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Background Identification of more promising microRNAs (miRNAs) are being extensively studied with respect to colorectal cancer (CRC), since CRC is the leading cause of cancer deaths and most common malignant tumors worldwide. A series of colon cancer (CCa) samples from The Cancer Genome Atlas (TCGA) were analyzed to provide a new perspective into this field. Methods The expression of miRNAs, mRNAs and the clinical data of 437 CRC patients were downloaded from the TCGA database. The survival-related differentially expressed miRNAs (sDMIRs) and mRNAs were detected by COX regression analysis. The high-risk group and low-risk group were separated by the median risk score of the risk score model. The potential clinical characteristics of these sDMIRs were analyzed by R software. The potential molecular mechanisms of these sDMIRs were explored by computational biology. The expression levels of three sDMIRs were explored by qPCR in CRC samples. Results Three DMIRs (hsa-miR-21-3p, hsa-miR-194-3p and hsa-miR-891a-5p) correlated with the most remarkable prognostic values of CRC patients were selected to establish the risk score model (RSM) by univariate and multivariate COX regression analysis and the survival probability of the low-risk group was longer than that in the high-risk group. We detected the target genes of three sDMIRs and the potential molecular mechanisms of these sDMIRs. We further verified the high expression levels of hsa-miR-21-3p and hsa-miR-194-3p were associated with the early T-stages, while hsa-miR-891a-5p illustrated the reversed result. Conclusion Our study demonstrated three sDMIRs with significantly clinical values illustrated the potential predicting values in the prognosis of CRC patients. Our results may provide a new perspective for the diagnostic methods and treatment strategies in CRC patients.

Background The clinical characteristics of Parkinson’s disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. Objective To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). Methods Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. Results Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. Conclusion More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.

Background The undergraduate program of psychiatry has been widely established in recent years to improve the education and recruitment of psychiatrists in China. We aim to investigate the career choice of medical students majoring in psychiatry in China and the influential factors. Method This multicenter study was conducted in 26 medical schools in China from May to October of 2019. Participants included 4610 medical students majoring in psychiatry and 3857 medical students majoring in clinical medicine. Multivariable logistic regression was used to investigate the influential factors of students’ choices of psychiatry at matriculation and as a career. Results 44.08% of psychiatry majored students gave psychiatry as a first choice at matriculation, and 56.67% of them would choose psychiatry as a career, which was in sharp contrast to the proportion of clinical medicine majored students who would choose psychiatry as a career (0.69%). Personal interest (59.61%), suggestions from family members (27.96%), and experiencing mental problems (23.19%) were main reasons for choosing psychiatry major at matriculation. Personal interest (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.87–2.40), experiencing a psychiatry clerkship (OR = 1.99, 95% CI = 1.28–3.08), being female (OR = 1.50, 95% CI = 1.30–1.68), experiencing mental problems (OR = 1.33, 95% CI = 1.28–1.56), and suggestions from family members (OR = 1.25, 95% CI = 1.08–1.46) correlated positively with students’ choice of psychiatry as career. Students who lacked psychiatry knowledge (OR = 0.49, 95% CI = 0.29–0.85) or chose psychiatry because of lower admission scores (OR = 0.80, 95% CI = 0.63–0.97) were less likely to choose psychiatry as a career. Conclusion More than half of psychiatry majored medical school students planned to choose psychiatry as their career, whereas very few students in the clinic medicine major would make this choice. Increasing students’ interest in psychiatry, strengthening psychiatry clerkships, and popularizing psychiatric knowledge are modifiable factors to increase the psychiatry career intention. The extent to which medical students’ attitudes toward psychiatry can be changed through medical school education and greater exposure to psychiatry will need further investigation.

Koi carp (Cyprinus carpio) are well-known and highly valuable fish in the international ornamental fish community that have been plagued by Aeromonas veronii infections in recent years. Some A. veronii infections are serious enough to cause death. Lactobacillus plantarum, a probiotic, is one of the most environmentally friendly and safe alternatives to antibiotics for use as a feed additive for aquatic animals such as fish. The present study investigated the effects of L. plantarum C20015 on growth performance, immune responses, and eradication of A. veronii infection in koi carp. During a 6-week feeding experiment in an indoor aquarium and a 14-day A. veronii artificial infection experiment, a control diet group was fed with untreated feed twice a day, while experimental groups were given different concentrations of L. plantarum in their feed. The results indicated that the specific growth rate and percent weight gain of fish were significantly higher in the experimental groups than in the control diet group (P < 0.05). The activity of superoxide dismutase (SOD), peroxidase (POD), and lysozyme (LZM) and the levels of IgM antibody were significantly higher in the L. plantarum–supplemented groups than in the control diet group, and the enzymatic activity in the 108 CFU/g C20015 group was higher than that in the 107 CFU/g C20015 and 109 CFU/g C20015 groups (P < 0.01). In contrast, alkaline phosphatase (AKP) activity in the experimental groups was the highest at 42 days. All fish in the control diet group died 7 days after A. veronii infection. After 14 days, the relative percent survival (%, RPS) of the fish in the L. plantarum–supplemented groups was significantly higher than that of the fish in the control group, and the 108 CFU/g C20015 group had the highest RPS. Therefore, we first reported that fish fed with 108 CFU/g of L. plantarum C20015 could promote food intake and growth for koi carp.

Proline-rich antimicrobial peptides (PR-AMPs) have attracted much interest as they target Gram-negative and do not act by lytic mechanisms. In this study, a novel hybrid peptide OM19R was designed based on the Oncocin and MDAP-2. OM19R showed specific and improved potency against Escherichia coli (E. coli), Salmonella and Shigella standard strains compared to parental peptides. The minimum inhibitory concentrations (MICs) ranged from 1 to 2 μM. However, the activity against Klebsiella pneumoniae (K. pneumoniae) was inhibited. The dependence of the SbmA protein for OM19R activity was also studied by a gene-knockout strain. The confocal laser scanning microscopy further revealed that OM19R could rapidly penetrate into E. coli cells without membrane damage. In summary, the hybrid peptide OM19R is a strong cell-selective antibacterial peptide and a promising specific antibacterial agent.

Isolation and characterization of a bacteriocin from Brevibacillus laterosporus DS-3 and its ability in producing antibacterial activity were examined in this study. We isolated 48 bacterial strains from different native ecological niches. Sources included lake water, soil, air, and food. Among the isolates from the soil sample, morphological and biochemical tests identified Brev. laterosporus DS-3, which showed great potential for bacteriocin production. It was purified by ammonium sulfate precipitation, then applied in a Sephadex G-15 gel filtration column connected to a purification of AKTA Pure (USA) and reverse phase chromatography. MALDI-TOF mass spectrometry indicated that bacteriocin DS-3 has a low molecular weight of 1592.579 Da. LNTLETEEWFFK was identified as the sequence by mass spectrometry analysis in tandem liquid chromatography and MASCOT research. This bacteriocin inhibited Gram-positive and Gram-negative bacteria and was effective against Methicillin-resistant Staphylococcus aureus (MRSA). Brev. laterosporus DS-3 present in here is thermostable and tolerant to extreme pH. However, inactivation of its antibacterial activity was observed when treated with papain and trypsin but not pepsin, proteinase K, and catalase.

The present study evaluated the antibacterial activity and mode of action of fibrauretine on Escherichia coli (E. coli) and Staphylococcus aureus, and synergistic effect with kanamycin against multi-drug resistant E. coli. The fibrauretine exhibited inhibitory effect on the growth of the tested bacteria with minimum inhibitory concentration (MIC) and minimum bactericidal concentration of 2.5–5 and 5–10 mg/ml, respectively. Morphological changes of cell microstructure were observed after adding fibrauretine at MIC. The mode of action was further confirmed by measuring release of 260-nm absorbing materials and extracellular potassium ions. Checkerboard dilution test suggested that fibrauretine exhibited synergistic activity when combined with kanamycin (FICI ranging from 0.5625 to 0.625). Our results indicated that fibrauretine exerted synergistic effect with kanamycin and its antibacterial mode of action mainly attributed to disruption of cell membrane integrity.

Background: Frequent overdose of paracetamol (APAP) has become the major cause of acute liver injury. The present study was designed to evaluate the potential protective effects of ginsenoside Rk1 on APAP-induced hepatotoxicity and investigate the underlying mechanisms for the first time. Methods: Mice were treated with Rk1 (10 mg/kg or 20 mg/kg) by oral gavage once per d for 7 d. On the 7th d, all mice treated with 250 mg/kg APAP exhibited severe liver injury after 24 h, and hepatotoxicity was assessed. Results: Our results showed that pretreatment with Rk1 significantly decreased the levels of serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor, and interleukin-1β compared with the APAP group. Meanwhile, hepatic antioxidants, including superoxide dismutase and glutathione, were elevated compared with the APAP group. In contrast, a significant decrease in levels of the lipid peroxidation product malondialdehyde was observed in the ginsenoside Rk1-treated group compared with the APAP group. These effects were associated with a significant increase of cytochrome P450 E1 and 4-hydroxynonenal levels in liver tissues. Moreover, ginsenoside Rk1 supplementation suppressed activation of apoptotic pathways by increasing Bcl-2 and decreasing Bax protein expression levels, which was shown using western blotting analysis. Histopathological observation also revealed that ginsenoside Rk1 pretreatment significantly reversed APAP-induced necrosis and inflammatory infiltration in liver tissues. Biological indicators of nitrative stress, such as 3-nitrotyrosine, were also inhibited after pretreatment with Rk1 compared with the APAP group. Conclusion: The results clearly suggest that the underlying molecular mechanisms in the hepatoprotection of ginsenoside Rk1 in APAP-induced hepatotoxicity may be due to its antioxidation, antiapoptosis, anti-inflammation, and antinitrative effects. Keywords: anti-inflammation, anti-apoptosis, APAP-induced hepatotoxicity, ginsenoside Rk1, oxidative stress

BACKGROUND Stroke has a great influence on the patient’s mental health, and reasonable psychological adjustment and disease perception can promote the recovery of mental health. AIM To explore the relationships among resilience, coping style, and uncertainty in illness of stroke patients. METHODS A retrospective study was used to investigate 154 stroke patients who were diagnosed and treated at eight medical institutes in Henan province, China from October to December 2019. We used the Mishel Uncertainty in Illness Scale, the Connor-Davidson Resilience Scale, and the Medical Coping Modes Questionnaire to test the uncertainty in illness, resilience, and coping style, respectively. RESULTS Resilience had a significant moderating role in the correlation between coping style and unpredictability and information deficiency for uncertainty in illness (P < 0.05). Further, the tenacity and strength dimensions of resilience mediated the correlation between the confrontation coping style and complexity, respectively (P < 0.05). The strength dimension of resilience mediated the correlation between an avoidance coping style and the unpredictability of uncertainty in illness (P < 0.05), as well as correlated with resignation, complexity, and unpredictability (P < 0.05). CONCLUSION Resilience has moderating and mediating roles in the associations between coping style and uncertainty in illness, indicating that it is vital to improve resilience and consider positive coping styles for stroke patients in the prevention and control of uncertainty in illness.

Background: To explore the prognostic value of radiomics-based and digital pathology-based imaging biomarkers from macroscopic magnetic resonance imaging (MRI) and microscopic whole-slide images for patients with nasopharyngeal carcinoma (NPC). Methods: We recruited 220 NPC patients and divided them into training ( n = 132), internal test ( n = 44), and external test ( n = 44) cohorts. The primary endpoint was failure-free survival (FFS). Radiomic features were extracted from pretreatment MRI and selected and integrated into a radiomic signature. The histopathological signature was extracted from whole-slide images of biopsy specimens using an end-to-end deep-learning method. Incorporating two signatures and independent clinical factors, a multi-scale nomogram was constructed. We also tested the correlation between the key imaging features and genetic alternations in an independent cohort of 16 patients (biological test cohort). Results: Both radiomic and histopathologic signatures presented significant associations with treatment failure in the three cohorts (C-index: 0.689–0.779, all p Conclusion: The multi-scale imaging features showed a complementary value in prognostic prediction and may improve individualized treatment in NPC.

Purpose The gross tumor volume (GTV) could be an independent prognostic factor for unresectable locally advanced non-small cell lung cancer (LANSCLC). We aimed to develop and validate a novel integrated GTV-TNM stratification system to supplement LANSCLC sub-staging in patients treated with concurrent chemoradiotherapy (CCRT). Methods We performed a retrospective review of 340 patients with unresectable LANSCLC receiving definitive CCRT. All included patients were divided into two randomized cohorts. Then the Kaplan–Meier method and Cox regression were calculated to access the prognostic value of the integrated GTV-TNM stratification system, which was further validated by the area under the receiver operating characteristic curve (AUC) score and F1-score. Results The optimal outcome-based GTV cut-off values (70 and 180 cm3) of the modeling cohort were used to determine each patient’s integrated GTV-TNM stratum in the whole cohort. Our results indicated that a lower integrated GTV-TNM stratum could had better overall survival and progression-free survival (all P P = 0.027) and F1-score (0.655 vs. 0.615, P Conclusions We proposed a novel integrated GTV-TNM stratification system to supplement unresectable LANSCLC sub-staging due to its prognostic value independent of TNM stage and other clinical characteristics, suggesting that it could be considered in individual treatment decision-making process.

Background: Ultrasound imaging has become one of the most widely utilized adjunct tools in breast cancer screening due to its advantages. The computer-aided detection of breast ultrasound is rapid development via significant features extracted from images. Objectives: The main aim was to identify features of breast ultrasound image that can facilitate reasonable classification of ultrasound images between malignant and benign lesions. Patients and Methods: This research was a retrospective study in which 85 cases (35 malignant [positive group] and 50 benign [negative group] with diagnostic reports) with ultrasound images were collected. The B-mode ultrasound images have manually selected regions of interest (ROI) for estimated features of an image. Then, a fractal dimensional (FD) image was generated from the original ROI by using the box-counting method. Both FD and ROI images were extracted features, including mean, standard deviation, skewness, and kurtosis. These extracted features were tested as significant by t-test, receiver operating characteristic (ROC) analysis and Kappa coefficient. Results: The statistical analysis revealed that the mean texture of images performed the best in differentiating benign versus malignant tumors. As determined by the ROC analysis, the appropriate qualitative values for the mean and the LR model were 0.85 and 0.5, respectively. The sensitivity, specificity, accuracy, positive predicted value (PPV), negative predicted value (NPV), and Kappa for the mean was 0.77, 0.84, 0.81, 0.77, 0.84, and 0.61, respectively. Conclusion: The presented method was efficient in classifying malignant and benign tumors using image textures. Future studies on breast ultrasound texture analysis could focus on investigations of edge detection, texture estimation, classification models, and image features.

Aeromonas veronii is a major pathogenic bacterium in humans and animals. When it causes outbreaks, there are enormous economic losses to the aquaculture industry. An effective live attenuated vaccine strain, ΔhisJ, was obtained in our previous studies by gene knockout in Aeromonas veronii TH0426 using the suicide vector pRE112. Here, we evaluated whether the live attenuated vaccine ΔhisJ was suitable for prevention of Aeromonas veronii infection by injection and immersion in loaches. Compared with that of the TH0426 wild-type strain, the virulence of the live vaccine was significantly weakened. Vaccine safety assessment results also indicated that 1 × 107 CFU/mL live vaccine was safe and did not induce clinical symptoms or obvious pathological changes. Additionally, after challenging loaches with Aeromonas veronii TH0426, the relative percent survival of the IN3 injection group was 65.66%, and that of the IM group was 50.78%. Our data show that the live attenuated vaccine ΔhisJ can improve the immune protection rate of loaches. Furthermore, increased enzyme activity parameters (SOD, LZM, ACP, and AKP) in the skin mucus, increased enzyme activity parameters (SOD, LZM, ACP, AKP, and GPx) in the serum, increased specific IgM antibodies and cytokine IL-1β contents in the serum, and increased cytokine (IL-15, pIgR, IL-1β, and TNF-α) expression in the liver and spleen were observed. These data are the first to indicate that the live attenuated vaccine ΔhisJ is suitable for the development of a safe and effective vaccine against Aeromonas veronii infection in loach aquaculture.

Proper bone age assessment is crucial for the clinical diagnosis and evaluation of treatment responses. We investigated the applicability of Greulich and Pyle (GP), and Tanner and Whitehouse 3 (TW3) methods for children in modern Taiwan, using computer‐aided diagnosis. Hand and wrist radiographs were obtained from 611 children (3‐17 years) who came to our emergency department due to trauma. Ages 0 to 2 years old were excluded because of a limited number of cases. Skeletal maturation was assessed using the BoneXpert (version 2.5.4.1 automated software), which determines GP and TW3 bone age. The two scoring systems were evaluated for comparing the chronological ages in each subgroup. In boys, mean GP bone age vs mean chronological ages were delayed for ages 3 to 11 and advanced for age 12 to 17. In girls, mean GP bone age vs mean chronological ages was delayed for ages 4 to 8 and 17, and advanced for ages 3 and 9 to 17. In boys, the mean TW3 bone ages vs mean chronological ages were delayed for ages 5 to 10 except age 8, and advanced for ages 3 to 4, 8, and 11 to 15. In girls, the mean TW3 bone ages vs mean chronological ages were delayed for ages 4 to 12, and advanced for ages 3 and 13 to 14. By using the BoneXpert automatic software, we established bone age reference standards for children in Taiwan. Clinical application of GP and TW3 scoring methods can be adjusted according to our results to better assess bone age.

Cobalt (Co) is an essential component of several enzymes and coenzymes in living organisms. Excess Co is highly toxic to plants. The knowledge of molecular response mechanisms to cobalt stress in plants is still limited, especially in woody plants. The responses of weeping willow (Salix babylonica) seedlings to Co stress were studied using morphological and physiochemical measurements and RNA-seq analysis. The physiological and biochemical indexes such as growth rate, the content of chlorophyll and soluble sugar, photosynthesis and peroxidase activity were all changed in willow seedlings under Co stress. The metal ion concentrations in willow including Cu, Zn and Mg were disturbed due to excess Co. Of 2002 differentially expressed genes (DEGs), 1165 were root-specific DEGs and 837 were stem and leaf-specific DEGs. Further analysis of DEGs showed there were multiple complex cascades in the response network at the transcriptome level under Co stress. Detailed elucidation of responses to oxidative stress, phytohormone signaling-related genes and transcription factors (TFs), and detoxification of excess cellular Co ion indicated the various defense mechanisms in plants respond to cobalt stress. Our findings provide new and comprehensive insights into the plant tolerance to excess Co stress.

Background Vasitis or inflammation of the vas deferens is a rare condition, and few case reports with computed tomography images have been published since 1980. Case presentation A 50-year-old man presented with severe right inguinal and lower abdominal pain. Initial diagnosis at the emergency department was incarcerated or strangulated inguinal hernia. The computed tomography scan revealed diffuse edematous changes of right spermatic cord and vas deferens with peripheral fat stranding. Correlating with his clinical symptoms, signs, and imaging findings, the diagnosis of vasitis was made. We report a case of acute vasitis about the cause, symptom, pathogen, differential diagnoses, image findings, and treatment. Conclusion Although very rare, vasitis should be listed as one of the differential diagnosis for inguinal mass lesions. Cross-sectional imaging may be necessary to confirm the diagnosis and exclude differentials such as an inguinal hernia. Recognition of the characteristic image findings can help to make the correct diagnosis and avoid unnecessary surgery.

Bacterial enteritis is the most important disease in lamb for breeding greatly affects the growth of animals. Changes in the community of intestinal flora can cause the disorder of the colonic environment induced diarrhea. This study aimed to investigate the relationship between the incidence of bacterial enteritis and the number of intestinal microbiome, then the prevalence of drug-resistant genes was detected. Fecal samples were collected at five fattening sheep farms with different incidence of bacterial enteritis, pathogenic bacteria were isolated and identified, drug sensitivity tests were performed. Then, changes in number and structure of intestinal flora were compared by 16S rDNA V3-V4 region high-throughput sequencing, and the ARGs were detected using high-throughput real-time PCR. Our results revealed that the microbial communities were positively correlated with the incidence of bacterial enteritis in different farms. Bacterial communities were higher in YJ (with highest incidence of diarrhea) than any other farms. However, the ARGs seemed not to be more affected by the incidence of bacterial enteritis, but one of the significant findings to emerge from this study is that MCR-1 and NDM are detected in manure. This study has provided an insight of the changes occurring in intestinal flora and AGRs in fattening sheep farms with diverse incidence of bacterial enteritis.

Eugenol, the major active essential oil component of clove, was reported to possess QS (quorum sensing) inhibitory activity. A previous study found that eugenol could bind to quorum sensing receptors of Pseudomonas aeruginosa and down-regulate the expression of Streptococcus mutans virulence genes at sub-MIC (minimum inhibitory concentration) without affecting the bacterial growth. However, the alterations of QS signal molecules at transcription levels was not well understood. To better understand interactions of Klebsiella pneumoniae in response to eugenol and explore molecular regulations, transcriptome sequencing was performed. A total of 5779 differentially expressed genes (DEGs) enriched in a variety of biological processes and pathways were identified. The transcriptional data was validated by qPCR and the results showed that the expression profiles of 4 major genes involved in autoinducers-2 (AI-2) synthesis, including luxS, pfs, and lsrK were consistent with transcriptome analysis except for lsrR, a transcriptional repressor gene of lsr operon, which may repress the expression of following genes responsible for AI-2 signal transmission in vivo. In vitro AI-2 synthesis assay also revealed that eugenol could inhibit AI-2 generation. The results of our study offer insights into the mechanisms of QS inhibitory activity and K. pneumoniae AI-2 alterations after eugenol treatment.

Glycyrrhizic acid has a variety of biological properties, including a protective function in the liver, and anti‑inflammatory, anti‑ulcer, anti‑anaphylaxis, anti‑oxidant, immunoregulatory, antiviral and anticancer activities. The efficacy of glycyrrhizic acid can be increased when combined with other medicines. In the present study, the potential protective effects of glycyrrhizic acid against enteritis in rats, and its role in regulating anti‑inflammation, anti‑oxidation, angiogenic and apoptotic mechanisms were investigated using enzyme‑linked immunosorbent and bicinchoninic acid assays, and reverse transcription‑quantitative polymerase chain reaction and western blotting analyses. Adult male Sprague‑Dawley rats were injected with 20 mg/kg methotrexate (MTX) to establish enteritis. Additionally, rats with MTX‑induced enteritis were peritoneally injected with 200 mg glycyrrhizic acid for 9 weeks. The current study demonstrated that glycyrrhizic acid could alleviate MTX‑induced increases of tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 levels, and raise IL‑10 levels, in rats with enteritis. Treatment with glycyrrhizic acid significantly reduced D‑lactate and intercellular adhesion molecule‑1 gene expression (P

Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH2, where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly&ndash, Gly (GG) or d-Pro&ndash, Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an &alpha, helical structure in membrane-mimetic environments. Among them, peptide LRpG (X: L, zz: pG) showed the highest geometric mean average treatment index (GMTI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LRpG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LRpG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LRpG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

Purpose To evaluate the outcomes of 45 Gy/15 fractions/once-daily and 45 Gy/30 fractions/twice-daily radiation schemes utilizing intensity-modulated radiation therapy (IMRT) in extensive stage small cell lung cancer (SCLC), and to build up a new radiobiological model for tumor control probability (TCP) considering multiple biological effects. Methods Fifty-eight consecutive patients diagnosed with extensive stage SCLC, treated with chemotherapy and chest irradiation, were retrospectively reviewed. Thirty-seven received hyperfractionated IMRT (Hyper-IMRT, 45 Gy/30 fractions/twice-daily) and 21 received hypofractionated IMRT (Hypo-IMRT, 45 Gy/15 fractions/once-daily). Local progression-free survival (LPFS) and overall survival (OS) were calculated and compared. An extended linear-quadratic (LQ) model, LQRG, incorporating cell repair, redistribution, reoxygenation, regrowth and Gompertzian tumor growth was created based on the clinical data. The TCP model was reformulated to predict LPFS. The classical LQ and TCP models were compared with the new models. Akaike information criterion (AIC) was used to assess the quality of the models. Results The 2-year LPFS (34.1% vs 27.9%, p = 0.44) and OS (76.9% vs 76.9%, p = 0.26) were similar between Hyper- and Hypo-IMRT patients. According to the LQRG model, the α/β calculated was 9.2 (95% confidence interval: 8.7–9.9) Gy after optimization. The average absolute and relative fitting errors for LPFS were 9.1% and 18.7% for Hyper-IMRT, and 8.8% and 16.2% for Hypo-IMRT of the new TCP model, compared with 29.1% and 62.3% for Hyper-IMRT, and 30.7% and 65.3% for Hypo-IMRT of the classical model. Conclusions Hypo- and Hyper-IMRT resulted in comparable local control in the chest irradiation of extensive stage SCLC. The LQRG model has better performance in predicting the TCP (or LPFS) of the two schemes.

Pasteurella multocida (P. multocida) is an important pathogen that causes bovine respiratory disease (BRD) in China and other countries. To investigate the antimicrobial susceptibility of P. multocida isolated from different provinces in China, we analyzed antimicrobial susceptibility phenotypes and pulsed-field gel electrophoresis (PFGE) types of P. multocida; then, we sequenced the complete genome of strain found to be multidrug-resistant. The isolates exhibited resistance to many antimicrobial agents, especially amikacin, sulfamethoxazole, sulfachloropyridazinesodium, macrolides, and fluoroquinolones. Pulsed-field gel electrophoresis analysis showed that a clonal spread of multidrug-resistant isolates occurred in various provinces. All of the isolates carried class I integron.

Spontaneous pneumomediastinum (SPM) is an uncommon condition that predominantly affects young males. Due to its rarity, the optimal management still remains uncertain without consensus.

Background Bacterial infections have become more challenging to treat due to the emergence of multidrug-resistant pathogenic bacteria. Combined antibiotics prove to be a relatively effective method to control such resistant strains. This study aim to investigate synergistic activity of eugenol combined with colistin against a collection of clinical isolated Escherichia coli (E.coli) strains, and to evaluate potential interaction. Methods Antimicrobial susceptibility, minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) of the bacteria were determined by disk diffusion assay, broth microdilution method and checkerboard assay, respectively. The mcr-1 mRNA expression was measured by Real-time PCR. To predict possible interactions between eugenol and MCR-1, molecular docking assay was taken. Results For total fourteen strains including eight colistin-resistant strains, eugenol was determined with MIC values of 4 to 8 μg/mL. Checkerboard dilution test suggested that eugenol exhibited synergistic activity when combined with colistin (FICI ranging from 0.375 to 0.625). Comparison analysis of Real-time PCR showed that synergy could significantly down-regulate expression of mcr-1 gene. A metal ion coordination bond with catalytic zinc atom and a hydrogen bond with crucial amino acid residue Ser284 of MCR-1 were observed after molecular docking, indicating antibacterial activity and direct molecular interactions of eugenol with MCR-1 protein. Conclusions Our results demonstrated that eugenol exhibited synergistic effect with colistin and enhanced its antimicrobial activity. This might further contribute to the antibacterial actions against colistin-resistant E.coli strains. Graphical abstract Synergistic effect of eugenol with colistin against colistin-resistant Escherichia coli isolates.

Choline chloride (ChCl) was demonstrated to efficiently separate phenols from model oils by forming deep eutectic solvents (DESs). The DES way is a non-aqueous process that avoids the use of mineral alkalis and acids, and prevents the production of wastewater containing phenol. However, real oils, such as coal tar oil and liquefaction oil, consist of a small amount of water, and ChCl is a strong hygroscopic compound, which may influence the removal of phenol in real oil. In this work, the effect of water in mixtures of phenol and toluene (defined as model oils) on the separation of phenol by forming DES with ChCl was studied. The results indicated that water could interact with ChCl to form DES and the interaction between water and ChCl was stronger than that between phenol and ChCl. In the presence of water in model oils, the amount of ChCl should be increased to get the same phenol removal as that without water. Moreover, with water in model oils, the influence of temperature on the phenol removal was more negative. After the reuse of ChCl for four cycles with the presence of water, ChCl accumulated about 23% water and the removal efficiency of phenol decreased from 92% to 87%. To reduce the effect of water on phenol separation, an air drying method could be used to remove water in regenerated ChCl.

This paper studies the interaction dynamics of a vehicle traveling on a simply supported beam. A simple quarter-car planar model of the vehicle is taken into account. The system of the quarter-car model is treated as a moving mass with a massless harmonic force rolling on a simply supported beam. The objective of this paper is to present analytical and numerical methodologies to evaluate the vehicle–beam coupling effects when the vehicle moves under variable speed condition. Due to the presence of friction and convective acceleration, the vehicle can be accelerated by a forward force. Meanwhile, the vehicle is capable of reducing speed by applying a retard force to the vehicle and/or increasing the friction between the vehicle and beam. This results in variable velocity, acceleration, and deceleration, as well as unknown location of the vehicle along the beam. Result shows that as the spring stiffness of the suspension is close to the resonant value, strong commensurability between the oscillating frequency of the vehicle and the vibrant frequency of beam occurs when the instantaneous speed of the vehicle becomes a small quantity. In other words, a commensurable condition between the vehicle and beam is weakened when the vehicle is accelerated by a positive driving force; it becomes strong if the vehicle is decelerated by a negative reverse force and friction. If the vehicle reduces its traveling speed sharply, large amplitude and high oscillating frequency of the vehicle were generated. This significantly reduces the riding comfort for passengers in the vehicle. The applied force and coefficient of friction can be treated as tuning parameters to determine the resonant region of the interaction dynamics of a vehicle–beam system.

microRNAs (miRNAs) have been hypothesized to function as oncogenes or tumor suppressors by targeting specific cancer-related genes. Previous studies have reported that miR-223 may serve as a tumor suppressor in a number of cancer types, however, knowledge of its targets in non-small cell lung cancer (NSCLC) remains limited. In the current study, miR-223 was found to inhibit cell proliferation in vitro by CCK-8 assay, growth curves and an anchorage-independent growth assay in a Lewis lung carcinoma (LLC) cell line. miR-223 transfection in the LLC cells was observed to significantly inhibit migration and invasion, induce G2/M arrest and decrease the expression levels of Sca-1, a marker of murine stem cells. In addition, miR-223 transfection markedly suppressed AKT and ERK signaling, as well as insulin-like growth factor-1 receptor (IGF-1R)-mediated downstream signaling, pathways that are crucial for cell proliferation and invasion in NSCLC cells. Analyses in C57BL/6 mice demonstrated that miR-223 suppresses tumorigenicity in vivo. Using a luciferase activity assay and western blot analysis, IGF-1R and cyclin-dependent kinase 2 (CDK2) were identified as direct targets of miR-223. In the present study, novel cancer-related targets of miR-223 were identified and verified in a LLC cell line, indicating that miR-223 functions as a tumor suppressor, which may fine-tune the activity of the IGF-1R pathway in lung cancer. Therefore, increasing miR-223 expression may provide a novel approach for the treatment of NSCLC.

This study aimed to investigate the risk factors influencing the prognosis of patients receiving conventional fractionation radiotherapy. A retrospective analysis of clinical data from 100 patients with nasopharyngeal carcinoma receiving radiotherapy was conducted. The Chi-square test was used to screen the relevant factors and Cox multiple-factor analysis was used to investigate the risk factors influencing the survival of patients. One-factor analysis results revealed that tumor stage, tumor diameter, prescription dose completion and radiotherapy regularity are related to the prognosis of nasopharyngeal carcinoma and multiple-factor analysis results revealed that tumor stage, radiotherapy dose and radiotherapy regularity are independent risk factors influencing prognosis. The prognosis of patients with nasopharyngeal carcinoma receiving radiotherapy is related to tumor progression and an adequate dose of regular radiotherapy improves the prognosis of patients.

Artificial dural substitutes are increasingly being used in decompressive craniectomy to prevent peridural fibrosis and facilitate cranioplasty for patients with head injury. The safety of the dural substitute should be systemically evaluated. We focus on Neuro-Patch (B. Braun, Boulogne, France), a nonabsorbable substitute and commonly used by neurosurgeons.In this retrospective study, 132 patients undergoing 135 craniectomies and cranioplasties for traumatic brain injury were enrolled. We subdivided the operations into two groups on the basis of whether Neuro-Patch was used (N = 50) or not (N = 85). Risk factors of neurosurgical site infection were assessed first. Then, we compared the occurrence of infective, hemorrhagic, and hydrodynamic morbidities after craniectomy and cranioplasty between the two groups.The incidence of neurosurgical site infection after craniectomy or cranioplasty showed no intergroup difference (p = 1.000). Postoperatively, extra-axial hematoma, which consists of subdural or epidural hematoma, occurred in 9 of 50 craniectomies (18.00%) with Neuro-Patch and 3 of 85 craniectomies (3.53%) without Neuro-patch, which was significantly different (p = 0.009). The rates of hydrodynamic morbidities (subdural hygroma or cerebrospinal fluid leakage) after the procedures were similar between the two groups.The use of Neuro-Patch does not increase the incidence of neurosurgical site infection and hydrodynamic complications, including subdural hygroma and cerebrospinal fluid leakage, after decompressive craniectomy or cranioplasty for severe traumatic brain injury. However, extra-axial hematoma at the site of craniectomy is more often encountered in patients with Neuro-Patch and forms a compressive lesion on the adjacent brain.

Canada, Australia and European countries, about 25% of deaths are related to malignant diseases. Chemotherapy is a central component in the fight against cancer. It is based on various classes of compounds, among which platinum-based drugs are a unique class. cis-Diamminedichloroplatinum(II) (cisplatin), first approved for clinical use in 1978 in the U.S.A., is one of the most effective anticancer drugs currently available for the treatment of testicular, lung and bladder carcinomas. Driven by the impressive impact of cisplatin on cancer therapy, numerous analogues have been prepared and evaluated in a search for alternative active agents, leading to the discovery of another important Pt drug, carboplatin, cis-diammine(1,1cyclobutanedicarboxylato)platinum(II) in 1986. Today, carboplatin has become one of the most successful anticancer drugs after cisplatin and has received worldwide approval for treating ovarian and small lung cancers (1, 2). Carboplatin shows a spectrum of activity identical with that of cisplatin, but is much less nephrotoxic and emetic. However carboplatin is not effective in treating cancer cells resistant to cisplatin, possibly due to the same diammine carrier, suggesting that crossresistance exists between the two Pt drugs (3, 4). Therefore, the search for new potent Pt complexes possessing high antitumour activity and lack of cross-resistance continues. The so-called ‘third generation’ Pt drug, oxaliplatin, (trans-1R,2Rcyclohexane-1,2-diamine)oxalatoplatinum(II), was approved in 1999 as the first line therapy for metastatic colorectal cancer in combination with 5-fluoroural. Oxaliplatin has also shown potency in many cancer cell lines, including some cells resistant to cisplatin and carboplatin (5). Further Pt-based drugs, nedaplatin, lobaplatin and eptaplatin, have gained regionally limited approval, respectively, in Japan, China and South Korea, for the treatment of certain kinds of cancers (6). Ptbased drugs currently in clinical use are shown in Figure 1. In the meantime, the rational design of Pt anticancer compounds with specific characteristics has led to the invention of the orally available drugs satraplatin (JM216) and picoplatin (AMD473, a sterically hindered complex), see

The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred on the NS3 protein of genotype 1b in the presence of NS4A, both in culture cells and with a mouse model system. No internal cleavage products were detected with the NS3 and NS4A proteins of genotype 2a. Three potential cleavage sites were detected in the NS3 protein (genotype 1b), with IPT 402 |S being the major one. The internal cleavage requires the polyprotein processing activity of NS3 protease, but when supplemented in trans , the internal cleavage efficiency is reduced. In addition, several mutations in NS4A disrupted the internal cleavage of NS3 but did not affect polyprotein processing, indicating that NS4A contributes differently to these two proteolytic activities. Furthermore, Ile-25, Val-26, and Ile-29 of the NS4A protein, important for the NS4A-dependent internal cleavages, were also shown to be critical for the transforming activity of NS3, but mutations at these critical residues resulted only in a slight increase of HCV replicating efficiency. The internal cleavage-associated enhancement of the transforming activity of NS3 was reduced when a T402A substitution at the major internal cleavage site was introduced. The multiple roles of NS4A in viral multiplication and pathogenesis make NS4A an ideal molecular target for HCV therapy.

The phenomenon of aging populations has produced widespread health awareness and magnified the need for improved medical quality and technologies. Statistics show that ischemic heart disease is the leading cause of death for older people and people with reduced mobility; therefore, wheelchairs have become their primary means of transport. Hence, an arrhythmia-detecting smart wheelchair was proposed in this study to provide real-time electrocardiography (ECG)-monitoring to patients with heart disease and reduced mobility. A self-developed, handheld ECG-sensing instrument was integrated with a wheelchair and a lab-written, arrhythmia-detecting program. The measured ECG data were transmitted through a Wi-Fi module and analyzed and diagnosed using the human-machine interface.

Supplemental Digital Content is available in the text, Background: Whether the preoperative administration of pregabalin plays a beneficial role in controlling acute pain after hysterectomy is unknown. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the efficacy and safety of the preoperative use of pregabalin to treat acute postoperative pain following hysterectomy. Methods: In April 2017, a systematic computer-based search was conducted in the PubMed, EMBASE, Web of Science, Cochrane Library, and Google databases. RCTs comparing pregabalin with placebo in patients undergoing hysterectomy were retrieved. The primary endpoint was the visual analog scale (VAS) score with rest or mobilization at 2 h, 4 and 24 hours and cumulative morphine consumption at 2, 4, 24, and 48 hours. The secondary outcomes were complications of nausea, vomiting, sedation, and dizziness. After tests for publication bias and heterogeneity among studies were performed, the data were aggregated for random-effects models when necessary. Results: Ten clinical studies with 1207 patients (pregabalin = 760, control = 447) were finally included in this meta-analysis. Preoperative administration of pregabalin was associated with a significant reduction of VAS with rest or mobilization at 2, 4, and 24 hours after hysterectomy. Further, the preoperative administration of pregabalin was associated with a reduction in total morphine consumption at 2, 4, 24, and 48 hours after hysterectomy. The occurrence of morphine-related complications (nausea and vomiting) was also reduced in the pregabalin group. However, the preoperative administration of pregabalin was associated with an increase in the occurrence of dizziness. There was no significant difference in the occurrence of sedation. Conclusions: The preoperative use of pregabalin reduced postoperative pain, total morphine consumption, and morphine-related complications following hysterectomy. The doses of pregabalin were different, and large heterogeneity was the limitation of the current meta-analysis. Further studies should determine the optimal dose for controlling acute pain after hysterectomy.

SNP (single-nucleotide polymorphism) of rs10903129 near the TMEM (transmembrane protein) 57 locus has been associated with TC (total cholesterol) in a previous GWAS (genome-wide association study), but the association of TMEM57 rs873308 SNP and serum lipid levels has not been previously reported. The current study was undertaken to detect the association of the TMEM57 rs873308 SNP and several environmental factors with serum lipid profiles in the Han Chinese and Mulao populations. The genotypes of the TMEM57 rs873308 SNP in 865 individuals of Han Chinese and 902 participants of Mulao nationality were determined by PCR and RFLP (restriction-fragment-length polymorphism) combined with gel electrophoresis and then confirmed by direct sequencing. The T allele frequency of TMEM57 rs873308 SNP was not different between Han and Mulao (23.18% versus 25.72%, P>0.05), but different between males and females in the two ethnic groups (P

Tetracyclines and tetracycline analogues are prepared by a convergent, single-step Michael-Claisen condensation of AB precursor 1 or 2 with D-ring precursors of wide structural variability, followed by removal of protective groups (typically in two steps). A number of procedural variants of the key C-ring-forming reaction are illustrated in multiple examples. These include stepwise deprotonation of a D-ring precursor followed by addition of 1 or 2, in situ deprotonation of a D-ring precursor in mixture with 1 or 2, and in situ lithium-halogen exchange of a benzylic bromide D-ring precursor in the presence of 1 or 2, followed by warming. The AB plus D strategy for tetracycline synthesis by C-ring construction is shown to be robust across a range of different carbocyclic and heterocyclic D-ring precursors, proceeding reliably and with a high degree of stereochemical control. Evidence suggests that Michael addition of the benzylic anion derived from a given D-ring precursor to enones 1 or 2 is quite rapid at -78 degrees C, while Claisen cyclization of the enolate produced is rate-determining, typically occurring upon warming to 0 degrees C. The AB plus D coupling strategy is also shown to be useful for the construction of tetracycline precursors that are diversifiable by latter-stage transformations, subsequent to cyclization to form the C ring. Results of antibacterial assays and preliminary data obtained from a murine septicemia model show that many of the novel tetracyclines synthesized have potent antibiotic activities, both in bacterial cell culture and in vivo. The platform for tetracycline synthesis described gives access to a broad range of molecules that would be inaccessible by semisynthetic methods (presently the only means of tetracycline production) and provides a powerful engine for the discovery and, perhaps, development of new tetracycline antibiotics.

To evaluate the clinical value of serum CA19-9 levels in predicting the respectability of pancreatic carcinoma according to receiver operating characteristic (ROC) curve analysis.Serum CA19-9 levels were measured in 104 patients with pancreatic cancer which were possible to be resected according to the imaging. ROC curve was plotted for the CA19-9 levels. The point closest to the upper left-hand corner of the graph were chosen as the cut-off point. The sensitivity, specificity, positive and negative predictive values of CA19-9 at this cut-off point were calculated.Resectable pancreatic cancer was detected in 58 (55.77%) patients and unresectable pancreatic cancer was detected in 46 (44.23%) patients. The area under the ROC curve was 0.918 and 95% CI was 0.843-0.992. The CA19-9 level was 353.15 U/mL, and the sensitivity and specificity of CA19-9 at this cut-off point were 93.1% and 78.3%, respectively. The positive and negative predictive value was 84.38% and 90%, respectively.Preoperative serum CA19-9 level is a useful marker for further evaluating the resectability of pancreatic cancer. Obviously increased serum levels of CA19-9 (353.15 U/mL) can be regarded as an ancillary parameter for unresectable pancreatic cancer.

Background The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. Methods We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of $13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. Results Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were $9,794, $9,335, and $7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. Conclusion In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.

Background/Aim: Nephropathy after ingestion of Chinese herbs is known as a rapidly progressive form of interstitial renal fibrosis after a slimming regimen containing aristolochic acid that was identified first in Belgium. Intake of traditional Chinese herbal medicines is very popular in Taiwan. So we looked for similar cases in our hospital. Methods: From 1994 to 1998, we observed 20 Taiwanese patients who underwent renal biopsy for rapidly progressive renal failure of unknown origin. The medical history of these patients gave no clue to the origin of renal impairment, except for the administration of Chinese herbs before the development of renal failure in all cases. Results: Although these patients took herbal medications from various sources for different purposes, their renal biopsy specimens showed strikingly similar histological patterns: extensive paucicellular interstitial fibrosis and tubular atrophy, but the glomeruli were apparently intact. They also had similar clinical features, such as a nearly normal blood pressure, obvious anemia, insignificant edema, low-grade proteinuria, and glucosuria. The renal function declined rapidly in most cases; 15 patients underwent dialysis within 3 months of renal biopsy, and 7 patients received emergency dialysis when they first came to our hospital. On clinical and morphological grounds, the nephropathy in our patients appears similar to Chinese herb nephropathy. Conclusions: Because of the diversity of the herbal regimens used, in addition to aristolochic acid, other unidentified phytotoxins may also play a role in this particular disease entity. There is a strong relation between rapidly progressive interstitial renal fibrosis and the consumption of Chinese herbs.