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Our understanding of interactions among intestinal helminths, gut microbiota and host is still in its infancy in fish. In this study, the effects of Schyzocotyle acheilognathi infection on the intestinal microbiota, growth and immune reactions of grass carp were explored under laboratory conditions. 16S rDNA amplification sequencing results showed that S. acheilognathi infection altered the composition of intestinal microbiota only at the genus level, with a significant increase in the relative abundance of Turicibacter and Ruminococcus (P < 0.05) and a significant decrease in the relative abundance of Gordonia, Mycobacterium and Pseudocanthomonas (P < 0.05). Schyzocotyle acheilognathi infection had no significant effect (P > 0.05) on the alpha diversity indices (including Chao1, ACE, Shannon, Simpson index) of intestinal microbiota in grass carp, but PERMANOVA analysis showed that microbial structure significantly (P < 0.01) differed between hindgut and foregut. PICRUST prediction showed that some metabolism-related pathways were significantly changed after S. acheilognathi infection. The relative abundance of Turicibacter was positively correlated with the fresh weight of tapeworm (foregut: r = 0.48, P = 0.044; hindgut: r = 0.63, P = 0.005). There was no significant difference in the body condition of grass carp between the S. acheilognathi infected group and the uninfected group (P > 0.05). Intestinal tissue section with HE staining showed that S. acheilognathi infection severely damaged the intestinal villi, causing serious degeneration, necrosis and shedding of intestinal epithelial cells. The real-time fluorescent quantitative PCR results showed that S. acheilognathi infection upregulated the mRNA expression of the immune-related genes: Gal1−L2, TGF−β1 and IgM.

BackgroundInadvertent intraoperative hypothermia is frequent during open surgeries; however, few studies on hypothermia during laparoscopic abdominal surgery have been reported. We aimed to investigate the incidence and risk factors for hypothermia in patients undergoing laparoscopic abdominal surgery.MethodsThis single-center prospective cohort observational study involved patients undergoing laparoscopic surgery between October 2018 and June 2019. Data on core body temperature and potential variables were collected. A multivariate logistic regression analysis was performed to identify the risk factors associated with hypothermia. A Cox regression analysis was used to verify the sensitivity of the results.ResultsIn total, 690 patients were included in the analysis, of whom 200 (29.0%, 95% CI: 26%-32%) had a core temperature < 36°C. The core temperature decreased over time, and the incident hypothermia increased gradually. In the multivariate logistic regression analysis, age (OR = 1.017, 95% CI: 1.000-1.034, P = 0.050), BMI (OR = 0.938, 95% CI: 0.880-1.000; P = 0.049), baseline body temperature (OR = 0.025, 95% CI: 0.010-0.060; P < 0.001), volume of irrigation fluids (OR = 1.001, 95% CI: 1.000-1.001, P = 0.001), volume of urine (OR = 1.001, 95% CI: 1.000-1.003, P = 0.070), and duration of surgery (OR = 1.010, 95% CI: 1.006-1.015, P < 0.001) were significantly associated with hypothermia. In the Cox analysis, variables in the final model were age, BMI, baseline body temperature, volume of irrigation fluids, blood loss, and duration of surgery.ConclusionsInadvertent intraoperative hypothermia is evident in patients undergoing laparoscopic surgeries. Age, BMI, baseline body temperature, volume of irrigation fluids, and duration of surgery are significantly associated with intraoperative hypothermia.

As a result of great diversity in life histories and a large number of described species, taxonomic and phylogenetic uncertainty permeates the entire crustacean order of Isopoda. Large molecular datasets capable of providing sufficiently high phylogenetic resolution, such as mitochondrial genomes (mitogenomes), are needed to infer their evolutionary history with confidence, but isopod mitogenomes remain remarkably poorly represented in public databases. We sequenced the complete mitogenome of Cymothoa indica, a species belonging to a family from which no mitochondrial genome was sequenced yet, Cymothoidae. The mitogenome (circular, 14484 bp, A+T = 63.8%) is highly compact, appears to be missing two tRNA genes (trnI and trnE), and exhibits a unique gene order with a large number of rearrangements. High compactness and the existence of palindromes indicate that the mechanism behind these rearrangements might be associated with linearization events in its evolutionary history, similar to those proposed for isopods from the Armadillidium genus (Oniscidea). Isopods might present an important model system to study the proposed discontinuity in the dynamics of mitochondrial genomic architecture evolution. Phylogenetic analyses (Bayesian Inference and Maximum Likelihood) conducted using nucleotide sequences of all mitochondrial genes resolved Oniscidea and Cymothoida suborders as paraphyletic. Cymothoa indica was resolved as a sister group (basal) to all remaining isopods, which challenges the accepted isopod phylogeny, where Cymothoida are the most derived, and Phreatoicidea the most basal isopod group. There is growing evidence that Cymothoida suborder might be split into two evolutionary distant clades, with parasitic species being the most basal split in the Isopoda clade, but a much larger amount of molecular resources carrying a high phylogenetic resolution will be needed to infer the remarkably complex evolutionary history of this group of animals with confidence.

The epithelial-to-mesenchymal transition (EMT) and the reverse process (the mesenchymal-to-epithelial transition [MET]) have been shown to be associated with tumor cell invasion and metastasis in different carcinomas. The EMT and MET have recently been shown to play a key role in the pathogenic processes of sarcomas, which are completely different from those of carcinomas. However, the definitive roles of the EMT in the tumorigenesis of synovial sarcomas remain unknown. Here, we explored whether transforming growth factor (TGF)-β signaling, an important oncogenic event in synovial sarcoma, modulates tumor cell characteristics related to the EMT, such as cell adhesion, migration, invasion, and proliferation. Interestingly, we found that TGF-β1 induced tumor cell activation, resulting in a tendency to aggregate and biphasic-like features. TGF-β1 also caused downregulation of E-cadherin and subsequent upregulation of N-cadherin, Snail, and Slug, which are responsible for EMT-like phenomena and increased cell motility and invasion. To further investigate the roles of TGF-β1 in the EMT, we established a SW982 cell line with stable TGF-β1 inhibition viaSB431542.These cells exhibited significantly decreased motility, migration, and proliferation (P = 0.001). Taken together, our data demonstrated that alterations in the TGF-β1/Smad signaling pathway could regulate the expression of EMT-related factors and the EMT process, resulting in changes in tumor cell invasion, migration, and proliferation in synovial sarcoma cells. These results may provide a important insights into therapeutic interventions and contribute to the present understanding of tumor progression in patients.

Male breast cancer (MBC) is known to be rare compared with female breast cancer (FBC) and to account for only 1% of all breast cancers. To date, male patients diagnosed with breast cancer are normally treated based on the guidelines for FBC. Specifically, studies have found that diagnosing and treating MBC patients under the guidelines for the treatment of post-menopausal FBC are more favorable than are those of pre/peri-menopausal FBC from a physiological perspective because MBC and post-menopausal FBC patients show high estrogen receptor (ER) expression in the tumor and low estrogen expression in the body. In this medical study, we aimed to examine whether MBC actually has the same prognosis as post-menopausal FBC.We identified MBC patients who were diagnosed as operable and who completed clinical treatment and we used follow-up data that were collected from January 2001 to January 2011. Each MBC patient was paired with four FBC patients who were diagnosed within the same period (two were pre/peri-menopausal, and two were post-menopausal). We compared disease-free survival (DFS) and overall survival (OS) among three groups, i.e., pre/peri-menopausal FBC (group A), post-menopausal FBC (group B) and MBC (group M), using the Kaplan-Meier method and a Cox proportional hazards regression model. We also evaluated the clinical characteristics of breast cancer patients using t-tests and chi-square tests. We used ten consecutive years of data that were collected at Zhejiang Provincial Cancer Hospital.We identified 91 MBC cases for group M, 182 FBC cases for group A and 182 FBC cases for group B. The median follow-up period was 112 months. MBC cases were much more frequently ER positive than those of group A and group B (p

A meta-analysis was conducted to assess the efficacy of mesenchymal stem cell (MSC) transplantation in small animal coronary vessels after balloon injury, to provide data for the design of future pre-clinical experiments and human clinical trials.The search strategy included the PubMed, EMBASE, Chinese Biomedical Literature (CBM), and China National Knowledge Infrastructure (CKNI) databases. The endpoint was the ratio of vascular neointima/media (I/M). Moreover, neointimal area, re-endothelialization, and proliferating cell nuclear antigen (PCNA) expression were analyzed. Pooled analyses were conducted using random effects models. Heterogeneity and publication bias were also explored. All data were analyzed using RevMan 5.2 and Stata 12.0.Fifteen studies were reviewed from 238 retrieved animal studies. Compared with controls, MSC transplantation resulted in greater I/M reduction (pooled difference, 0.39; 95% CI, 0.57-0.21; P < 0.0001), greater neointimal area reduction (pooled difference, 0.16; 95% CI, 0.22-0.10; P < 0.0001), decreased PCNA expression (pooled difference, 17.69; 95% CI, 28.94-6.44; P = 0.002), and enhanced re-endothelialization (pooled difference, 3.37; 95% CI, 1.78-4.95; P < 0.0001). The multivariable meta-regression analysis showed that a higher number of transplanted cells (>106; P = 0.017) and later time point of I/M measurement (P = 0.022) were significantly associated with I/M reduction. Subgroup analysis demonstrated a trend for a greater reduction in the ratio of I/M with late MSC transplantation (>1 day), MSCs transplanted through intravenous injection, and atherosclerotic vessels.The meta-analysis results demonstrate that MSC transplantation might improve injured vascular remodeling. In addition to greater efficacy with a greater number of transplanted MSCs (>106), the long-term effect of MSC transplantation appears to be more significant. The findings of this meta-analysis may help to design future, effective MSC trials.

PurposeTo conduct a meta-analysis to evaluate the prognostic role of E-cadherin expression in bone and soft tissue sarcomas.MethodsThe PubMed, EMBASE, and Web of Science databases were searched using terms related to E-cadherin, sarcoma, and prognosis for all articles published in English before March 2014. Pooled effect was calculated from the available data to evaluate the association between negative E-cadherin expression and 5-year overall survival and tumor clinicopathological features in sarcoma patients. Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model.ResultEight studies met the selection criteria and reported on 812 subjects. A total of 496 subjects showed positive E-cadherin expression (59.9%). Negative E-cadherin expression in bone and soft tissue sarcomas was correlated with lower 5-year overall survival (OR = 3.831; 95% CI: 2.246-6.534), and was associated with higher clinical stage (RR = 1.446; 95% CI: 1.030-2.028) and with male sex (RR = 0.678; 95% CI: 0.493-0.933).ConclusionIn the E-cadherin negative group, 5-year overall survival was significantly worse than in the E-cadherin positive group. However, further studies are required to confirm these results.

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. The genetic etiology of RMS remains largely unclear underlying its development and progression. To reveal novel genes more precisely and new therapeutic targets associated with RMS, we used high-resolution array comparative genomic hybridization (aCGH) to explore tumor-associated copy number variations (CNVs) and genes in RMS. We confirmed several important genes by quantitative real-time polymerase chain reaction (QRT-PCR). We then performed bioinformatics-based functional enrichment analysis for genes located in the genomic regions with CNVs. In addition, we identified miRNAs located in the corresponding amplification and deletion regions and performed miRNA functional enrichment analysis. aCGH analyses revealed that all RMS showed specific gains and losses. The amplification regions were 12q13.12, 12q13.3, and 12q13.3-q14.1. The deletion regions were 1p21.1, 2q14.1, 5q13.2, 9p12, and 9q12. The recurrent regions with gains were 12q13.3, 12q13.3-q14.1, 12q14.1, and 17q25.1. The recurrent regions with losses were 9p12-p11.2, 10q11.21-q11.22, 14q32.33, 16p11.2, and 22q11.1. The mean mRNA level of GLI1 in RMS was 6.61-fold higher than that in controls (p = 0.0477) by QRT-PCR. Meanwhile, the mean mRNA level of GEFT in RMS samples was 3.92-fold higher than that in controls (p = 0.0354). Bioinformatic analysis showed that genes were enriched in functions such as immunoglobulin domain, induction of apoptosis, and defensin. Proto-oncogene functions were involved in alveolar RMS. miRNAs that located in the amplified regions in RMS tend to be enriched in oncogenic activity (miR-24 and miR-27a). In conclusion, this study identified a number of CNVs in RMS and functional analyses showed enrichment for genes and miRNAs located in these CNVs regions. These findings may potentially help the identification of novel biomarkers and/or drug targets implicated in diagnosis of and targeted therapy for RMS.

Invasion and metastasis are the major causes of death in patients with esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression and transforming growth factor-β1 (TGF-β1) signaling has been shown to play an important role in EMT. In this study, we investigated how TGF-β1 signaling pathways contributed to EMT in three ESCC cell lines as well as 100 patients of nomadic ethnic Kazakhs residing in northwest Xinjiang Province of China. In vitro analyses included Western blotting to detect the expression of TGF-β1/Smad and EMT-associated proteins in Eca109, EC9706 and KYSE150 cell lines following stimulation with recombinant TGF-β1 and SB431542, a potent inhibitor of ALK5 that also inhibits TGF-β type II receptor. TGF-β-activated Smad2/3 signaling in EMT was significantly upregulated as indicated by mesenchymal markers of N-cadherin and Vimentin, and in the meantime, epithelial marker, E-cadherin, was markedly downregulated. In contrast, SB431542 addition downregulated the expression of N-cadherin and Vimentin, but upregulated the expression of E-cadherin. Moreover, the TGF-β1-induced EMT promoted invasion capability of Eca109 cells. Tumor cells undergoing EMT acquire fibroblastoid-like phenotype. Expressed levels of TGF-β1/Smad signaling molecules and EMT-associated proteins were examined using immunohistochemical analyses in 100 ESCC tissues of Kazakh patients and 58 matched noncancerous adjacent tissues. The results showed that ESCC tissues exhibited upregulated expression of TGF-β1/Smad. We also analyzed the relationship between the above proteins and the patients' clinicopathological characteristics. The TGF-β1/Smad signaling pathway in human Eca109 ESCC cells may carry similar features as in Kazakh ESCC patients, suggesting that TGF-β1/Smad signaling pathway may be involved in the regulation of EMT in ethnic Kazakh patients with ESCC from Xinjiang, China.

Hand, foot and mouth disease (HFMD) was an emerging viral infectious disease in recent years in Shenzhen. The underlying risk factors have not yet been systematically examined. This study analyzed the short-term effect of El Niño-Southern Oscillation on pediatric HFMD in Shenzhen, China. Daily count of HFMD among children aged below 15 years old, Southern Oscillation Index (SOI), and weather variables were collected to construct the time series. A distributed lag non-linear model was applied to investigate the effect of daily SOI on pediatric HFMD occurrence during 2008-2010. We observed an acute effect of SOI variation on HFMD occurrence. The extremely high SOI (SOI = 45, with 0 as reference) was associated with increased HFMD, with the relative risk (RR) being 1.66 (95% Confidence Interval [CI]: 1.34-2.04). Further analyses of the association between HFMD and daily mean temperature and relative humidity supported the correlation between pediatric HFMD and SOI. Meteorological factors might be important predictors of pediatric HFMD occurrence in Shenzhen.

BACKGROUND: Lung cancer is one of the leading causes of cancer death worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Immunotherapy has yielded no consistent benefit to date for those patients. Assessing the objective efficacy and safety of immunotherapy for advanced NSCLC patients will help to instruct the future development of immunotherapeutic drugs. METHODOLOGY AND PRINCIPAL FINDINGS: We performed a meta-analysis of 12 randomized controlled trials including 3134 patients (1570 patients in the immunotherapy group and 1564 patients in the control group) with histologically confirmed stage IIIA, IIIB, or IV NSCLC. The analysis was executed with efficacy end points regarding overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), and total effective rate. Overall unstratified OS, PFS, PR, and total effective rate were significantly improved in advanced NSCLC patients in the immunotherapy group (P = 0.0007, 0.0004, 0.002, 0.003, respectively), whereas CR was not improved (P = 0.97). Subgroup analysis showed that monoclonal antibody (mAb) immunotherapy significantly improved the PFS, PR, and total effective rate and showed a trend of improving OS of advanced NSCLC patients compared with the control group, with one kind of adverse event being significantly dominant. Compared with the control group, the vaccine subgroup showed no significant difference with regard to serious adverse events, whereas cytokine immunotherapy significantly induced three kinds of serious adverse events. CONCLUSIONS: Immunotherapy works efficiently on advanced NSCLC patients. Of several immunotherapies, mAb therapy may be a potential immunotherapy for advanced NSCLC patients, and become a standard complementary therapeutic approach in the future if the issues concerning toxicity and allergenicity of mAbs have been overcome.

Gut microbiota has become an integral component of the host, and received increasing attention. However, for many domestic animals, information on the microbiota is insufficient and more effort should be exerted to manage the gastrointestinal bacterial community. Understanding the factors that influence the composition of microbial community in the host alimentary canal is essential to manage or improve the microbial community composition. In the present study, 16S rRNA gene sequence-based comparisons of the bacterial communities in the grass carp (Ctenopharyngodon idellus) intestinal contents and fish culture-associated environments are performed. The results show that the fish intestinal microbiota harbors many cellulose-decomposing bacteria, including sequences related to Anoxybacillus, Leuconostoc, Clostridium, Actinomyces, and Citrobacter. The most abundant bacterial operational taxonomic units (OTUs) in the grass carp intestinal content are those related to feed digestion. In addition, the potential pathogens and probiotics are important members of the intestinal microbiota. Further analyses show that grass carp intestine holds a core microbiota composed of Proteobacteria, Firmicutes, and Actinobacteria. The comparison analyses reveal that the bacterial community in the intestinal contents is most similar to those from the culture water and sediment. However, feed also plays significant influence on the composition of gut microbiota.

The 17,922 base pairs (bp) nucleotide sequence of the linear mitochondrial DNA (mtDNA) molecule of the freshwater jellyfish Craspedacusta sowerbyi (Hydrozoa, Trachylina, Limnomedusae) has been determined. This sequence exhibits surprisingly low A+T content (57.1%), containing genes for 13 energy pathway proteins, a small and a large subunit rRNAs, and methionine and tryptophan tRNAs. Mitochondrial ancestral medusozoan gene order (AMGO) was found in the C. sowerbyi, as those found in Cubaia aphrodite (Hydrozoa, Trachylina, Limnomedusae), discomedusan Scyphozoa and Staurozoa. The genes of C. sowerbyi mtDNA are arranged in two clusters with opposite transcriptional polarities, whereby transcription proceeds toward the ends of the DNA molecule. Identical inverted terminal repeats (ITRs) flank the ends of the mitochondrial DNA molecule, a characteristic typical of medusozoans. In addition, two open reading frames (ORFs) of 354 and 1611 bp in length were found downstream of the large subunit rRNA gene, similar to the two ORFs of ORF314 and polB discovered in the linear mtDNA of C. aphrodite, discomedusan Scyphozoa and Staurozoa. Phylogenetic analyses of C. sowerbyi and other cnidarians were carried out based on both nucleotide and inferred amino acid sequences of the 13 mitochondrial energy pathway genes. Our working hypothesis supports the monophyletic Medusozoa being a sister group to Octocorallia (Cnidaria, Anthozoa). Within Medusozoa, the phylogenetic analysis suggests that Staurozoa may be the earliest diverging class and the sister group of all other medusozoans. Cubozoa and coronate Scyphozoa form a clade that is the sister group of Hydrozoa plus discomedusan Scyphozoa. Hydrozoa is the sister group of discomedusan Scyphozoa. Semaeostomeae is a paraphyletic clade with Rhizostomeae, while Limnomedusae (Trachylina) is the sister group of hydroidolinans and may be the earliest diverging lineage among Hydrozoa.

Our understanding of interactions among intestinal helminths, gut microbiota and host is still in its infancy in fish. In this study, the effects of Schyzocotyle acheilognathi infection on the intestinal microbiota, growth and immune reactions of grass carp were explored under laboratory conditions. 16S rDNA amplification sequencing results showed that S. acheilognathi infection altered the composition of intestinal microbiota only at the genus level, with a significant increase in the relative abundance of Turicibacter and Ruminococcus (P < 0.05) and a significant decrease in the relative abundance of Gordonia, Mycobacterium and Pseudocanthomonas (P < 0.05). Schyzocotyle acheilognathi infection had no significant effect (P > 0.05) on the alpha diversity indices (including Chao1, ACE, Shannon, Simpson index) of intestinal microbiota in grass carp, but PERMANOVA analysis showed that microbial structure significantly (P < 0.01) differed between hindgut and foregut. PICRUST prediction showed that some metabolism-related pathways were significantly changed after S. acheilognathi infection. The relative abundance of Turicibacter was positively correlated with the fresh weight of tapeworm (foregut: r = 0.48, P = 0.044; hindgut: r = 0.63, P = 0.005). There was no significant difference in the body condition of grass carp between the S. acheilognathi infected group and the uninfected group (P > 0.05). Intestinal tissue section with HE staining showed that S. acheilognathi infection severely damaged the intestinal villi, causing serious degeneration, necrosis and shedding of intestinal epithelial cells. The real-time fluorescent quantitative PCR results showed that S. acheilognathi infection upregulated the mRNA expression of the immune-related genes: Gal1-L2, TGF-ß1 and IgM. [ABSTRACT FROM AUTHOR]