Prognostic impact of H3K27me3 expression on locoregional progression after chemoradiotherapy in esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Trimethylation of lysine 27 on histone H3 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that mediates gene silencing. EZH2 is overexpressed and correlates with poor prognosis in many cancers. However, the clinical implication of H3K27me3 in human malignancies has not been well established. We wished to ascertain whether a correlation exists between the expression of H3K27me3 and clinical outcome in a group of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy (CRT).</p> <p>Methods</p> <p>The method of immunohistochemistry (IHC) was utilized to examine the protein expression of H3K27me3 in 98 pretreatment biopsy specimens of ESCC and in 30 samples of normal esophageal mucosa. The clinical/prognostic significance of H3K27me3 expression was statistically analyzed.</p> <p>Results</p> <p>The expression frequency and expression levels of H3K27me3 were significantly higher in ESCCs than in normal tissues. There was a positive correlation between H3K27me3 expression and WHO grade (<it>P </it>= 0.016), tumor size (<it>P </it>= 0.019), T status (<it>P </it>= 0.024), locoregional progression (<it>P </it>= 0.009) and EZH2 expression (<it>P </it>= 0.036). High H3K27me3 expression was associated with poor locoregional progression-free survival (LPFS) (<it>P </it>= 0.010) in ESCC. Further analysis demonstrated that H3K27me3 could stratify patient outcome in T2-3 (<it>P </it>= 0.048), N0 (<it>P </it>= 0.005) and M0 (<it>P </it>= 0.018) stages as well as in CRT effective group (<it>P </it>= 0.022).</p> <p>Conclusions</p> <p>Our data suggests that H3K27me3 expression examined by IHC might be useful for stratifying LPFS for different subsets of ESCC patients treated with definitive CRT.</p

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

AbstractObjectiveTo understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness.MethodsDNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening themtDNA 12SrRNA, GJB2andSLC26A4mutations in population–based samples.ResultsA total of 2, 572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X–linked, one Y–linked, 28 large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147GJB2induced hearing loss cases, 230 cases with enlarged vestibular aqueduct (EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1, 283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X–linked families were found transmitting two novel mutations in thePOU3F4gene, while another X–linked family was mapped onto a novel locus, nominated asAUNX1(auditory neuropathy, X–linked locus 1). The only Y–linked family was mapped onto theDFNY1locus (Y–linked locus 1,DFNY1). Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2, 567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes:mtDNA 12S rRNA 1555G, GJB2andSLC26A4.The auditory neuropathy cases in our samples were screened forOTOFgene mutations.ConclusionsThese data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalized surveillance and prevention models for hearing loss based on genetic research will provide the opportunity to decrease the prevalence of deafness in the Chinese population

Acute Mountain Sickness Is Associated With a High Ratio of Endogenous Testosterone to Estradiol After High-Altitude Exposure at 3,700 m in Young Chinese Men

Background: A large proportion of populations suffer from acute mountain sickness (AMS) after exposure at high altitude. AMS is closely related with age and gender implying that the sex hormones may play critical roles in AMS. Our observational study aimed to identify the association between the endogenous testosterone (T), estradiol (E2) and AMS.Methods: A total of 113 subjects were recruited in 2012. The participants were evaluated at 500 m and after acute (1 day) and short-term (7 days) high-altitude exposure at 3,700 m. The subjects also completed a case report form questionnaire and underwent blood pressure measurements and an echocardiography examination. The red blood cell (RBC) count, Hb concentration ([Hb]), hematocrit (HCT), E2, T, and erythropoietin (EPO) were measured.Results: Upon acute high-altitude exposure, E2 and EPO were significantly lower in AMS+ group, and T/E2 and stroke volume were higher. On the 1st day, AMS score correlated positively with the T/E2 ratio while it negatively correlated with E2. After 7 days at 3,700 m, the AMS+ subjects had higher erythropoietic parameters: EPO, T, and T/E2 were significantly higher in the AMS+ group. [Hb], RBC count, HCT, EPO, T and T/E2 were also correlated with AMS score. EPO, HCT, and the RBC count were also correlated with T/E2. Regression analyses indicated that T/E2 significantly correlated to AMS score and T/E2 on the 1st day was an independent predictor for AMS on the 7th day.Conclusion: AMS was correlated with T/E2 ratio and EPO. After short-term exposure, higher T/E2 may contribute to AMS together with EPO via erythropoiesis. Furthermore, T/E2 level at high altitude in the early stage was an independent predictor for AMS in the latter stage

Scenarios Simulation on Carrying Capacity of Water Resources in Kunming City

AbstractWith high-speed development of social economy, rapid urbanization, the impact of drought, water resources supply and demand imbalance in Kunming City, improving carrying capacity of water resources will become the hot topic of sustainable development research in Kunming City. Based on the carrying capacity theory of water resources (CCWR) and system dynamics (SD) principle, a dynamic model which related with water resources, society, economy and eco-environment was established. Using this model, four scenarios were set up. They were remaining current water utilization scenario, improving the utilization of water resource scenario, water conservation strategy scenario, and comprehensive strategy scenario. The results of simulations showed that comprehensive strategy was the optimal strategy that can improve the carrying capacity of water resource in Kunming City from 2010 to 2020. The comprehensive strategy included optimization and adjustment of industry structure, improving the utilization of water resources, water conservation and finally pollutant reduction and sewage recycling

CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: A matched case-control analysis in a single institution

<p>Abstract</p> <p>Background</p> <p>HIV-negative, CD20-negative <it>de novo</it> diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive <it>de novo</it> DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011.</p> <p>Methods</p> <p>The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL.</p> <p>Results</p> <p>The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (<it>P</it> = 0.008) and OS (<it>P</it> = 0.008) rates of 52% and 74.1%, respectively.</p> <p>Conclusions</p> <p>This study suggests that HIV-negative, CD20-negative <it>de novo</it> DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative <it>de novo</it> DLBCL.</p

Coprecipitation synthesis and properties of color tunable and upconversion luminescence in Tb³⁺ and Yb³⁺ co-doped Y(PO₃)₃ materials

Tb3+ and Yb3+ co-doped Y(PO3)3 upconversion luminescence phosphors were prepared by coprecipitation method. The structure and optical properties of the as-synthesized Y(PO3)3: Tb3+,Yb3+ samples were investigated by XRD, SEM, FI-IR and upconversion luminescence spectrophotometer (UPL), respectively. XRD results show that the as-synthesized samples are Tb3+ and Yb3+ co-doped Y(PO3)3 crystals with monoclinic structure (space group P21/c). UPL results display that the obtained Tb3+ and Yb3+ co-doped Y(PO3)3 samples emit the Tb3+ characteristic upconversion blue-green luminescence under 980 nm excitation. The doping content of Tb3+ ions affects the upconversion luminescence properties of the as-prepared Y(PO3)3: x Tb3+, 20%(mole fraction,the same below) Yb3+ samples. When the doping amount of Tb3+ is 2%-10%, the 5D4→7F6 emission peak of the Y(PO3)3: x Tb3+, 20% Yb3+ samples splits into two emission peaks centered at 481 nm and 491 nm. The dominant upconversion peak is located at 547 nm for the Y(PO3)3: x Tb3+, 20% Yb3+ samples when the Tb3+ doping content is 10%-20%. The concentration quenching can be observed when the doping amount of Tb3+ is over 20%. The doping ratio of Tb3+ to Yb3+ and the excitation power density also exhibit effect on the upconversion luminescence properties of the prepared samples. The upconversion blue-green emission color of the as prepared Tb3+ and Yb3+ co-doped Y(PO3)3 samples can be tuned by changing the doping amount ratio of Tb3+ to Yb3+.The upconversion luminescence mechanism of Y(PO3)3: Tb3+, Yb3+ samples was also discussed. The 5D3→7FJ (J=6,5,4) and 5D4→7FJ (J=6,5,4,3) upconversion luminescence are attributed to a three- and two-photon absorption mechanisms, respectively