A large scale outbreak of hand-foot-and-mouth disease (HFMD) occurred in Taiwan in 1998, in which more than 80 children died of shock syndrome with pulmonary edema/hemorrhage. Enterovirus 71 was ...implicated as the cause of this outbreak. In order to understand the virological basis responsible for mortality on this scale, nucleotide sequences of VP1 that is important for serotypic specificity, and the 5′-non-coding region (5′-NCR) that is important for replication efficiency, were analyzed comparatively. Phylogenetic analysis of both VP1 and 5′-NCR of nine EV71 isolates derived from specimens of fatal patients and seven isolates derived from uncomplicated HFMD patients showed that all but one isolate fell into genotype B. The one distinct isolate from a case of uncomplicated HFMD belonged to genotype C that was clustered along with one isolate from Taiwan in 1986. Complete sequence analysis of two selected isolates, one from the spinal cord of a fatal case and one from the vesicle fluid of a patient with mild HFMD, confirmed a high degree (97–100%) of identity in nucleotide sequence throughout the entire genome, except focal regions of 3C and 3′-NCR where the nucleotide homology was 90–91%. The identity of the deduced amino acid sequence in the 3C region that encodes viral proteinase dropped further to 86%, a result of missense mutations at the first nucleotide position of many codons.
Pancreatic cancer is characterized by rapid onset, high malignancy and high mortality, thus its early diagnosis is effective for improving the survival rate of patients. To discuss the values of ...detection of carbohydrate antigen (CA) 50, CA242 and CA199 in the diagnosis of pancreatic cancer, this study randomly selected 112 patients who were confirmed as having stage Ia~IIb pancreatic ductal adenocarcinoma (PDAC) in the Shandong Provincial Hospital, China, from May 2012 to May 2013 as a malignant group. One hundred patients with benign pancreatic lesions and 90 healthy people were selected in the same period as a benign group and a healthy control group, respectively. The levels of serum CA199, CA242 and CA50 were detected using electrochemiluminescence. Results demonstrated that the levels of serum CA199, CA242 and CA50 of the malignant group were significantly higher than those of the benign group and the healthy control group (P=0.001; P=0.003; P=0.000). The positive rate of the tumor markers of the malignant group was higher than that of the benign group and the healthy control group, and the differences had statistical significance (P=0.006; P=0.004; P=0.005). In the malignant group, sensitivity of CA199 was the highest (81.42%) as was the specificity of CA242 (80.14%). The detection of two or more markers could improve sensitivity (joint detection based on parallel tests) and specificity (joint detection based on serial tests). Thus the levels of serum tumor markers including CA199, CA242 and CA50 could be used as the assisted indicators for the diagnosis of early-stage PDAC. Joint detection of the three tumor markers is of great significance to improve the diagnostic sensitivity and accuracy of early PDAC.
Current cytotoxic chemotherapy produces clinical benefit in patients with breast cancer but the survival impact is modest. To explore novel cytotoxic agents for the treatment of advanced disease, we ...have characterized a new and pharmacokinetically improved Hec1-targeted compound, TAI-95. Nine of 11 breast cancer cell lines tested were sensitive to nanomolar levels of TAI-95 (GI(50) = 14.29-73.65 nmol/L), and more importantly, TAI-95 was active on a number of cell lines that were resistant (GI(50) > 10 μmol/L) to other established cytotoxic agents. TAI-95 demonstrates strong inhibition of in vivo tumor growth of breast cancer model when administered orally, without inducing weight loss or other obvious toxicity. Mechanistically, TAI-95 acts by disrupting the interaction between Hec1 and Nek2, leading to apoptotic cell death in breast cancer cells. Furthermore, TAI-95 is active on multidrug-resistant (MDR) cell lines and led to downregulation of the expression of P-glycoprotein (Pgp), an MDR gene. In addition, TAI-95 increased the potency of cytotoxic Pgp substrates, including doxorubicin and topotecan. Certain clinical subtypes of breast cancer more likely to respond to Hec1-targeted therapy were identified and these subtypes are the ones associated with poor prognosis. This study highlights the potential of the novel anticancer compound TAI-95 in difficult-to-treat breast cancers.
Tissue-engineered flexor tendon grafts may allow reconstruction of severe tendon losses. One critical factor is the optimization of cell proliferation and reseeding. Use of growth factors--basic ...fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and platelet-derived growth factor (PDGF)-BB--may improve culture conditions for human fibroblasts, tenocytes, and adipose-derived stem cells and increase repopulation of a tendon scaffold.
All cell types were plated at a density of 10,000 cells per well and cultured in F12 media supplemented with varying concentrations of bFGF, IGF-1, and PDGF-BB. After 72 hours, cell proliferation was determined using the CellTiter assay. Human flexor tendon segments were acellularized and reseeded in a cell suspension of 5 × 10(5) cells/ml. After 5 days, tendon repopulation was determined using the MTS assay and histology. Statistical significance was determined with analysis of variance and a t test.
For all cell types, there was enhanced proliferation with growth factors. Among single growth factors, PDGF-BB at 50 ng/ml was the most efficient stimulator of proliferation. With multiple growth factors, the optimal concentration was determined to be 5 ng/ml bFGF, 50 ng/ml IGF-1, and 50 ng/ml PDGF-BB (increase when compared with control: fibroblasts, 2.92-fold; tenocytes, 2.3-fold; and adipose-derived stem cells, 2.4-fold; p < 0.05). Tendons reseeded with this optimal combination of growth factors showed improved reseeding compared with the control group (fibroblasts, 2.01-fold; tenocytes, 1.78-fold; and adipose-derived stem cells, 1.76-fold; p < 0.05).
bFGF, IGF-1, and PDGF-BB can be used to improve cellular proliferation and repopulation of an acellularized scaffold. The use of growth factors may be an important step in the tissue engineering of human flexor tendons.
We study the evolution of the temporal properties of MAXI J1820+070 during the 2018 outburst in its hard state from MJD 58,190 to 58,289 with Insight-HXMT in a broad energy band 1-150 keV. We find ...different behaviors of the hardness ratio, the fractional rms and time lag before and after MJD 58,257, suggesting a transition occurred around this point. The observed time lags between the soft photons in the 1-5 keV band and the hard photons in higher energy bands, up to 150 keV, are frequency-dependent: the time lags in the low-frequency range, 2-10 mHz, are both soft and hard lags with a timescale of dozens of seconds but without a clear trend along the outburst; the time lags in the high-frequency range, 1-10 Hz, are only hard lags with a timescale of tens of milliseconds; they first increase until around MJD 58,257 and decrease after this date. The high-frequency time lags are significantly correlated to the photon index derived from the fit to the quasi-simultaneous NICER spectrum in the 1-10 keV band. This result is qualitatively consistent with a model in which the high-frequency time lags are produced by Comptonization in a jet.
Bearing capacity and durability of corroded steel bars is strongly deteriorated, and the degradation of mechanical properties versus corrosion ratio is topical. Given the random nature of corrosion ...process, stochastic method can be used to describe mechanical performance of corroded steel bars. In this paper, to simulate marine tidal zone environment, steel bars corroded by chloride solution under dry-wet cycling are studied experimentally, while mechanical performance deterioration of corroded steel bars is analyzed statistically. The corrosion ratios of specimens are found to increase over time for several phases, while their strength dropped with corrosion ratio. The residual nominal strength to corrosion ratio of steel bars is found to be well fitted with the Gumbel distribution, which parameters are calculated and discussed in detail.
Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in ...children following fetal exposure to TDF.
Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured.
One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926).
Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6–7 years after delivery.
NCT01312012 (ClinicalTrials.gov)
Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.
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•Short-term TDF use during pregnancy to prevent maternal HBV transmission is safe.•Children with and without fetal exposure to TDF have comparable long-term growth.•Children's renal function and bone development are unaffected.
This study aimed to investigate the value of shear wave elastography (SWE) for characterization of breast masses in a Chinese population.
Two thousand two hundred seventy-three women consented to be ...prospectively enrolled for the characterization of breast masses with ultrasound and SWE. Breast masses were known from symptoms, palpability, and/or previous imaging screening with mammography and/or ultrasound. Correlation of SWE qualitative and quantitative features with malignancy risk and impact on diagnostic performance of combining SWE features were assessed, and the Breast Imaging Reporting and Data System (BI-RADS) scoring was calculated using histopathology as reference.
Data of 2,262 masses (median size: 13 mm; range: 1.3-50) from 2,262 patients (median age: 43 years; range: 18-91) were investigated, of which 752 (33.3%) were malignant. Sensitivity and specificity of BI-RADS diagnosis were 97.5% (733/752) and 54.8% (827/1,510), respectively. By logistic regression, the combination of maximum elasticity (
) measurements with BI-RADS assessments increased the area under the receiver operating characteristic curve from 0.908 (95% CI: 0.896-0.920) to 0.954 (95% CI: 0.944-0.962). Using
of 30 kPa or lower to selectively downgrade BI-RADS 4a masses to follow-up, and
of 160 kPa or higher to selectively upgrade BI-RADS 3 lesions to biopsy, specificity significantly increased from 54.8% (827/1,510) to 66.1% (998/1,510) (
<0.001) while sensitivity decreased nonsignificantly from 97.5% (733/752) to 96.9% (729/752) (
=0.2891). Positive predictive value for biopsy recommendation increased from 51.7% (733/1,417) to 58.7% (729/1,241) (
<0.001).
Adding SWE maximum stiffness to BI-RADS 3 and BI-RADS 4a breast masses in a Chinese population increased significantly the specificity of breast ultrasonography, without significant change in sensitivity.
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