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Background: Antihistamines alleviate the side effects of antitumor drugs and exert antitumor effects. This study aimed to investigate the potential impact of short-term concomitant use of antihistamines with immune checkpoint inhibitor (ICI) therapy on the efficacy and immune-related adverse events (irAEs) of immunotherapy for patients with advanced lung cancer., Methods: We retrospectively analyzed the medical records of 211 patients diagnosed with advanced primary lung cancer and treated with immunotherapy at Tianjin Medical University Cancer Institute and Hospital between January 1, 2018, and January 1, 2022. Among these patients, 109 who received H1 antihistamine during the infusion of anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) antibodies were assigned to the experimental group; meanwhile, the remaining 102 patients who did not receive H1 antihistamines were assigned to the control group. Balancing was achieved through inverse probability of treatment weight (IPTW) estimation. The data were analyzed using Kaplan-Meier curves and Cox regression analyses., Results: The median progression-free survival (mPFS) was 12.7 months in the experimental group and 4.3 months in the control group, while the median overall survival (mOS) was 32.8 months in the experimental group and 18.1 months in the control group. In the experimental group, patients treated with only H1 antihistamines had longer mPFS and mOS compared with those who received H1 plus H2 antihistamines. Similarly, in the control group, patients who did not receive antihistamines had a longer mPFS and mOS than those who only received H2 antihistamines. After conducting multivariate analyses, we found that H1 and H2 antihistamines were respectively identified as good and poor independent prognostic factors for both progression-free survival (PFS) and overall survival (OS). The rates of irAEs in the experimental and control groups were 52.4% and 69.2%, respectively, and grade ≥3 irAEs occurred in 4.5% and 25.9% of patients, respectively., Conclusions: Concomitant use of H1 antihistamines can improve immunotherapy efficacy and reduce irAEs. Meanwhile, concomitant use of H2 antihistamines is associated with reduced PFS and OS time., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-795/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6-18.0) for the immunotherapy group compared with 9.9 months (8.0-11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40-0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3-32.8) for the control group (HR, 0.57 [95% CI, 0.33-0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC., (© 2024. The Author(s).)

Background: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC., Patients and Methods: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety., Results: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group., Conclusion: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975., (Copyright © 2023 X. Yan, M. Ye, Q. Zou, P. Chen, Z. He, B. Wu, D. He, C. He, X. Xue, Z. Ji, H. Chen, S. Zhang, Y. Liu, X. Zhang, C. Fu, D. Xu, M. Qiu, J. Lv, J. Huang, X. Ren, Y. Cheng, W. Qin, X. Zhang, F. Zhou, L. Ma, J. Guo, D. Ding, S. Wei, Y. He, H. Guo, B. Shi, L. Liu, F. Liu, Z. Hu, X. Jin, L. Yang, S. Zhu, J. Liu, Y. Huang, T. Xu, B. Liu, T. Sun, Z. Wang, H. Jiang, D. Yu, A. Zhou, J. Jiang, G. Luan, C. Jin, J. Xu, J. Hu, Y. H, Jun, W. Zhai, X. Sheng, Shanghai Junshi Biosciences Co. LTD, Shanghai Junshi Biosciences Co. LTD., a. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitor (ICI) rechallenge in non-small cell lung cancer (NSCLC) is a promising therapeutic strategy. The situation for ICI rechallenge can be divided into three categories: adverse events (AEs); resistance to ICIs, and rechallenge becomes compulsive because of tumor relapse while the patients had completed a 2 year course of immunotherapy. However, these categories are still controversial and should be explored further. Through voting at the 6th Straits Summit Forum on Lung Cancer, in this study we summarize the consensus of 147 experts in ICI rechallenges. A total of 97.74% experts agreed to rechallenge; 48.87% experts rechallenge with the original drug, and the others rechallenge with a different drug; 40.3% agreed to rechallenge directly after progression; 88.06% experts agreed to ICI rechallenge with a combination regimen; and factors such as previous performance status score, PD-1 expression, and age should also be considered. Understanding the the clinical studies in ICI rechallenge could bring us one step closer to understanding the consensus. In patients with advanced NSCLC who have suffered recurrent or distant metastasis after immunotherapy, the option of rechallenge with ICIs is a promising treatment option., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The degradation of high molecular weight organic matter (HMWOM) is a core process of oceanic carbon cycle, which is determined by the activity of microbial communities harboring hundreds of different species. Illustrating the active microbes and their interactions during HMWOM processing can provide key information for revealing the relationship between community composition and its ecological functions. In this study, the genomic and transcriptional responses of microbial communities to the availability of alginate, an abundant HMWOM in coastal ecosystem, were elucidated. The main degraders transcribing alginate lyase (Aly) genes came from genera Alteromonas, Psychrosphaera and Colwellia. Meanwhile, some strains, mainly from the Rhodobacteraceae family, did not transcribe Aly gene but could utilize monosaccharides to grow. The co-culture experiment showed that the activity of Aly-producing strain could promote the growth of Aly-non-producing strain when alginate was the sole carbon source. Interestingly, this interaction did not reduce the alginate degradation rate, possibly due to the easily degradable nature of alginate. This study can improve our understanding of the relationship between microbial community activity and alginate metabolism function as well as further manipulation of microbial community structure for alginate processing., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 blockade) have revolutionized the treatment landscape in non-small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO-IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Marinimicrobium sp. C6131, which had the ability to degrade chitin, was isolated from deep-sea sediment of the southwest Indian Ocean. Here, the genome of strain C6131 was sequenced and the chitin metabolic pathways were constructed. The genome contained a circular chromosome of 4,207,651 bp with a G + C content of 58.50%. A total of 3471 protein-coding sequences were predicted. Gene annotation and metabolic pathway reconstruction showed that strain C6131 possessed genes and two metabolic pathways involved in chitin catabolism: the hydrolytic chitin utilization pathway initiated by chitinases and the oxidative chitin utilization pathway initiated by lytic polysaccharide monooxygenases. Chitin is the most abundant polysaccharide in the ocean. Degradation and recycling of chitin driven by marine bacteria are crucial for biogeochemical cycles of carbon and nitrogen in the ocean. The genomic information of strain C6131 revealed its genetic potential involved in chitin metabolism. The strain C6131 could grow with colloidal chitin as the sole carbon source, indicating that these genes would have functions in chitin degradation and utilization. The genomic sequence of Marinimicrobium sp. C6131 could provide fundamental information for future studies on chitin degradation, and help to improve our understanding of the chitin degradation process in deep-sea environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Oxidative degradation of chitin, initiated by lytic polysaccharide monooxygenases (LPMOs), contributes to microbial bioconversion of crystalline chitin, the second most abundant biopolymer in nature. However, our knowledge of oxidative chitin utilization pathways, beyond LPMOs, is very limited. Here, we describe a complete pathway for oxidative chitin degradation and its regulation in a marine bacterium, Pseudoalteromonas prydzensis. The pathway starts with LPMO-mediated extracellular breakdown of chitin into C1-oxidized chitooligosaccharides, which carry a terminal 2-(acetylamino)-2-deoxy-D-gluconic acid (GlcNAc1A). Transmembrane transport of oxidized chitooligosaccharides is followed by their hydrolysis in the periplasm, releasing GlcNAc1A, which is catabolized in the cytoplasm. This pathway differs from the known hydrolytic chitin utilization pathway in enzymes, transporters and regulators. In particular, GlcNAc1A is converted to 2-keto-3-deoxygluconate 6-phosphate, acetate and NH 3 via a series of reactions resembling the degradation of D-amino acids rather than other monosaccharides. Furthermore, genomic and metagenomic analyses suggest that the chitin oxidative utilization pathway may be prevalent in marine Gammaproteobacteria., (© 2022. The Author(s).)

Chitooligosaccharides (COSs) have been widely used in agriculture, medicine, cosmetics, and foods, which are commonly prepared from chitin with chitinases. So far, while most COSs are prepared from colloidal chitin, chitinases used in preparing COSs directly from natural crystalline chitin are less reported. Here, we characterize three chitinases, which were identified from the marine bacterium Pseudoalteromonas flavipulchra DSM 14401 T , with an ability to degrade crystalline chitin into (GlcNAc) 2 ( N,N '-diacetylchitobiose). Strain DSM 14401 can degrade the crystalline α-chitin in the medium to provide nutrients for growth. Genome and secretome analyses indicate that this strain secretes six chitinolytic enzymes, among which chitinases Chia4287, Chib0431, and Chib0434 have higher abundance than the others, suggesting their importance in crystalline α-chitin degradation. These three chitinases were heterologously expressed, purified, and characterized. They are all active on crystalline α-chitin, with temperature optima of 45-50 °C and pH optima of 7.0-7.5. They are all stable at 40 °C and in the pH range of 5.0-11.0. Moreover, they all have excellent salt tolerance, retaining more than 92% activity after incubation in 5 M NaCl for 10 h at 4 °C. When acting on crystalline α-chitin, the main products of the three chitinases are all (GlcNAc) 2 , which suggests that chitinases Chia4287, Chib0431, and Chib0434 likely have potential in direct conversion of crystalline chitin into (GlcNAc) 2 .

Based on 16S rRNA gene analyses, the same bacterial operational taxonomic units (OTUs) are common to both the Arctic and Antarctic oceans, supporting the concept 'everything is everywhere'. However, whether the same OTUs from both poles have identical genomes, i.e. whether 'everything is still everywhere' at the genomic level has not yet been examined systematically. Here, we isolated, sequenced and compared the genomes of 45 culturable marine bacteria belonging to three genera of Salinibacterium, Psychrobacter and Pseudoalteromonas from both polar oceans. The bacterial strains with identical 16S rRNA genes were common to both poles in every genus, and four identical genomes were detected in the genus Salinibacterium from the Arctic region. However, no identical genomes were observed from opposite poles in this study. Our data, therefore, suggest that 'everything is not everywhere' at the genomic level. The divergence time between bacteria is hypothesized to exert a strong impact on the bacterial biogeography at the genomic level. The geographical isolation between poles was observed for recently diverged, highly similar genomes, but not for moderately similar genomes. This study thus improves our understanding of the factors affecting the genomic-level biogeography of marine microorganisms isolated from distant locations., (© 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Tripartite motif containing 46 was initially identified as the oncogene in several human tumors. However, the clinical value and potential functions of tripartite motif containing 46 (TRIM46) in clear cell renal cell carcinoma (ccRCC) remained largely unclear. Methods: The expressing patterns, clinical involvement, and prognostic values of TRIM46 were analyzed using the data obtained from TCGA and GEO databases. A nomogram was constructed to examine the outcome of patients with ccRCC. We estimated the association between TRIM46 with tumor immunity in ccRCC. Results: Tripartite motif containing 46 was highly expressed in ccRCC, and its upregulation revealed an unfavorable prognosis. A nomogram based on TRIM46 expressions and other independent prognostic factors could robustly predict the overall survival of tumor patients. TRIM46 has a strong positive correlation with NUMBL, CACNB1, THBS3, ROBO3, MAP3K12, ANKRD13D, PIF1, PRELID3A, ANKRD13B, and PCNX2. Mechanically, TRIM46 displayed regulatory functions in ccRCC progression via several tumor-associated pathways. Besides, we observed that TRIM46 was distinctly related to tumor immunity in ccRCC. Conclusions: Our findings provide a novel tumor promotive role regarding TRIM46 function in the malignant progression of ccRCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ren, Zhao, Liang, Guo, Jiang and Xiang.)

Pelagovum pacificum SM1903 T , belonging to a novel genus of the family Rhodobacteraceae, was isolated from the surface seawater of the Mariana Trench. Here, we report the first complete genome sequence of the novel genus Pelagovum. The genome of strain SM1903 T consists of a circular chromosome of 4,040,866 bp and two plasmids of 41,363 bp and 9705 bp, respectively. Gene annotation and metabolic pathway analyses showed that strain SM1903 T possesses a series of genes related to adaptation to marine oligotrophic environments, which are involved in utilization of aromatic compounds, allantoin, and alkylphosphonate, and second messenger signaling in response to the oligotrophic stress. This strain also contains a variety of genes involved in coping with other stresses including osmotic stress, oxidative stress, cold shock, and heat shock. These features would assist this strain to survive under the natural nutrient limitation and other stresses from the environment. The genome of strain SM1903 T of the novel genus Pelagovum would deepen our knowledge on marine bacterioplankton and their adaption strategies to marine oligotrophic environments., (Copyright © 2021. Published by Elsevier B.V.)

In insects, trehalose accumulation is associated with the insulin/insulin-like growth factor signalling (IIS) pathway. However, whether insulin-like peptide is involved in the regulation of the trehalose metabolism during diapause termination remains largely unknown. This study assessed whether insulin-like peptide ( ApILP ) enhances the trehalose catabolism in the pupae of Antheraea pernyi during their diapause termination process. Injection of 10 μg of bovine insulin triggered diapause termination and synchronous adult eclosion in diapausing pupae. Moreover, treatment with bovine insulin increased the expression of trehalase 1A ( ApTre-1A ) and trehalase 2 ( ApTre-2 ), as well as the activity of soluble and membrane-bound trehalase, resulting in a decline in trehalose levels in the haemolymph. Silencing ApILP via RNA interference significantly suppressed the expression of ApTre-1A and ApTre-2 , thus leading to an increase in the trehalose concentration during diapause termination. However, neither injection with bovine insulin nor ApILP knockdown directly affected trehalase 1B ( ApTre-1B ) expression. Moreover, overexpression of the transcription factor forkhead box O ( ApFoxO ) induced an increase in trehalose levels during diapause termination; however, depletion of ApFoxO accelerated the breakdown of trehalose in diapausing pupae by increasing the expression of ApTre-1A and ApTre-2 . The results of this study help to understand the contributions of ApILP and ApFoxO to the trehalose metabolism during diapause termination.

Objectives: Diabetes is a risk factor for poor COVID-19 prognosis. The analysis of related prognostic factors in diabetic patients with COVID-19 would be helpful for further treatment of such patients. Methods: This retrospective study involved 3623 patients with COVID-19 (325 with diabetes). Clinical characteristics and laboratory tests were collected and compared between the diabetic group and the non-diabetic group. Binary logistic regression analysis was applied to explore risk factors associated in diabetic patients with COVID-19. A prediction model was built based on these risk factors. Results: The risk factors for higher mortality in diabetic patients with COVID-19 were dyspnea, lung disease, cardiovascular diseases, neutrophil, PLT count, and CKMB. Similarly, dyspnea, cardiovascular diseases, neutrophil, PLT count, and CKMB were risk factors related to the severity of diabetes with COVID-19. Based on these factors, a risk score was built to predict the severity of disease in diabetic patients with COVID-19. Patients with a score of 7 or higher had an odds ratio of 7.616. Conclusions: Dyspnea is a critical clinical manifestation that is closely related to the severity of disease in diabetic patients with COVID-19. Attention should also be paid to the neutrophil, PLT count and CKMB levels after admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiao, He, Xu, Liu, Lin, Li, Xu, Hu, Ren, Zhang, Zhang, Duan, Tian, Li, Wu, Song, Liu and Yang.)

Alginate, mainly derived from brown algae, is an important carbon source that can support the growth of marine microorganisms in the Arctic and Antarctic regions. However, there is a lack of systematic investigation and comparison of alginate utilization pathways in culturable bacteria from both polar regions. In this study, 88 strains were isolated from the Arctic and Antarctic regions, of which 60 strains could grow in the medium with alginate as the sole carbon source. These alginate-utilizing strains belong to 9 genera of the phyla Proteobacteria and Bacteroidetes . The genomes of 26 alginate-utilizing strains were sequenced and genomic analyses showed that they all contain the gene clusters related to alginate utilization. The alginate transport systems of Proteobacteria differ from those of Bacteroidetes and there may be unique transport systems among different genera of Proteobacteria . The biogeographic distribution pattern of alginate utilization genes was further investigated. The alginate utilization genes are found to cluster according to bacterial taxonomy rather than geographic location, indicating that the alginate utilization genes do not evolve independently in both polar regions. This study systematically illustrates the alginate utilization pathways in culturable bacteria from the Arctic and Antarctic regions, shedding light into the distribution and evolution of alginate utilization pathways in polar bacteria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cha, Wang, Ren, Li, Wang, Li, Fu, Zhang, Chen, Zhang, Xu and Qin.)

A Gram-stain-negative, aerobic, ovoid-rod-shaped bacterium, designated strain SM1903 T , was isolated from surface seawater of the Mariana Trench. The strain grew at 15-37 °C (optimum, 35 °C) and with 1-15 % (optimum, 4 %) NaCl. It hydrolysed aesculin but did not reduce nitrate to nitrite and hydrolyse Tween 80. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain SM1903 T formed a separate lineage within the family Rhodobacteraceae , sharing the highest 16S rRNA gene sequence similarity with type strains of Pseudooceanicola antarcticus (95.7 %) and Roseisalinus antarcticus (95.7 %). In phylogenetic trees based on single-copy OCs and whole proteins sequences, strain SM1903 T fell within a sub-cluster encompassed by Oceanicola granulosus , Roseisalinus antarcticus and Histidinibacterium lentulum and formed a branch adjacent to Oceanicola granulosus . The major cellular fatty acids were summed feature 8 (C 18 : 1  ω 7 c and/or C 18 : 1  ω 6 c ), C 16 : 0 and 11-methyl-C 18 : 1  ω 7 c . The polar lipids mainly comprised phosphatidylglycerol, phosphatidylcholine, one unidentified lipid, one unidentified aminolipid, and one unidentified glycolipid. The solo respiratory quinone was ubiquinone-10. The genomic DNA G+C content of strain SM1903 T was 66.0 mol%. Based on the results of phenotypic, chemotaxonomic, and phylogenetic characterization for strain SM1903 T , it is considered to represent a novel species of a novel genus in the family Rhodobacteraceae , for which the name Pelagovum pacificum gen. nov., sp. nov. is proposed. The type strain is SM1903 T (=MCCC 1K03608 T =KCTC 72046 T ).

Background: Fishermen and boatmen are a population at-risk for contracting schistosomiasis due to their high frequency of water contact in endemic areas of schistosomiasis in the People's Republic of China (P. R. China). To develop specific interventions towards this population, the present study was designed to assess the knowledge, attitudes and practices (KAPs) towards schistosomiasis of fishermen and boatmen, and to identify the risk factors associated with schistosome infection using a molecular technique in a selected area of Hunan Province in P. R. China., Methods: A cross sectional survey was conducted in the Dongting Lake Basin of Yueyang County, Hunan Province. A total of 601 fishermen and boatmen were interviewed between October and November 2017. Information regarding sociodemographic details and KAPs towards schistosomiasis were collected using a standardized questionnaire. Fecal samples of participants were collected and tested by polymerase chain reaction (PCR). Logistic regression analysis was conducted to explore the risk factors related to the positive results of PCR., Results: Of the 601 respondents, over 90% knew schistosomiasis and how the disease was contracted, the intermediate host of schistosomes and preventive methods. The majority of respondents had a positive attitude towards schistosomiasis prevention. However, only 6.66% (40/601) of respondents had installed a latrine on their boats, while 32.61% (196/601) of respondents defecated in the public toilets on shore. In addition, only 4.99% (30/601) respondents protected themselves while exposed to freshwater. The prevalence of schistosomiasis, as determined by PCR, among fishermen and boatmen in Yueyang County was 13.81% (83/601). Age, years of performing the current job, number of times receiving treatment, and whether they were treated in past three years were the main influencing factors of PCR results among this population., Conclusions: Fishermen and boatmen are still at high risk of infection in P. R. China and gaps exist in KAPs towards schistosomiasis in this population group. Chemotherapy, and health education encouraging behavior change in combination with other integrated approaches to decrease the transmission risk in environments should be improved.

Objective: To investigate adipocytokine expression levels, platelet-to-lymphocyte ratio (PLR) and transforming growth factor (TGF)-β1/Smad signaling activity in diabetic patients with pulmonary infection., Methods: Eighty-two type 2 diabetic patients with pulmonary infection were included in the observation group and 75 patients with simple type 2 diabetes were recruited into the control group. The fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and PLR in the two groups were compared. Complement-C1q/tumor necrosis factor related protein 3 (CTRP-3), complement-C1q/tumor necrosis factor related protein 9 (CTRP-9), leptin, adiponectin, and TGF-β1/Smad signaling pathway activity in peripheral blood mononuclear cells (PBMCs) was detected., Results: Compared with patients in the control group, patients in the observation group presented with increased levels of FGB, HbA1c, and leptin, an increase in the PLR, and decreased serum CTRP-3, CTRP-9, and adiponectin levels. TGF-β1, p-Smad2, and p-Smad3 protein expression levels were up-regulated in PBMCs from patients in the observation group compared with the control group., Conclusions: These results show that in type 2 diabetic patients with pulmonary infection, adipocytokine expression is altered, PLR is disturbed, and the TGF-β1/Smad signaling pathways in PBMCs are significantly activated.

A Gram-stain-negative, facultatively anaerobic, flagellated and rod-shaped bacterium, designated strain SM1901 T , was isolated from a brown algal sample collected from Kings Bay, Svalbard, Arctic. Strain SM1901 T grew at -4‒30 °C and with 0-7.0 % (w/v) NaCl. It reduced nitrate to nitrite and hydrolysed DNA and Tween 80. Results of phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SM1901 T was affiliated with the genus Shewanella , showing the highest sequence similarity to the type strain of Shewanella litoralis (97.5%), followed by those of Shewanella vesiculosa , Shewanella livingstonensis and Shewanella saliphila (97.3 % for all three). The major cellular fatty acids were summed feature 3 (C 16 : 1 ω 7 с and/or C 16 : 1 ω 6 с ), C 16 : 0 , C 18 : 0 , iso-C 15 : 0 and C 17 : 1 ω 8 с and the major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The respiratory quinones were ubiquinones Q-7, Q-8, menaquinones MK-7(H) and MK-8. The genome of strain SM1901 T was 4648537 nucleotides long and encoded a variety of cold adaptation related genes, providing clues for better understanding the ecological adaptation mechanisms of polar bacteria. The genomic DNA G+C content of strain SM1901 T was 40.5 mol%. Based on the polyphasic evidence presented in this paper, strain SM1901 T was considered to represent a novel species, constituting a novel psychrotolerant lineage out of the known SF clade encompassed by polar Shewanella species, within the genus Shewanella , for which the name Shewanella polaris sp. nov. is proposed. The type strain is SM1901 T (=KCTC 72047 T =MCCC 1K03585 T ).

A symmetry-breaking nanostructure is proposed to achieve multiple Fano resonances. The nanostructure consists of an asymmetric ring resonator coupled to a plasmonic waveguide. The broken symmetry is introduced by deviating the centers of regular ring. New resonant modes that are not accessible through a regular symmetric ring cavity are excited. Thus, one asymmetric cavity can provide more than one resonant mode with the same mode order. As a result, the interval of Fano resonances is greatly reduced. By combining different rings with different degrees of asymmetry, multiple Fano resonances are generated. Those Fano resonances have different dependences on structural parameters due to their different physical origin. The resonance frequency and resonance peak number can be arbitrarily adjusted by changing the degree of asymmetry. This research may provide new opportunities to design on-chip optical devices with great tuning performance., (Copyright © 2019, Ren et al.; licensee Beilstein-Institut.)

Background: Anlotinib is a tyrosine kinase inhibitor inhibiting angiogenesis. This multicenter, randomized phase II trial aimed to investigate the efficacy and safety of anlotinib in comparison with sunitinib as first-line treatment for patients with metastatic renal cell carcinoma (mRCC)., Materials and Methods: Patients with mRCC from 13 clinical centers were randomly assigned in a 2:1 ratio to receive anlotinib ( n = 90) or sunitinib ( n = 43). Anlotinib was given orally at a dose of 12 mg once daily (2 weeks on/1 week off), and sunitinib was given orally at 50 mg once daily (4 weeks on/2 weeks off). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety., Results: The median PFS was similar with anlotinib and sunitinib (17.5 vs. 16.6 months, p > .05). The median OS (30.9 vs. 30.5 months, p > .05), ORR (30.3% vs. 27.9%), and 6-week DCR (97.8% vs. 93.0%) were similar in the two groups. Adverse events (AEs) of grade 3 or 4 were significantly less frequent with anlotinib than with sunitinib (28.9% vs. 55.8%, p < .01), especially in terms of thrombocytopenia and neutropenia. AEs occurring at a lower frequency with anlotinib were hand-foot syndrome, eyelid edema, hair depigmentation, skin yellowing, neutropenia, thrombocytopenia, and anemia. The incidence of serious AEs was lower with anlotinib than with sunitinib., Conclusion: The clinical efficacy of anlotinib was similar to that of sunitinib as the first-line treatment for mRCC, but with a more favorable safety profile., Implications for Practice: This study evaluated the efficacy and safety of anlotinib for the first-line treatment of metastatic renal cell carcinoma. Anlotinib, which was developed independently in China, is a new tyrosine kinase inhibitor inhibiting multiple kinases involved in angiogenesis and tumor proliferation. Results indicated that the efficacy of anlotinib is comparable to and the safety is better than that of sunitinib., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Diprophylline (DPL) is identified as a methylxanthine (MX) derivative. A number of MX derivatives are reported to have anti-tumor effects. However, it is not clear whether DPL has a therapeutic effect on non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the effects of DPL on NSCLC and to elucidate the potential underlying mechanism. A Cell Counting Kit-8 assay was used to evaluate the potential effect of DPL on A549 cell proliferation. Transwell invasion and migration assays were performed to assess the effect of DPL on A549 cell migration and invasion. Furthermore, the percentage of apoptotic cells was detected by flow cytometric analysis, and proteins associated with apoptosis, including apoptosis regulator Bcl-2, apoptosis regulator BAX and active caspase-3, were examined by western blotting. Finally, the expression levels of molecules relevant to phosphoinositide 3-kinase (PI3K) signaling were detected by western blot analysis. The present study demonstrated that DPL may significantly inhibit A549 cell proliferation, migration and invasion. Furthermore, treatment with DPL may significantly induce A549 cell apoptosis. Finally, the protein expression levels associated with the PI3K signaling pathway were significantly inhibited in A549 cells following treatment with DPL. In conclusion, DPL may inhibit the proliferation and migration of NSCLC by inactivating the PI3K signaling pathway, and DPL is a promising novel therapeutic drug for NSCLC.

We propose a novel algorithm to numerically retrieve the phase of the exit-wave function from a high-resolution transmission electron microscopy (HRTEM) image of a weak-phase object material, e.g., graphene and hexagonal boron nitride monolayers. It theoretically only requires a single HRTEM image to retrieve the phase under the assumption of a weak-phase object. In addition, it can remove the effects of geometrical aberrations up to fifth order, and also improve the degraded information due to the finite temporal and spatial coherence. We further present its applications and successfully demonstrate the identification of the lattice atoms and line defects in single HRTEM image of graphene., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this paper, we propose a multiple-ellipse fitting method to accurately determine the atomic column positions in transmission electron microscopy (TEM) images. The column is enclosed by a series of ellipses fitted from contour lines at equidistant intensity levels, and each atomic column is shaped by an averaged elliptical shape to obtain its positions. In particular, the intensity profile of the atomic column can be obtained by an elliptically rotational average based on its shape; therefore, the intensities of the neighbouring atomic column can be subtracted for each atomic column during subsequent position refinement. This method can achieve precision in the picometre range, and we quantitatively measure this precision by analysing an image containing two Gaussian-shaped atoms and some simulated high-resolution transmission electron microscopy (HRTEM) images of SrTiO 3 ., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: We report the first prospective study of sunitinib for metastatic renal cell carcinoma (mRCC) in China., Methods: Chinese mRCC patients received first-line sunitinib 50 mg daily (4/2 regimen). Overall survival (OS), progression-free survival (PFS), objective response rate and safety were assessed. Potential efficacy biomarkers were explored in post hoc analyses., Results: Median PFS was 61.7 weeks; median OS was 133.4 weeks; objective response rate was 31.1%. Most frequent adverse events (AEs) were: hand-foot syndrome (63.8%), decreased white blood cell count (52.4%), fatigue (51.4%) and decreased platelet count (51.4%). AEs were identified that predicted longer PFS and OS., Conclusion: Sunitinib showed efficacy and manageable AE profile in treatment-naive Chinese mRCC patients. Larger prospective studies are required to confirm identified AEs as predictors of efficacy.

Strain DSM9414, the type strain of Pseudoalteromonas espejiana, is a Gram-negative, and amino-acid-requiring stain isolated from seawater off the coast of Northern California. In this study, we report the complete genome sequence of Pseudoalteromonas espejiana DSM9414 T . The genome (4,500,451bp; 40.3% G+C) is composed of two circular chromosomes: chromosome I is 3,720,756bp with 40.4% G+C content and chromosome II is 779,695bp with 39.8% G+C content. Genomic analysis showed that chromosome I encodes a complete set of ABC transporters responsible for branched-chain amino acids, whose homologous proteins were not discovered in other Pseudoalteromonas genomes released. This result indicated the tight dependence of extracellular amino acids for strain DSM9414 T , which is consistent with its phenotype. The complete genome sequence of P. espejiana provides further genetic insights into the diversity of dependence on extracellular amino acids for Pseudoalteromonas species., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Dysregulation of microRNAs has been confirmed to serve an important role in cancer development and progression. However, the role of microRNA (miR)-544 in colorectal cancer progression remains unknown. In the present study, it was observed that the expression level of miR-544 was increased in breast cancer cell lines and tissues using the quantitative polymerase chain reaction. Overexpression of miR-544 promoted cell proliferation and invasion in colorectal cancer, whereas inhibition of miR-544 suppressed colorectal cancer progression as determined using MTT, colony formation and Transwell assays. Furthermore, forkhead box O1 (FOXO1) was a direct target of miR-544. FOXO1 mediated miR-544-regulated colorectal cancer progression and cell cycle distribution. In conclusion, the results of the present study revealed that miR-544 serves an important role in promoting human colorectal cancer cell progression.

The molecular pathogenesis of T-2 toxin-induced cartilage destruction has not been fully unraveled yet. The aim of this study was to detect changes in serum metabolites in a rat anomaly model with articular cartilage destruction. Thirty healthy male Wistar rats were fed a diet containing T-2 toxin (300 ng/kg chow) for 3 months. Histopathological changes in femorotibial cartilage were characterized in terms of chondrocyte degeneration/necrosis and superficial cartilage defect, and the endogenous metabolite profile of serum was determined by UPLC/Q-TOF MS. Treated rats showed extensive areas of chondrocyte necrosis and superficial cartilage defect in the articular cartilage. In addition, 8 metabolites were found to change significantly in these rats compared to the control group, including lysoPE (18:0/0:0), lysoPC(14:0), lysoPC[18:4 (6Z,9Z,12Z,15Z)], lysoPC[(16:1(9Z)], lysoPC(16:0), L-valine, hippuric acid, and asparaginyl-glycine. These 8 metabolites associated with cartilage injury are mainly involved in phospholipid and amino acid metabolic pathways., (Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

High-carbon martensite steels (with C > 0.5 wt.%) are very hard but at the same time as brittle as glass in as-quenched or low-temperature-tempered state. Such extreme brittleness, originating from a twin microstructure, has rendered these steels almost useless in martensite state. Therefore, for more than a century it has been a common knowledge that high-carbon martensitic steels are intrinsically brittle and thus are not expected to find any application in harsh loading conditions. Here we report that these brittle steels can be transformed into super-strong ones exhibiting a combination of ultrahigh strength and significant toughness, through a simple grain-refinement treatment, which refines the grain size to ~4 μm. As a result, an ultra-high tensile strength of 2.4~2.6 GPa, a significant elongation of 4~10% and a good fracture toughness (K 1C ) of 23.5~29.6 MPa m 1/2 were obtained in high-carbon martensitic steels with 0.61-0.65 wt.% C. These properties are comparable with those of "the king of super-high-strength steels"-maraging steels, but achieved at merely 1/30~1/50 of the price. The drastic enhancement in mechanical properties is found to arise from a transition from the conventional twin microstructure to a dislocation one by grain refinement. Our finding may provide a new route to manufacturing super-strong steels in a simple and economic way.

Purpose: To investigate how necroptosisis, i.e. programmed necrosis, is involved in MODS, and to examine whether Nec-1, a specific necroptosis inhibitor, ameliorates multiorgan injury in MODS., Experimental Design: A model of MODS was established in six-week old SD rats using fracture trauma followed by hemorrhage. Control animals received sham surgery. Cell death form and necrosome formation were measured by fluorescence-activated cell sorting and western blotting. MODS rats were randomly assigned to receive Nec-1 or saline with pretreatment and once daily. The first end-point was 72 hours survival. Organ injury and dysfunction, inflammatory cytokine levels, and necroptotic execution protein expression were also recorded., Results: Organ injury and dysfunction were significantly more severe in the MODS group than the sham group (all p <0.01). Furthermore, MODS-induced liver, lung and kidney tissue injury was characterized by necroptosis rather than apoptosis, and accompanied by necrosome formation. Compared to MODS group, Nec-1 administration significantly improved 72 hours survival ( p <0.01). Nec-1 administration significantly reduced necroptosis-induced liver, lung and kidney injury and dysfunction, inhibited inflammatory cytokines production, inhibited release of necroptotic execution proteins such as high-mobility group box 1 and mixed-lineage kinase domain-like protein pseudokinase in MODS rats (all p <0.01)., Conclusions: These results suggest that necroptosis is involved the pathology of MODS. Further, a necroptotic inhibitor Nec-1 may be considered as an adjunct treatment for MODS., Competing Interests: CONFLICTS OF INTEREST The manuscript describes original research and has not been submitted or is under consideration for publication in another journal. We also confirm that all the listed authors have participated actively in the study and have seen and approved the submitted manuscript. The authors do not have any possible conflicts of interest.

We investigated the effects of ulinastatin on early postoperative cognitive dysfunction (POCD) after one-lung ventilation (OLV) surgery in elderly patients receiving neoadjuvant chemotherapy. Eighty elderly patients with preoperative neoadjuvant chemotherapy scheduling for radical esophagectomy under OLV were recruited. They were randomly divided into an ulinastatin pretreatment group (U group, n = 40) and a control group (C group, n = 40). The U group received 10,000 U/kg ulinastatin before anesthesia and 5000 U/kg daily on postoperative days 1 to 3, while C group received saline. Levels of interleukin (IL)-6, IL-10, C-reactive protein (CRP), and S-100β protein were assayed before surgery, at the end of surgery, and on postoperative days 1 and 3. Patients underwent cognitive assessment 1 day before and 7 days after surgery. 38 patients in U group and 37 patients in C group completed the neuropsychological tests. The U group had a lower incidence of POCD than C group (23.7 % versus 45.9 %, P = 0.043). The levels of S-100β protein, IL-6, IL-10, and CRP in both groups increased after surgery. The postoperative concentrations of S-100β protein, IL-6, and CRP in U group were lower than those in C group. On postoperative day 3, compared with C group, the level of CRP in U group was lower, while that of IL-10 was higher. These findings demonstrate that ulinastatin can attenuate the elevation of S100β protein levels and the incidence of POCD, most likely by the mechanism of reducing serum IL-6 and CRP levels and increasing IL-10 levels.

Objective: To examine the association between serum lipids, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the risk and progression of breast cancer in postmenopausal and premenopausal women. Methods: A review analysis of female patients who underwent breast cancer surgery and blood lipid metabolism testing in Tianjin One Hospital, from January 2013 to October 2013, was performed. A total of 1 081 patients were included in the final analysis. The control group consisted of 2 981 women without breast cancer. We collected all of the cases' demographic, pathology, lymph nodes metastasis information, was used to testify the difference of serum lipid level between patient and control group, also the postmenopausal and pre-menopausal groups. Results: The average age of the patients and control subjects were (51.6±0.3) and (51.0±0.2) years, respectively. Serum TC and LDL-C levels in the patient group, (5.16± 0.03) and (3.28±0.26) mmol/L, respectively, were significantly higher than in the control group, (5.02±0.01) and (2.51 ± 0.01) mmol/L, respectively ( t values 3.89 and 4.81 and P< 0.001). HDL-C levels in the patient group, (1.60±0.01) mmol/L, were significantly lower than in the control group, (1.65±0.01) mmol/L ( t= 3.90, P< 0.001). Similar observations were made in postmenopausal patients. Serum TC and LDL-C levels in the postmenopausal patient group, (5.48±0.04) and (3.27±0.03) mmol/L, respectively, were significantly higher than in control subjects, (5.24±0.02) and (2.71±0.02) mmol/L, respectively ( t values 4.75 and 15.30, all P values <0.001). HDL-C levels in postmenopausal patients, (1.60±0.02) mmol/L, were significantly lower than in the control group, (1.69±0.01) mmol/L ( t= 4.85 , P< 0.001). In the breast cancer patient group, those at pathological stages 0-Ⅱ had lower TG levels than those at Ⅲ-Ⅳ. These values were (1.19±0.05) and (1.43± 0.09) mmol/L, respectively ( t= 2.69, P< 0.001). Meanwhile, patients with no lymph node metastases had lower TG levels than the lymph node-positive group, with values of (1.15 ± 0.05) and (1.37 ± 0.07) mmol/L, respectively ( t= 2.53, P= 0.012). Conclusion: We found that dyslipidemia may affect the incidence of breast cancer, particularly among postmenopausal women. Serum lipids may promote cancer progression through higher TG and low HDL-C levels.

Vascular endothelial growth factor (VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors (VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells (DCs), macrophages, and lymphocytes further express certain types of VEGF receptors. VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness. This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.

Graphene/hexagonal boron nitride (h-BN) heterostructures have attracted a great deal of attention in recent years due to their unique and complementary properties for use in a wide range of potential applications. However, it still remains a challenge to synthesize large-area high quality samples by a scalable growth method. In this work, we present the synthesis of both in-plane and stacked graphene/h-BN heterostructures on Cu foils by sequentially depositing h-BN via ion beam sputtering deposition (IBSD) and graphene with chemical vapor deposition (CVD). Due to a significant difference in the growth rate of graphene on h-BN and Cu, the in-plane graphene/h-BN heterostructures were rapidly formed on h-BN domain/Cu substrates. The large-area vertically stacked graphene/h-BN heterostructures were obtained by using the continuous h-BN film as a substrate. Furthermore, the well-designed sub-bilayered h-BN substrates provide direct evidence that the monolayered h-BN on Cu exhibits higher catalytic activity than the bilayered h-BN on Cu. The growth method applied here may have great potential in the scalable preparation of large-area high-quality graphene/h-BN heterostructures.

Despite the clinical success of tamoxifen, its resistance remains a major challenge in breast cancer. Here we show that Aurora-A determines tamoxifen sensitivity by regulation of oestrogen receptor (ER)α. Ectopic expression of Aurora-A decreases and depletion of Aurora-A enhances tamoxifen sensitivity in ERα-positive breast cancer. Elevated Aurora-A was significantly associated with the recurrence of ERα-positive tumours. Notably, Aurora-A inhibitor MLN8237, which is currently in clinical trial, synergizes with tamoxifen and overcomes tamoxifen resistance. Furthermore, Aurora-A interacts with and phosphorylates ERα on serine-167 and -305, leading to increase in ERα DNA-binding and transcriptional activity. Elevated levels of Aurora-A are significantly associated with disease-free survival in ERα-positive but not ERα-negative breast cancers. These data suggest that Aurora-A has a pivotal role in tamoxifen resistance and ERα is a bona fide substrate of Aurora-A. Thus, Aurora-A represents a prognostic marker in ERα-positive tumour and a critical therapeutic target in tamoxifen-resistant breast cancer, and Aurora-A inhibitor could be used as either an independent or concurrent agent in tamoxifen-resistant tumour.

Mold contamination is an important issue in insect mass rearing. Frequently used antifungal agents such as sorbic acid and methylparaben have negative impact on many lepidopteran larvae, which might be one of the reasons for the difficulty in rearing rice leaffolder, Cnaphalocrocis medinalis (Güenée). In this study, 19 antifungal agents, including 7 food preservatives, 6 antifungal drugs, and 6 agricultural fungicides, were screened for their inhibitory activities on Aspergillus niger in diets. The results demonstrated that most of the tested chemicals are unsuitable as mold inhibitors in the diets of the rice leaffolder, and the rice leaffolder neonate is sensitive to sorbic acid and methylparaben. These two mold inhibitors at commonly used concentrations were shown to impact the survival of rice leaffolder larvae fed on artificial diets. Among the tested mold inhibitors, natamycin was the safest for the rice leaffolder larvae. Much higher larva survival was observed for the larvae fed on diets containing natamycin as an antifungal agent (59 and 72% at 200 and 400 ppm, respectively). Two agricultural fungicides, tebuconazole and azoxystrobin, are also potent as mold inhibitors when used in insect diets. The mixed use of natamycin and sorbic acid, or methylparaben, and the mixed use of sorbic acid and azoxystrobin resulted in significantly higher larva survival than sorbic acid + methylparaben. Natamycin + azoxystrobin and sorbic acid + tebuconazole resulted in larva survival similar to that of sorbic acid + methylparaben. The ternary combination of natamycin, sorbic acid, and methylparaben was the best combination for the rearing of rice leaffolder.

Angiosarcomas account for a mere 2-3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas (PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan-Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra-abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The optimal surgical treatment for displaced proximal humeral fractures continues to be controversial. One of the new treatment options is the minimally invasive intramedullary nail. The purpose of this study was to evaluate the functional outcome of using the TRIGEN proximal humeral nail (PHN) for the treatment of displaced proximal humeral fractures in elderly patients. From January 2004 to December 2008, 64 elderly patients (age > 60 years old) with displaced proximal humeral fractures were treated using TRIGEN PHN. A complete 12-month postoperative follow-up was available for 54 patients. The study cohort included two-part (29 shoulders), three-part (22 shoulders), and four-part (3 shoulders) Neer classification fracture types. The Constant-Murley score was used to assess functional outcome. Radiological outcomes were evaluated, and all complications were recorded. All fractures were united. The Constant-Murley score data indicated that the patients experienced improvement from 6 to 12 months postoperatively. The mean absolute Constant-Murley score on the injured side increased from 71.2 ± 11.2 points at 6 months to 82.4 ± 16.4 points at 12 months (P = 0.01). The mean neck-shaft angle 1 year after surgery was 125° ± 8.1° (95°-140°). Secondary complications were minimal and observed in only 6 of 54 patients. In conclusion, the TRIGEN intramedullary humeral nail is effective for the treatment of proximal humeral fractures.

The control of rice leaffolder, Cnaphalocrocis medinalis (Guenée), depended mainly on the insecticide application in China for a long time, and the resistance development impacted the effects of insecticide application. In this study, 13 conventional and new chemistry insecticides were assayed for the toxicities to the larvae of rice leaffolder collected from Nanning, Changsha, and Nanjing, China, with rice seedling dip method during 2011-2013. Among the tested chemicals, macrolide insecticides spinetoram, spinosad, abamectin, and emanectin benzoate have the highest toxicities, whereas monosultap and Bt have the least toxicities to this insect. Comparing with the baseline data established in 2010, the susceptibilities of rice leaffolder to chlorantraniliprole, metaflumizone, and tebufenozide are declining simultaneously and gradually in the three regions from 2011 to 2013, and C. medinalis are becoming resistance to chlorantraniliprole, metaflumizone, and tebufenozide. The synchronous decreases of susceptibility in three geographic populations were not observed for macrolide insecticides, indoxacarb, chlorpyrifos, monosultap, and Bt. The synchronous insecticide susceptibility declines in field populations of the migratory insect collected from different areas indicated resistance evolution, and the sequence application patterns of different insecticides should be scheduled to delay the further development of resistance along the migratory pathway of the rice leaffolder in China.

Sulfur dioxide (SO2) is naturally synthesized by glutamate-oxaloacetate transaminase (GOT) from L-cysteine in mammalian cells. We aim to investigate the role of SO2 in inflammation in acute lung injury (ALI) following limb ischemia/reperfusion (I/R). Male Wistar rats were subjected to limb I/R and were injected with saline, GOT inhibitor hydroxamate (HDX, 0.47 mmol/kg), or the SO2 donor Na2 SO3 /NaHSO3 (0.54 mmol/kg/0.18 mmol/kg). Compared with the sham operation, the plasma SO2 levels were significantly decreased by limb I/R treatment. In addition, SO2 concentration and GOT activity in the lung tissue were also reduced in ALI. The occurrence of ALI following limb I/R can be prevented by Na2 SO3 /NaHSO3 treatment, whereas it can be significantly aggravated by HDX. The plasma IL-1β, IL-6, and IL-10 levels were consistent with myeloperoxidase activity and inflammation in lung tissue. In conclusion, our data suggest that downregulation of endogenous SO2 production might be involved in pathogenesis of ALI following limb I/R in rats., (© 2013 Wiley Periodicals, Inc.)

Objective: To discuss the influence of intensive insulin therapy on insulin resistance of patients with severe burn or trauma., Methods: Sixty patients with severe burn or trauma hospitalized in the Third People's Hospital of Chongqing or Southwest Hospital of the Third Military Medical University from January 2010 to December 2011 were randomly divided into intensive insulin therapy group (IT, treated with intensive insulin therapy to control the blood glucose to the level of 6.0-8.0 mmol/L) and control group (C, treated with routine therapy) according to the paired grouping method, with 30 patients in each group. Before treatment and on post treatment day (PTD) 1, 3, 7, 10, 14, the levels of fasting blood glucose and fasting plasma insulin were determined. Insulin resistance index and β-cell function index were calculated using homeostasis model assessment. Data were processed with t test, analysis of variance, and LSD test., Results: On PTD 1, 3, 7, 10, levels of fasting blood glucose in group IT [(6.8 ± 1.4), (6.7 ± 1.3), (5.8 ± 1.9), (5.4 ± 1.6) mmol/L] were significantly lower than those of group C [(14.8 ± 4.9), (12.7 ± 3.7), (7.7 ± 1.9), (6.6 ± 1.3) mmol/L, with t values respectively 12.453, 11.386, 5.563, 4.731, P < 0.05 or P < 0.01]. On PTD 3, 7, levels of fasting insulin in group IT [(14 ± 5), (10 ± 3) mU/L] were significantly lower than those of group C [(16 ± 4), (13 ± 4) mU/L, with t values respectively 4.212, 4.364, P values below 0.05]. Levels of fasting blood glucose and fasting insulin in the two groups at each time point were statistically significantly different from those before treatment (with P values below 0.01), except for the level of fasting blood glucose on PTD 3. On PTD 1, 3, 7, 10, levels of insulin resistance index in group IT (1.60 ± 0.80, 1.46 ± 0.70, 0.96 ± 0.21, 0.90 ± 0.23) were significantly lower than those in group C (2.15 ± 1.35, 2.21 ± 1.21, 1.50 ± 0.95, 1.17 ± 0.66, with t values respectively 8.316, 10.607, 7.825, 5.217, P < 0.05 or P < 0.01). Levels of insulin resistance index of patients in the two groups at each time point after treatment were significantly lower than those before treatment (with P values below 0.01). On PTD 1, 3, 7, levels of β-cell function index in group IT (4.6 ± 2.9, 4.5 ± 3.3, 4.5 ± 3.6) were significantly higher than those in group C (3.4 ± 2.5, 3.6 ± 2.2, 4.2 ± 2.5, with t values respectively 8.243, 7.914, 4.338, P < 0.05 or P < 0.01). Levels of β-cell function index in group C on PTD 1 and 3 were significantly lower than that before therapy (with P values below 0.05)., Conclusions: Intensive insulin therapy can alleviate insulin resistance of patients with severe burn or trauma.

Non-small cell lung cancer (NSCLC) is found worldwide with high incidence and poor prognoses. Nowadays, insights in the interaction between tumors and immune system have led to the development of immunotherapy as a fundamentally new concept for the treatment of NSCLC. Adoptive cell transfer represents an important advancement in cancer immunotherapy such as cytokine-induced killer and γδ T-cells. Recent clinical research studies provide evidence for the positive effects of adoptive immunotherapy, which is probably associated with levels of cytokines, cell doses, and immune microenvironment. This review summarizes the current condition of adoptive immunotherapy in NSCLC and the long-standing confusion in this field.

Dendritic cells (DCs) have traditionally been viewed as constituting an 'information management' system that functions solely to integrate a diverse array of incoming signals, in order to induce immune reactivity. In recent years, however, there has been a shift towards viewing these cells as key regulators in the orchestration of immunological tolerance, with increasing recognition that they are capable of suppressing T-cell responses depending on signalling processes and localised biochemical conditions. Indoleamine 2,3-dioxygenase (IDO) competent (IDO⁺) DCs are a subset of human DCs which are programmed to a tolerogenic state and play a vital role in establishing and maintaining a tumour-suppressing milieu. The expression of IDO in these DCs represents a key mechanism responsible for inducing the tolerogenic state. However, the mechanisms by which IDO becomes dysregulated in this subset of DCs have not yet been described. In this review, the function of IDO⁺ DCs within the cancer-tolerogenic milieu, as well as the signals responsible for expression of IDO in this subset, will be discussed.

MicroRNAs (MiRNAs) are small non-coding RNAs that regulate their target genes expression at the post-transcriptional level. As accumulating properties of miR-205 have been identified, complex roles of miR-205 in tumor initiation and progression are emerging. MiR-205 acts either as a tumor suppressor through inhibiting proliferation and invasion, or as an oncogene through facilitating tumor initiation and proliferation, depending on the specific tumor context and target genes. In this review, we focus on the properties of miR-205 in cancers to shed light on better management of various fatal malignancies. Moreover, we discuss epigenetics that may account for the fluctuation of miR-205 expression. In addition, we sketch a network of miR-205 and its targets to further elucidate the mechanisms through which miR-205 exerts its multiple functions., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Interferon (IFN)-λs are a new addition to the old IFN family and share many similarities, such as antiviral and antiproliferative characteristics, with type I IFNs. IFN-λs also exhibit unique characteristics in immunomodulation. Accumulating studies have indicated the interactions between IFN-λs and immune cells, which lead to the regulation of the latter. IFN-λs can influence dendritic cells (DCs) and their product, IFN-λs-DCs, can then regulate the function of T cells. On the other hand, IFN-λs can also directly affect T cells through inhibition of the T helper 2 cell (Th2) responses. IFN-λs have varying immunomodulatory functions under different physiological conditions or in different organs and can inhibit tumor growth via regulation of the immune system. Diseases associated with IFN-λs include asthma, allergy, and systemic lupus erythematosus. In this review, we summarize the current knowledge of the biology of IFN-λs and their immunomodulatory function in relevant human diseases., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To investigate the effect of epirubicin on soluble CD25 (sCD25) secretion by CD4+CD25+ regulatory T (Treg) cells isolated from diffuse large B-cell lymphoma (DLBCL) patients., Methods: Treg cells were isolated from the peripheral blood mononuclear cells isolated from the newly diagnosed DBLCL patients. The concentration of sCD25 in the supernatant was determined with a commercial sCD25 (IL-2R) enzyme-linked immunosorbent assay (ELISA) kit. The fluorescence intensity of CD25 was detected by flow cytometry., Results: Cell survival rate was significantly decreased along with the increase of epirubicin concentration after treatment for 24 h. There was also a significant difference in the concentration of sCD25 between the epirubicin group and the control group (P<0.01). A positive correlation between the Treg cells survival rate and the concentration of sCD25 was detected (r=0.993, P<0.01). When equal numbers of CD4+CD25+ Treg cells of the epirubicin group and the control group were cultured for another 24 h without epirubicin the CD25 fluorescence intensity on the surface of Treg cells was obviously higher in the epirubicin group than that in the control group (P<0.01), while the sCD25 concentration in the supernatant in the epirubicin group was significantly lower than that in the control group (P<0.05)., Conclusion: Epirubicin may improve the body's immune functions by inhibiting the sCD25 secretion by Treg cells in DLBCL patients.

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group 1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positive ERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated with response to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKI databases were used for searching studies relating to ERCC1 protein expression and response to platinum-based chemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis. Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinum- based chemotherapy were generated. Publication bias was investigated with Begg's test. Five studies involving 306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, those with negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was 5.264 (95% CI: 2.928 - 9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similar in both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein expression status is significantly associated with response to platinum-based chemotherapy in ovarian cancers.

Background: Papillary thyroid carcinoma (PTC) represents one of the most frequent endocrine malignancies. Several factors have been found to be involved in determining the outcome of treatment for patients with PTC. Large tumor size, diagnosis at an early age, extra-thyroidal invasion, aggressive histological variants, and distant metastases are the most important determinants of a poor outcome. BRAF(V600E) mutation has been found to be a major genetic alteration in PTC. This study aimed to evaluate progression in patients with multifocal and solitary PTC., Methods: We performed a retrospective study to analyze 368 patients with PTC who underwent surgery, including 282 patients with solitary PTC and 86 patients with multifocal PTC. The status of BRAF(V600E) mutation in all tumor foci from multifocal PTC was detected., Results: Our study suggested that multifocal PTC was more related to lymph node metastasis and vascular invasion than solitary PTC. However, the distant metastasis rate and 10-year survival rate showed no difference between these two groups. The number of tumor foci did not affect progression of disease in multifocal PTC patients. Lymph node metastasis in multifocal PTC patients was associated with larger tumors, diagnosis at early stage, and extra-thyroidal invasion., Conclusion: The status of BRAF(V600E) mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age.