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Purpose: This study was designed to construct and validate a nomogram that was available for predicting cancer-specific survival (CSS) in patients with pulmonary large-cell neuroendocrine carcinoma (LCNEC). Patients and Methods: Using the US Surveillance, Epidemiology, and End Results (SEER) database, we identified patients pathologically diagnosed as LCNEC from 1975 to 2016. Univariate and multivariate Cox regression was conducted to assess prognostic factors of CSS. A novel nomogram model was constructed and validated by the concordance index (C-index), calibration curves and decision curve analysis (DCA). Results: A total of 624 LCNEC patients were enrolled. Five prognostic factors for CSS were identified and merged to establish nomograms. In the training and validation cohorts, calibration curves displayed the nomogram predictions are in a good agreement with the actual survival. The C-Index of the training and validation cohorts were both higher than 0.8, and the DCA results showed that the nomogram has clinical validity and utility. Conclusion: The proposed nomogram resulted in accurate CSS prognostic prediction for patients with LCNEC. [ABSTRACT FROM AUTHOR]

ABSTRACT Bisphenol-A polycarbonate (BAPC) was synthesized by solid-state polymerization (SSP) using a semicrystalline prepolymer crystallized by antisolvent method. The antisolvent crystallization was investigated as a function of antisolvent types using X-ray diffraction (XRD), different scanning calorimetry (DSC), and scanning electron microscopes (SEM). The results showed antisolvent types had a significant effect on the crystallization of BAPC. Prepolymer induced by acetone as an antisolvent gained a higher crystallinity of 37.0%, more uniform particle size, and mature crystal structure compared with the samples crystallized by methanol and ethanol. Then crystallization of BAPC by acetone was carried out at crystallization temperature in the range of 40-80 °C for 1-5 h. A high crystallinity of 42.0% was acquired with the crystallization conducted at 70 °C for 2 h. Prepolymer with appropriate crystallinity of 37.8% resulted in high-molecular-weight polymer of 57,411 via SSP due to the effect of crystallinity and plasticization of residual solvent. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43636. [ABSTRACT FROM AUTHOR]

Manypeptide-based therapeutics have short circulatory half-lives.We report here that the pharmacokinetics of an anti-HIV peptide drugenfuvirtide (ENF) can be dramatically improved by a chemical glycosylationapproach. A set of glycosylated ENFs with varying glycosylation sitesand glycan structures were synthesized. Among these, a sialic acid-introducedpeptide (SL-ENF) demonstrated a 15-fold extended half-life in ratsrelative to ENF (T1/2: 23.1 vs 1.5 h),and its antiviral potency was comparable to that of ENF (EC50: 2 vs 3 nM). SL-ENF bound to a functional fragment of the HIV fusogenicprotein gp41 and formed complexes with high affinity and α-helicity,revealing the mechanism behind its potent antiviral activity. Becauseit is widely accepted in biology that glycosylation protects proteinsfrom denaturation and proteases, our approach may be useful for thedevelopment of novel protein and peptide drugs with enhanced pharmaceuticalproperties. [ABSTRACT FROM AUTHOR]

Objective: Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation., Methods: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis., Results: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae., Conclusion: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wu, Wu, He, Chang, Deng, Zhou, Chen and Zhang.)

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has emerged as a significant obstacle in managing patients with EGFR-mutant non-small-cell lung cancer (NSCLC), necessitating the exploration of novel therapeutic approaches. Tanreqing injection (TRQ) is a kind of Chinese patent medicine known for its heat-clearing and detoxifying properties. Studies have shown a correlation between tumor drug resistance and enrichment of cancer stem cells (CSCs). We aim to investigate the feasibility of TRQ enhancing sensitivity to gefitinib by targeting CSCs and reactive oxygen species (ROS). In our study, TRQ significantly inhibited cell proliferation in gefitinib-resistant non-small-cell lung cancer (NSCLC) models including 2D cell lines, 3D cell spheres, tumor-bearing animal and organoids. Compared with the gefitinib group alone, addition of TRQ elevated ROS levels, attenuated upregulation of the protein levels of sex-determining region Y-box 2 (SOX2) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) induced by gefitinib treatment, and inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Scavenging ROS could restore tumor stemness, attenuate the inhibitory effect on the phosphorylation of STAT3, and promote cell proliferation. These results suggested that TRQ could enhance sensitivity of NSCLC models to gefitinib, providing a new combined treatment strategy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Although acupuncture has been recommended for alleviating cancer pain by clinical guidelines, the level of the supporting evidence needs to be improved. A pragmatic randomised controlled trial (pRCT) in a hospital setting would provide real-world assessments of the overall clinical effects of acupuncture. This pilot trial aims to explore the feasibility and provide data for sample size calculations for a pRCT evaluating the effectiveness of acupuncture as an adjunctive therapy to routine medical care for cancer pain., Methods and Analysis: Thirty patients with cancer admitted to the oncology department with moderate or severe pain will be recruited. Participants will be randomised at a ratio of 1:1 to the adjunctive acupuncture group or a control group which receives routine pain management without acupuncture. The standardised section of the acupuncture protocol will be developed based on the results of reviews of the literature, recommendations in clinical guidelines and interviews with clinical experts. The acupuncturist will be allowed to tailor the protocol according to the individual situation of each participant. Primary outcomes relevant to the feasibility of conducting a fully powered trial include: numbers and proportions of participants recruited, screened, consented and randomised; numbers and reasons for withdrawals and dropouts; numbers and types of adverse events; feasibility of implementing the trial procedures; evaluation of the comprehensiveness and ease-of-use of the case report form. Secondary outcomes are clinical measurements of the effectiveness of the treatment that are intended for use in the full-scale trial. Analysis of feasibility will be descriptive and pain intensity measures will be analysed using mixed-effects regression., Ethics and Dissemination: Ethics approval was obtained from the Institutional Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (approval no: Z2017-184-01) and RMIT University Human Research Ethics Committee (reference no: 21361). Results will be disseminated in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls., Trial Registration Number: ChiCTR1800017023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)