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Background This study was designed to investigate the prognostic value of the lymphocyte to monocyte ratio (LMR) in patients with gallbladder carcinoma (GBC). Patients and methods We retrospectively enrolled 154 consecutive GBC patients from 2005 to 2017 in this study. The LMR of preoperative blood samples was calculated by dividing the lymphocyte count by the monocyte count. A receiver operating characteristic (ROC) curve was employed to identify the optimal cut-off value of the LMR in the determination of overall survival (OS). The Kaplan-Meier method was utilized to assess OS, and the Log rank test was employed to compare survival differences. Univariate and multivariate Cox regression analyses were conducted to detect independent prognostic indicators. Results The optimal cut-off point for the LMR was 4.76 according to the ROC curve. Patients ≤60 years old with an LMR ≤4.76 experienced significantly worse OS than those with an LMR >4.76 (hazard ratio (HR): 0.399, 95% confidence interval (CI): 0.265-0.602, P 60 years old or among the entire study cohort (both P>0.05). Significantly poorer OS was observed in patients >60 years with an LMR ≤4.21 compared to those with an LMR >4.21 (HR: 1.830, 95% CI: 1.129-2.967, P=0.014). Multivariate Cox regression analysis indicated that both the high and low LMR cut-off values were independent risk factors for OS (HR: 0.272, 95% CI: 0.105-0.704, P=0.007; HR: 0.544, 95% CI: 0.330-0.895, P=0.017). Conclusion The LMR is an independent prognostic indicator for GBC patients, the cut-off value of which is age dependent.

The choline-binding proteins play essential roles in pneumococcal colonization and virulence. It has been suggested that the choline-binding protein J (termed CbpJ; encoded by the gene sp_0378) from Streptococcus pneumoniae TIGR4 involves in the colonization in host and contributes to evasion of neutrophil killing. Here we report the 2.0 A crystal structure of CbpJ in complex with choline. CbpJ consists of an N-terminal putative functional domain (N-domain) followed by a C-terminal choline-binding domain (CBD). The N-domain harbors four degenerated choline-binding repeats (CBRs) that lose the capacity of binding to choline, whereas the CBD is composed of seven typical CBRs. Further functional assays showed that the CBD contributes to the pneumococcal adhesion to human lung epithelial cell A549. These findings provide insights into the pneumococcal pathogenesis and broaden our understanding on the functions of choline-binding proteins.

Objective To analyse the application of a new narrow-band imaging (NBI) classification in the diagnosis of vocal cord leukoplakia by laryngologists with different levels of laryngoscopic experience and to explore the impact of NBI training programmes on laryngologists' identification of benign and malignant leukoplakia. Design Prospective multicentre study. Setting Tertiary hospitals. Participants Sixteen laryngologists were divided into less-experienced and experienced groups and received NBI training course. Thirty cases of vocal cord leukoplakia were investigated. Main outcome measures Diagnostic accuracy and interobserver agreement under white light imaging (WLI), before and after NBI training, were analysed among doctors with varying levels of experience. Results The accuracy in the less-experienced group was significantly lower than that of experience group (0.59 vs 0.69) under WLI. There was no significant difference in the diagnostic accuracy between the less-experienced group and the experienced group before NBI training (0.75 vs 0.74) and after NBI training (0.79 vs 0.83). NBI training could improve the interobserver agreement from fair or moderate to good agreement. Conclusion The new NBI diagnostic classification is helpful for identifying benign and malignant vocal cord leukoplakia. In addition, the NBI training programme can improve the diagnostic accuracy and interobserver agreement of less-experienced doctors to the level of experienced laryngologists.

BACKGROUND Stromal and immune cells play important roles in hepatocellular carcinoma (HCC) development and progression. However, tools for predicting the prognosis of patients with HCC based on stromal and immune scores are not well established. We aimed to develop nomograms that predicted the disease-free survival (DFS) and overall survival (OS) of patients after radical surgery. METHODS Basic information of 251 patients were retrieved from The Cancer Genome Atlas. Multivariate Cox analyses identified variables predicting the prognosis of patients. DFS and OS nomograms were constructed based on the stromal and immune scores of the training group and verified in the well-matched test group. RESULTS An intermediate stromal score (hazards ratio [HR] = 3.177; P

Weeping is a specific plant architecture with high ornamental value. Despite the considerable importance of the weeping habit to landscaping applications and knowledge of plant architecture biology, little is known regarding the underlying molecular mechanisms. In this study, growth and phytohormone content were analyzed among the progeny of different branch types in an F1 mapping population of Prunus mume with varying plant architecture. Bulked segregant RNA sequencing was conducted to compare differences among progeny at a transcriptional level. The weeping habit appears to be a complex process regulated by a series of metabolic pathways, with photosynthesis and flavonoid biosynthesis highly enriched in differentially expressed genes between weeping and upright progeny. Based on functional annotation and homologous analyses, we identified 30 candidate genes related to weeping that merit further analysis, including 10 genes related to IAA and GA3 biosynthesis, together with 6 genes related to secondary branch growth. The results of this study will facilitate further studies of the molecular mechanisms underlying the weeping habit in P. mume.

Background/Aims: Erinacine, which is extracted from the medicinal mushroom Hericium erinaceus, is known to play anticancer roles in human cancers. The following study aims to investigate the role of erinacine in the opening of the mitochondrial permeability transition pore (MPTP) in hepatocellular carcinoma (HCC) through the PI3K/Akt/GSK-3β signaling pathway and highlights the applicability of erinacine in HCC treatments. Methods: HCC and paracancerous tissues were obtained from 85 HCC patients who’ve undergone surgical resection. Immunohistochemistry was adopted to detect positive expression of PI3K, Akt, and GSK-3β. Treatment of HepG-2 with LY294002 (an inhibitor of the PI3K/Akt/GSK-3β signaling pathway) and different concentration of erinacine was performed to determine the involvement of LY294002 in erinacine action. The expressions of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, Bcl-2, E-cadherin, Bax, and caspase-9 were determined by RT-qPCR and Western blot analysis. Cell viability, colony formation rate, migration, invasion, cycle, and apoptosis were detected by MTT, colony formation, wound healing assay, Transwell assay, and flow cytometry, respectively. The size and weight of xenograft tumors were observed in nude mice. Mitochondrial membrane potential in HepG-2 was determined using laser scanning confocal microscopy following JC-1 staining. Mitochondrial Ca2+ indicator Rhod-2, AM was used to detect the changes of mitochondrial Ca2+, while western blot analysis was employed to detect the presence levels of cytochrome C (cyt-C). Results: The results revealed that PI3K, Akt, and GSK-3β were up-regulated in HCC tissues. Erinacine or LY294002 led to a decrease in mitochondrial membrane potential, increase in intracellular mitochondrial Ca2+, and the release of cyt-C in mitochondria. In addition, Erinacine was found to decrease the mitochondrial membrane potential, expression of PI3K, Akt, GSK-3β, CyclinD1, Vimentin, β-catenin, and Bcl-2, cell proliferation, colony formation ability, migration, invasion, and xenograft tumor size, while E-cadherin, Bax, and caspase-9 expression, and cell apoptosis were elevated in a dose-dependent manner. Erinacine also stimulated the effects of LY294002 on the HCC. Following the addition of 500 μM Erinacine and MPTP opening inhibitor CsA, we found that the mitochondrial membrane potential level increased, while mitochondrial Ca2+ and Cyt-C decreased from the mitochondria. Conclusion: The results from the study demonstrated that erinacine induced MPTP opening, facilitates the release of cyt-C, and inhibited cell proliferation, migration, and invasion, while it promotes apoptosis by inactivating the PI3K/Akt/GSK-3β signaling pathway, preventing the progression of HCC.

Supplemental Digital Content is available in the text, Background: The role of fruit and vegetables (FVs) consumption in decreasing gallstone disease risk remains contradictory. We performed a meta-analysis to analyze this potential correlation, followed by investigation of dose-response relationship of FVs consumption with gallstone disease. Materials and methods: PubMed, Embase, as well as Web of Science were searched to determine all published researches about the connection of FVs consumption with gallstone disease before March 2018. Relative risks (RRs) or odds ratios (ORs) along with corresponding 95% confidence intervals (CIs) was pooled utilizing random effect models, aiming at examining the correlation of FVs consumption with gallstone disease risk. Results: One cross-sectional study, our case-control studies as well as nine cohort studies were enrolled, covering approximately 33,983 patients with gallstone disease and 1,53,3752 participants. In a pooled analysis, vegetables consumption was significantly related to a decreased gallstone disease risk, (RR = 0.83, 95% CI, 0.74–0.94, I2 = 91.1%), and for fruits consumption, RR was similar (RR = 0.88, 95%CI, 0.83–0.92, I2 = 0.01%). This inverse correlation of FVs consumption with gallstone disease risk was solid in most subgroup analysis. The nonlinear dose-response correlation indicated that gallstone risk was reduced by 4% (RR = 0.96, 95%CI, 0.93–0.98) and 3% (RR = 0.97, 95%CI, 0.96–0.98) for every 200 g per day increment in vegetables consumption (P = .001) and fruits consumption (P = .001), respectively. Conclusion: This study suggests vegetables and fruits consumption is correlated with a significantly reduced risk of gallstone disease.

Post traumatic stress disorder (PTSD) is a mental illness that affected numerous people. The anti-PTSD-like effects of puerarin is unknown, although the antidepressant- and anxiolytic- like effects of puerarin have been reported. The PTSD behavioral deficits in rats were induced by single prolonged stress (SPS), mainly including the reduced time/entries in the open arms and the elevated time/entries in the closed arms in elevated plus maze test, increased freezing duration in contextual fear paradigm and lowered time/entries in the central zone in open field test. However, the behavioral deficits were attenuated by puerarin (50 and 100 mg/kg) without affecting the locomotor activity. For the evaluation of mechanism, the decreased levels of progesterone, allopregnanolone, and the increased levels of corticosterone, corticotropin releasing hormone, and adrenocorticotropic hormone in the brain or serum were induced by SPS, which is blocked by puerarin. In summary, the anti-PTSD-like effects of puerarin were associated with biosynthesis of neurosteroids and normalized levels of stress hormones in HPA axis.

In allusion to deficiencies of traditional medical image enhancement algorithms such as poor applicability, large calculated amount and manual parameter setting and local optimum problem of FOA algorithm, this paper introduces chaos theory into FOA algorithm for improvement based on good global optimum searching performance of fruit fly optimization algorithm and optimizes normalized incomplete Beta function with IFOA for medical image enhancement. The experimental result shows that the improved FOA algorithm can highlight image features effectively, improve visual effect of images and efficiency, avoid invariability of manual parameter adjustment, configure best parameters of normalized incomplete Beta function automatically while guaranteeing best image quality and achieve adaptive enhancement of medical images.

Small heat shock proteins (sHSPs) have been shown to be involved in stress tolerance. However, their functions in Prunus mume under heat treatment are poorly characterized. To improve our understanding of sHSPs, we cloned a sHSP gene, PmHSP17.9, from P. mume. Sequence alignment and phylogenetic analysis indicated that PmHSP17.9 was a member of plant cytosolic class III sHSPs. Besides heat stress, PmHSP17.9 was also upregulated by salt, dehydration, oxidative stresses and ABA treatment. Leaves of transgenic Arabidopsis thaliana that ectopically express PmHSP17.9 accumulated less O2 − and H2O2 compared with wild type (WT) after 42 °C treatment for 6 h. Over-expression of PmHSP17.9 in transgenic Arabidopsis enhanced seedling thermotolerance by decreased relative electrolyte leakage and MDA content under heat stress treatment when compared to WT plants. In addition, the induced expression of HSP101, HSFA2, and delta 1-pyrroline-5-carboxylate synthase (P5CS) under heat stress was more pronounced in transgenic plants than in WT plants. These results support the positive role of PmHSP17.9 in response to heat stress treatment.

AIM To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.

The Gamma interferon inducible lysosomal thiol reductase (GILT) plays a key biological role in the immune responses and involves in the processing of class II MHC-restricted antigen by stimulating disulfide bond reduction in mammals. To determine the biological function of GILT in the innate immune system of crustaceans, we sequenced and cloned GILT gene from red swamp crayfish, Procambarus clarkii (Pc-GILT). The deduced amino acid sequence of Pc-GILT contained the putative conserved structures of the GILT family proteins: the GILT signature (CQHGX2ECX2NX4C) sequence and the active site (CXXS) motif. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis suggested that a recombinant Pc-GILT protein was successfully expressed in Escherichia coli (E. coli). Quantitative real-time PCR analysis showed that Pc-GILT transcript level was highest in the hepatopancreas followed by the gut, heart and muscles. Additionally, we analyzed the transcription level of Pc-GILT gene in hepatopancreas of red swamp crayfish under biotic stress conditions. The expression of Pc-GILT gene upregulated after viral (poly I:C) and bacterial (peptidoglycan, lipopolysaccharide) infection. The suppression of Pc-GILT by double stranded RNA influenced the transcript levels of various immune-related genes. These observations indicate that the Pc-GILT probably plays a key biological role in the innate immune responses of red swamp crayfish, since it modulates the expression of genes associated with immune pathways.

The transcriptional activation of heat shock proteins (Hsps) by heat shock transcription factors (Hsfs) is presumed to have a pivotal role in plant heat stress (HS) response.Prunus mumeis an ornamental woody plant with distinctive features, including rich varieties and colors. In this study, 18 Hsfs and 24 small Hsps (sHsps) were identified inP. mume. Their chromosomal locations, protein domains, conserved motifs, phylogenetic relationships, and exon–intron structures were analyzed and compared withArabidopsis thalianaHsfs or sHsps. A total of 18 PmHsf members were classified into three major classes, A, B, and C. A total of 24 PmsHsps were grouped into eight subfamilies (CI to CIII, P, endoplasmic reticulum, M, and CI- or P-related). Quantitative reverse transcription PCR analysis revealed that members of the A2, A7, and A9 groups became the prominent Hsfs after heat shock, suggesting their involvement in a key regulatory role of heat tolerance. Most of thePmsHspgenes were up-regulated upon exposure to HS. Overall, our data contribute to an improved understanding of the complexity of theP. mume HsfandsHspgene families, and provide a basis for directing future systematic studies investigating the roles of theHsfandsHspgene families.

Carnosol is an ortho-diphenolic diterpene with excellent antioxidant potential. The present study was designed to identify the protective role of carnosol against spinal cord injury (SCI)-induced oxidative stress and inflammation in Wistar rats.In the present study, oxidative stress status was determined through estimating total antioxidant capacity, total oxidant status, lipid peroxide content, protein carbonyl and sulfhydryl levels, reactive oxygen species (ROS), antioxidant status (superoxide-dismutase, catalase, glutathione, glutathione peroxidase, glutathione-S-transferase). Inflammatory effects were determined by analyzing the expression of NF-κB and COX-2 through Western blot analysis. Further, carnosol-mediated redox homeostasis was analyzed by determining p-AKT and Nrf-2 levels.SCI resulted in a significant increase in oxidative stress status through increased ROS generation, total oxidant levels, lipid peroxide content, protein carbonyl and sulfhydryl levels. The antioxidant status in SCI rats was significantly reduced, indicating imbalance in redox status. In addition, the expression of NF-κB and COX-2 was significantly upregulated, while p-AKT and Nrf-2 levels were downregulated in SCI rats. However, treatment with carnosol showed a significant enhancement in the antioxidant status with concomitant decline in oxidative stress parameters. Further, carnosol treatment regulated the key proteins in inflammation and redox status through significant downregulation of NF-κB and COX-2 levels and upregulation of p-AKT and Nrf-2 expression.Thus, the present study shows for the first time on the protective role of carnosol against SCI-induced oxidative stress and inflammation through modulating NF-κB, COX-2 and Nrf-2 levels in Wistar rats.

Rationale: Lymphoepithelioma-like cholangiocarcinoma (LEL-CC) is a rare variant of intrahepatic cholangiocarcinoma (ICC), which is characterized by the better outcome than normal ICC. There is no report about the treatment for the metastasis of the LEL-CC. Here, we describe a rare case of LEL-CC of the liver and report the treatment for metastasis of it. Patient concerns: A 38-year-old woman with a chronic hepatitis B infection was referred to the department of liver surgery in our hospital with a mass in the liver. Diagnoses: A past ultrasound examination had revealed a 28 mm × 16 mm nodular lesion in the right posterior lobe of the liver in May 2013. She had undergone partial resection of the thyroid gland for papillary carcinoma 1 year earlier. Intervention: Suspicious of the metastasis from thyroid cancer, she underwent surgery with liver segmentectomy. The pathologic diagnosis of the lesion was LEL-CC. After surgery, she regularly got checked in our hospital, and in the 6 months after surgery, there was enlargement of lymph node before the inferior vena cava in CT. The doctor did not detect the enlargement of the lymph node until June 2017. The PET-CT was done in June of 2017, which showed the lymph node was hypermetabolic. Outcomes: The patient got her second surgery for lymph node three years after the first surgery, which was proved that the lymph node was metastasis from LEL-CC. The patient was free from recurrence 9 months after surgery. Lessons: We report the first case of surgery for metastasis from LEL-CC in the liver that was diagnosed 3 years after hepatectomy. Our findings suggest that surgery could be an effective way of treating lymph node metastasis of LEL-CC and early PET-CT can help to identify metastasis.

Background Perioperative blood loss is still an unsolved problem in total knee arthroplasty (TKA). The efficacy of the preoperative use of tranexamic acid (TXA) plus drain-clamping to reduce blood loss in TKA has been debated. This meta-analysis aimed to illustrate the efficacy of TXA plus drain-clamping to reduce blood loss in patients who underwent a TKA. Methods In February 2017, a systematic computer-based search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews, and Google Scholar. Data from patients prepared for TKA in studies that compared TXA plus drain-clamping versus TXA alone, drain-clamping alone, or controls were retrieved. The primary endpoint was the need for transfusion. The secondary outcomes were total blood loss, blood loss in drainage, the decrease in hemoglobin, and the occurrence of deep venous thrombosis. After testing for publication bias and heterogeneity between studies, data were aggregated for random-effects models when necessary. Results Ultimately, 5 clinical studies with 618 patients (TXA plus drain-clamping group = 249, control group = 130, TXA-alone group = 60, and drain-clamping group = 179) were included. TXA plus drain-clamping could decrease the need for transfusion, total blood loss, blood loss in drainage, and the decrease in hemoglobin than could the control group, the TXA-alone group, and the drain-clamping group (P .05). Conclusions TXA plus drain-clamping can achieve the maximum effects of hemostasis in patients prepared for primary TKA. Because the number and the quality of the included studies were limited, more high-quality randomized controlled trials are needed to identify the optimal dose of TXA and the clamping hours in patients prepared for TKA.