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Bacterial infection is among the most common diseases that threaten human health. Antibiotics are effective in treating bacterial infections. However, the overuse of antibiotics will lead to an increase in bacterial resistance. To reduce the overuse of antibiotics and improve the effective use of antibiotics through slow release, silk fibroin (SF)/polyethylene oxide (PEO) nanofiber membranes with different SF and PEO proportions were prepared by electrospinning. The ecofriendly solvent ethanol solution was used for electrospinning for better protection of antibiotic activity. The SEM showed that the surface of SF/PEO (2:8) and SF/PEO (3:7) was smoother and more uniform. With the increase of SF content, the thermal stability and hydrophilicity of SF/PEO nanofiber membranes were improved. The SF/PEO (3:7) nanofiber membrane had the best mechanical property and its maximum stress and strain were 4.6 1 ± 0.24 MPa and 16.36 ± 0.41%, respectively. Based on these good properties, SF/PEO (3:7) nanofiber membrane was chosen for loading and releasing gentamicin sulfate (GS). The fabricated (GS)/SF/PEO (3:7) nanofiber membrane exhibited good release efficiency and showed the good antibacterial activity against Staphylococcus aureus and Escherichia coli. These investigations indicated the GS/SF/PEO (3:7) nanofiber membrane (GS/SF/PEO) has a great potential for application in antibacterial materials.

BACKGROUND Oleanolic acid (OA) is a pentacyclic triterpenoid compound that is present at high levels in olive oil and has several promising pharmacological effects, such as liver protection and anti-inflammatory, antioxidant, and anticancer effects. The purpose of the present study was to assess whether OA treatment affects gut health compared to a control condition, including gut microbiota and intestinal epithelial immunity. RESULTS Illumina MiSeq sequencing (16S rRNA gene) was used to investigate the effect of OA on the microbial community of the intestinal tract, while Illumina HiSeq (RNA-seq) technology was used to investigate the regulatory effect of OA on gene expression in intestinal epithelial cells, which allowed for a comprehensive analysis of the effects of OA on intestinal health. The results showed that the consumption of OA initially controlled weight gain in mice and altered the composition of the gut microbiota. At the phylum level, OA significantly increased the relative abundances of cecum Firmicutes but decreased the abundance of Actinobacteria, and at the genus level it increased the relative abundance of potentially beneficial bacteria such as Oscillibacter and Ruminiclostridium 9. Oleanolic acid treatment also altered the expression of 12 genes involved in the Kyoto Encyclopedia of Genes and Genomes（KEGG）pathways of complement and coagulation cascades, hematopoietic cell lineage, and leukocyte transendothelial migration in intestinal epithelial cells to improve gut immunity. CONCLUSION Intake of OA can contribute beneficial effects by optimizing gut microbiota and altering the immune function of intestinal epithelial cells, potentially to improve intestinal health status. © 2021 Society of Chemical Industry.

Updated and expert-quality knowledge bases are fundamental to biomedical research. A knowledge base established with human participation and subject to multiple inspections is needed to support clinical decision making, especially in the growing field of precision oncology. The number of original publications in this field has risen dramatically with the advances in technology and the evolution of in-depth research. Consequently, the issue of how to gather and mine these articles accurately and efficiently now requires close consideration. In this study, we present OncoPubMiner (https://oncopubminer.chosenmedinfo.com), a free and powerful system that combines text mining, data structure customisation, publication search with online reading and project-centred and team-based data collection to form a one-stop ‘keyword in–knowledge out’ oncology publication mining platform. The platform was constructed by integrating all open-access abstracts from PubMed and full-text articles from PubMed Central, and it is updated daily. OncoPubMiner makes obtaining precision oncology knowledge from scientific articles straightforward and will assist researchers in efficiently developing structured knowledge base systems and bring us closer to achieving precision oncology goals.

Purpose Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are being used for the first-line treatment of metastatic clear cell renal cell carcinoma (mccRCC). Here, we set out to explore associations between genomic statuses, gene expression clusters and clinical outcomes of mccRCCs upon the application of VEGFR-TKIs. Methods A retrospective study of 56 patients with mccRCC who received first-line VEGFR-TKIs and who underwent genomic profiling and whole transcriptome sequencing was conducted. Survival analysis was carried out using log-rank tests and Cox regression analyses, and Kaplan–Meier curves were plotted. Clustering was performed using the K-means method. Results Among the 56 patients tested, 17 harbored DNA Damage and Repair (DDR) pathway alterations and 35 VHL mutations. The median progression-free survival (PFS) rates for the DDR and VHL alteration groups were 18 and 18 months, respectively, compared with 14 and 10 months for the nonmutant groups. DDR mutations, VHL mutations and co-mutations were identified as prognostic biomarkers of a longer PFS (p = 0.017, 0.04, 0.014). K-means clustering of expressed transcripts revealed three clusters of 40 patients: C_1, C_2 and C_3. The C_1 cluster exhibited the best PFS and objective response rate (ORR) to TKI therapy, with the highest proportion of DDR and VHL mutations. Further analysis of the tumor immune environment revealed that the C_1 cluster was enriched in activated CD8 T cells and effector CD4 T cells, whereas the C_2 cluster was enriched in eosinophils, mast cells and DC cells and, thus, in immunosuppressive cells. Conclusions We found that patients with mccRCC harboring DDR and VHL alterations were more likely to benefit from first-line VEGF-TKI systemic therapy than patients with wild-type disease. In addition, we found that a three-cluster prognostic model based on gene expression can predict PFS and ORR, which was well-matched with activated TIL infiltration.

Renal cell carcinoma (RCC) is a lethal urinary malignancy. Circular RNAs (circRNAs) contribute to the malignant phenotype and progression of several types of human cancers, including RCC. In this study, we identified relatively low hsa_circ_0060927 (circCYP24A1) expression in RCC tissue through high-throughput sequencing and RT–qPCR. Fluorescence in situ hybridization (FISH) was used to validate the expression and subcellular localization of circCYP24A1 in RCC tissues. CCK-8, Transwell, EdU, and wound-healing assays indicated that circCYP24A1 overexpression inhibited the proliferation, invasion, and migration of RCC cells. Dual-luciferase reporter, RNA immunoprecipitation (RIP), FISH, and RNA-pulldown assays verified that circCYP24A1 inhibited RCC progression by sponging miR-421, thus inducing CMTM-4 expression. Xenograft assays and metastasis models further indicated that circCYP24A1 significantly inhibited the metastasis and proliferation of RCC cells in vivo. Taken together, circCYP24A1 is a prognosis-related circRNA in RCC that functions through the circCYP24A1/miR-421/CMTM-4 axis to modulate RCC progression.

Purpose To report the clinicopathological features and mid- to long-term oncologic results of Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion renal cell carcinomas (Xp11.2 translocation RCCs) in a single large-volume centrecentre. Methods Clinical and follow-up data of 46 patients who were diagnosed with Xp11.2 translocation RCC and underwentunderwent surgical intervention were retrospectively reviewed. Result Forty-six Xp11.2 translocation RCC patients were identified from 4218 renal tumour patients who were underwentunderwent surgery in our centrecentre from Jan. 2014 to Apr. 2020. The incidence of Xp11.2 translocation RCCs in our centre was 1.09%. During a median follow-up period of 30.5 months, 4 patients died of the disease. The total median overall survival and cancer specific survival were 30.0 months and 24.0 months, respectively. The 1-year, 3-year and 5-year OS rates were 97.4%, 88.8%, and 88.8%, respectively. In multivariable analysis, displaying symptoms when diagnosed (p = 0.019), lymph node metastasis (p = 0.002) and distal metastasis (p = 0.020) were identified as risk factors for poor prognosis. Conclusion Xp11.2 translocation RCC is a type of renal cell carcinoma with a relatively low incidence and various prognoses. Early-stage Xp11.2 translocation RCCs have a similar prognosis to most typical RCCs, but late-stage Xp11.2 translocation RCCs can lead to poor oncological outcomes.

This study was designed to evaluate the role and expression of MEK5 signalling in clear cell renal cell carcinoma (ccRCC) and to determine the relevance of MEK5 and mTOR signalling in ccRCC.The expression of MEK5 was compared between ccRCC and normal tissues using the ONCOMINE and TCGA databases. MEK5 expression was evaluated in 14 human ccRCC samples. CCK8, wound-healing, and clone formation assays were performed to examine the cell proliferation, migration, and clone formation abilities of ccRCC cells treated with MEK5 and the inhibitor BIX02189. Furthermore, Western blotting was performed to verify the regulation and influence of MEK5 on the mTOR signalling pathway. Finally, a murine subcutaneous tumour model was constructed, and the effect and safety of BIX02189 were evaluated in vivo.The ONCOMINE and TCGA databases indicated that MEK5 expression in ccRCC was significantly higher than that in normal tissues, which was further confirmed in clinical specimens. MEK5 knockdown markedly inhibited ccRCC cell proliferation, colony formation, and migration, whereas MEK5 overexpression resulted in the opposite results. Western blotting revealed that overexpression of MEK5 could further activate the mTOR signalling pathway. Moreover, the MEK5 inhibitor BIX02189 significantly inhibited cell proliferation, arrested the cell cycle in the G0/G1 phase, induced apoptosis, and effectively inhibited cell migration and clone formation. BIX02189 also showed an excellent antitumor effect and a favourable safety profile in murine models.MEK5 expression was aberrantly increased in ccRCC, which activated the mTOR signalling pathway and regulated cell proliferation, cell cycle progression, migration, and clone formation in ccRCC. Targeted inhibition of MEK5 represents a promising new strategy in patients with ccRCC.

Photothermal therapy is a promising treating method for cancers since it is safe and easily controllable. Black phosphorus (BP) nanosheets have drawn tremendous attention as a novel biodegradable thermotherapy material, owing to their excellent biocompatibility and photothermal properties. In this study, silk fibroin (SF) was used to exfoliate BP with long-term stability and good solution-processability. Then, the prepared BP@SF was introduced into fibrous membranes by electrospinning, together with SF and polylactic-co-glycolic acid (PLGA). The SF/PLGA/BP@SF membranes had relatively smooth and even fibers and the maximum stress was 2.92 MPa. Most importantly, the SF/PLGA/BP@SF membranes exhibited excellent photothermal properties, which could be controlled by the BP@SF content and near infrared (NIR) light power. The temperature of SF/PLGA/BP@SF composite membrane was increased by 15.26 °C under NIR (808 nm, 2.5 W/cm2) irradiation for 10 min. The photothermal property of SF/PLGA/BP@SF membranes significantly killed the HepG2 cancer cells in vitro, indicating its good potential for application in local treatment of cancer.

To report our preliminary results of thermal ablation, including microwave and radiofrequency ablation assisted laparoscopic partial nephrectomy for cT1b renal tumors.A total of 56 patients with cT1b renal tumors who underwent microwave ablation or radiofrequency ablation assisted laparoscopic partial nephrectomy between January 2014 and May 2018 were enrolled. Thirty of them underwent microwave ablation assisted laparoscopic partial nephrectomy (MWA-LPN group), and the other 26 received radiofrequency ablation assisted laparoscopic partial nephrectomy (RFA-LPN group). Baseline, perioperative and follow-up data were compared between the two groups.There were no statistical differences with respect to patients' gender, age, tumor size, RENAL score, BMI and estimated glomerular filtration rate between the MWA-LPN and RFA-LPN group, nor were any differences observed in warm ischemia time, post-operative complications and hospital stay. Patients in the MWA-LPN group had shorter median operative time (Thermal ablation assisted laparoscopic partial nephrectomy is a safe, effective nephron-sparing treatment which provides acceptable results for selective cT1b renal tumors.

High pathologic tumor-node-metastasis (pTNM) stage grade or Fuhrman grade indicates poor oncological outcome in renal cell carcinoma (RCC). Early diagnosis and screening of these RCCs and adjust surgical planning accordingly are greatly beneficial to patients. Raman spectroscopy is a highly specific fingerprint spectrum on molecular level, pretty appropriate for label-free and noninvasive cancer diagnosis. In this work we established a Raman spectrum-based supporting vector machine (SVM) model to accurately ex vivo distinguish human renal tumor from normal tissues and fat with an accuracy of 92.89%. The model can also be used to determine tumor boundary, showing consistent results to pathological staining analysis. This method can be additionally used to accomplish the classification purposes of renal tumor subtypes and grades with an accuracy of 86.79% and 89.53%, respectively. Therefore, we prove that Raman spectroscopy has great potential in the rapid and accurate clinical diagnosis of renal cancers.

Gemcitabine (GEM)-based chemotherapy is a commonly used treatment for pancreatic cancer. However, acquired drug resistance, a major problem in pancreatic cancer treatment, causes a reduction in the survival rate of patients with cancer. In this study, we attempted to reveal the molecular mechanism of GEM resistance. Our data showed that GEM treatment inhibits cell growth, induces apoptosis, and activates autophagy via the AMP-activated protein kinase (AMPK) pathway. The combination of GEM treatment and AMPK knockdown resulted in a dramatic increase of apoptosis and inhibition of autophagy. Additionally, inhibition of mammalian target of Rapamycin induced autophagy. Our findings show the potential therapeutic implications of the combined treatment with GEM and AMPK inhibitors for pancreatic cancer.

We report a rare case of culture negative L4-L5 discitis and epidural abscess in an immunocompetent child who had dry cupping therapy performed to treat low back strain. The causative pathogen was identified as Stenotrophomonas maltophilia by shotgun metagenomic sequencing of spinal cord aspirate after more than one month of unsuccessful empirical treatment with 6 different antibiotics. The patient was successfully treated with Sulfamethoxazole-trimethoprim and minocycline. Cupping therapy is a very popular medical procedure widely used in China, but the potential risk for severe infections such as discitis and epidural abscess described in this case should be recognized. Keywords: Stenotrophomonas maltophilia, Discitis, Epidural abscess, Shotgun metagenomic sequencing, Dry cupping therapy

Background. Due to the redundant information contained in multichannel electroencephalogram (EEG) signals, the classification accuracy of brain-computer interface (BCI) systems may deteriorate to a large extent. Channel selection methods can help to remove task-independent electroencephalogram (EEG) signals and hence improve the performance of BCI systems. However, in different frequency bands, brain areas associated with motor imagery are not exactly the same, which will result in the inability of traditional channel selection methods to extract effective EEG features. New Method. To address the above problem, this paper proposes a novel method based on common spatial pattern- (CSP-) rank channel selection for multifrequency band EEG (CSP-R-MF). It combines the multiband signal decomposition filtering and the CSP-rank channel selection methods to select significant channels, and then linear discriminant analysis (LDA) was used to calculate the classification accuracy. Results. The results showed that our proposed CSP-R-MF method could significantly improve the average classification accuracy compared with the CSP-rank channel selection method.

Background Many upper respiratory pathogens cause similar symptoms. In China, routine molecular tests for upper respiratory pathogens are not widely performed and antibiotics abuse in treating upper respiratory tract infections (URTIs) is a major public health concern. Methods We performed qualitative real-time PCR tests to detect common upper respiratory tract pathogens including 9 viruses and 3 bacteria in 1221 nasopharyngeal swabs from patients with fever and influenza-like symptoms in a Chinese city. A quantitative real-time PCR was also performed to measure the bacterial density of the colonizing Streptococcus pneumoniae in these samples. Results We found very diverse pathogens including 81.7% viruses, 11.6% bacteria and 6.7% mixed viruses and bacteria. S. pneumoniae colonization was found in 8.0% of the cases but most of them had low bacterial density (Mean = 3.9 log cfu/ml). We also discovered an increase of S. pneumoniae colonization frequency (but not the density) in patients with detectable upper respiratory tract pathogens, in a pathogen variety-dependent manner. Conclusions Our study provided strong evidence against empiric antibiotic use for treating URTIs, and highlighted a strong need for improving the diagnostic capacity for URTIs by using more molecular testing in China.

Background Certain early-phase clinical trials have suggested that bone marrow-derived stem cell transplantation might improve left ventricular function in patients with non-ischaemic dilated cardiomyopathy (NIDCM), whereas others trials have revealed no benefit from this approach. We sought to evaluate the therapeutic effects of bone marrow-derived stem cell therapy on NIDCM. Methods We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases (through February 2016) for randomised controlled clinical trials that reported on bone marrow-derived stem cell transplantation for patients with NIDCM with a follow-up period ≥12 months. The co-primary endpoints were changes in mortality rate and left ventricular ejection fraction (LVEF); the secondary endpoints were changes in the 6-minute-walk test (6MWT) and left ventricular chamber size. Seven trials involving bone marrow-derived stem cell therapy that included 482 patients satisfied the inclusion and exclusion criteria. Results Subjects who received bone marrow-derived stem cell therapy exhibited a significant reduction in mortality rate (19.7% in the cell group vs. 27.1% in the control group; 95% confidence interval (CI) –0.16 to –0.00, I2 = 52%, p = 0.04). Bone marrow-derived stem cell therapy tended to produce LVEF improvement within 6 months (1.83% increase; 95% CI –0.27 to 3.94, I2 = 74%, p = 0.09) and significantly improved LVEF after mid-term (6–12 months) follow-up (3.53% increase; 95% CI 0.76 to 6.29, I2 = 88%, p = 0.01). However, this therapy produced no significant benefit in the 6MWT (p = 0.18). Finally, the transplantation of increased numbers of stem cells resulted in no observable additional benefit with respect to LVEF. Conclusions Bone marrow-derived stem cell therapy might have improved prognoses and appeared to provide moderate benefits in cardiac systolic function at mid-term follow-up. However, this therapy produced no observed improvement in exercise tolerance.