Noise effective masking level for bone conduction of wide-spectrum short-duration signals in normal hearing adults.

OBJECTIVE: The objective of this study is to determine the noise effective masking level (EML) and inter-aural attenuation (IA) for click and CE-Chirp signals presented though a Radioear B-81 to elicit the auditory brainstem responses in normally hearing, young adults. DESIGN AND STUDY SAMPLE: A total of 26 conveniently sampled adults (13 male and 13 female, aged 18-25 years; 52 ears), with pure-tone hearing thresholds not >15 dB nHL at octave frequencies from 250 to 8000 Hz, and subjective thresholds for the bone-conducted click and CE-Chirp not >10 dB nHL. RESULTS: At stimulus intensities of 30 and 40 dB nHL, the contralateral EML was 67.86 ± 0.78 and 77.80 ± 0.81 dB SPL (respectively) for the click and 72.11 ± 0.74 and 83.53 ± 0.78 dB SPL (respectively) for the CE-Chirp. At stimulus intensities of 30 and 40 dB nHL, the IA was 3.46 ± 2.34 and 3.38 ± 2.03 dB (respectively) for both the click and the CE-Chirp. CONCLUSION: EML and IA values are reported for click and CE-Chirp signals presented at 30 and 40 dB nHL though a Radioear B-81 to elicit the ABR in normally hearing, young adults.

Retinal dehydrogenase 5 (RHD5) attenuates metastasis via regulating HIPPO/YAP signaling pathway in Hepatocellular Carcinoma.

Retinal dehydrogenase 5 (RDH5) is an important enzyme in the visual cycle. Several studies have reported that the RDH family may play crucial roles in tumor prognosis. However, the role of RDH5 in tumor prognosis is still unclear. We examined the mRNA level of RDH5 by using q-PCR in hepatocellular carcinoma (HCC) and adjacent non-cancerous tissues. The proliferation rate of HCC cells was detected by MTS assay, and the invasive ability was examined by transwell and scratch wound assays. The YAP protein localization and expression were visualized by immunofluorescence in two different cell lines. CpG islands in the promoter region were predicted by using the methprimer database. Clinical characteristics of a patient cohort data came from The Cancer Genome Atlas database. RDH5 was significantly downregulated in hepatocellular carcinoma tissues, and low RDH5 expression was associated with metastasis and poor patient prognosis. Functional assays revealed that the RDH5 promoter is methylated in HCC cell lines. Moreover, overexpressing RDH5 can suppress metastasis by reversing the epithelial-mesenchymal transition (EMT) process, and RDH5 also inhibits cell proliferation in HCC cell lines. Furthermore, suppressing RDH5 can activate the Hippo/YAP signaling pathway and promote the nuclear translocation of YAP. Clinical data demonstrated that RDH5 is an independent prognostic factor in HCC. In our study, we provided the first evidence that RDH5 plays a crucial role in suppressing proliferation and metastasis, and the RDH5 promoter is methylated in hepatocellular carcinoma. And as an important regulator, RDH5 can suppress the Hippo/YAP signaling pathway. Taken together, it revealed that RDH5 might be a potential therapeutic target in HCC patients.

Identification of the Active Compounds and Significant Pathways of Artemisia Annua in the Treatment of Non-Small Cell Lung Carcinoma based on Network Pharmacology.

BACKGROUND Artemisia annua exerts powerful effects in non-small cell lung carcinoma (NSCLC). Some studies have shown that Artemisia annua possesses the characteristics of new therapeutic drugs for NSCLC patients. However, the underlying molecular mechanism of Artemisia annua anti-NSCLC is not yet fully elucidated because Artemisia annua contains hundreds of ingredients. This study aimed to conduct network pharmacological analysis on the mechanism of action of Artemisia annua against NSCLC. MATERIAL AND METHODS The active ingredients and corresponding potential targets of Artemisia annua were searched and screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Then through The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) databases to establish NSCLC related targets. Based on the matching results of Artemisia annua potential targets and NSCLC targets, a protein-protein interaction (PPI) network was constructed to analyze the interactions between these targets and topologically screen the central targets. Furthermore, Gene Ontology (GO) biological functions analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathways enrichment were carried out. RESULTS There were 19 main active ingredients of Artemisia annua screened for target prediction; 40 NSCLC-related common targets were identified via multiple NSCLC databases. The node area and corresponding degree value of AKT1, MYC, CCND1, VEGFA, JUN, MAPK1, EGFR, and ESR1 were large and could be easily found in the PPI network. The aforementioned results were further verified by the analysis of GO biological function and KEGG enrichment analysis. CONCLUSIONS The network pharmacology analysis reveals the molecular biological mechanism of Artemisia annua anti-NSCLC via multiple active components, multi-channels, and multi-targets. This suggests that Artemisia annua might be developed as a promising anti-NSCLC drug.

[Study on molecular mechanism of Solanum nigrum in treatment of hepatocarcinoma based on network pharmacology and molecular docking].

This study aimed to explore the main active ingredients and potential targets of Solanum nigrum(SN), so as to reveal the potential molecular mechanism of SN in the treatment of hepatocellular carcinoma(HCC) based on network pharmacology and molecular docking. First,the main active ingredients and predictive targets of SN were collected in the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Then,the targets relating to HCC were collected through retrieval of integrated bio-pharmacological network database for traditional Korean medicine(PharmDB-K), oncogenomic database of hepatocellular carcinoma(OncoDB.hcc). The common targets of disease-drug component were selected through intersection between predictive targets and disease targets. Next, based on the String platform, protein-protein interaction network(PPI) model of the potential anti-HCC targets was constructed using the software Cytoscape 3.7.1. ClueGO and CluePedia APP in Cytoscape were used to analyze the gene function of SN in the treatment of HCC, and construct the main active ingredients-potential targets-signal pathways topology network of SN. Finally,DISCOVERY STUDIO software was applied in verifying the molecular docking between the key active ingredient and potential protein target. The results showed that there were 4 main active ingredients of SN, involving 22 potential targets relating to HCC and 7 signal pathways relating to potential anti-HCC targets of SN. Network analysis showed that SN may play a therapeutic role in HCC by acting on key targets, such as EGFR, TP53, MYC, CCND1 and CTNNB1. Molecular docking results showed that quercetin and EGFR could bind stably and interact through amino acid residues LEU718, LYS745 and GLN791. This study revealed the potential active ingredients and the possible molecular mechanism of SN for treatment of HCC, providing scientific basis for follow-up exploration of the molecular mechanism of SN against HCC.

The Accuracy of Renal Function Measurements in Obstructive Hydronephrosis Using Dynamic Contrast-Enhanced MR Renography.

OBJECTIVE. The objective of our study was to assess the accuracy of glomerular filtration rate (GFR) evaluation in patients with obstructive hydronephrosis using dynamic contrast-enhanced MR renography (DCE-MRR). MATERIALS AND METHODS. A group of 28 adult volunteers were enrolled in this study: 13 without hydronephrosis, eight with low-grade hydronephrosis, and seven with high-grade hydronephrosis. The GFR obtained from DCE-MRR (GFRMRR) and the GFR obtained from renal scintigraphy (GFRRS) were compared with the reference GFR (GFRRef) acquired using the two plasma sample method. The correlation and agreement between GFRMRR and GFRRef, GFRRS and GFRRef, and single-kidney GFRMRR (skGFRMRR) and single-kidney GFRRS (skGFRRS) were assessed. The interrater reliability of DCE-MRR and the interrater reliability of renal scintigraphy (RS) were measured. RESULTS. Both GFRMRR and GFRRS correlated well with GFRRef. In patients with hydronephrosis, DCE-MRR and RS overestimated GFR by 12.8 ± 13.9 mL/min (mean ± SD) and 11.5 ± 12.3 mL/min, respectively. The skGFRRS was higher than skGFRMRR by 5.7 ± 3.8 mL/min in high-grade hydronephrotic kidneys (p = 0.004). Good interrater reliability was observed for skGFRMRR (intraclass correlation coefficient [ICC] = 0.82-0.92) and skGFRRS (ICC = 0.79-0.90) for both nonhydronephrotic kidneys and hydronephrotic kidneys. The overall mean SDs of repeated measurements from three investigators were 4.0 and 3.8 mL/min for skGFRMRR and skGFRRS, respectively. CONCLUSION. Both DCE-MRR and RS tend to overestimate GFR in patients with hydronephrosis. RS-derived skGFR is slightly higher than that of DCE-MRR in kidneys with high-grade hydronephrosis. DCE-MRR is comparable to RS and may serve as an alternative noninvasive method for GFR measurement.

Host Prdx6 contributing to the intracellular survival of Brucella suis S2 strain.

BACKGROUND: Brucellosis is a worldwide zoonotic infectious disease that is transmitted in various ways and causes great harm to humans and animals. The brucellosis pathogen is Brucella, which mainly resides in macrophage cells and survives and replicates in host cells. However, the mechanisms underlying Brucella survival in macrophage cells have not been thoroughly elucidated to date. Peroxiredoxin 6 (Prdx6) is a bifunctional protein that shows not only GSH peroxidase activity but also phospholipase A2 activity and plays important roles in combating oxidative damage and regulating apoptosis. RESULTS: Recombinant mouse (Mus musculus) Prdx6 (MmPrdx6) was expressed and purified, and monoclonal antibodies against MmPrdx6 were prepared. Using the Brucella suis S2 strain to infect RAW264.7 murine macrophages, the level of intracellular Prdx6 expression first decreased and later increased following infection. Overexpressing Prdx6 in macrophages resulted in an increase in B. suis S2 strain levels in RAW264.7 cells, while knocking down Prdx6 reduced the S2 levels in cells. CONCLUSIONS: Host Prdx6 can increase the intracellular survival of B. suis S2 strain and plays a role in Brucella infection.

MicroRNA-645 promotes metastasis of osteosarcoma via targeting tumor suppressor NM23 nucleoside diphosphate kinase 2.

Osteosarcoma is the most common non-hematological primary bony malignancy in children and young adults with tumor metastasis being a common event at diagnosis. Understanding the pathogenesis of metastatic osteosarcoma may help identify potential therapeutic targets. In this study, we found that the level of microRNA-645 (miR-645) in osteosarcoma tumor tissues was significantly increased compared with their paired non-tumorous tissues, and was associated with histologic grade, TNM staging, lymph metastasis and distant metastasis. Knockdown of miR-645 caused a remarkable inhibition of migration of osteosarcoma U2OS cells. Furthermore, miR-645 inhibited NME2 (nucleoside diphosphate kinase 2) expression through directly binding to its 3' untranslated region. In human osteosarcoma tissues, we also found that NME2 was significantly decreased in tumor tissues, and its level was negatively correlated with miR-645. In addition, silencing NME2 attenuated the decreased cell migration by knockdown of miR-645, suggesting that it was involved in the miR-645 induced cell migration of osteosarcoma cells. Taken together, we found that miR-645 was up-regulated in osteosarcoma tissues and could promote osteosarcoma cell migration through directly inhibiting the tumor suppressor NME2. Our data provide novel insight into the role of miR-645 in osteosarcoma and indicate that miR-645 might be a potential therapeutic target of osteosarcoma.

Diagnosis and outcomes of collateral arterial formation after irreversible early hepatic artery thrombosis in pediatric liver recipients.

BACKGROUND: Early hepatic artery thrombosis (eHAT) has been recognized as an important cause of graft loss and mortality. However, the incidence, etiology and outcome are not clear, especially for children. The present study was to investigate the formation of collateral artery flow after irreversible eHAT and its impact on patient's prognosis. METHODS: We analyzed eHAT after liver transplantation in children from October 2006 to April 2015 in our center, illustrated the formation of collateral hepatic artery flow after irreversible eHAT and explored the diagnosis, complications, treatment and prognosis. The basic and follow-up ultrasonographic images were also compared. RESULTS: Of the 330 pediatric liver recipients, 22 (6.67%) developed eHAT within 1 month. Revascularization attempts including surgical thrombectomy, interventional radiology and conservational treatment (thrombolysis) were successful in 5 patients. Among the 17 patients who had irreversible eHAT, follow-up ultrasonography revealed that collateral artery flow was developed as early as 2 weeks after eHAT. Liver abscess and bile duct complication occurred secondary to eHAT in variable time. CONCLUSIONS: Collateral arterial formation is a compensatory adaptation to eHAT to supply blood to liver grafts. However, the severe bile duct damage secondary to eHAT is irreversible and retransplantation is unavoidable.

Myocardial T1 rho mapping of patients with end-stage renal disease and its comparison with T1 mapping and T2 mapping: A feasibility and reproducibility study.

PURPOSE: To evaluate the feasibility of T1 rho mapping in myocardium at 3T and to determine whether T1 rho mapping could better characterize myocardial injury in end-stage renal disease (ESRD) patients compared to T1 and T2 mapping. MATERIALS AND METHODS: T1 rho mapping, T1 mapping, and T2 mapping were performed at 3T on 35 healthy volunteers (15 males, 20 females, 40.7 ± 13.6 years) and 32 ESRD patients (16 males, 16 females, 48.6 ± 11.9 years). The mean T1 rho, T1 , and T2 values were compared using Student's t-test and correlated with cardiac function parameters, including peak ejection rate (PER), short-axis percent thickening (SAPT), peak filling rate (PFR), and time to peak filling (TTPF). RESULTS: The mean T1 rho values (49.4 ± 2.6 msec vs. 52.2 ± 4.0 msec, P = 0.001) and T2 values (50.5 ± 2.5 msec vs. 54.1 ± 4.0 msec, P < 0.001) were significantly different between the volunteers and patients, but there were no significant differences between the two groups in the T1 values (1253.1 ± 71.6 msec vs. 1273.4 ± 41.7 msec, P = 0.157). The mean T1 rho values were negatively correlated with the PER (r = -0.397; P = 0.03), SAPT (r = -0.688; P < 0.001), and PFR (r = -0.537; P = 0.002), whereas positively correlated with the TTPF (r = 0.677; P < 0.001). The mean T2 values were negatively correlated only with the SAPT (r = -0.427; P = 0.019) in the ESRD patients. CONCLUSION: T1 rho mapping of the myocardium is feasible at 3T. T1 rho values are higher in ESRD patients and relate to cardiac function, which may better characterize myocardial injury than can T1 and T2 . J. Magn. Reson. Imaging 2016;44:723-731.

[Effects of Jianpi Jiedu Recipe on TCRVßCDR3 Spectratyping of Liver Cancer Rats with Pi Deficiency Syndrome].

OBJECTIVE: To observe anti-cancer effects of Jianpi Jiedu Recipe (JJR) on liver cancer (LC) rats with Pi deficiency syndrome (PDS) and its relation with the third complementary-determining region gene spectratyping of TCRVß-chain (TCRVßCDR3). METHODS: Rats were divided into 8 groups according to random digit table, i.e., the blank control group (normal), the PDS group, the LC model group, the LC-PDS group, high, middle, and low dose JJR groups (75.00, 37.50, 18.75 g/kg, respectively by gastrogavage, once per day), the thymus pentapeptide group (5 mg/kg, intramuscular injection, twice per week), 8 in each group. Rats in the normal group were administered with physiological saline by gastrogavage once per day. PDS rat model was prepared by bitter-cold purgation. LC model was prepared by orthotopic transplantation method. Twenty gene subfamilies of TCRßCDR3 in the thymus, liver, and LC tissues were detected by Gene Scan. RESULTS: High and middle dose JJR could postpone the growth of LC volume (P < 0.05), with equivalent liver index and thymus index to those of the normal group (P > 0.05). In thymus and liver tissue of the normal group, the number of clones (20 and 19), gene fragment number (220 and 113), Quasi-Gaussian distribution ratio of TCRVßCDR3 gene repertoire (100.0% and 42.1%), and fragment fluorescence peak area (6,539 ± 2,325 and 1,238 ± 439) were at the highest level among the 8 groups. TCRVßCDR3 expressions in thymus and liver tissue of high and middle dose JJR groups were approximate to those of the normal group. They were in the middle of the thymus pentapeptide group, the PDS group, the LC model group, and poorest in the LC-PDS group. TCRVßCDR3 in liver tissue expressed the best in the thymus pentapeptide group. CONCLUSION: JJR might inhibit the growth of LC cells, and its mechanism might be related to enhancing TCRVßCDR3 spectratype expression.

Preoperative hepatic hemodynamics in the prediction of early portal vein thrombosis after liver transplantation in pediatric patients with biliary atresia.

BACKGROUND: Portal vein thrombosis (PVT) is one of the main vascular complications after liver transplantation (LT), especially in pediatric patients with biliary atresia (BA). This study aimed to assess the preoperative hepatic hemodynamics in pediatric patients with BA using Doppler ultrasound and determine whether ultrasonographic parameters may predict early PVT after LT. METHODS: One hundred and twenty-eight pediatric patients with BA younger than 3 years of age underwent Doppler ultrasound within seven days before LT, between October 2006 and June 2013. The preoperative hepatic hemodynamic parameters were then compared between patients with early PVT (within 1 month following LT) and those without PVT. Receiver operating characteristic analysis was performed to determine the optimal cutoff value for predicting early PVT. RESULTS: Of the 128 transplant recipients, 41 (32.03%) had a hypoplastic portal vein (PV), 52 (40.63%) had hepatofugal PV flow and 40 (31.25%) had a high hepatic artery resistance index (HARI) of ≥1. Nine cases (7.03%) experienced early PVT. A PV diameter ≤4 mm (sensitivity 88.89%, specificity 72.27%), and a hepatofugal PV flow (sensitivity 77.78%, specificity 62.18%) with a high HARI ≥1 (sensitivity 77.78%, specificity 72.27%) were hepatic hemodynamic risk factors for early PVT. CONCLUSIONS: Hepatic hemodynamic disturbances in pediatric recipients with BA were more common. Small PV diameter (≤4 mm) and hepatofugal PV flow combined with high HARI (≥1) are strong warning signs of early PVT after LT in pediatric patients with BA. Intense monitoring of vascular patency and prophylactic thrombolytic therapy should be considered in pediatric patients undergoing LT for BA.

[Exploring the Correlation between Pi and Shen from the Excretion of AA-I and Expressions of Or- ganic Anion Transporting Polypeptide 2al and 2 b1 in Pi Deficiency Model Rats].

OBJECTIVE: To explore the correlation between Pi and Shen by observing the relationship between the metabolism of aristolochic acid (AA) and mRNA and protein expression levels of organic anion transporting polypeptide (oatp) superfamily member 2a1 and 2 b1 (oatp2al and oatp2bl) in renal, small intestinal, and large intestinal tissues of Pi deficiency syndrome (PDS) model rats. METHODS: Totally 46 Sprague-Dawley (SD) rats were randomly divided into four groups, i.e., the blank group (n = 12), the PDS group (n = 22), the AA-I group (n = 6), and the PDS AA-I group (n = 6). PDS model was established by subcutaneously injecting Reserpine at the daily dose of 5 mg/kg for 16 successive days. Carotid intubation was performed in 6 rats selected from the blank group and the PDS group. Pharmacokinetics of AA-I were detected at 5, 15, 30, 45, and 60 min after gastrogavage of AA-I. AA-I concentrations in renal, small intestinal, and large intestinal tissues of 10 rats selected from the PDS group were determined. Normal saline was administered to 6 rats selected from the PDS group and the blank group by gastrogavage. Renal, small intestinal, and large intestinal tissues were collected in the AA-I group and the PDS AA-I group at 60 min after gastrogavage of AA-I. mRNA and protein expression levels of oatp2a1 and oatp2b1 in each tissue were detected using real-time polymerase chain reaction (RT- PCR) and Western blot. RESULTS: Compared with the blank group, plasma concentrations of in vivo AA-I were obviously higher in the PDS group at 15, 30, 45, and 60 min after gastrogavage of AA-I with statistical difference (P < 0.05). Plasma concentrations of AA-I were obviously decreased at 60 min after gastrogavage of AA-I; AA-I concentrations in renal and large intestinal tissues were elevated; AA-I concentrations in small intestinal tissues were obviously reduced in the PDS group. There was no statistical difference in mRNA expression levels of oatp2a1 and oatp2b1 in the aforesaid three tissues of rats between the blank group and the PDS group. Compared with the blank group, mRNA expression levels of oatp2a1 and oatp2b1 decreased in small intestinal tissues of the AA-I group, and the mRNA expression level of oatp2a1 in large intestinal tissues significantly decreased (P < 0.05, P < 0.01). Compared with the PDS group, mRNA expression levels of oatp2a1 and oatp2b1 increased in renal tissues of the PDS AA-I group (P < 0.05); mRNA expression levels of oatp2b1 increased in large intestinal tissues of the PDS AA-I group (P < 0.05). CONCLUSIONS: The difference in AA-I metabolism might be associated with changed expression levels of oatp2a1 and oatp2b1 in renal, small intestinal, and large intestinal tissues under Pi deficiency induced loss of transportation. Shen and Dachang played important roles in substance metabolism under Pi deficiency state, which proved Pi-Shen correlated in Chinese medical theories.

[Formula Optimization in Renshen Jianxin Capsule Based on Uniform Design and Anti-myocardial Ischemia Effect].

OBJECTIVE: To realize quadratic formula optimization of Renshen Jianxin Capsule (RJC) by screening Chinese herbs with major anti-myocardial ischemia effect in RJC and optimize their optimal dosages. METHODS: By following "uniform design-pharmacodynamic experiment-mathematical modeling-formula optimization", authors employed U10(10(8)) uniform design in the experiment. Eight Chinese herbs contained in RJC were taken as observatory factors. Electrocardiograph (ECG) changes of myocardial ischemia induced by isoproterenol were taken as pharmacodynamic indices. The mathematical model between herbal factors and pharmacodynamic indices was established using stepwise regression analysis to screen Chinese herbs with major anti-myocardial ischemia effect. Their optimal dosages were optimized using the grid algorithm. RESULTS: The regression equation was y =1. 7889 -0. 3247 Ginseng xSalvia Miltiorrhiza -0. 0663 Astragalus membranaceus xOriental Waterplantain tuber. Forecasting factors included were Ginseng, Salvia Miltiorrhiza, Astragalus membranaceus, and Oriental Waterplantain tuber. The optimal formula dosage calculated by the grid algorithm was Ginseng 1. 62 g, Astragalus membranaceus 4. 62 g, Salvia Miltiorrhiza 2. 43 g, and Oriental Waterplantain tuber 1. 66 g. CONCLUSION: Uniform design combined with stepwise regression analysis and grid algorithm were able to realize quadratic formula optimization of RJC.

Interleukin-1 beta guides the migration of cortical neurons.

BACKGROUND: Proinflammatory cytokine interleukin-1beta (IL-1ß) is expressed at high levels in the developing brain and declines to low constitutive levels in the adult. However, the pathophysiological function of IL-1ß during brain development remains elusive. In this study, we investigated the role of IL-1ß in neuronal migration. METHODS: The Boyden transwell assay was used to examine the effects of IL-1ß on the migration of dissociated primary cortical neurons. To determine the role of IL-1ß in neuron leading process pathfinding, we employed a growth cone turning assay. In utero electroporation combined with RNAi technology was used to examine the neuronal migration in vivo during brain development in Sprague-Dawley rats. RESULTS: IL-1ß at concentrations ranging from 0.1 to 10 ng/mL in the lower chamber of a transwell induced a significant increase in the number of migrating neurons in a dose-dependent manner. When IL-1ß was simultaneously put in both the upper and lower chambers to eliminate the gradient, no significant differences in cell migration were observed. IL-1 receptor antagonist IL-1RA dose-dependently blocked the attractive effect of IL-1ß on neuronal migration. Microscopic gradients of IL-1ß were created near the growth cones of isolated neurons by repetitive pulsatile application of picoliters of a IL-1ß-containing solution with a micropipette. We found that growth cones exhibited a clear bias toward the source of IL-1ß at the end of a one hour period in the IL-1ß gradient. No significant difference was observed in the rate of neurite extension between IL-1ß and controls. We electroporated specific siRNA constructs against IL-1R1 mRNA into cortical progenitors at embryonic day 16 and examined the position and distribution of transfected cells in the somatosensory cortex at postnatal day 5. We found that neurons transfected with IL-1R1-siRNA displayed a severe retardation in radial migration, with about 83% of total cells unable to arrive at the upper cortical layers. CONCLUSIONS: Our study suggests an essential contribution of IL-1ß to neuronal migration during brain development, which provides a basis to understand the physiological roles of IL-1ß in the developing brain and could have significant implications for the prevention of some neurodevelopment disorders due to abnormal neuronal migration.

Oral Chinese herbal medicine for improvement of quality of life in patients with chronic heart failure: a systematic review and meta-analysis.

PURPOSE: Chronic heart failure (CHF) is not only a leading cause of death, hospitalization, and rehospitalization, but also significantly decreases quality of life (QoL). This study aims to evaluate published clinical trials of oral Chinese herbal medicine (OCHM) for improvement of QoL in patients with CHF that employ the Minnesota Living with Heart Failure Questionnaire (MLHFQ) score as an outcome measure. METHODS: A systematic literature search was performed using five databases up to June 2013 to identify randomized control trials (RCTs). RCTs involving OCHM plus conventional medicine treatment (CMT) with or without blinding, compared with CMT with or without placebo, with MLHFQ score as an outcome measure were identified. The methodological quality of RCTs was assessed independently using the Cochrane Handbook for Systematic Review of Interventions. RevMan 5.2.5 and Stata 11.0 were used for data analysis. RESULTS: Thirty-eight RCTs with a total of 3,170 participants were identified. The majority of the included trials were assessed to be of high clinical heterogeneity and poor methodological quality. The main results of meta-analysis showed improvement of total MLHFQ score when OCHM plus CMT compared with CMT with or without placebo [MD = -5.71 (-7.07, -4.36), p < 0.01]. CONCLUSIONS: There is some encouraging evidence of OCHM combined with CMT for the improvement of QoL in CHF patients. However, the evidence remains weak due to the small sample size, high clinical heterogeneity, and poor methodological quality of the included trials. Further, large sample size and well-designed trials are needed.

Selective estrogen receptor modulator effects of epimedium extracts on breast cancer and uterine growth in nude mice.

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women.

Phytoplankton blooms: an overlooked marine source of natural endocrine disrupting chemicals.

BACKGROUND: We had previously reported high androgenic and estrogenic activities in seawaters in confined clusters close to Singapore. Further investigations revealed a hitherto unsuspected link between estrogenic/androgenic activity and net phytoplankton count. OBJECTIVE: The primary objective of this study was to investigate the cause of a correlation between net phytoplankton and endocrine activity, and corroborate this observation, and rule out other possible confounding factors. Our secondary objective was to study if these estrogenic secretions can impact human health. METHODS: Five species of phytoplankton, Gymnodinium catenatum, Prorocentrum minimum, Alexandrium leei, Chattonella marina, and Fibrocapsa japonica, were isolated from Singapore waters and mass cultured and the cells and culture media screened for estrogenic and androgenic activity using human cell-based bioassays. RESULTS: The raphidophytes C. marina and F. japonica displayed significant estrogenic activity whilst the dinoflagellates G. catenatum and P. minimum displayed significant androgenic activity in both the cell extracts and the cell culture media extract. CONCLUSIONS: Our data shows that selected phytoplankton isolates are potent secretors of estrogenic and androgenic substances, which are potential endocrine disrupting chemicals (EDCs). As the harmful nature of EDCs is largely due to their bioaccumulation in the aquatic food chain our findings imply that the impact of these phytoplankton secretions needs to be investigated especially for seafoods, which are only a single trophic level away from phytoplankton. Alternatively, should these phytoplankton-origin EDCs not accumulate through marine food chains to significantly impact humans or marine mammals, our results indicate that functional assays could greatly over-estimate the risk from naturally occurring EDCs produced by marine phytoplankton. It remains to be determined if these EDCs affect zooplankton and other organisms that directly feed on marine phytoplankton, or if the secreted EDCs can directly impact other marine fauna.

[Effect of invigorating spleen and detoxification decoction on MHC I/MHC II in spleen-deficiency liver cancer rats survival].

OBJECTIVE: To explore that Invigorating Spleen and Detoxification Decoction (ISD) enhanced the survival of spleen-deficiency liver cancer rats and the effect on major histocompatibility complex I (MHC I) and major histocompatibility complex II (MHC II). METHODS: 105 male Wistar rats were randomly divided into blank control group, liver cancer model group, spleen-deficiency model group, spleen-deficiency liver cancer model group, Thymopentin group and spleen-deficiency liver cancer model groups treated by low and high-concentration ISD for modeling and intervention. Recorded the animals' weight, survival time, moribund state and cachexia score of liver cancer rats, and collected specimens in the experiment. Immunohistochemistry and Western blot were used to detect MHC I/MHC II expression in liver tissue and liver cancer tissue. RESULTS: The cumulative survival of high concentration ISD group and Thymopentin group were higher than that of the other groups (P < 0.05), and whose cachexia score were lower than the rest (P < 0.05). In the spleen-deficiency liver cancer model groups, MHC I expression in liver tissue was higher than that in liver cancer tissue, both in these two tissues, expression of high-concentration ISD group was the strongest (P < 0.01). MHC II expression in liver cancer tissue was stronger than that in liver tissue, expression of high-concentration ISD group was the strongest in liver tissue, but in liver cancer tissue, the spleen-deficiency liver cancer model group was the strongest (P < 0.01). CONCLUSION: ISD can significantly decrease the progression of cachexia caused by transplantable tumor and prolong the survival time, the effect may be related to increasing MHC I/MHC II expression.

Unveiling the Diagnostic Value of Strain Parameters Across All 4 Cardiac Chambers in Patients With Acute Myocarditis With Varied Ejection Fraction: A Cardiovascular Magnetic Resonance Feature-Tracking Approach.

BACKGROUND: This study assesses the diagnostic utility of strain parameters from cardiovascular magnetic resonance feature tracking across all cardiac chambers in patients with acute myocarditis, stratified by ejection fraction. METHODS AND RESULTS: Our cohort included 65 patients with acute myocarditis and 25 healthy controls; all underwent cardiac magnetic resonance imaging. Patients were divided into 2 groups based on left ventricular ejection fraction (EF)with a 55% cutoff: acute myocarditis with preserved EF, EF ≥55%, n=48; and acute myocarditis with reduced EF, EF <55%, n=17. The control group matched for age and sex. Cardiovascular magnetic resonance feature tracking evaluated strain parameters across all cardiac chambers. Both acute myocarditis with preserved EF and acute myocarditis with reduced EF groups showed significant decreases in left atrial peak early negative strain rate compared with controls. The acute myocarditis with reduced EF group had significantly reduced left ventricular circumferential strain relative to acute myocarditis with preserved EF and controls. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy in distinguishing patients with acute myocarditis with preserved EF from controls, with left atrial peak early negative strain rate achieving 92.9% specificity, left ventricular circumferential strain demonstrating an area under the curve of 0.832, and similarly effective results for left ventricular longitudinal strain and right ventricular longitudinal strain. Additionally, left atrial peak early negative strain rate and left ventricular circumferential strain showed significant correlations with troponin I levels, indicating myocardial injury. CONCLUSIONS: Cardiovascular magnetic resonance feature-tracking-derived strain parameters, particularly left atrial peak early negative strain rate and left ventricular circumferential strain, effectively diagnose acute myocarditis across different EFs, enhancing diagnostic accuracy and facilitating early detection, notably in patients with preserved EF.

The biomedical knowledge graph of symptom phenotype in coronary artery plaque: machine learning-based analysis of real-world clinical data.

A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.