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The cytokinin oxidase / dehydrogenase (CKX) gene plays a principal role in controlling cyto-kinin levels and has been shown to be a major quantitative trait locus (QTL) affecting grain number in rice. However, the function and evaluation of the haplotypes of the wheat CKX gene have yet to be illustrated. In this study, TaCKX6-D1, a wheat ortholog of rice OsCKX2, was cloned and its haplotype variants were determined to be significantly associated with the 1000-grain weight on the basis of linkage mapping, association analysis and gene expression analysis. Five TaCKX6-D1 haplotypes, designated a–e, were identified. An indel marker was developed to identify haplotype a, which was associated with higher grain weight. Haplotype a showed decreased expression relative to haplotype b in seeds at 8 d after pollination. Sequence variations among modern cultivars, landraces and wild species suggest a significant domestication signature at the TaCKX6-D1 locus in Chinese wheat germplasm. TaCKX6-D1 may serve as a useful gene for the breeding of high-yielding wheat. A strategy for allele mining and utilization of TaCKX6-D1 was proposed. Our study also sheds light on the mechanisms of grain development and domestication of wheat, as well as the functional divergence of orthologs in comparative genomics.

Derived from our original nomogram study by using the risk variables from multivariable analyses in the derivation cohort of 1383 patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL) who were mostly treated with anthracycline-based chemotherapy, we propose an easily used nomogram-revised risk index (NRI), validated it and compared with Ann Arbor staging, the International Prognostic Index (IPI), Korean Prognostic Index (KPI), and prognostic index of natural killer lymphoma (PINK) for overall survival (OS) prediction by examining calibration, discrimination, and decision curve analysis in a validation cohort of 1582 patients primarily treated with non-anthracycline-based chemotherapy. The calibration of the NRI showed satisfactory for predicting 3- and 5-year OS in the validation cohort. The Harrell’s C-index and integrated Brier score (IBS) of the NRI for OS prediction demonstrated a better performance than that of the Ann Arbor staging system, IPI, KPI, and PINK. Decision curve analysis of the NRI also showed a superior outcome. The NRI is a promising tool for stratifying patients with ENKTCL into risk groups for designing clinical trials and for selecting appropriate individualized treatment.

Background Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. Methods We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. Results During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44–1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44–1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk ( P trend <0.001). The results were similar when excluding participants with less than two years of follow-up. Conclusions The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people’s health.

Aberrant microRNA expression is involved in the regulation of various cellular processes, such as proliferation and metastasis in multiple diseases including cancers. MicroRNA‐30e‐5p (miR‐30e) was previously reported as an oncogenic or tumour suppressing miRNA in some malignancies, but its function in lung adenocarcinoma (LAC) remains largely undefined. In this study, we found that the expression of miR‐30e was increased in LAC tissues and cell lines, associated with tumour size and represented an independent prognostic factor for overall survival and recurrence of LAC patients. Further functional experiments showed that knockdown of miR‐30e suppressed cell growth while its overexpression promoted growth of LAC cells and xenografts in vitro and in vivo. Mechanistically, PTPN13 was identified as the direct target of miR‐30e in LAC, in which PTPN13 expression was down‐regulated in LAC tissues and showed the inverse correlation with miR‐30e expression. Overexpression of PTPN13 inhibited cell growth and rescued the proliferation‐promoting effect of miR‐30e through inhibition of the EGFR signalling. Altogether, our findings suggest that miR‐30e could function as an oncogene in LAC via targeting PTPN13 and act as a potential therapeutic target for treating LAC.

Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9–81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34–2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.

More than 90% of lung cancers are caused by cigarette smoke and air pollution, with polycyclic aromatic hydrocarbons (PAHs) as key carcinogens. In Xuanwei City of Yunnan Province, the lung cancer incidence is among the highest in China, attributed to smoky coal combustion-generated PAH pollution. Here, we screened for abnormal inflammatory factors in non-small cell lung cancers (NSCLCs) from Xuanwei and control regions (CR) where smoky coal was not used, and found that a chemokine CXCL13 was overexpressed in 63/70 (90%) of Xuanwei NSCLCs and 44/71 (62%) of smoker and 27/60 (45%) of non-smoker CR patients. CXCL13 overexpression was associated with the region Xuanwei and cigarette smoke. The key carcinogen benzo(a)pyrene (BaP) induced CXCL13 production in lung epithelial cells and in mice prior to development of detectable lung cancer. Deficiency in Cxcl13 or its receptor, Cxcr5, significantly attenuated BaP-induced lung cancer in mice, demonstrating CXCL13’s critical role in PAH-induced lung carcinogenesis. Lung cancer causes the most cancer deaths worldwide. For decades, people have known that lung cancer is associated with environmental factors, and both cigarette smoke and air pollution are known to cause cancers in humans. Smoke and air pollution both contain chemicals called polycyclic aromatic hydrocarbons (or PAHs). These chemicals cause chronic inflammation of the lung, which in turn is a major risk factor for developing lung cancer. However, it is unclear exactly how PAHs trigger inflammation and cancer. Xuanwei City in China is suited to the study of this question because until the 1970s its inhabitants used 'smoky coal' for cooking in unventilated indoor spaces; this produced high levels of small particles that contain high concentrations of PAHs. Women from this region, who traditionally do most of the cooking, have rates of lung cancer comparable to those of men. In other parts of China a woman’s chance of getting lung cancer is approximately half that of a man’s. Therefore, Xuanwei City provides a setting in which air pollution is a main contributor to lung cancer risk. Wang, Cheng et al. have now compared the levels of certain proteins (which are linked to inflammation) in lung cancer patients from Xuanwei City with those in control regions of China. The level of one such protein marker, called CXCL13, was particularly high in almost all patients from Xuanwei City, but only highly expressed in half of the patients from the control regions. Moreover, there was also a clear link between cigarette smoke and CXCL13 expression because, in control regions, smokers were much more likely to have high levels of CXCL13 than non-smokers. To test whether PAHs cause CXCL13 expression, Wang, Cheng et al. first exposed normal lung epithelial cells, cancer cells and then mice to a PAH. These experiments showed that CXCL13 levels did indeed increase and the mice developed lung tumours. However, when the genes for CXCL13 or its binding partner were deleted, the mice no longer got cancer when exposed to the PAH. This shows that CXCL13 signalling is an important mechanism by which PAHs cause lung cancer. Lastly, further experiments showed that CXCL13’s binding partner is highly expressed on some immune cells that can promote lung cancer. Importantly, the over-expression of CXCL13 occurred before the lung tumours developed. This might provide a new treatment strategy in which CXCL13 signalling could be inhibited after the exposure to PAHs. Future studies may now focus on discovering new drugs, or modifying existing drugs, to achieve this goal.

Lung cancer is the leading cause of cancer-related deaths worldwide, and non-small-cell lung cancer (NSCLC) accounts for about 80% of all cases, which is the major subgroup of lung cancer. G protein-coupled receptor kinase 5 (GRK5) has been demonstrated to play pivotal roles in both development and progression of several pathological conditions including cancer. Here, we found that GRK5 expression was significantly increased in 539 NSCLC cancerous tissues than that in 99 normal non-cancerous tissues by immunohistochemistry analysis; we also showed intensive higher positive staining percentage in female and adenocarcinoma (ADC) NSCLC patients than that in male and squamous cell carcinoma (SCC) patients, respectively. In addition, GRK5 high expression NSCLC patients had a worse overall survival rate than the low expression patients. We provided evidence showing that both the mRNA and protein expression levels of GRK5 were increased in NSCLC cancerous cell lines (GLC-82, SPC-A-1, H520, H838, H358, A549, and H1299) comparing with that in normal human bronchial epithelium cell line (BEAS-2B), and identified many GRK5 mutations in NSCLC cancerous tissues. In addition, we found that depletion of GRK5 inhibited NSCLC cancerous cell proliferation, migration in vitro, and xenograft tumor formation in vivo. Furthermore, GRK5 knockdown promoted cell cycle arrest at G2/M phase and induced cellular apoptosis. In summary, our data reveal an oncogenic role of GRK5 in NSCLC progression, indicating that GRK5 could be used as a new therapeutic target in future.

Background： Image-guided radiation therapy （IGRT） is the preferred method for curative treatment of localized prostate cancer, which could improve disease outcome and reduce normal tissue toxicity reaction. 1GRT using cone-beam computed tomography （CBCT） in combination with volumetric-modulated arc therapy （VMAT） potentially allows smaller treatment margins and dose escalation to the prostate. The aim of this study was to compare the difference of dos~metric diffusion in conventional IGRT using 7-field, step-and-shoot intensity-modulated radiation therapy （IMRT） and hypofractionated IGRT using VMAT for patients with localized prostate cancer. Methods： We studied 24 patients who received 78 Gy in 39 daily fractions or 70 Gy in 28 daily fractions to their prostate with/without the seminal vesicles using IMRT （n = 12） or VMAT （n = 12） for prostate cancer between November 2013 and October 2015. Image guidance was performed using kilovoltage CBCT scans equipped on the linear accelerator. Offline planning was performed using the daily treatment images registered with simulation computed tomography （CT） images. A total of 212 IMRT plans in conventional cohort and 292 VMAT plans in hypofractionated cohort were enrolled in the study. Dose distributions were recalculated on CBCT images registered with the planning CT scanner. Results： Compared with 7-field, step-and-shoot IMRT, VMAT plans resulted in improved planning target volume （PTV） D95% （7663.17 ± 69.57 cGy vs. 7789.17± 131.76 cGy, P 〈 0.001）. VMAT reduced the rectal D25 （P 〈 0.001）, D35 （P 〈 0.001）, and D50 （P 〈 0.001）, bladder V50 （P 〈 0.001）, D25 （P = 0.002）, D35 （P = 0.028）, and D50 （P = 0.029）. However, VMAT did not statistically significantly reduce the rectal V50, compared with 7-field, step-and-shoot IMRT （25.02 ± 5.54% vs. 27.43 ±8.79%, P - 0.087）. Conclusions： To deliver the hypofractionated radiotherapy in prostate cancer, VMAT significantly increased PTV D95% dose and decreased the dose of radiation delivered to adjacent normal tissues comparing to 7-field, step-and-shoot IMRT. Daily online image-guidance and better management of bladder and rectum could make a more precise treatment delivery.

Background The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI‐ENKTL). Methods The clinical data of GI‐ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. Results A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty‐nine patients received chemotherapy, of whom 15 patients received asparaginase‐based (ASP‐based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP‐based regimens, and 50.0% and 25.0% for those treated with non‐ASP‐based regimens, respectively. The median follow‐up was 12.9 months and the 1‐year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP‐based regimens resulted in a superior 1‐year progression‐free survival rate compared to non‐ASP‐based regimens (100.0% vs. 36.0%, p = .07). However, ASP‐based regimens did not improve survival in patients at an advanced stage. Conclusion GI‐ENKTL still has a poor prognosis, even in the era of modern asparaginase‐based treatment strategies.

Prolonged maintenance of surgical position often results in postoperative pain and discomfort in patients. The present study aimed to investigate the effect of preoperative practice of surgical position on postoperative pain and general comfort in patients receiving kidney surgeries. For this nonrandomized pilot study, 74 patients receiving kidney surgeries were selected using the probability sampling method. Patients from ward 1 were assigned to the practice group (n=35), and those from ward 2 were assigned to the control group (n=39). The practice group were instructed to practice the surgical position for 3 days prior to the surgery. Postoperative pain and comfort were surveyed using two questionnaires for 3 days, respectively. The postoperative pain scores were compared using the Student's -test. The two groups did not differ significantly in wound pain on postoperative days 1-3 ( > 0.05). However, the practice group showed significantly reduced low back pain and contralateral shoulder pain than the control group for 3 postoperative days ( < 0.05). The physical domain score was significantly higher in the practice group than in the control group ( < 0.01). Preoperative practice of surgical position can effectively reduce postoperative low back pain and contralateral shoulder pain in patients receiving kidney surgeries and improve the physical comfort.