[Potential action mechanism of Yishen Tongluo Prescription on male infertility: An analysis based on network pharmacology].

OBJECTIVE: To analyze the main active components and potential molecular mechanism of Yishen Tongluo Prescription (YTP) in the treatment of male infertility based on network pharmacological technology. METHODS: We searched and sorted the main active components of YTP and their individual potential targets in the databases of Systematic Pharmacology of Traditional Chinese Medicine (TCM) and Bioinformatics Analysis Tool of the Molecular Mechanism of TCM, and screened the targets related to male infertility diseases in the databases of Genecards, DisGeNET and OMIM. We made a Venn diagram by intersecting the predicted targets of YTP and those of male infertility diseases, constructed visualized networks for the association of the intersection targets and protein-protein interaction (PPI) using the Cytoscape software and STRING platform respectively, and conducted gene ontology (GO) and KEGG enrichment analyses using the DAVID database and R language "Cluster Profiler" software package respectively. RESULTS: A total of 99 active components, 250 targets of YTP, 4 397 targets of male infertility and 127 common targets were identified. GO analysis revealed that the biological processes of the common targets mainly included transcriptional regulation of RNA polymerase promoter Ⅱ, regulation of gene expressions, regulation of apoptosis, responses to estrogen, and cell responses to hypoxia. KEGG analysis showed significant enrichment of the common targets in the estrogen signaling pathway, cell apoptosis pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway. CONCLUSION: Through network pharmacology, we identified the main active components of YTP and its multi-target and multi-pathway mechanism in the treatment of male infertility, which has paved the ground for animal and cell experiments in verifying the action mechanism of YTP on male infertility.

Anti-nociceptive and anti-inflammatory activities of the extracts of Stauntonia chinensis.

The aim of this investigation was to study the anti-nociceptive and anti-inflammatory activities of Stauntonia chinensis (S. chinensis) and the possible action mechanisms of effective fractions. The anti-nociceptive and anti-inflammatory activities of S. chinensis extracts, including the 60% EtOH extract (YMG), the n-BuOH extract (YMGB) and the aqueous residue (YMGW) of YMG, and the fractions from YMGB (YMGB1~YMGB7) were investigated by using the mouse acetic acid-induced writhing test and the rat formalin test. The effect of these extracts on the PGE2 production was tested as well. In the mouse acetic acid-induced writhing test and the rat formalin test, YMGW and YMGB displayed anti-nociceptive and anti-inflammatory activities, suggesting that they were the active ingredients of YMG. Among the fractions isolated from YMGB, YMGB1, YMGB3, YMGB4 and YMGB6 were the main active ingredients producing anti-nociceptive activity and YMGB3, YMGB5, YMGB6 and YMGB7 were the main active ingredients producing anti-inflammatory activity. Additionally, YMGW, YMGB and its separations reduced the production of PGE2, which might be the mechanism of them producing anti-inflammatory activity. These results demonstrated the active ingredients of S. chinensis producing anti-nociceptive and anti-inflammatory activities, which is valuable to validate the substance basis of S. chinensis's pharmacological actions.

On the accuracy of code complexity metrics: A neuroscience-based guideline for improvement.

Complexity is the key element of software quality. This article investigates the problem of measuring code complexity and discusses the results of a controlled experiment to compare different views and methods to measure code complexity. Participants (27 programmers) were asked to read and (try to) understand a set of programs, while the complexity of such programs is assessed through different methods and perspectives: (a) classic code complexity metrics such as McCabe and Halstead metrics, (b) cognitive complexity metrics based on scored code constructs, (c) cognitive complexity metrics from state-of-the-art tools such as SonarQube, (d) human-centered metrics relying on the direct assessment of programmers' behavioral features (e.g., reading time, and revisits) using eye tracking, and (e) cognitive load/mental effort assessed using electroencephalography (EEG). The human-centered perspective was complemented by the subjective evaluation of participants on the mental effort required to understand the programs using the NASA Task Load Index (TLX). Additionally, the evaluation of the code complexity is measured at both the program level and, whenever possible, at the very low level of code constructs/code regions, to identify the actual code elements and the code context that may trigger a complexity surge in the programmers' perception of code comprehension difficulty. The programmers' cognitive load measured using EEG was used as a reference to evaluate how the different metrics can express the (human) difficulty in comprehending the code. Extensive experimental results show that popular metrics such as V(g) and the complexity metric from SonarSource tools deviate considerably from the programmers' perception of code complexity and often do not show the expected monotonic behavior. The article summarizes the findings in a set of guidelines to improve existing code complexity metrics, particularly state-of-the-art metrics such as cognitive complexity from SonarSource tools.

Polyketides from a marine sponge-derived fungus Mycelia sterilia and proton-proton long-range coupling.

A series of polyketide-originated metabolites (1-5) were isolated from a marine sponge-derived fungus Mycelia sterilia. Of these, 1-3 were new compounds. Their structures were elucidated by spectroscopic methods as (4R*, 5S*, 6S*, 8S*, 13R*)-1-(2,8-dihydroxy-1,2,6-trimethyl-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl)-3-methoxy-propan-1-one (1), 4,8-dihydroxy-7-(2-hydroxy-ethyl)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one (2) and 1-methyl-naphthalene-2,6-dicarboxylic acid (3). In 1, the proton-proton long-range coupling phenomenon claimed attention and was discussed.

Five new bidesmoside triterpenoid saponins from Stauntonia chinensis.

Eleven triterpenoid saponins (1-11) were isolated from Stauntonia chinensis DC. (Lardizabalaceae), including five new compounds, yemuoside YM(21-25) (1-3, 6, 7) structures of which were elucidated by chemical methods and a combination of MS, 1D- and 2D- NMR experiments including DEPT, (1)H--(1)H COSY, HSQC, HMBC, TOCSY, and NOESY as 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-rhamnopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonicacid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (1), 3-O-beta-D-xylopyranosyl-(1 --> 3)-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-akebonic acid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (2), 3-O-beta-D-glucopyranosyl-(1 --> 3)-alpha-L-arabinopyranosyl-akebonic acid-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (3), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-rhamnopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonic acid-28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (6), 3-O-alpha-L-arabinopyranosyl-(1 --> 3)-[alpha-L-arabinopyranosyl-(1 --> 2)-]alpha-L-arabinopyranosyl-akebonic acid-28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (7).

Duplexed on-microbead binding assay for competitive inhibitor of epidermal growth factor receptor by quantitative flow cytometry.

Upon binding agonist, the epidermal growth factor receptor (EGFR) is dimerized and auto-phosphorylated to activate downstream pathway that induces diverse physiology and pathology processes. Conventional methods for evaluation of EGFR inhibitors are limited. This study describes a duplexed on-microbead binding assay allowing competitive EGFR inhibitors to be quantificationally evaluated in vitro. Polystyrene microbeads barcoded by fluoresceine isothiocyanate fluorescence as high brightness and low brightness microspheres were coated with receptor tyrosine kinase (RTK) ligand-epidermal growth factor (EGF)/stem cell factor (SCF) and ATP/GTP, respectively. High and low brightness microbeads were mixed and incubated with EGFR and its competitive inhibitor in binding assay buffer. Phycoerythrin (PE) fluorescence-labelled antibody was employed to report the level of EGFR binding to EGF/SCF and ATP/GTP. Values were numbered via PE molecules assessed by quantitative flow cytometry. Results from this study demonstrated that incubation with EGFR identified by PE-labelled antibody can make EGF- and ATP-coated microbeads luminous. And EGF or ATP-competitive EGFR inhibitors, respectively, alleviated this in a concentration-dependent manner. Coating microbeads with SCF or GTP as a negative control cannot capture EGFR. The duplexed on-microbead binding assay in this study might be useful for discovering ligand- and ATP-competitive EGFR inhibitors in a rapid and quantificational approach.

[Relationship of concentration of lactoferrin and lysozyme in saliva and dental caries in primary dentition].

OBJECTIVE: To explore the relationship between the concentrations of lactoferrin and lysozyme in saliva and dental caries in primary dentition among Chinese children. METHODS: Forty children with high dmft score (dmft > or = 5) and 40 caries-free children (dmft = 0) were sampled and assigned into two groups. Total salivary proteins was measured by means of bicinchoninic acid. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) was performed to analyze the images of target straps. Lactoferrin and lysozyme were detected using Western blotting method. RESULTS: The total salivary protein in high dmft group [(852.02 +/- 206.14) mg/L] was lower than that of caries-free group [(1032.44 +/- 221.99) mg/L, P < 0.001]. The ratio of 77,000 protein in high dmft group [(12.50 +/- 7.73) IA/microg] was significantly higher than that of the caries-free children [(8.71 +/- 4.28) IA/microg, P = 0.009], while there was no significant difference for 14,500 protein between them (P = 0.137). The ratio of lactoferrin was higher in high dmft group [(229.04 +/- 197.14) IA/microg] than that in caries-free children [(144.07 +/- 99.91) IA/microg, P = 0.018], while no significant difference for lysozyme between the two groups (P = 0.091). CONCLUSIONS: Saliva protein is closely related to caries in primary dentition. Lactoferrin may be one of the important components.

2-D mathematical models of Tumor-induced angiogenesis.

Angiogenesis, the formation of blood vessels from a pre-existing vasculature, is a process in which capillary sprouts are formed in response to externally supplied chemical stimuli. Tumor-induced angiogenesis plays a significant role in tumor's growth, metastasis, in which endothelia-cell is the most active member engaging in various stages, including the secretion and diffusion of various tumor-induced angiogenesis factors (TAF); the nascent endothelial cell migrates towards a particular direction and position under the interaction of a series of internal and external factors; eventually the new formed capillaries reach and penetrate the tumor. At present there is no technique of medical image to accurately investigate the micro-vessel net of tumor, it makes some hard in clinical treatment of tumor. In this paper we present a 2-D mathematical model, which takes into account essential endothelial cell-extra cellular matrix interactions, and the response to chemical stimuli (TAF) mentioned above, to describes the formation of the capillary sprout network in response to physiological conditions around tumor especially investigate the process inside tumor in terms of the complex features of tumor. This theoretical capillary networks generated by computer simulations provide a premise for the further research.

The simulation of intracranial pressure dynamics.

Intracranial pressure (ICP) research has significant importance in clinic. There are many internal or external factors which cause the vibration of ICP, including heart beat, breath, neural regulation, and so on. A lumped parameter mathematical model of ICP dynamics is established based on animal (dogs) experiments, which includes cerebrovascular bed, cerebrospinal fluid (CSF) formation and absorption, brain compliance, lumbar cerebrospinal fluid, and interactions between these factors. An exponential volume-pressure relationship is employed in this simulation to describe cerebrovascular compliance. The model well simulates intracranial pressure dynamics and the vibration of ICP when compared to animal experiments; the changes of parameters in simulation are consistent with animal experiments. It offers certain values for clinical ICP ward and diagnosis.

[Assessment of retropharyngeal lymph node by comparing CT with MRI].

BACKGROUND & OBJECTIVES: The incidence of nasopharyngeal carcinoma (NPC) is high as part of malignancy of head and neck in South China. Some of the foreign radiologists investigated on it by comparing CT (computed tomography) with MRI (magnetic resonance imaging), but there was no description for metastatic retropharyngeal lymph node (RPN) of NPC. None of this kind of article published in domestic. The current study was designed to evaluate CT and MRI in identifying retropharyngeal node by comparing the finding of CT and MRI in 56 patients with NPC. METHODS: Fifty-six cases pathologically proven as nasopharyngeal carcinoma were selected from August, 1993 to December, 2000; CT scan were performed by Elscient CT Twin flash, axial scan were parallel to the OM line routinely from soft palate to the supracellar cistern. MRI scan were performed by Philip T5-II super-conducting magnetic resonance imaging system(0.5T). The standard quadrature head coil was used. Routine axial, saggital, and coronal scan with SE sequences were obtained. Scanned field ranged from soft palate to the supracellar cistern. After plain scaned, contrast material were administrated in 40 cases by intravenous injection of Gd-DTPA 0.1 mmol per kilogram body weight. And then repeat axial, saggital and coronal scan. RESULTS: MRI recovered the RPN more exactly than CT (13 cases by CT and 24 cases by MRI) and there was significant differentiation 0(P < 0.05). It is possible to distinguish the metastatic RPN of NPC from the directly infiltration of tumor by MRI. CONCLUSIONS: MRI is more precise than CT in differentiating the RPN from the directly invasion by tumor tissue of NPC, which will affects the 92 Chinese staging systems, for NPC obviously.

Segmental transcatheter arterial embolization for primary hepatocellular carcinoma.

AIM:To evaluate the therapeutic effects of segmental transcatheter arterial embolization for primary hepatocellular carcinoma, and to recognize the menifestation and clinical value of lipiodol overflow into portal veins surrounding the tumors.METHODS:A total of 50 cases of nonresectable primary hepatocellular carcinoma underwent segmental transcatheter arterial embolization. Two methods of superselective segmental catheterization were used, one was the method of wire-guiding, and the other the technic of co-axial infusion catheter.RESULTS:The 1-, 2-, 3- and 4-year cumulative survival rates of 50 cases with segmental transcatheter arterial embolization for primary hepatocellular carcinoma were 83.8%, 65.4%, 42.9% and 24.5% respectively. The in cidence of the lipiodol overflow into portal veins was 64%. The overflow of lipiodol intoportal veins, represented as 3-5 grade branches of portal veins visualized by lipiodol, was star-like or tree-like , and there was a relatively large vessel in the center surrounded with radicalized small branches of vessels.CONCLUSION:The lipiodol overflow into portal veins was one of the signs of complete embolization for tumors, and may play a partial role in embolizating the portal venous supply for hepatocellular carcinoma.

[Clinical evaluation of three methods of fine-needle aspiration, large-core needle biopsy and frozen section biopsy with focus staining for non-palpable breast disease].

BACKGROUND & OBJECTIVE: Early detection of breast cancer is crucial to improve the therapeutic effect and to increase the survival rate. However, it is difficult because breast cancer in early stage was usually occult, impalpable, and could not be detected by laboratory test. This study was designed to compare the effectiveness of three methods for diagnosis of non-palpable breast cancer. METHODS: Twenty-four patients with impalpable breast mass suggested by computer-aided stereotactic mammography were performed with three kinds of methods, including fine-needle aspiration cytology (FNAC), large-core needle biopsy (LCNB), and frozen section biopsy (FSB) with focus staining. The results were compared with postoperative pathology. RESULTS: Compared with postoperative pathology results, the diagnostic consistent rates of FNAC, LCNB and FSB with staining focus were 75%, 92%, and 100%, respectively (P< 0.05). CONCLUSION: Frozen section with focus staining guided by computer-aided stereotactic mammography was the effective diagnostic technique for non-palpable breast cancer.

CT arterial portography and CT hepatic arteriography in detection of micro liver cancer.

AIM:To recognize the characteristic findings of micro-liver cancer (MLC) and to evaluate the effect of CT arterial portography (CTAP) and CT hepatic arteriography (CTHA) in diagnosis of MLC.METHODS:Between April 1996 to December 1998, CTAP and CTHA were performed in 12 patients with MLC, which were not detected by conventional CT examinations. After CTHA, 3mL-5mL mixture of lipiodol, doxorubicin and mitoycin C were injected into hepatic artery through the catheter, and the followed up by CT three or four weeks later (Lipiodol CT Lp-CT).RESULTS:A total of 22 micro-tumors (0.2cm-0.6cm in diameter) were detected in 12 patients, which manifested as small perfusion defects in CTAP and small round enhancement in CTHA. The rate of detectability of CTAP and CTHA was 68.2% (15/22) and 77.3% (17/22) respectively, and the rate of the simultaneous use of both procedures reached 86.4% (19/22).All micro-tumors were demonstrated as punctate lipiodol deposit foci in Lp-CT. After Lp-CT, the elevated serum level of alpha-fetoprotein (AFP) dropped to the normal level in all patients.CONCLUSION:The CTAP and CTHA are the most sensitive imaging methods for detecting micro-liver cancer.Confirmed by the change of the elevated serum AFP level and lipiodol deposit foci in Lp-CT, small perfusion defects in CTAP and puntuate enhancement in CTHA may suggest micro-liver cancer.

Findings of non-pathologic perfusion defects by CT arterial portography and non-pathologic enhancement of CT hepatic arteriography.

AIM:To recognize the characteristic findings of non-pathologic perfusion defects with CT arterial portography (CTAP) and nonpathologic enhancement found in CT hepatic arteriography (CTHA).METHONDS:The manifestations of nonpathologic perfusion defects with CTAP and non pathologic enhancement found in CTHA were analyzed in 50 patients with primary hepatocellular carcinoma.RESULTS:The false-positive rate of perfusion defects detected in CTAP was 15.1% The shapes of perfusion defects were peripheral wedge, small, round, and patchy. The occurrence rate of non-pathologic enhancement found in CTHA was 22.0%. The shapes of non-pathologic enhancement were small, round, irregular, and wedge.CONCLUSION:There was high frequency of non-pathologic perfusion defects detected with CTAP and non-pathologic enhancement found in CTHA. The simultaneous use of both procedures may help decrease the false-positive rate, and increase the veracity of diagnosis for hepatocellular carcinoma.

[Spiral computed tomography (CT) and magnetic resonance imaging (MRI) in assessment of the skull base encroachment in nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: With the general using of computed tomography (CT) and magnetic resonance imaging (MRI), it is important to determine which method is more sensitive in detecting the skull base encroachment in clinic. This article was designed to investigate the diagnostic value of CT and MRI in detecting the skull base erosion in nasopharyngeal carcinoma patients. METHODS: Sixty-one cases pathologically proven as nasopharyngeal carcinoma were selected from August 1993 to September 2001. three-dimensional reconstruction with spiral CT thin slices scan were performed in 8 cases. CT scan was performed with Elscient CT Twin Flash; axial scan was parallel to the OM line routinely from soft palate to the suprasellar cistern. There were 13 cases with enhancement scan. MRI scan was performed by Philips T5-II super-conducting magnetic resonance imaging system (0.5T). The standard quadrature head coil was used. Routine axial, sagittal, and coronal image with SE sequences were obtained. Scanned field ranged from the soft palate to the suprasellar cistern. After plain scan, enhanced scan was performed in 55 of 61 cases. RESULTS: MRI discovered the skull base encroached more precisely than CT, 17 cases by CT and 26 cases by MRI, respectively. The early bone marrow infiltration was seen at clivus, basilar pterygoid, and basilar sphenoid in 6 cases by MRI scan while CT scan showed no abnormal lesion at these sites. In addition, MRI revealed nasopharyngeal carcinoma tissue infiltrated along the mandibular nerve (3 cases) while CT scan showed no change of these structures. CONCLUSION: Both CT and MRI can reveal that the tumor encroaches on the skull base by either destroying the bony structure or breaking through the natural foramen. MRI is more sensitive than CT in detecting the skull base encroachment. MRI could reveal the early infiltration of the bone marrow and tumor infiltration along the mandibular nerve. MRI confirms the dimension of nasopharyngeal carcinoma more precisely than CT. The three dimension reconstructional spiral CT was directer in discovering the dimension of the tumor.