CDR1, CDR2 and FLU1 (rs of 0.704, 0.772 and 0.779, respectively, P < 0.01), were observed in the 20 clinical C. albicans samples. The relative expression of ADH1 was upregulated 10.63- to 17.61-fold in all of the drug-resistant isolates. No correlations were found between the mRNA levels of ADH1 and those of MDR1 or ERG11 (P > 0.05). The mRNA levels of the examined drug resistance genes were higher in the CA-16(R) strain than in CA-1(S), and the mRNA levels of ADH1 in CA-16(R) were 11.64-fold higher than those in CA-1(S) (P < 0.05).

CONCLUSIONSThese results suggest that high levels of ADH1 transcription are implicated in FLC resistance in C. albicans and that the mRNA expression levels of ADH1 are positively correlated with those of CDR1, CDR2 and FLU1.

ATP-Binding Cassette Transporters ; genetics ; Alcohol Dehydrogenase ; genetics ; Candida albicans ; drug effects ; Candidiasis, Vulvovaginal ; microbiology ; Drug Resistance, Fungal ; genetics ; Drug Resistance, Multiple ; genetics ; Female ; Fluconazole ; pharmacology ; Fungal Proteins ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; RNA, Messenger ; analysis

This study was aimed to investigate the significance of detecting the antigen-receptor gene rearrangement clonality in the diagnosis of lymphoma. Paraffin-embedding and HE staining of samples from 31 patients with lymphomas were performed for morphologic observation by light microscope. Immunophenotype was analyzed by the immunohistochemistry (IHC) method. The clonality of antigen-receptor gene rearrangement was detected by BIOMED-2 Assay Kit. The results showed that among the 31 cases, 12 cases were suspected to be T-cell lymphoma, 1 case was suspected to be T-cell reactive hyperplasia, and 16 cases were suspected to be B-cell lymphoma, 2 cases were B-cell reactive hyperplasia. The detection results showed that the positivity of Ig gene rearrangement clonality was 94.44% (17/18), the positivity of TCR gene rearrangement clonality was 92.31% (12/13), the other two cases were negative. Finally, 12 cases were diagnosed to be T-cell lymphoma and 17 cases were B-cell lymphoma. The other two cases were reactive lymphoid proliferations. And the positivity rate in the 31 patients with lymphomas was 93%. It is concluded that the detection of antigen-receptor gene rearrangement clonality is a useful assistant method in the diagnosis of lymphoma.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Gene Rearrangement, T-Lymphocyte ; Humans ; Lymphoma ; diagnosis ; pathology ; Lymphoma, B-Cell ; diagnosis ; pathology ; Lymphoma, T-Cell ; diagnosis ; pathology ; Male ; Middle Aged ; Receptors, Antigen, T-Cell ; genetics ; Young Adult

OBJECTIVETo determine whether tanycytes be able to support the regeneration of completely transected spinal cord in adult rats.

METHODSSubcultured tanycytes was transplanted into completely T8 transected spinal cord using the untranslated completely transected rats as control. After transplantation the rubrospinal motor evoked potentials were recorded below the injury level at the end of 12th week, assistant by Basso-Beatie-Bresnahan locomotor rating scale and histology method.

RESULTSAt the end of 12th week the total peak amplitude of rubrospinal motor evoked potentials (MD = 133.2 microV, P < 0.01) and BBB locomotor rating scale (MD = 5.0000, P < 0.01) were both significantly improved in cell transplanted group compared with that in the untranslated control group, while the latency of the first peak was shortened (MD = 0.061 ms, P = 0.040). HE staining showed more integrity in transected spinal cords in cells transplanted groups.

CONCLUSIONTransplanted tanycytes can support the regeneration of transected spinal cords in rats.

Animals ; Cell Transplantation ; Cells, Cultured ; Evoked Potentials, Motor ; Male ; Neuroglia ; cytology ; transplantation ; Rats ; Rats, Wistar ; Recovery of Function ; Spinal Cord Injuries ; physiopathology ; surgery

Aged ; Animals ; Asphyxia ; etiology ; Asthma ; physiopathology ; Catheter Ablation ; Female ; Fundoplication ; Gastroesophageal Reflux ; complications ; surgery ; Humans ; Laryngismus ; etiology ; Male ; Middle Aged ; Rats ; Rats, Sprague-Dawley ; Respiration Disorders ; etiology ; physiopathology ; Treatment Outcome

BACKGROUNDGastroesophageal reflux disease with extra-esophageal symptoms, especially those with respiratory distress was attracting more and more attention. The related mechanisms were still in controversy. The purpose of the work was to explore airway inflammation triggered by gastroesophageal reflux.

METHODSSixteen Sprague-Dawley rats were used as study group and 9 as control. In the study group, a plastic extender with a trumpet-shaped distal end was inserted into the lower esophagus to dilate the cardia, the pylorus was ligated. One ml of 0.1 mol/L hydrochloric acid was injected into the stomach. While a simple laparotomy was performed for control animals. All animals from two groups were sacrificed 24 hours after operation. Then tracheotomy was carried and the bronchoalveolar lavage fluid was collected in all animals. Cells in the fluid were counted and levels of interleukin (IL)-5, -6, -8 in it were measured.

RESULTSCompared with control group, the study group presented a neutrophil pattern of airway inflammation and an elevated concentration of IL-5, -6, -8 with no significant difference regarding eosinophil count.

CONCLUSIONThe gastroesophageal reflux-triggered airway inflammation is characterized by a neutrophilic airway inflammation which differed from that caused by asthma, and enhanced levels of IL-5, -6 and -8, which are similar to that caused by asthma.

Animals ; Asthma ; etiology ; Bronchoalveolar Lavage Fluid ; immunology ; Disease Models, Animal ; Female ; Gastroesophageal Reflux ; complications ; Inflammation ; etiology ; Interleukin-5 ; analysis ; Interleukin-6 ; analysis ; Interleukin-8 ; analysis ; Male ; Rats ; Rats, Sprague-Dawley