The role of additional gastrectomy after non-curative endoscopic resection remains uncertain. The present meta-analysis aimed to explore the risk factors for early-stage gastric-cancer patients after ...non-curative endoscopic resection and evaluate the efficacy of additional gastrectomy.
Relevant studies that reported additional gastrectomy after non-curative endoscopic resection were comprehensively searched in MedLine, Web of Science and EMBASE. We first investigated the risk factors for residual tumor and lymph-node metastasis after non-curative endoscopic resection and then analysed the survival outcome, including 5-year overall survival (OS) and 5-year disease-free survival, of additional gastrectomy.
Twenty-one studies comprising 4870 cases were included in the present study. We found that residual tumor was associated with larger tumor size (>3 cm) (odds ratio OR = 2.81,
< 0.001), undifferentiated tumor type (OR = 1.78,
= 0.011) and positive horizontal margin (OR = 9.78,
< 0.001). Lymph-node metastasis was associated with larger tumor size (>3 cm) (OR = 1.73,
< 0.001), elevated tumor type (OR = 1.60,
= 0.035), deeper tumor invasion (>SM1) (OR = 2.68,
< 0.001), lymphatic invasion (OR = 4.65,
< 0.001) and positive vertical margin (OR = 2.30,
< 0.001). Patients who underwent additional gastrectomy had longer 5-year OS (hazard ratio HR = 0.34,
< 0.001), 5-year disease-free survival (HR = 0.52,
= 0.001) and 5-year disease-specific survival (HR = 0.50,
< 0.001) than those who did not. Moreover, elderly patients also benefited from additional gastrectomy regarding 5-year OS (HR = 0.41,
= 0.001).
Additional gastrectomy with lymph-node dissection might improve the survival of early-stage gastric-cancer patients after non-curative endoscopic resection. However, risk stratification should be performed to avoid excessive treatment.
Much correlative evidence indicates that the oxidative modification of protein by reactive oxygen species (ROS) is involved in normal aging as well as the pathogenesis of neurodegenerative diseases ...such as Alzheimer's disease. In this study, we explored the antioxidative and neuroprotective effects of a naphthoquinone, 2-methoxy-6-acetyl-7-methyljuglone (MAM), purified from the dried rhizome of Polygonum cuspidatum (Chinese name Hu-Zhang). Pretreatments with MAM (24 h) were investigated for their protective effects against apoptosis induced by the oxidizing agent tert-butyl hydroperoxide (t-BHP) in PC12 cells. The results indicated that MAM pretreatments could effectively protect PC12 cells against cytotoxicity induced by t-BHP in a dose-dependent manner. Cell viability was determined by both MTT and LDH assays. Increasing concentrations of MAM enhanced cell viability significantly and completely prevented cell death induced by t-BHP at 2.5 µM. The corresponding extracellular lactate dehydrogenase (LDH) levels were also attenuated significantly by various concentrations of MAM. In addition, it was found that the antioxidative effect of MAM was stronger than those of resveratrol and lipoic acid. The antiapoptotic property of MAM was further investigated with Hoechst 33342 nuclear staining and TUNEL assay. Pretreatments of MAM were able to prevent the t-BHP-induced nucleus fragmentation and accumulation of apoptotic bodies (commonly accepted as markers of apoptosis) inside the cells in a dose-dependent manner. t-BHP induced the phosphorylation of ERK 1/2, JNK and p38 MAPK, which were all impeded by pretreatments with MAM, indicating that MAM may act as a potent antioxidant which significantly interferes with the MAPK apoptotic cascades, probably rescuing cells by inhibiting the death pathways.
Callicarpa nudiflora,which is a big brand of Li nationality medicine with Hainan characteristics,has the effects of dissolving stasis,hemostasis,anti-inflammatory and antibacterial. At present,there ...is a lack of information about the reference genome of C. nudiflora. The study of the genome size,heterozygosity rate and characteristics of SSR of C. nudiflora,can provide an effective basis for the formulation of the whole genome de novo sequencing strategy and development of SSR molecular markers of C. nudiflora. To realize this purpose,high throughput sequencing platform Illumina Hiseq was used to sequence the genome structure of C. nudiflora and K-mer analysis was applied to estimate genome size,repeat sequences and heterozygosity rate. Simple-sequence repeat( SSR) loci that are suitable as markers were identified by MISA software. The results showed the estimated genome size of C. nudiflora was 822. 43 Mb,with a 0. 85% heterozygosity rate and 71. 67% repeats,and the GC content of genome was about 49. 20%. Th
Backgrounds and aims
Although a number of studies have been conducted on the association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and diabetic nephropathy (DN) in Chinese ...population, this association remains elusive and controversial. To further assess the effects of PAI-1 4G/5G polymorphism on the risk of DN, a meta-analysis was performed in the Chinese population.
Methods
Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine through November, 2015. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the associations.
Results
This meta-analysis identified nine studies, including 777 DN cases, 413 healthy controls, and 523 DM controls. In the total analyses, a significantly elevated risk of DN was associated with variants of PAI-1 4G/5G when compared with the healthy group (4G vs. 5G, OR 2.46, 95 % CI 1.45–4.16; 4G/4G vs. 5G/5G, OR 4.32, 95 % CI 1.79–10.39; 4G/4G vs. 4G/5G +5G/5G, OR 2.96, 95 % CI 1.59–5.53; 4G/4G +4G/5G vs. 5G/5G, OR 2.78, 95 % CI 1.34–5.75) and DM group (4G vs. 5G, OR 1.93, 95 % CI 1.28–2.92; 4G/4G vs. 5G/5G, OR 2.99, 95 % CI 1.44–6.21; 4G/4G vs. 4G/5G +5G/5G, OR 2.84, 95 % CI 1.77–4.54). In the subgroup analyses stratified by ethnicity and geographic areas, it revealed the significant results in Chinese Han, in North and South China.
Conclusions
This meta-analysis showed that the PAI-1 4G/4G variant, 4G allele might be risk alleles for DN susceptibility in the Chinese population, and further studies in other ethic groups are required for definite conclusions.
Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which regulate systemic calcium homeostasis and also participate in cell proliferation, differentiation and apoptosis. We have ...previously shown that CaSR can induce apoptosis in isolated rat adult hearts and in normal rat neonatal cardiomyocytes. However, no knowledge exists concerning the role of CaSR in apoptosis induced by ischemia and reperfusion in neonatal cardiac myocytes. Therefore, in the present study, we incubated primary neonatal rat ventricular cardiomyocytes in ischemia-mimetic solution for 2
h, then re-incubated them in a normal culture medium for 24
h to establish a model of simulated ischemia/reperfusion (I/R). We assayed the apoptotic ratio of the cardiomyocytes by flow cytometry; observed morphological alterations by transmission electron microscope; analyzed the expression of caspase-3, Bcl-2, CaSR, extracellular signal-regulated protein kinase (ERK), and Fas/Fas ligand (FasL) by Western blotting; and measured the concentration of intracellular calcium by Laser Confocal Scanning Microscopy. The results showed that simulated I/R increased the expression of CaSR and cardiomyocyte apoptosis. GdCl
3, a specific activator of CaSR, further enhanced CaSR expression, along with increases in intracellular calcium and apoptosis in cardiomyocytes during I/R. Activation of CaSR down-regulated Bcl-2 expression, up-regulated caspase-3 and Fas/FasL expression and stimulated ERK1/2 phosphorylation. In summary, CaSR is involved in I/R injury and apoptosis of neonatal rat ventricular cardiomyocytes by inhibiting Bcl-2, inducing calcium overload and activating the Fas/FasL death receptor pathway.
Background
Approximately one-third of prostate cancer (PCa) patients show biochemical failure after radical prostatectomy (RP) and are prone to develop metastasis with significant mortality. Although ...aberrant Wnt/β-catenin (CTNNB1) signaling has been observed in numerous types of human cancers, including PCa, to our knowledge there is currently no information on the role of Wnt signaling gene polymorphisms in PCa.
Methods
We comprehensively studied the contribution of genetic variations in
CTNNB1
and
adenomatous polyposis coli
(
APC
), one of the key genes encoding the CTNNB1 destruction complex, to PCa risk and prognosis after RP using a hospital-based case–control study. We selected and genotyped 13 tagged single-nucleotide polymorphisms (tSNP) to predict common variants across entire
APC
and
CTNNB1
genes in 307 patients with clinically localized PCa who received RP and 371 unaffected controls.
Results
Four tSNPs (rs3846716, rs2431238, rs41115, and rs565453) and a specific haplotype (GTAAGA) in the
APC
tumor suppressor gene were associated with a 0.57- to 0.71-fold lower risk of localized PCa. The association of tSNPs with prostate-specific antigen (PSA) recurrence in PCa patients was then analyzed by Kaplan–Meier analysis and Cox regression model. Interestingly, we found that the
APC
rs3846716 GA/AA genotypes were also significantly associated with poorer PSA-free survival (log-rank test,
P
= 0.037) compared with the GG genotype.
Conclusions
This is the first report documenting the potential prognostic role of the
APC
rs3846716 GA/AA genotype on PSA recurrence after RP.
The mechanisms underlying lung cancer radioresistance remain to be fully elucidated. The DNA repair pathway is a predominant target of radiotherapy, which is considered to be involved in the acquired ...radioresistance of cancer cells. The present study aimed to establish a radioresistant cell model using the A549 human lung cancer cell line, and to further investigate the potential mechanisms underlying the radioresistance. The A549R radioresistant lung cancer cell variant was established by exposing the parental A549 cells to repeated γ-ray irradiation at a total dose of 60 Gy. Colony formation assays were then used to determine cell survival following γ-ray exposure. The established radioresistant cells were subsequently treated with or without the NU7026 DNA-PKcs inhibitor. The levels of DNA damage were determined by counting the number of fluorescent γ-H2AX foci in the cells. The cellular capacity for DNA repair was assessed using antibodies for the detection of various DNA repair pathway proteins. The radioresistant sub-clones exhibited significantly decreased survival following NU7026 treatment, compared with the parental cells, as determined by colony formation assays (P<0.05), and this finding was found to be dose-dependent. Treatment with the DNA-dependent protein kinase (DNA-PK) inhibitor significantly reduced γ-H2AX foci formation (P<0.05) following acute radiation exposure in the radioresistant sub-clones, compared with the parental control cells. The decreased levels of γ-H2AX were accompanied by an increase in the percentage of apoptotic cells in the radioresistant cell line following post-radiation treatment with the DNA-PKcs inhibitor. The expression levels of proteins associated with the DNA repair pathway were altered markedly in the cells treated with NU7026. The results of the present study suggested that radioresistance may be associated with enhanced DNA repair following exposure to radiation, resulting in reduced apoptosis. Therefore, the quantity of γ-H2AX determines the radioresistance of cells. The DNA repair pathway is important in mediating radioresistance, and treatment with the DNA-PKcs inhibitor, NU7026 restored the acquired radiation resistance.
AIM： To introduce and evaluate a new method to re- pair bile duct defect with a degradable stent and au- tologous tissues. METHODS： Eight Ba-Ma mini-pigs were used in this study, Experimental models ...with common bile duct （CBD） defect （0,5-1,0 cm segment of CBD resected） were established and then CBD was reconstructed by duct to duct anastomosis with a novel degradable stent made of poly sebacic acid-co-（1,3-propanediol）-co- （1,2-propanediol）. In addition, a vascularized greater omentum was placed around the stent and both ends of CBD. Cholangiography via gall bladder was per- formed for each pig at postoperative months 1 and 3 to rule out stent translocation and bile duct stricture. Complete blood count was examined pre- and post- operatively to estimate the inflammatory reaction. Liver enzymes and serum bilirubin were examined pre- and post-operatively to evaluate the liver function. Five pigs were sacrificed at month 3 to evaluate the healing of anastomosis. The other three pigs were raised for one year for long-term observation. RESULTS： All the animals underwent surgery success- fully. There was no intraoperative mortality and no bile leakage during the observation period, The white blood cell counts were only slightly increased on day 14 and month 3 postoperatively compared with that before operation, the difference was not statistically significant （P = 0.652）. The plasma level of alanine aminotrans- ferase on day 14 and month 3 postoperatively was also not significantly elevated compared with that before operation （P = 0.810）. Nevertheless, the plasma level of y-glutamyl transferase was increased after opera- tion in both groups （P = 0.004）, especially 2 wk after operation. The level of serum total bilirubin after opera- tion was not significantly elevated compared with that before operation （P = 0.227）, so did the serum direct bilirubin （P = 0.759）. By cholangiography yia gall blad- der, we found that the stent maintained its integrity of shape and was stillin situ at month 1, and it disap- peared completely at month 3. No severe CBD dilation and stricture were observed at both months 1 and 3. No pig died during the 3-too postoperative observation period. No sign of necrosis, bile duct stricture, bile leak- age or abdominal abscess was found at reoperation at month 3 postoperatively. Pigs had neither fragments of stent nor stones formed in the CBD. Collagen deposit was observed in the anastomosis by hematoxylin and eosin （HE） and Masson＇s trichrome stains. No severe cholestasis was observed in liver parenchyma by HE staining. Intestinal obstruction was found in a pig 4 mo after operation, and no bile leakage, bile duct stricture or biliary obstruction were observed in laparotomy. No sign of bile duct stricture or bile leakage was observed in the other two pigs. CONCLUSION： The novel method for repairing bile duct defect yielded a good short-term effect without postoperative bile duct stricture. However, the long- term effect should be further studied.
Exposure to environmental noise has been associated with hypertension, but the related mechanism of vascular structural changes is unclear. This repeated-measure study investigated the effects of ...noise exposure on the 24-h ambulatory vascular structural properties in 66 adults aged 18-32 years. Individual noise exposure and personal vascular parameters were measured simultaneously in all subjects. Linear mixed-effects regressions were used to estimate the effects. A 1-A-weighted decibel (dBA) increase was significantly associated with the transient effects of 1.39 (95% confidence interval: 1.07, 1.79) %mL/mmHg in arterial compliance at nighttime but -1.70 (-2.05, -1.10) kdynes·s/cm(5) in arterial resistance during the daytime and -2.38 (-3.44, -1.64) kdynes·s/cm(5) in arterial resistance at nighttime among all subjects. Such effects were observed in arterial distensibility only during the daytime after the 30-min (-1.84 -2.61, -1.29 %/mmHg) and 60-min (-2.06 -2.95, -1.44 %/mmHg) time-lagged noise exposures. For 24-h environmental noise, a 1-dBA increment was significantly associated with a sustained increase of 1.25 (1.10, 1.42) %mL/mmHg in arterial compliance but a decrease of 2.12 (-2.51, -1.80) kdynes·s/cm(5) in arterial resistance. Environmental noise exposure may have transient and sustained effects on adult vascular properties.
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