Serum Dickkopf-1 levels as a clinical and prognostic factor in patients with bladder cancer.

Dickkopf-1 (DKK-1) is a secreted protein that inhibits Wnt signaling. However, the clinical significance and prognostic value of serum DKK-1 levels have not been previously investigated in bladder cancer in Chinese patients. Blood samples were taken from 94 consecutive patients diagnosed with bladder cancer and 60 healthy control subjects. Serum DKK-1 expression levels were measured by enzyme-linked immunosorbent assay according to the manufacturer's directions. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used to test differences between the survival curves. Multivariate survival analysis was performed for all parameters deemed significant in the univariate analyses using the Cox regression model. The mean serum DKK-1 level in patients with bladder cancer was 35.91 ± 16.09 ng/mL, which was significantly higher than that in healthy individuals (9.08 ± 5.21 ng/mL, P < 0.001). Furthermore, serum DKK-1 levels were correlated significantly with lymph node metastasis (P = 0.021), distant metastasis (P = 0.013), and TNM stage (P = 0.008). Kaplan-Meier analysis using the log-rank test indicated that high serum DKK-1 levels were linked to poorer survival (33.4 vs 70.1%; P = 0.007). Multivariate analysis revealed that serum DKK-1 levels represented an independent prognostic factor for overall survival (hazard ratio = 2.365, 95% confidence interval = 1.873-8.881, P = 0.029). High serum DKK-1 levels may be associated with tumor progression and poor prognosis in bladder cancer and may be used as a potential biomarker to predict the prognosis of patients with bladder cancer.

Characterization of agronomic and quality traits and HSW-G5 compositions from the progenies of common wheat (Triticum aestivum L.) with different protein content.

High molecular weight glutenin subunits (HMW-GS) play an essential role in wheat processing quality. In this study, we evaluated the genetic pattern with HMW-GS composition between generations and examined whether agronomic and quality traits were correlated with each other. A wheat (Triticum aestivum L.) cultivar with high protein content and 2 cultivars with low protein content were subjected to a reciprocal cross. Sixteen agronomic and 4 quality characteristics were investigated. A total of 216 seeds from each F2 generation were chosen randomly and analyzed for HMW-GS composition using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Agronomic and quality characteristics were not significantly different between reciprocal crosses, indicating no cytoplasmic effect on the characteristics studied. The separation ratio of 2 HMW-GS loci was 9:3:3:1, indicating no linkage between any 2 loci. The novel HMW-GS N was detected in cultivar R145, which did not follow the Mendelian segregation ratio. A Glu-A1a(1) band was not detected in 1 individual from Tian8901xR145. Average grain weight per spike was significantly correlated with quality characteristics and may be a suitable criterion for selecting high protein content in wheat breeding programs.

Pathway crosstalk analysis based on protein-protein network analysis in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is a highly prevalent disease in older men of the western world and overall greatly affects the quality of life of elderly people. AIM: Understanding the mechanism of prostate cancer onset and metastasis is the key to treating this disease successfully and increasing survivability. MATERIALS AND METHODS: In this study, we constructed crosstalk networks among prostate cancer (primary and metastatic) related pathways by integrating protein-protein interactions (PPI) and KEGG (Kyoto encyclopedia of genes and genomes) pathways information. Total 11 pathways crosstalk with each other in primary prostate cancer and 7 pathways crosstalk with each other in metastatic prostate cancer. RESULTS: Among these pathways, Notch signaling pathway and chemokine signaling pathway were found regulate multiple processes during prostate cancer progression. CONCLUSIONS: Results from these studies will provide the groundwork for a combination therapy approach targeting multiple pathways which will likely be more effective than targeting one pathway alone.

Neutralization of HTLV-III/LAV replication by antiserum to thymosin alpha 1.

An antiserum prepared against thymosin alpha 1, a hormone secreted by the thymus gland, effectively neutralized the AIDS-associated virus [HTLV-III/LAV (clone BH-10)] and blocked its replication in H9 cells. Reverse transcriptase activity and expression of the HTLV-III/LAV antigens p15 and p24 were inhibited by purified immunoglobulin G preparations of antisera to thymosin alpha 1. The antiviral activity of the antiserum was found to be due to a region of homology between thymosin alpha 1 and p17, a product of the gag gene of HTLV-III/LAV. Comparison of the primary sequences of thymosin alpha 1 and the gag protein revealed a 44% to 50% homology in an 18-amino acid region, between positions 11 and 28 on thymosin alpha 1 and 92 and 109 on the gag protein. The effectiveness of the thymosin alpha 1 antiserum and of immunoglobulin G-enriched preparations in blocking replication of HTLV-III(BH-10) in H9 cells suggests a novel approach to the development of an AIDS vaccine. A vaccine directed against the gag protein might overcome the problem of genetic drift in the envelope region of the virus and be useful against all genetic variants of HTLV-III/LAV.

Up-regulated circular RNA hsa_circ_0067934 contributes to glioblastoma progression through activating PI3K-AKT pathway.

OBJECTIVE: Circular RNAs (circRNAs) are involved in cancer progression and metastasis, although little is known about their role in glioblastoma (GBM). The aim of this study was to investigate the expression pattern and molecular mechanism of hsa_circ_0067934 in GBM. PATIENTS AND METHODS: Hsa_circ_0067934 expression was detected in GBM tissues and cell lines by using RT-PCR. The prognostic value of the hsa_circ_0067934 expression in GBM patients was statistically analyzed. The effects of hsa_circ_0067934 expression on growth and apoptosis of GBM cells were analyzed by CCK-8, colony formation, and flow cytometry. Migration and invasion ability was evaluated by transwell and wound-healing assays. The protein expression of signaling pathways was determined by using Western blot. RESULTS: The expression level of hsa_circ_0067934 was significantly increased in GBM tissues and cancer cells. Kaplan-Meier survival curves showed that patients with higher expression of hsa_circ_0067934 had a more favorable overall survival and disease-free survival. The functional investigations revealed that the knockdown of hsa_circ_0067934 suppressed GBM cell proliferation, metastasis and EMT, and promoted apoptosis. Moreover, the mechanistic analysis demonstrated that the down-regulation of hsa_circ_0067934 significantly suppressed the activation of the PI3K-AKT pathway. CONCLUSIONS: Hsa_circ_0067934 is overexpressed and plays an oncogenic role in GBM by promoting cancer cell proliferation and metastasis via upregulation of PI3K-AKT pathway, which suggests that hsa_circ_0067934 is likely to serve as an efficient therapeutic approach in respect of GBM treatment.

[Strategy of schistosomiasis elimination and its effects in Jinhu County, Jiangsu Province].

OBJECTIVE: To understand the strategy of schistosomiasis elimination and its effects in Jinhu County, Jiangsu Province. METHODS: The data of schistosomiasis control in Jinhu County at different stages from 1970 to 2017 were collected and analyzed. RESULTS: From 1970 to 2017, there were three stages of schistosomiasis control, including transmission control, transmission interruption, and monitoring and elimination stages in Jinhu County. The main measures included Oncomelania hupensis snail control, infectious source control, and health education. A total of area of 290 691.78 hm2 was detected in Jinhu County, and the area with snails was 3 420.98 hm2. There were 8 729.37 hm2 area with snails was controlled. Since 2014, no O. hupensis snails were found. A total of 525 377 person-times were examined for schistosomiasis, with 2 815 schistosomiasis patients identified, and 2 844 person-times were treated by chemotherapy. In addition, 977 cases received the expand chemotherapy. Since 1990, no local schistosome-infected persons were found. In 2017, the awareness rate of schistosomiasis control knowledge and the correct rate of health behavior were increased by 54.59% and 14.23% respectively compared with those in 1992. CONCLUSIONS: The comprehensive schistosomiasis control measures implemented in Jinhu County at different periods have achieved remarkable outputs and accelerated the schistosomiasis elimination process. However, the precise control measures should be implemented in the future to consolidate the prevention and control achievements.

The correlation between cognitive impairment and ambulatory blood pressure in patients with cerebral small vessel disease.

OBJECTIVE: The present study was aimed to analyze the correlation between cognitive impairment and ambulatory blood pressure in patients with cerebral small vessel disease (CSVD). PATIENTS AND METHODS: 108 patients with CSVD received in our hospital were selected. Assessment of cognitive impairment was by the Montreal Cognitive Assessment (MoCA). 39 cases were established as the impairment group and 69 cases were established as the normal group. 24 h ambulatory blood pressure was monitored, and changes in ambulatory blood pressure parameters between the two groups were compared. Also, the correlation between blood pressure parameters and MoCA score were analyzed. RESULTS: Comparisons of ambulatory systolic blood pressure, ambulatory pulse pressure and the ratios of night blood pressure reduction of patients in both groups showed statistical differences (p < 0.05), while the changes in diastolic blood pressure showed no statistical differences (p > 0.05). The comparison of the blood pressure curves in both groups showed statistical differences (p < 0.05). The ambulatory systolic blood pressure, ambulatory pulse pressure and the ratio of night blood pressure reduction of patients with CSVD showed prominently negative correlations with MoCA score (p < 0.05). CONCLUSIONS: Cognitive impairment and the ambulatory blood pressure of patients with CSVD are intimately correlated. The rise of ambulatory systolic blood pressure, pulse pressure, and the decline of blood pressure may represent risk factors for cognitive impairment in patients with CSVD. Improving blood pressure management will reduce the incidence of cognitive impairment caused by CSVD.

The relationship between intracranial pressure and neurocognitive function before and after the repair of a skull injury.

OBJECTIVE: This study examines the relationship between intracranial pressure (ICP) changes after skull injury repair and neurocognitive function before and after the repair. PATIENTS AND METHODS: Sixty patients undergoing skull injury repair participated in the study. A non-invasive detection analyzer was used to detect the ICP 2 days before operation, 10 days after the operation and one month after the operation in all patients. Additionally, the mean cerebral blood flow velocities (MV) in the internal carotid and the medial cerebral arteries were detected using a transcranial Doppler ultrasound (TCD). The neurological and cognitive functions were assessed using the NIHSS and the MMSE scales, respectively. And finally, an ELISA assay was used to detect the plasma insulin-like growth factor (IGF)-1 and beta-amyloid peptide (Ab) levels. RESULTS: The results showed that all parameters studied improved significantly and continuously after surgery. CONCLUSIONS: We suggest that the improvement in the ICP values and the neurocognitive functions are related to the resulting decreased expression levels of IGF-1 and Abeta after the repair.

Inhibition of HIV replication by Hyssop officinalis extracts.

Crude extracts of dried leaves of Hyssop officinalis showed strong anti-HIV activity as measured by inhibition of syncytia formation, HIV reverse transcriptase (RT), and p17 and p24 antigen expression, but were non-toxic to the uninfected Molt-3 cells. Ether extracts from direct extraction (Procedure I), after removal of tannins (Procedure II), or from the residue after dialysis of the crude extract (Procedure III), showed good antiviral activity. Methanol extracts, subsequent to ether, chloroform and chloroform ethanol extractions, derived from procedure I or II, but not III, also showed very strong anti-HIV activity. In addition, the residual material after methanol extractions still showed strong activity. Caffeic acid was identified in the ether extract of procedure I by HPLC and UV spectroscopy. Commercial caffeic acid showed good antiviral activity in the RT assay and high to moderate activity in the syncytia assay and the p17 and p24 antigen expression. Tannic acid and gallic acid, common to other teas, could not be identified in our extracts. When commercial products of these two acids were tested in our assay systems, they showed high to moderate activity against HIV-1. Hyssop officinalis extracts contain caffeic acid, unidentified tannins, and possibly a third class of unidentified higher molecular weight compounds that exhibit strong anti-HIV activity, and may be useful in the treatment of patients with AIDS.

Adverse dermatologic reactions from antiarrhythmic drug therapy.

Undesirable cutaneous reactions to drugs may occur early or late in the course of treatment. The ingestion of drugs may also aggravate existing dermatologic conditions. The adverse dermatologic reactions from antiarrhythmic drug therapy are reviewed. The exact incidence of dermatologic side effects from cardiovascular drugs has been difficult to estimate because of sporadic reporting. In this review, the cutaneous side effects are discussed according to drug class and the type of dermatologic reaction.

Inhibition of HIV replication by naphthalenemonosulfonic acid derivatives and a bis naphthalenedisulfonic acid compound.

Several naphthalenemonosulfonic acid analogs and a bis naphthalenedisulfonic acid have been evaluated for anti-HIV activity in assays using H9 and MOLT-3 cells. Among the naphthalenemonosulfonic acids, a 4-amino-5-hydroxy compound and a 4,5-diamino compound showed low anti-HIV activity (upto 50% inhibition) at non-toxic doses. The bis naphthalenedisulfonic acid compound demonstrated significant suppression of HIV-1 antigen expression as measured by monoclonal antibodies to p17 (95%), p24 (94%) and syncytia inhibition (82%) at a dose of 20 micrograms/ml that was non-toxic to the host cells. The bis naphthalenedisulfonic acid analog represents a new class of compounds which may be effective in the treatment of HIV infected patients. The structure activity relationship and a probable mode of action of these compounds is discussed.

Brainstem auditory evoked responses from birth to adulthood: normative data of latency and interval.

Development of wave latency and interpeak interval (IPI) in brainstem auditory evoked responses (BAER) from birth to adulthood was examined. Adult equivalence was reached for most wave latencies and IPIs between the ages of 9 months and 3 years. The observation of the III-V/I-III interval ratio suggests that after term data the I-III IPI decreases more than the III-V IPI. I-III, III-V and I-V IPIs shortened from the l-month old group to the 4-6 year old group by 22%, 15% and 19% respectively. The III-V/I-III interval ration may be a useful BAER measure. Normative data of various BAER measures at different ages are presented. The slope of the L-I function for wave V was slightly steeper in younger groups than in older groups (40 microseconds/dB in the 1-month old group 32 microseconds/dB in the adult group). This change which was accompanied by an age-related difference in the absolute wave latency. It is suggested that age-dependent norms should be used in evaluation of the L-I function.

[Multiple primary lung cancer].

From November 1957 to June 1984, 30 patients with multiple primary lung cancer were diagnosed, basing on clinical features, diagnostic means, histologic type, treatment and prognosis. Out of 3,815 cases of resected primary lung cancer, the incidence of multiple primary cancer was 0.8%. There were 10 synchronous and 20 metachronous cases. There were 17 unilateral, only 1 simultaneous bilateral and 12 contralateral after resection of cancer in the opposite lung. Four of the 10 synchronous cases were definitely diagnosed preoperatively. Among the 20 metachronous cases, 9 were definitely diagnosed as a second primary lesion and the other 11 were proved by thoracotomy. Pathologically, 19 had identical types (15 squamous cell and 4 adenocarcinoma) but 11 had double types (9 squamous cell + adenocarcinoma, 2 squamous cell + anaplastic). The average survival of these 30 patients was 27.1 months, that in the synchronous group was 29 months and that in the metachronous group was 26.2 months. The 5 year survival rate of the synchronous cases was 35%, that of the metachronous cases was 42%. The clinicopathological criteria of multiple primary lung cancer, early diagnostic and operative procedure are also discussed.

Adverse dermatologic effects of cardiovascular drug therapy.

Cardiovascular disease is common, affecting an increasing number of persons as the population ages. To combat this growing health problem, physicians use a multitude of medications in the treatment of their patients. Although pharmacologic therapy greatly enhances quality of life for a majority of patients, there is always the potential for an unfavorable reaction. For example, cardiovascular drugs can induce a vast array of adverse dermatologic responses. This article reviews the various cutaneous reaction patterns that can occur as a result of treatment with specific cardiovascular agents.

Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture.

A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 microM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence, suggests that a mechanism other than "antisense inhibition" may be operative in these systems.

The effect of click rate on latency and interpeak interval of the brain-stem auditory evoked potentials in children from birth to 6 years.

Latency and interpeak interval of the brain-stem auditory evoked potentials at different click rates were measured in 80 healthy children from birth to 6 years, and 21 adults. Clicks were presented at 10, 30, 50, 70 and 90/sec, and 70, 40 and 20 dB HL. At high stimulus intensity (70 dB SL), all latencies of waves I, III and V and the I-V, I-III and III-V intervals showed a progressive prolongation with increasing repetition rate. The latency- and the interval-rate functions were similar for all age groups but their slopes were slightly steeper in younger than in older. As click rate increased from 10/sec to 90/sec, the latencies of waves I, III and V at different age groups were prolonged by 4-10%, 9-13% and 12-15% respectively, and the intervals of I-V, I-III and III-V were prolonged by 15-16%, 8-16% and 14-24% respectively. The mean increments of wave V latency and I-V interval in different age groups were 0.404-0.575 and 0.332-0.526 msec respectively with increasing click rate from 10 to 50/sec, and 0.697-1.009 and 0.629-0.776 msec respectively with increasing click rate from 10 to 90/sec. The younger the age the larger the absolute increments for all these BAEP parameters, but the increasing rates for a BAEP measure were similar among different age groups, exhibiting no age-dependent differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid conjugates of antiretroviral agents. I. Azidothymidine-monophosphate-diglyceride: anti-HIV activity, physical properties, and interaction with plasma proteins.

3'-Azido-3'-deoxythymidine-5'-phosphate diglyceride (16:0/18:1 omega 9), a phosphatic acid conjugate of AZT, is active against HIV replication in H9 cells and syncytia formation in MOLT-3 cells. The activities rank as AZT greater than pure conjugate greater than conjugate in mixed liposomes, with the pure conjugate having about one-third the activity of free AZT. The compound binds very rapidly to serum lipoproteins, but not to serum albumin, alpha and beta globulins, or red cells. Pancreatic phospholipase A2 hydrolyzes it to the lysophosphatidic acid conjugate.

Lipid conjugates of antiretroviral agents. II. Disodium palmityl phosphonoformate: anti-HIV activity, physical properties, and interaction with plasma proteins.

Disodium palmityl phosphonoformate, a novel lipid phosphoester of the anti HIV agent phosphonoformate (foscarnet), inhibits HIV replication in H9 cells and syncytia formation in MOLT-3 cells as effectively as foscarnet itself, as shown by dose-response data from assays for expression of p17 and p24 viral antigens and syncytia formation. Protein binding studies indicate that in serum, the derivative exists bound to albumin and the lipoproteins, and would therefore be likely to exhibit improved serum lifetime in vivo.