Phragmalin-Type Limonoids from the Fruits of Chukrasia tabularis and Their Anti-Inflammatory Activity.

Phytochemical investigation on the fruits of C. tabularis led to the isolation of five new phragmalin-type limonoids (1-5) and four known ones (6-9). The structures of the new compounds 1-5, named chuktabamalins A-E, were elucidated via spectroscopic techniques (HRESIMS, 1D and 2D NMR) and were comparable with the literature data of known compounds. In addition, new compounds were evaluated for in vitro anti-inflammatory activity. Compounds 1, 2, 3 and 5 showed moderate anti-inflammatory activity with IC50 values of 21.72 ± 2.79, 23.29 ± 1.00, 47.08 ± 3.47 and 66.67 ± 2.89 µM, respectively.

Dietary phosphorus deficiency impaired growth, intestinal digestion and absorption function of meat ducks.

OBJECTIVE: An experiment was conducted to investigate the effects of dietary non-phytate phosphorus (nPP) deficiency on intestinal pH value, digestive enzyme activity, morphology, nutrient utilization, and gene expression of NaPi-IIb in meat ducks from 1 to 21 d of age. METHODS: 525 one-d-old Cherry Valley ducklings were fed diets (with 7 pens of 15 ducklings, or 105 total ducklings, on each diet) with five levels of nPP (0.22, 0.34, 0.40, 0.46 or 0.58%) for 21 d in a completely randomized design. Five experimental diets contained a constant calcium (Ca) content of approximately 0.9%. Body weight (BW), body weight gain (BWG), feed intake (FI), and feed to gain ratio (F: G) were measured at 14 and 21 d of age. Ducks were sampled for duodenum and jejunum digestion and absorption function on 14 and 21 d. Nutrient utilization was assessed using 25- to 27-d-old ducks. RESULTS: The results showed ducks fed 0.22% nPP had lower (P<0.05) growth performance and nutrient utilization and higher (P<0.05) serum Ca content and alkaline phosphatase (ALP) activity. When dietary nPP levels were increased, BW(d 14 and 21), BWG and FI (all intervals), and the serum phosphorus (P) content linearly and quadratically increased (P<0.05); and the jejunal pH value (d 14), duodenal muscle layer thickness (d 14), excreta dry matter, crude protein, energy, Ca and total P utilization linearly increased (P<0.05); however, the serum alkaline phosphatase (ALP) activity, jejunal Na+-K+-ATPase activity, and duodenal NaPi-IIb mRNA level (d 21) linearly decreased (P<0.05). CONCLUSION: The results indicated that ducks aged from 1 to 21d fed diets with 0.22% nPP had poor growth performance related to poor intestinal digestion and absorption ability; but when fed diets with 0.40%, 0.46% and 0.58% nPP, ducks presented a better growth performance, intestinal digestion and absorption function.

Doxorubicin-loaded poly(ε-caprolactone)-Pluronic micelle for targeted therapy of esophageal cancer.

There is still lack of effective treatment of esophageal cancer, and it is urgently necessary to develop a new programs to treat this disease. More and more evidence suggests that the combination of 2 or more treatment strategies can enhance the antitumor activity in cancer treatment. We have established a new therapeutic strategy that combines doxorubicin-loaded poly(ε-caprolactone) (PCL)-Pluronic micelles and miR-34a to better combat esophageal cancer. Doxorubicin was loaded into PCL-Pluronic micelle to achieve better uptake. Confocal microscopy was used to assess in vitro cellular uptake of PCL-Pluronic micelle. Finally, the in vivo effect of this new combination therapy strategy was also studied. The results showed that PCL-Plannick micelles significantly enhanced the uptake of doxorubicin in esophageal cancer cells in vitro, thereby improving the accumulation of doxorubicin in the cells. In vitro and in vivo combination of doxorubicin-loaded PCL-Pluronic micelles and miR-34a, achieving a significantly synergistic therapeutic effect over the corresponding single treatment. These results suggested that the combinational therapy based on doxorubicin-loaded PCL-Pluronic micelle and miR-34a may provide a reasonable strategy for improving the outcome of esophageal cancer treatment.

DCE-MRI-Derived Volume Transfer Constant (Ktrans) and DWI Apparent Diffusion Coefficient as Predictive Markers of Short- and Long-Term Efficacy of Chemoradiotherapy in Patients With Esophageal Cancer.

This study aimed to evaluate both the short- and long-term efficacies of chemoradiotherapy in relation to the treatment of esophageal cancer . This was achieved through the use of dynamic contrast-enhanced magnetic resonance imaging-derived volume transfer constant and diffusion weighted imaging-derived apparent diffusion coefficient . Patients with esophageal cancer were assigned into the sensitive and resistant groups based on respective efficacies in chemoradiotherapy. Dynamic contrast-enhanced magnetic resonance imaging and diffusion weighted imaging were used to measure volume transfer constant and apparent diffusion coefficient, while computed tomography was used to calculate tumor size reduction rate. Pearson correlation analyses were conducted to analyze correlation between volume transfer constant, apparent diffusion coefficient, and the tumor size reduction rate. Receiver operating characteristic curve was constructed to analyze the short-term efficacy of volume transfer constant and apparent diffusion coefficient, while Kaplan-Meier curve was employed for survival rate analysis. Cox proportional hazard model was used for the risk factors for prognosis of patients with esophageal cancer. Our results indicated reduced levels of volume transfer constant, while increased levels were observed in ADCmin, ADCmean, and ADCmax following chemoradiotherapy. A negative correlation was determined between ADCmin, ADCmean, and ADCmax, as well as in the tumor size reduction rate prior to chemoradiotherapy, whereas a positive correlation was uncovered postchemoradiotherapy. Volume transfer constant was positively correlated with tumor size reduction rate both before and after chemoradiotherapy. The 5-year survival rate of patients with esophageal cancer having high ADCmin, ADCmean, and ADCmax and volume transfer constant before chemoradiotherapy was greater than those with respectively lower values. According to the Cox proportional hazard model, ADCmean, clinical stage, degree of differentiation, and tumor stage were all confirmed as being independent risk factors in regard to the prognosis of patients with EC. The findings of this study provide evidence suggesting that volume transfer constant and apparent diffusion coefficient as being tools allowing for the evaluation of both the short- and long-term efficacies of chemoradiotherapy esophageal cancer treatment.

Inter- and intra-observer reproducibility of ADC measurements in esophageal carcinoma primary tumors.

The apparent diffuse coefficient (ADC) may correlate with the treatment response to chemotherapy/radiotherapy in solid tumors. Our aim was to determine the inter- and intra-observer reproducibility of ADC measurements in primary esophageal squamous cell carcinoma (ESCC). ADCs were blindly measured in 31 patients diagnosed with ESCC by two observers before treatment (pre-ADC) and after 5th fraction radiotherapy (intra-ADC) twice with a 2-week interval. The mean pre-ADC of primary tumors was 1.25±0.22 and 1.27±0.23 (in 10-3mm2/s) from observer A for measurements 1 and 2, respectively, and the intra-observer measurements were -0.02 bias vs. -0.13-0.09 limits of agreement. From observer B, the mean pre-ADC varied between 1.25±0.23 and 1.27±0.23 (in 10-3mm2/s) for measurements 1 and 2, respectively, and intra-observer measurements were -0.02 bias vs. -0.17∼0.16 limits of agreement. The mean pre-ADC of primary tumors was 1.26±0.24 (in 10-3mm2/s) from observers A and B, and inter-observer measurements were 0.01 bias vs. -0.09-0.09 limits of agreement, revealing a low inter-observer variance. Similar measurements of the intra-SD parameters showed that the pre- and intra-ADC of primary tumors differed significantly. Thus ADC measurements may have sufficient inter-observer and intra-observer reproducibility to measure primary tumor responses to treatment, and the ADCs before and during treatment differed.

Long-term tolerance and cardiac function in breast cancer patients receiving trastuzumab therapy.

We examined the long-term clinical tolerance and cardiac safety of trastuzumab treatment in ninety-four female patients diagnosed with breast cancer with human epidermal growth factor receptor 2 (HER-2) overexpression. Electrocardiography (ECG) was monitored throughout trastuzumab treatment, and left ventricular ejection fractions (LVEFs) were estimated using echocardiography prior to treatment with trastuzumab and every 3 months after its first application. The duration of trastuzumab treatments ranged from 3 to 60 months. Declines in LVEF ≥ 15% were seen mainly after 3-15 months of trastuzumab treatment, and LVEF was lowest at 15 months, which coincided with the largest decline in LVEF from baseline. Spearman correlation coefficients indicated that accumulation of anthracycline, the use of cyto/cardioprotective drugs (CPD) and the duration of trastuzumab treatment were all associated with the change of LVEF, and there was a strong correlation between these factors and the change of LVEF (ρ=0.81, ρ=0.734 and ρ=0.777 respectively). These results indicate that significant decreases of LVEF may be seen after 3-15 months of trastuzumab treatment, but that there is a favorable benefit-risk ratio for patients undergoing long-term trastuzumab treatment.

Effect of wave-current interactions on sediment resuspension in large shallow Lake Taihu, China.

The disturbance of the water-sediment interface by wind-driven currents and waves plays a critical role in sediment resuspension and internal nutrient release in large, shallow lakes. This study analyzed the effects of the interactions between wind-induced currents an1d waves on the driving mechanism of sediment resuspension in Lake Taihu, the third largest freshwater lake in China, using acoustic and optic techniques to collect long-term, high-frequency, synchronous in situ measurements of wind, currents, waves, and suspended solid concentrations (SSCs). The results suggested that water turbidity started to increase at wind speeds of approximately 4 m/s and significantly increased when wind speeds exceeded 6 m/s. In most cases, wind-induced waves were the main energy source for changes in turbidity. Wave-generated shear stress contributed more than 95% to sediment resuspension and that only in weak wind conditions (<4 m/s) did the lake bottom shear stresses generated by currents and waves contributed equally. The relationship between SSC and bottom shear stress generated by wave was established by fitting the observed results. The processes of sediment dynamics were divided into four stages (A through D) according to three shear-stress thresholds. In stage A, SSC remained stable (about 45 mg/L) and τw was less than 0.02 N/m2. In stage B, the sediment bed was starting to be activated (SSC 45∼60 mg/L) and τw was in the range of 0.02∼0.07 N/m2. In stage C, a medium amount of sediment was suspended (SSC 60∼150 mg/L) and τw ranged from 0.07 to 0.3 N/m2. In stage D, large amount of sediment was suspended (SSC 150∼300 mg/L) and τw was larger than 0.3 N/m2. The findings of this paper reveal the driving mechanism of sediment resuspension, which may further help to evaluate internal nutrient release in large shallow Lake Taihu.

Using ADV for suspended sediment concentration and settling velocity measurements in large shallow lakes.

Sediment resuspension plays an important role to provide nutrient release for algal growth in large shallow lakes. The settling velocity (w s ) is the key parameter for understanding the suspended sediment transport. In this paper, acoustic Doppler velocimeter (ADV) and optical backscatter sensor (OBS) instruments were used to measure in situ velocities and suspended sediment concentration (SSC) simultaneously without affecting the ambient turbulence in the bottom layer of Lake Taihu. The results showed that (1) ADV echo intensity (EI) could be transferred into SSC successfully by using a simple logarithmic relationship with a strong correlation of 0.87. (2) Three methods from a balance of settling and diffusive flux gradients for calculating settling velocities were applied, including Reynolds concentration flux, estimation of eddy diffusivity using the von-Karman Prandtl equation, and Kwon's power equation. The average settling velocity during the observation period was 0.11 mm/s for Lake Taihu. (3) The fitted power function, w s = 1.85 × 10-3 C 1.04, could be used to estimate w s according to SSC. (4) Settling velocity changes with SSC, vertical velocities, and wind speed, which describes suspended sediment instantaneous and continuous motions. This paper provides an effective approach for estimating the settling velocity, provides a reference value of settling velocity for hydrodynamic model, and supports a better understanding of sediment transport process and nutrient release in large shallow lakes.

MicroRNA-34a induces a senescence-like change via the down-regulation of SIRT1 and up-regulation of p53 protein in human esophageal squamous cancer cells with a wild-type p53 gene background.

MiR-34a has been reported as a non-coding RNA universally expressed in normal old cells and a probable suppressor of diverse cancer cells; however, this miRNA's expression and anti-tumor mechanism in esophageal squamous cancer cells (ESCC) remains unclear. We explored these questions in three human ESCC lines, KYSE-450, KYSE-410, and ECa-109, with wild-type p53 and mutant p53 backgrounds. Through a specific stem-loop RT primer for miR-34a, we examined the relevant expression level of miR-34a in these three cell lines using real-time reverse transcription PCR (qRT-PCR). We found that the expression level of miR-34a induced by the DNA damage agent adrmycin (ADR) was both p53- and time-dependent. Following incubation with miR-34a, cellular growth inhibition was exhibited differently in the three cell lines harbored with different p53 backgrounds. Furthermore, the MTT assay demonstrated an miR-34a-related cytotoxic effect in cell growth. Senescence-associated ß-galactosidase (SA-ß-Gal) staining was used to examine senescence-like phenotypes induced by miR-34a. Mechanistic investigation suggested that the down-regulation of Sirtuin1 (SIRT1) and up-regulation of p53/p21 contributed to the anti-tumor mechanism of miR-34a in wild-type p53 ECa-109 cells, while neither of the apoptosis-related proteins PARP and caspase-3 caused significant changes. In summary, our findings indicated that the intrinsic expression of miR-34a was relatively low and was expressed differently among different p53 backgrounds and ADR treatment times. The anti-tumor effect of miR-34a was primarily dependent on the regulation of SIRT1 and p53/p21 protein, not apoptosis-associated proteins.

The reproductive toxicity of saponins isolated from Cortex Albiziae in female mice.

Saponin frsom Cortex Albiziae (SCA) are extensively used in the clinical treatment of tumor and depression. However, SCA may cause several adverse effects, including reproductive toxicity. The present study was designed to assess the mechanism by which SCA cause reproductive toxicity in female mice. The general reproductive toxicity testing was accomplished in female Kunming mice. The animals were divided into four groups: three groups that were treated by oral gavage with 135, 270, and 540 mg·kg(-1)·d(-1) of SCA prepared in physiological saline, respectively, and one vehicle control group that was treated with physiological saline only. The gestational toxicity tests were conducted at 540 mg·kg(-1)·d(-1). The general reproductive toxicity results showed that the pregnancy rate of the SCA-treated group decreased with the pregnancy rate being decreased by 70% at 540 mg·kg(-1)·d(-1). SCA elicited maternal toxicity in the ovary and the uterus, but no fetal toxicity or teratogenicity was observed. The rates of implantation in the early, middle, and late pregnancy were all decreased, with stillbirths and maternal deaths being observed. Histopathological changes showed that SCA adversely affected the ovary and the uterus. In conclusion, SCA-induced reproductive toxicity in female mice is most likely caused by its damage to the ovary and the uterus.

Sub-chronic lead and cadmium co-induce apoptosis protein expression in liver and kidney of rats.

The combined subchronic effects of exposure to lead acetate and cadmium chloride on apoptosis protein expression were detected in the liver and kidney of rats to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. The TUNEL assay showed that there were increased numbers of apoptotic cells. Immunohistochemical tests showed increased numbers of positive cells under Bax and caspase-3 protein detection and decreased Bcl-2 protein. Furthermore, mitochondrial injury and increased numbers of apoptotic cells with condensed nuclei were observed by TEM. These results suggested that low-dose exposure to Pb and Cd can cause significant hepatic and renal apoptosis and finally impair their function. Hepatic and renal apoptosis induced by low-dose exposure is associated with mitochondrial injury and changes in levels of apoptogenic proteins, such as Bcl-2, Bax, and caspase-3.

Effects of mixed subchronic lead acetate and cadmium chloride on bone metabolism in rats.

This study aimed to determine the effects of administering a mixture of subchronic lead acetate (Pb (NO3)2) and cadmium chloride (CdCl2·2.5H2O) on the bone metabolism of rats. A control group and three experimental groups consisted of randomly selected rats. Rats in each experimental group were orally administered with a mixture of Pb (NO3)2 and CdCl2·2.5H2O with the following respective doses for 90 consecutive days: 0 mg/kg body weight b.w. (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25 + 0.71), 89.88 mg/kg b.w. (Group III, 87.74 + 2.14), and 269.65 mg/kg b.w. (Group IV, 263.23 + 6.42). Serum osteocalcin (OC) and bone-specific alkaline phosphates (BALP) were considered as bone-formation markers, whereas carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum acted as bone resorption markers. Calcitonin (CT) and parathormone (PTH) were tested as calciotropic hormones markers. The (Ca) and phosphorus (Pi) concentrations in the serum and urine were determined. These results were indicated by a significant (P < 0.05 - P < 0.01) increase in BALP, CTX, and PTH concentrations and decrease in CT and OC concentrations. Moreover, the concentrations of Ca and Pi in the serum were decreased, whereas those in urine increased. Results indicated that the administration of Pb and Cd induced bone metabolism disorders by decreasing bone formation and increasing bone resorption to destroy the hormonal regulation of mineral metabolism as a result of Ca and Pi imbalance.

[Combined effects of sub-chronic exposure to lead and cadmium on physiological and biochemical indexes of blood in SD rats].

OBJECTIVE: The combined subchronic effects of exposure to lead acetate [Pb (NO3)2] and cadmium chloride [CdCl2 x 2.5H2O] on blood physiological and biochemical indexes of rats were detected to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. METHODS: 80 SD rats were randomly divided into three experiment groups and one control group. The rats in the three experiment groups were orally administrated with Pb(NO3)2 and CdCl2 x 2.5H2O combined solution at the doses of 29.96, 89.88 and 269.65 mg/kg for 90 days respectively, and the rats in control group were orally administrated with water. Blood were collected every 30 days to determine physiological and biochemical indexes. RESULTS: In each poisoning groups, WBC, RBC and HGB increased during early experiment period and then decreased. ALT, AST and BU increased all the experiment time. GLU decreased in the experiment time. Compared with control group, TC increase at high-dose poisoning group and TG decrease at low-dose poisoning group. The TP, ALB, GLO and CRE in the poisoning groups were not significantly different from those in the control group. And the hepatic cells and renal tubule epithelial cells showed granular degeneration, vacuolar degeneration and necrosis in poisoning groups. CONCLUSION: Low-dose Pd-Cd combined exposure could significantly change physiological and biochemical indexes of blood and cause hepatic and renal pathological injury of SD rats.

Effects of subchronic exposure to lead acetate and cadmium chloride on rat's bone: Ca and Pi contents, bone density, and histopathological evaluation.

This study aims to investigate the effects of low-dose subchronic exposure to lead acetate (Pb(NO3)2) and cadmium chloride (CdCl2·2.5H2O) on bone in rats. The rats were assigned randomly to a control group and three experimental groups that were given the mixture of Pb(NO3)2 and CdCl2·2.5H2O by gastric gavage at doses of 0 mg/kg body weight (b.w.) (Group I, to serve as a control), 29.96 mg/kg b.w. (Group II, 29.25+0.71), 89.88 mg/kg b.w. (Group III, 87.74+2.14), and 269.65 mg/kg b.w. (Group IV, 263.23+6.42) for at least 90 consecutive days. Calcium (Ca) and phosphorus (Pi) contents in the bone were determined. Bone mineral density (BMD) was measured at the tibia and femur region by dual-energy X-ray absorbsiometry. The histopathology of bone was evaluated by light microscope, scanning electron microscope, and transmission electron microscope. The BMD of rats in the experimental group was significantly lower and the contents of Ca and Pi were decreased than those in the control group. The histopathological evaluation showed that co-induction of Pb and Cd results in bone microstructure damage, especially to trabecular bone, marrow cavity, collagen fiber, and osteoblast. In general, results indicate that combining Pb with Cd induces bone damage and increases the risk of osteoporosis.

Toxicological assessment of combined lead and cadmium: acute and sub-chronic toxicity study in rats.

The exposure to chemical mixtures is a common and important determinant of toxicity and receives concern for their introduction by inhalation and ingestion. However, few in vivo mixture studies have been conducted to understand the health effects of chemical mixtures compared with single chemicals. In this study, the acute and 90day sub-chronic toxicity tests of combined Pb and Cd were conducted. In the acute toxicity test, the LD50 value of Pb(NO3)2 and CdCl2 mixture by the oral route was 2696.54mg/kg by Bliss method. The sub-chronic treatment revealed that the low-dose combination of Pb and Cd exposures can significantly change the physiological and biochemical parameters of the blood of Sprague-Dawley (SD) rats with dose-response relationship and causes microcytic hypochromic anemia and the damages of liver and kidney of the SD rats to various degrees. Histopathological exams showed that the target organs of Pb and Cd were testicle, liver, and kidneys. These observations suggest that Pb and Cd are practically additive-toxic for the SD rats in oral acute toxicity studies. The lowest observed adverse-effect level in rats may be lower than a dose of 29.96mg/(kgbwday) when administered orally for 90 consecutive days.

Quantification of metallothionein on the liver and kidney of rats by subchronic lead and cadmium in combination.

The combined subchronic effects of exposure to lead acetate and cadmium chloride on oxidative stress and metallothionein (MT) gene expression were detected in the liver and kidney of rats to investigate the hazards of environmentally relevant, low-dose exposure to these compounds. Pb and Cd co-induced oxidative stress in liver and kidney tissues. This result was indicated by a significant (P<0.01) increase in the maleic dialdehyde level and decreased levels of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. MT mRNA and protein significantly increased (P<0.01) in the liver and kidney of rats. Furthermore, the expression levels of MT-1 mRNA and MT-2 mRNA differed between the liver and kidney. The findings indicate that Pb combined with Cd induced oxidative damage in the liver and kidney of rats, and MT may be a biochemical environmental indicator.

Antiviral activity of sulfated Chuanmingshen violaceum polysaccharide against Newcastle disease virus.

Newcastle disease virus (NDV) is a member of Paramyxovirinae subfamily and can infect most species of birds causing severe economic losses. The current control measure is vaccination, but infections cannot be completely prevented. It remains a constant threat to the poultry industry and new control measures are urgently needed. This study demonstrates that sulfated Chuanmingshen violaceum polysaccharides (sCVPSs) were potent inhibitors of NDV, with 50 % inhibitory concentrations (IC50) ranging from 62.55 to 76.31 µg ml(-1) in Baby hamster kidney fibroblasts clone 21 (BHK-21) and from 101.57 to 125.90 µg ml(-1) in chicken embryo fibroblasts (CEF). sCVPS is more effective than heparan sulfate (HS; as a positive control) with IC50 values of 99.28 µg ml(-1) in BHK-21 and 118.79 µg ml(-1) in CEF. sCVPSs and HS exhibit anti-NDV activity by prevention of the early stages of viral life. The mechanism of action study indicated that virus adsorption in BHK-21, and both virus adsorption and penetration in CEF were inhibited by sCVPSs. When the number of viruses was increased to an m.o.i. of 0.1 in the immunofluorescence study and to an m.o.i. of 1 in the fluorescent quantitative PCR study, viral infection was also significantly suppressed; the antiviral activity of sCVPSs was independent of the m.o.i. sCVPSs also prevented the cell-to-cell spread of NDV. In vivo tests carried out on specific pathogen-free (SPF) chickens showed that sCVPSs also inhibited virus multiplication in heart, liver, spleen, lung and kidney. These results indicated that sCVPSs perform more effectively than HS as antiviral agents against NDV, and can be further examined for their potential as an alternative control measure for NDV infection.

Inhibitory effect of resveratrol against duck enteritis virus in vitro.

Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 µg/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol.

[Analysis of prognostic factors in patients with stage IV lung adenocarcinoma after failure of second-line EGFR-TKIs therapy].

BACKGROUND: The prognostic factors and salvage therapy after the failure of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) therapy have brought concerns. This study aims to analyze retrospectively the clinical data of patients with advanced lung adenocarcinoma and explore their prognostic factors. METHODS: Patients with integral clinic dates and staged IV lung adenocarcinoma with performance status (PS) scores from 0 to 2 were enrolled between January 2009 and February 2012 and followed up until death. The primary endpoint was survival time after the failure of EGFR-TKI therapy. RESULTS: A total of 81 patients were enrolled into the study, and the median overall survival time was 9.6 months (QL-QU: 5.4-19.2). Univariate analysis showed that PS score, metastatic status, and the presence of plural effusion were significantly correlated with patient survival time (P<0.05), whereas normal levels of carcinoembryonic antigen after EGFR-TKI therapy and history of operation showed a trend towards longer survival time. Multivariate analysis showed that the PS score, metastatic status, and plural effusion are independent prognostic factors for advanced adenocarcinoma after the failure of targeted therapy (P<0.05). CONCLUSIONS: A PS score from 0 to 1, single metastasis, and none or less plural effusion may attribute to the good outcome of stage IV lung adenocarcinoma and should further undergo chemotherapy.