Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Low energy consumption electrically regenerated ion-exchange for water desalination.

A new regeneration method of ion exchange resin named Adjacent Bed Electrically Regenerated Ion-exchange (ABERI) was proposed to eliminate the environmental impact of traditional chemical regeneration and improve the economy of replacing chemical regeneration with electrical regeneration. The desalting operation of ABERI was the same as the conventional mixed bed. When the resins were exhausted, anion and cation resins were separated and then packed in a dedicated regenerator adjacently. The resins were regenerated by the H+ and OH- ions produced from a pair of electrodes installed on both sides of the resin bed. By optimizing the regeneration time, current, and feed water flow rate, the energy consumption of ABERI was 0.38 kWh/m3 water; that is, 54% of that of another electrical regeneration technology, membrane-free electrodeionization (MFEDI). Compared with MFEDI, the quality and quantity of purified water produced after regeneration were improved. In ABERI, the average conductivity and the volume (times of bed volumes) of the purified water are 0.9 µS/cm and 109; that is, 75 and 133% of that of MFEDI, respectively. The preliminary economic analysis showed that ABERI offers the potential to regenerate ion exchange resin in an eco-friendly and cost-effective manner.

Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments.

Global climate change has a significant effect on extreme environments and a profound influence on species survival. However, little is known of the genome-wide pattern of livestock adaptations to extreme environments over a short time frame following domestication. Sheep (Ovis aries) have become well adapted to a diverse range of agroecological zones, including certain extreme environments (e.g., plateaus and deserts), during their post-domestication (approximately 8-9 kya) migration and differentiation. Here, we generated whole-genome sequences from 77 native sheep, with an average effective sequencing depth of ∼5× for 75 samples and ∼42× for 2 samples. Comparative genomic analyses among sheep in contrasting environments, that is, plateau (>4,000 m above sea level) versus lowland (<100 m), high-altitude region (>1500 m) versus low-altitude region (<1300 m), desert (<10 mm average annual precipitation) versus highly humid region (>600 mm), and arid zone (<400 mm) versus humid zone (>400 mm), detected a novel set of candidate genes as well as pathways and GO categories that are putatively associated with hypoxia responses at high altitudes and water reabsorption in arid environments. In addition, candidate genes and GO terms functionally related to energy metabolism and body size variations were identified. This study offers novel insights into rapid genomic adaptations to extreme environments in sheep and other animals, and provides a valuable resource for future research on livestock breeding in response to climate change.

Removal of a large number of foreign bodies in the maxillofacial region with navigation system.

The removal of a large number of foreign bodies in the maxillofacial region can be complicated and challenging. In this case report, a specific strategy for removal of multiple foreign bodies in the maxillofacial region is presented. A girl diagnosed with 24 foreign bodies in her left lower face and neck underwent the surgery using a computer-assisted navigation system. A specific strategy was used in this case, which included from one sub-region to the next and from the easiest to the most difficult. This strategy is recommended for the removal of a large number of foreign bodies in the maxillofacial region with a navigation system.

Bioinformatics analyses of gene expression profile identify key genes and functional pathways involved in cutaneous lupus erythematosus.

BACKGROUND: Lupus erythematosus is an autoimmune disease that causes damage to multiple organs ranging from skin lesions to systemic manifestations. Cutaneous lupus erythematosus (CLE) is a common type of lupus erythematosus (LE), but its molecular mechanisms are currently unknown. The study aimed to explore changes in the gene expression profiles and identify key genes involved in CLE, hoping to uncover its molecular mechanism and identify new targets for CLE. METHOD: We analyzed the microarray dataset (GSE109248) derived from the Gene Expression Omnibus (GEO) database, which was a transcriptome profiling of CLE cutaneous lesions. The differentially expressed genes (DEGs) were identified, and the functional annotation of DEGs was performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Protein-protein interaction (PPI) network was also constructed to identify hub genes involved in CLE. RESULT: A total of 755 up-regulated DEGs and 405 down-regulated DEGs were identified. GO enrichment analysis showed that defense response to virus, immune response, and type I interferon signaling pathway were the most significant enrichment items in DEGs. The KEGG pathway analysis identified 51 significant enrichment pathways, which mainly included systemic lupus erythematosus, osteoclast differentiation, cytokine-cytokine receptor interaction, and primary immunodeficiency. Based on the PPI network, the study identified the top 10 hub genes involved in CLE, which were CXCL10, CCR7, FPR3, PPARGC1A, MMP9, IRF7, IL2RG, SOCS1, ISG15, and GSTM3. By comparison between subtypes, the results showed that ACLE had the least DEGs, while CCLE showed the most gene and functional changes. CONCLUSION: The identified hub genes and functional pathways found in this study may expand our understanding on the underlying pathogenesis of CLE and provide new insights into potential biomarkers or targets for the diagnosis and treatment of CLE. Key Points • The bioinformatics analysis based on CLE patients and healthy controls was performed and 1160 DEGs were identified • The 1160 DEGs were mainly enriched in biological processes related to immune responses, including innate immune response, type I interferon signaling pathway, interferon-γ-mediated signaling pathway, positive regulation of T cell proliferation, regulation of immune response, antigen processing, and presentation via MHC class Ib and so on • KEGG pathway enrichment analysis indicated that DEGs were mainly enriched in several immune-related diseases and virus infection, including systemic lupus erythematosus, primary immunodeficiency, herpes simplex infection, measles, influenza A, and so on • The hub genes such as CXCL10, IRF7, MMP9, CCR7, and SOCS1 may become new markers or targets for the diagnosis and treatment of CLE.

Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer: A Pairwise and Network Meta-Analysis of Pathological Complete Response.

We performed a pairwise and network meta-analysis to compare pathological complete response (pCR) among neoadjuvant chemotherapy in patients with triple-negative breast cancer. We searched PubMed for randomized clinical trials between January 1, 2000 and December 1, 2020. Abstracts from meetings were also searched. A frequentist random-effect model was applied to compare pCR and toxicities. The P-score was used to rank treatment effects. Nineteen trials with 16 treatments and 7794 patients were included. On the basis of SoC, the addition of carboplatin (OR = 1.82, 95% CI, 1.24 to 2.68, P < .01) and the addition of checkpoint inhibitors (OR = 1.69, 95% CI, 1.23 to 2.32, P < .01) increased pCR in pairwise meta-analysis; compared with paclitaxel, nab-paclitaxel did not improve pCR rates (OR = 1.81, 95% CI, .80 to 4.12, P = .16). The anthracycline-sparing regimen led to similar pCR compared with the anthracycline-containing regimen (OR = 1.50, 95% CI, .82 to 2.76, P = .19). In network meta-analysis, the addition of carboplatin plus a PD-1 inhibitor (pembrolizumab), carboplatin plus bevacizumab, and carboplatin plus veliparib ranked as the top three treatments for achieving pCR, with corresponding P-scores of .91, .84, and .72, respectively. Among patients with homologous recombination deficiency, the addition of carboplatin (OR = 1.31, 95% CI, .69 to 2.50, P = .41) or carboplatin plus PARP inhibitors (OR = 1.19, 95% CI, .58 to 2.47, P = .63) did not increase pCR. For triple-negative breast cancer, combining carboplatin with taxane-anthracycline-containing neoadjuvant chemotherapy could be the standard of care, and the combination containing checkpoint inhibitor is promising. However, their role in long-term oncologic outcome remains to be determined.

Development and validation of a radiomics-based model to predict local progression-free survival after chemo-radiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

[Polymorphism at codons 136, 141 and 154 in the ovine prion protein gene in the state of Xinjiang].

Scrapie is a fatal and infectious neurodegenerating disease. The polymorphism in the prion protein (PRNP) gene is linked to the development of clinical signs of scrapie. The most important polymorphism appears to be at codons at 136(V/A), 154(H/R), and 171(H/Q/R). In this study, we investigated the polymorphisms at these codons in 746 individuals among ten sheep breeds (i.e., ALeTai, BaShiBai, BaYinBuLuKe, Celehei, DuoLang, He Tian, Chinese Merino, German Merino, Texel, and Suffolk sheep) in Xinjiang in order to evaluate the relative susceptibility of sheep to scrapie. A total of 8 alleles (i.e., ARQ, ARR, ARH, ARK, VRQ, AHR, AHQ and AHH) were observed. The alleles ARQ and ARR were found in all of the breeds with the highest frequency for allele ARQ. Allele ARH was found in eight breeds except for Suffolk and German Merino, while the ARK was only identified in ALeTai, BaShiBai, BaYinBuLuKe, and DuoLang native sheeps. The alleles VRQ, AHR, AHQ and AHH were detected exclusively in Chinese Merino with extremely low frequencies. Moreover, the genotypes contained by the eight alleles were also determined subsequently. A total of thirteen genotypes, such as ARQ/ARQ, ARQ/ARK, ARR/ARR, ARH/ARH, ARQ/ARR, ARH/ARQ, ARH/ARR, ARK/ARK, ARH/ARK, ARQ/VRQ, ARQ/AHQ, ARQ/AHR and ARH/AHH were detected. The genotype ARQ/ARQ with moderate susceptibility was found with the highest frequency among the ten breeds, whereas the genotype ARR/ARR with highest resistance to scrapie was merely identified in BaYinBuLuKe, Celehei, Chinese Merino, Texel and German Merino sheep, which had very low frequencies. In addition, the genotype VRQ/ARQ with high susceptibility was first variant reported in Chinese Merino sheep. Our data, therefore, indicate that the general genetic resistance of dominating sheep breeds in Xinjiang to scrapie was considerably low.

A nomogram based on pretreatment CT radiomics features for predicting complete response to chemoradiotherapy in patients with esophageal squamous cell cancer.

PURPOSE: To develop and validate a nomogram model to predict complete response (CR) after concurrent chemoradiotherapy (CCRT) in esophageal squamous cell carcinoma (ESCC) patients using pretreatment CT radiomic features. METHODS: Data of patients diagnosed as ESCC and treated with CCRT in Shantou Central Hospital during the period from January 2013 to December 2015 were retrospectively collected. Eligible patients were included in this study and randomize divided into a training set and a validation set after successive screening. The least absolute shrinkage and selection operator (LASSO) with logistic regression to select radiomics features calculating Rad-score in the training set. The logistic regression analysis was performed to identify the predictive clinical factors for developing a nomogram model. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of the predictive nomogram model and decision curve was used to analyze the impact of the nomogram model on clinical treatment decisions. RESULTS: A total of 226 patients were included and randomly divided into two groups, 160 patients in training set and 66 patients in validation set. After LASSO analysis, seven radiomics features were screened out to develop a radiomics signature Rad-score. The AUC of Rad-score was 0.812 (95% CI 0.742-0.869, p < 0.001) in the training set and 0.744 (95% CI 0.632-0.851, p = 0.003) in the validation set. Multivariate analysis showed that Rad-score and clinical staging were independent predictors of CR status, with p values of 0.035 and 0.023, respectively. A nomogram model incorporating Rad-socre and clinical staging was developed and validated, with an AUC of 0.844 (95% CI 0.779-0.897) in the training set and 0.807 (95% CI 0.691-0.894) in the validation set. Delong test showed that the nomogram model was significantly superior to the clinical staging, with p < 0.001 in the training set and p = 0.026 in the validation set. The decision curve showed that the nomogram model was superior to the clinical staging when the risk threshold was greater than 25%. CONCLUSION: We developed and validated a nomogram model for predicting CR status of ESCC patients after CCRT. The nomogram model was combined radiomics signature Rad-score and clinical staging. This model provided us with an economical and simple method for evaluating the response of chemoradiotherapy for patients with ESCC.

Prognostic Significance of Baseline Neutrophil Count and Lactate Dehydrogenase Level in Patients With Esophageal Squamous Cell Cancer Treated With Radiotherapy.

Background: This present study aimed to explore the prognostic value of pretreatment neutrophil and lactate dehydrogenase (LDH) and to develop a prognostic risk scoring model to predict prognosis in esophageal squamous cell cancer (ESCC) patients treated with definitive radiotherapy. Methods: Retrospectively collected data of patients who received definitive radiotherapy for ESCC at Shantou Central Hospital between January 2009 and December 2015 were included for the analysis. The association between the level of LDH and neutrophil and clinicopathological characteristics were analyzed. We performed univariate and multivariate analyses to identify the prognostic predictors for patients with ESCC. Based on the results, we also developed a prognostic risk scoring model and assessed its predictive ability in the subgroups. Results: A total of 567 patients who received definitive radiotherapy for ESCC were included in the present study. The optimal cutoff values were 4.5 × 109/L, 3.25, and 220 U/L for neutrophil, neutrophil-to-lymphocyte ratio (NLR), and LDH, respectively. A high level of LDH was significantly associated with advanced N stage (p = 0.031), and neutrophil count was significantly associated with gender (p = 0.001), T stage (p < 0.001), N stage (p = 0.019), clinical stage (p < 0.001), and NLR (p < 0.001). Multivariate survival analysis identified gender (p = 0.006), T stage (p < 0.001), N stage (p = 0.008), treatment modality (p < 0.001), LDH level (p = 0.012), and neutrophil count (p = 0.038) as independent prognostic factors for overall survival. Furthermore, a new prognostic risk scoring (PRS) model based on six prognostic factors was developed, in which the patients were divided into three groups with distinct prognosis (χ2 = 67.94, p < 0.0001). Conclusions: Elevated baseline LDH level and neutrophil count predicted poor prognosis for ESCC patients treated with definitive radiotherapy. A PRS model comprised of LDH, neutrophil count, and other prognostic factors would help identify the patients who would benefit the most from definitive radiotherapy.

Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study

BACKGROUND: Genetic variations of some driver genes in non-small cell lung cancer (NSCLC) had shown potential impact on immune microenvironment and associated with response or resistance to programmed cell death protein 1 (PD-1) blockade immunotherapy. We therefore undertook an exploratory analysis to develop a genomic mutation signature (GMS) and predict the response to anti-PD-(L)1 therapy. METHODS: In this multicohort analysis, 316 patients with non-squamous NSCLC treated with anti-PD-(L)1 from three independent cohorts were included in our study. Tumor samples from the patients were molecularly profiled by MSK-IMPACT or whole exome sequencing. We developed a risk model named GMS based on the MSK training cohort (n=123). The predictive model was first validated in the separate internal MSK cohort (n=82) and then validated in an external cohort containing 111 patients from previously published clinical trials. RESULTS: A GMS risk model consisting of eight genes (TP53, KRAS, STK11, EGFR, PTPRD, KMT2C, SMAD4, and HGF) was generated to classify patients into high and low GMS groups in the training cohort. Patients with high GMS in the training cohort had longer progression-free survival (hazard ratio (HR) 0.41, 0.28-0.61, p<0.0001) and overall survival (HR 0.53, 0.32-0.89, p=0.0275) compared with low GMS. We noted equivalent findings in the internal validation cohort and in the external validation cohort. The GMS was demonstrated as an independent predictive factor for anti-PD-(L)1 therapy comparing with tumor mutational burden. Meanwhile, GMS showed undifferentiated predictive value in patients with different clinicopathological features. Notably, both GMS and PD-L1 were independent predictors and demonstrated poorly correlated; inclusion of PD-L1 with GMS further improved the predictive capacity for PD-1 blockade immunotherapy. CONCLUSIONS: Our study highlights the potential predictive value of GMS for immunotherapeutic benefit in non-squamous NSCLC. Besides, the combination of GMS and PD-L1 may serve as an optimal partner in guiding treatment decisions for anti-PD-(L)1 based therapy.

Fabrication and propagation characterization of As2S8 chalcogenide channel waveguide made by UV irradiation annealing.

Changes in the refractive index of amorphous chalcogenide As2S8 films upon ultraviolet (UV) exposure and annealing at different temperatures are investigated in detail, indicating an index contrast of the order of 10(-2) in the As2S8 channel waveguide. An As2S8 channel waveguide is fabricated using UV well irradiation and then annealing near the glass transition temperature and shows a low propagation loss of 0.76 dB/cm and good propagation characterization at the 1310 nm guided mode.

Identification of miR-375 as a potential prognostic biomarker for esophageal squamous cell cancer: A bioinformatics analysis based on TCGA and meta-analysis.

Accumulating evidence has demonstrated that aberrantly expressed miRNAs in cancer tissues regulated various cellular processes related to carcinogenesis. The present study aimed to identify the differentially expressed miRNAs between esophageal squamous cell cancer (ESCC) and adjacent normal esophageal tissue (ANET). In our present study, we identified 129 differentially expressed miRNAs between ESCC and ANET by analyzing high-throughput miRNA data downloaded from TCGA database. After investigating the prognostic value of the 129 differential expressed miRNAs, eight miRNAs were found to be associated with prognosis of patients with ESCC. The clinical significance and bio-function of miR-375 was further examined. We performed Gene Set Enrichment Analysis (GSEA) to identify the top three gene sets that significantly altered between the patients with miR-375 low expression and high expression. In order to explore the mechanism of the development and progression of ESCC, the role of miR-375 in ESCC and its four candidate target genes was examined. At last, we performed a meta-analysis to verify the prognostic value of miR-375 in ESCC. In conclusion, our findings suggest that miR-375 serves as a promising independent prognostic factor for ESCC and function as a tumor suppressor.

Effect of modern high-dose versus standard-dose radiation in definitive concurrent chemo-radiotherapy on outcome of esophageal squamous cell cancer: a meta-analysis.

BACKGROUND AND OBJECTIVES: Radiation Therapy Oncology Group (RTOG) 94-05 has demonstrated that higher dose radiation didn't improve outcome of patients with esophageal cancer (EC). However, several retrospective studies showed that a higher dose radiation based on modern radiotherapy techniques could improve overall survival (OS) and local control rate (LCR) of patients with EC, especially esophageal squamous cell cancer (ESCC). As trials have provided updated and controversial data, we performed this updated meta-analysis to investigate whether high-dose (> = 60 Gy) radiotherapy in definitive concurrent chemo-radiotherapy (CCRT) could yield benefit compared to standard dose radiotherapy. METHODS: A systematic literature search was carried out in the database of MEDLINE, PubMed and Embase. All studies published between 1 January 1990 and 31 December 2018 on the association between radiation dose and curative efficiency in EC were included in this meta-analysis. The hazard ratio (HR) was used to evaluate the time-to-event data employing RevMan version 5.3. RESULTS: Eight articles with a total of 3736 patients were finally included. Results indicated that there was a significant benefit in favor of high dose radiotherapy (HD-RT) regarding OS (HR = 0.78, 95%CI: 0.72-0.84, p < 0.001; 2-year OS risk ratio (RR) = 1.25, 95%CI: 1.14-1.37, p < 0.001), progression-free survival (PFS) (P = 0.001, HR = 0.7, 95%CI: 0.57-0.87) and LRFS (P < 0.001, HR = 0.52, 95%CI: 0.36-0.74) . CONCLUSIONS: HD-RT (> = 60 Gy) based on modern radiotherapy techniques in definitive CCRT appears to improve OS, PFS amd LRFS compared to the SD-RT in patients with ESCC.

Definitive chemoradiation therapy or surgery for clinical T1-3N0-1M0 thoracic esophageal squamous cell carcinoma: A propensity score matching analysis.

BACKGROUND: To compare overall survival in patients with clinical T1-3N0-1 thoracic esophageal squamous cell carcinoma treated with surgery or definitive chemoradiation therapy (CRT). METHODS: We used propensity-score matching to derive 1:1 cohorts of surgery versus definitive CRT. Statistical analysis was performed using χ2 or Fisher's exact tests. Survival functions were estimated using Kaplan-Meier survival plots, and survival distributions were compared using log-rank tests. Cox proportional hazards modeling was used to analyze the factors affecting overall survival. RESULTS: A total of 334 patients treated with surgery and 252 treated with definitive CRT were included. 129 (38.6%) of 334 patients had recurrence after surgery versus 118 (46.8%) of 252 after definitive CRT. Before matching, the median overall survival were 39.5 months (95% CI, 28.8-50.2) and 23.5 months (95% CI, 18.5-28.5) (P < 0.001) in the surgery and definitive CRT group, respectively. After matching (112 patients in each treatment group), median overall survival was 43.6 months (95% CI, 28.1-59.1) with surgery versus 19.3 months (95% CI, 14.4-24.2) with CRT (P < 0.001). CONCLUSIONS: In this retrospective analysis, surgery was associated with better overall survival compared with definitive CRT.

Impact of sex on the prognosis of patients with esophageal squamous cell cancer underwent definitive radiotherapy: a propensity score-matched analysis.

BACKGROUND: The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. METHODS: Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. RESULTS: A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567-0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575-0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611-0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615-0.926, P = 0.007). CONCLUSIONS: This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism.

First-line checkpoint inhibitors for wild-type advanced non-small-cell cancer: a pair-wise and network meta-analysis.

AIM: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. MATERIALS & METHODS: Prospective randomized trials were included. p-score was used to rank treatment effects. RESULTS: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. CONCLUSION: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.

Preoperative Administration of Olive Oil Reduces Chylothorax After Minimally Invasive Esophagectomy.

BACKGROUND: Chylothorax after esophagectomy is uncommon but potentially fatal. We performed a retrospective study to assess the effect of olive oil administered orally before surgery on reducing chylothorax in patients who underwent minimal invasive esophagectomy. METHODS: Between May 2013 and December 2016, patients with esophageal squamous cell cancer who underwent minimal invasive esophagectomy were screened. Patients in the investigational group were preoperatively administered olive oil orally 8 hours before surgery, and patients in the control arm received no olive oil. We used a propensity score matching model to derive 1:1 cohorts. Statistical analysis was performed by using the t test or χ2 or Fisher's exact test. RESULTS: The propensity score matching model finally selected 384 of 425 patients, with 192 patients in each group. The patient characteristics were balanced. Oral olive oil was well tolerated. The thoracic duct identification rate was higher in the investigational group (100% versus 45.31%, χ2 = 141.78, p < 0.01). The investigational group was associated with a reduced incidence of ligation (7.81% versus 18.22%, χ2 = 8.03, p = 0.003). The incidence of chylothorax was significantly reduced in the investigational group compared with that of the control group (0% versus 3.12%, χ2 = 4.23, p = 0.03). CONCLUSIONS: Preoperative administration of olive oil is a simple and safe method to minimize chylothorax complicating minimal invasive esophagectomy.

Elevated heat shock proteins in bipolar disorder patients with hypothalamic pituitary adrenal axis dysfunction.

BACKGROUND: Heat shock proteins (HSP) might be useful as biomarkers for bipolar disorder (BD) which would be clinically valuable since no reliable biomarker for BD has so far been identified. The purpose of this study was to assess the heat shock proteins CPN10, CPN60, and CPN70 as potential biomarkers of BD. METHODS: The study included 100 BD patients recruited from a hospital during 2012 and 2013. The study also included 94 healthy controls. Among the BD patients, 33 had abnormal hypothalamic-pituitary-adrenal (HPA) axis activity. Blood samples were obtained from the patients and controls. The chemiluminescence method, mass spectrometry, and flow cytometry were used for analysis. RESULTS: The BD patients compared with the controls had a significantly lower level of CPN10 and significantly higher levels of CPN60 and CPN70. The BD patients with abnormal HPA axis activity had a significantly lower level of CPN60 compared with the normal HPA axis activity group of BD patients. The CPN60 level significantly inversely correlated with adrenocorticotropic hormone (ACTH) level in patients with bipolar depression and in patients with bipolar hypomania, and CPN70 significantly correlated with ACTH level in patients with bipolar depression and hypomania. CONCLUSIONS: Our findings suggest that the heat shock proteins CPN10, CPN60, and CPN70 might have potential as biomarkers for BD and CPN60 blood level might distinguish patients with abnormal HPA axis activity from those with normal HPA axis activity.

Analysis of definitive chemo-radiotherapy for esophageal cancer with supra-clavicular node metastasis based on CT in a single institutional retrospective study: a propensity score matching analysis.

BACKGROUND: The prognostic value of supra-clavicular lymph node (SCLN) metastases in esophageal cancer (EC) is still not clear. METHOD: From January 2009 to December 2015, a survival analysis was performed to retrospectively identify the prognostic value of SCLN metastasis on survival on 751 patients with EC treated with definitive chemo-radiotherapy (dCRT). RESULTS: The median follow-up duration for living patients was 56.6 months. The median overall survival (OS) for all patients was 16.6 months. Patients with SCLN metastasis had a much poorer prognosis for OS (χ2 = 17.342, P < 0.001), distant metastasis-free survival (DMFS) (χ2 = 24.793, P < 0.001) and progression-free survival (PFS) (χ2 = 25.802, P < 0.001) than those without SCLN metastasis. The same results were found after propensity score matching. Nonetheless, the prognosis of patients with cervical or upper thoracic EC metastasis in SCLN was better than those of patients with middle or lower thoracic EC metastasis in SCLN for OS (χ2 = 4.516, P = 0.038), DMFS (χ2 = 8.326, P = 0.004) and PFS (χ2 = 6.255, P = 0.012). Univariate analysis showed that gender, middle or lower thoracic EC with SCLN metastasis, tumor length, tumor diameter, concurrent chemo-radiotherapy (CCR) and number of lymph nodes were prognostic factors for PFS. Gender, age, middle or lower thoracic EC with SCLN metastasis, tumor diameter, tumor length, and number of lymph nodes were prognostic factors for DMFS. According to the multivariate analysis, only middle or lower thoracic EC with SCLN metastasis and number of lymph nodes were independent prognostic factors for DMFS and PFS. CONCLUSION: For patients with cervical or upper thoracic EC, metastasis in SCLN should be considered to be regional lymph nodes and treated with curative intent if the total number of lymph nodes is limited. However, for patients with middle or lower thoracic EC, metastasis should be considered to be a higher level N stage or M1 stage, and it is thus necessary to provide consolidation chemotherapy after dCRT.