In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl₂ was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L^-1 CoCl₂ for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.

BACKGROUNDThe mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODSMedian effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTSFrom a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONSThree Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Anesthetics, Inhalation ; pharmacology ; Animals ; Chloroform ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; Enflurane ; pharmacology ; Female ; Halothane ; pharmacology ; Isoflurane ; analogs & derivatives ; pharmacology ; Male ; Methoxyflurane ; pharmacology ; Methyl Ethers ; pharmacology ; Trichloroethylene ; pharmacology

Objective To compare the effect of intravenous infusion of low dosage fructose with glucose infusion on blood glucose variability in type 2 diabetic patients in stable phase.Methods Data of 22 patients (male:female,18:4)with type 2 diabetes mellitus in stable phase were collected for the study.From 9am to 11 am,all the subjects were administrated one of the following solutions at constant speed on consecutive days randomly:5% glucose injection 200 mL with insulin 3 U,0.9% normal saline 200 mL or 5%fructose injection 200 mL. The blood glucose concentrations were detected every 5 minutes after infusion by confinuous glucose monitoring system(CGMS).The variability of blood glucose was compared using these 3 kinds of solutions.A two-tailed P value of ≤0.05 was considered statistically significant. Statistical analysis was carried out with SPSS version 13.0.Results No significant difference was found among these 3 kinds of solutions.In addition,no adverse effects were founded.Conclusion Low dosage infusion of neither fructose nor glucose had apparent effect on blood variability of patients with type 2 diabetes mellitus in stable phase.

To introduce a method of classification with high precision-the artificial neural network (ANN),and to compare the results using logistic method. Using data from 1070 landless peasants'mental health survey,the artificial neural network models and logistic regression model were built and compared on their advantages and disadvantages of the two models.The prediction accuracy for artificial neural network was 94.229% and for logistic regression it was 51.028%. ANN appeared to have had good ability on generalization. ANN displayed advantages when conditions of classical statistical techniques could not be met or the predictive effect appeared to be unsatisfactory. Hence, ANN would make a better facture of its application in medical researche.

OBJECTIVE: To analyze the reliability of disyllabic Mandarin speech test materials (MSTM) which had previously been evaluated the equivalence of difficulty, and to establish the performance-intensity function (P-I function) for people with normal hearing. METHOD: Thirty-five subjects (the age-range 18-25 years) with normal hearing who speak Mandarin well in their daily lives were enrolled in this study. Five of them participated the pilot study, which aimed to identify a presentation level for the formal test. The other thirty subjects participated in the formal speech perception test. The results were analyzed statistically using SPSS 11.0 software. Nine lists of the Mandarin disyllabic materials with equal difficulty were utilized. RESULT: P-I function was y = -200.9 + 13.4x - 0.14x2. The sound pressure level of speech corresponding to a 50% recognition score was 26.4 dB SPL, or 6.4 dB HL. CONCLUSION This study has established the P-I function of the Mandarin disyllabic materials with equal difficulty, which provides the normative data for identifying the normal hearing in a clinical setting.
Adult ; Audiometry, Speech ; statistics & numerical data ; Humans ; Reference Standards ; Speech Discrimination Tests ; statistics & numerical data ; Speech Perception ; Young Adult

OBJECTIVETo edit the spondee (disyllable) word lists as a part of mandarin speech test materials (MSTM). These will be basic speech materials for routine tests in clinics and laboratories.

METHODSTwo groups of professionals (audiologists, Chinese and Mandarin scientists, linguistician and statistician) were set up at first. The editing principles were established after 3 round table meetings. Ten spondee lists, each with 50 words, were edited and recorded into cassettes. All lists were phonemically balanced (3-dimensions: vowels, consonants and Chinese tones). Seventy-three normal hearing college students were tested. The speech was presented by earphone monaurally. Three statistic methods were used for equivalent analysis.

RESULTSRelated analysis showed that all lists were much related, except List 5. Cluster analysis showed that all ten lists could be classified as two groups. But Kappa test showed that the lists' homogeneity were not well.

CONCLUSIONSSpondee lists are one of the most routine speech test materials. Their editing, recording and equivalent evaluation are affected by many factors. This also needs multi-discipline cooperation. All lists edited in present study need future modification in recording and testing in order to be used clinically and in research. The phonemic balance should be kept.

Adult ; Asian Continental Ancestry Group ; Audiometry, Speech ; Female ; Humans ; Language ; Male ; Speech Discrimination Tests ; Young Adult

OBJECTIVETo investigate the adverse effects of high-dose methotrexate (HDMTX) therapy, and to provide a theoretical basis for optimizing clinical treatment.

METHODSA retrospective analysis was performed for the clinical data of 120 children with acute lymphoblastic leukemia or non-Hodgkin lymphoma who underwent 601 times of HDMTX therapy. The adverse effects of various systems were analyzed according to the WHO criteria for the classification of adverse effects of anticancer drugs.

RESULTSAlmost all the children experienced bone marrow suppression, and 93.3% had granulocytopenia. The most common adverse effects in the digestive system and urinary system were elevated glutamic-pyruvic transaminase (60.4%) and proteinuria (9.2%) respectively. For skin symptoms, skin erythema had the highest incidence rate (7.2%). The adverse effects in the nervous system (hyperpathia, numbness of extremities, or headache) were only observed in 7 cases. Serious adverse effects were only seen in the blood system and digestive system. Compared with the 3 g/mmethotrexate (MTX) group, the 5 g/mHDMTX group had a significantly higher 24-hour plasma MTX concentration, significant reductions in hemoglobin and platelet count, and significantly higher incidence rates of oral mucositis, proteinuria, and skin symptoms (P<0.05).

CONCLUSIONSSerious adverse effects of HDMTX therapy mainly involve the blood system and digestive system, and the adverse effects such as bone marrow suppression, oral mucositis, proteinuria, and skin symptoms occur in a dose-dependent manner.

Antimetabolites, Antineoplastic ; adverse effects ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Methotrexate ; adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Retrospective Studies

OBJECTIVETo investigate the value of magnetic resonance imaging (MRI) in the preoperative assessment of endometrial cancer.

METHODSNinety-four patients with histopathologically confirmed endometrial carcinoma were retrospectively enrolled in this study. MRI findings were compared with the pathologic findings in all cases. The depth of myometrial invasion and lymph node metastasis were evaluated by T2 weighted imaging (T2WI) combined with contrast enhancement or diffusion weighted imaging (DWI).

RESULTSAmong these 94 patients,62 had no or superficial myometrial involvement and 32 cases had deep myometrial involvement. Meanwhile, 24 groups of metastatic lymph nodes and 164 groups of non-metastatic lymph nodes were detected. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in discriminating no/superficial myometrial involvement from deep myometrial involvement were 88.3%, 90.3%, 84.4%, 91.8%, and 81.8%, whereas those of T2WI combined with DWI were 81.9%, 87.1%, 71.9%, 85.7%, and 74.2%, respectively. The accuracy, specificity, sensitivity, negative predictive value, and positive predictive value of T2WI combined with contrast enhancement in identifying metastatic lymph nodes were 89.4%, 96.8%, 54.5%, 90.9%, and 78.3%, whereas those of T2WI combined with DWI were 91.5%, 95.5%, 72.7%, 94.3%, and 77.4%, respectively.

CONCLUSIONST2WI combined with contrast enhancement is superior to T2WI combined with DWI in evaluation of the depth of myometrial invasion. However, DWI is more sensitive in identifying lymph node metastasis than T2WI combined with contrast enhancement.

Adult ; Aged ; Endometrial Neoplasms ; diagnosis ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Middle Aged ; Retrospective Studies ; Sensitivity and Specificity

OBJECTIVETo edit the sentence list for mandarin speech test materials (MSTM) and to test their equivalence in order to use the list as routine clinical speech tests for evaluation of cochlear implants and hearing aids in different stages of the intervention and rehabilitation.

METHODSFirstly, two groups of professionals were set up: one for establishing the principles of the edit, another for experiments. The criteria to guide the selection of spoken sentences were as following: (1) suitable for everyday speech audiometry, esp. clinically usage; (2) a normal sampling of everyday spoken sentences in mandarin. Totally, 300 sentences were selected in 30 lists for the experiment. The record cassette was used by a male speaker. The college students (54 persons,54 ears) with normal hearing participated in the equivalence test. Two statistic methods were used for equivalence analysis. RESULTS Through speech tests and statistic analysis, 2 sets with 29 lists (290 sentences) were selected as our equivalent lists for further evaluation and clinical trial.

CONCLUSIONSBy setting up the strict criteria of selecting sentences, speech test method and statistic analysis, 2 sets of 29 lists (290) sentences were chosen as our speech evaluation materials, but it was necessary for further analysis in different laboratories and clinics. The sentence lists should also get used for hearing impaired subjects, hearing aid users and cochlear implant recipients.

Adult ; Audiometry, Speech ; methods ; Female ; Humans ; Language ; Male ; Young Adult