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Immune checkpoint inhibitors (ICIs) have been widely used in the treatment of various types of cancers worldwide, which is the most significant breakthrough in cancer therapy in recent years. Despite their excellent benefits in anti-tumor efficacy, a subset of patients will experience various autoimmune toxicities, termed as immune-related adverse events (irAEs), which can affect almost any organ systems, but related to the pulmonary and pancreatic islets simultaneously has rarely been reported and discussed.In this report, we describe a rare case of a 65-year-old man patient with advanced small cell lung cancer (SCLC) who suffered general fatigue, dry cough, chest tightness, shortness of breath and polyuria-polydipsia syndrome after the eighth cycle treatment with programmed cell death ligand-1 (PD-L1) inhibitor durvalumab.According to the results of laboratory tests, chest computed tomography and multidisciplinary discussion, the patient was eventually diagnosed with ICI-related pneumonitis and autoimmune diabetes mellitus.Multiple daily subcutaneous insulin injections, empirical anti-infection and immunosuppression treatment with corticosteroids were performed.After the cessation of durvalumab and comprehensive treatment, the patient's respiratory condition was relieved significantly and his blood glucose was well controlled with insulin therapy.With the widespread use of ICIs, there will be more patients developing these rare but severe irAEs in clinical practice, which should attract great attention of both clinicians and patients.

During the processing of mango, a huge amount of peel is generated, which is environmentally problematic. In the present study, a compressional-puffing process was adopted to pretreat the peels of various mango cultivars, and then the bioactive compounds of mango peels were extracted by water or ethanol. The phenolic compound compositions as well as the free radical-scavenging, anti-inflammatory, and antibacterial activities of water extract (WE) and ethanol extract (EE) from nonpuffed (NP) and compressional-puffed (CP) mango peels were further evaluated. It was found that compressional-puffing could increase the yield of extracts obtained from most mango varieties and could augment the polyphenol content of extracts from Jinhwang and Tainoung number 1 (TN1) cultivars. The WE and EE from TN1 exhibited the highest polyphenol content and the greatest free radical-scavenging activities among the mango cultivars tested. Seven phenolic compounds (gallic acid, pyrogallol, chlorogenic acid, p-hydroxybenzoic acid, p-coumaric acid, ECG, and CG) were detected in CPWE (compressional-puffed water extract) and CPEE (compressional-puffed ethanol extract) from TN1, and antioxidant stability of both CPWE and CPEE was higher than that of vitamin C. Further biological experiments revealed that CPEE from TN1 possessed the strongest anti-inflammatory and antibacterial activities, and thus it is recommended as a multibioactive agent, which may have applications in the food, cosmetic, and nutraceutical industries.

This study investigates a new semi-fixed-abrasive, ultra-fine finishing method for optical glass using a magneticcompound fluid (MCF) wheel. This MCF wheel generates a thin, uniform MCF slurry layer on the entire circumferentialsurface of a ring-shaped permanent magnet placed between two non-magnetic plates. The MCF slurry is composed ofnano-sized magnetite particles, micron-sized iron particles, several 10 μm-sized α-cellulose fibres and sub-micron-sizedabrasive particles that react to the magnetic field. Following modifications to the design of the MCF, experiments wereconducted to evaluate the performance of the modified wheel in spot-polishing fused silica glass. This paper describes themodifications to the MCF wheel and the experimental setup used to measure its performance. The improvement of themodified wheel over the unmodified wheel in terms of material removal and surfaces roughness is experimentallyconfirmed. The effects of the wheel rotational speed and the clearance between the wheel and the workpiece on materialremoval and the workpiece surface roughness are investigated. The polishing forces are measured, the structure of the MCFslurry is examined and the magnetic field distribution is analysed. A model of material removal in polishing with themodified MCF wheel is developed. The results indicate the following: (1) more material was removed, i.e., greater spotdepths, and better surfaces were obtained in the regions that were near the edges of the magnet; (2) the modified MCF wheelperformed much better than the unmodified wheel in terms of material removal and surface roughness, e.g., 3.1 μm vs. 1.7μm for the maximum spot depth, 0.04 mm3 vs. 0.0088 mm3 for the volume of material removed and Ra = 5.624 nm vs.14.67 nm for the surface roughness; (3) a better work surface and greater material removal were obtained with smallerworking clearances and higher wheel rotational speeds.

A kind of zirconia-coated carbonyl-iron-particles (CIPs), which show long-time stability against aqueous, is installed in magnetic compound fluid (MCF) to polish PMMA. Performance (normal polishing force and surface roughness) of zirconia-coated CIP based MCF slurry with different CIP concentrations is investigated. For comparison, the performances of the conventional non-coated CIP (i.e., HQ) based MCF slurry and MRF slurry in which DI-water is employed instead of MF are also examined. In the presence of Al2O3 abrasive particles, the use of zirconia-coated CIP based MCF slurry can not result in better polishing performances compared with conventional HQ CIP based MCF slurry; In the absence of Al2O3 abrasive particles, higher normal polishing force and smoother work-surface were obtained with the zirconia-coated CIP based MCF slurry rather than the MRF slurry; For the zirconia-coated CIP based MCF slurry without abrasive particles, the concentration of zirconia-coated CIP should be less than a certain value (in the current work, 70 wt. %), otherwise MCF slurry shows bad particle dispersion and is easily dried, resulting in the loss of its polishing ability.

Ultrasonic vibration assisted processing is well known for the improvement in machined surface quality and processing efficiency due to the reduced forces and tribology-generated heating when grinding hard-brittle materials. We transplanted this philosophy to chemo-mechanical fixed abrasive polishing of optical glass, namely fused silica, in an attempt to improve surface roughness and/or material removal rate. Experiments were conducted to elucidate the fundamental characteristics of chemo-mechanical fixed abrasive polishing of fused silica in the presence and absence of ultrasonic vibration on a setup with an in-house built gadget. The experimental results show that ultrasonic vibration assisted chemo-mechanical fixed abrasive polishing can yield increased material removal rate while maintaining the surface roughness of manufactured optics compared to conventional fixed abrasive polishing without ultrasonic vibration. The mechanism of material removal in fixed abrasive polishing was also delved. We found that the glass material is removed through the synergic effects of chemical and mechanical actions between abrasives and glass and the resultant grinding swarf contains ample Si element as well as Ce element, standing in stark contrast to the polisher that contains abundant Ce element and minor Si element.

The present work deals with the simulation investigation of chip formation in ultrasonically assisted grinding (UAG) of SiC ceramics with single diamond abrasive grain in order to reveal the material removal mechanism in UAG of SiC materials. In simulation, smooth particle hydrodynamic (SPH）method coupling FEM modeling is employed to overcome the large material distortions that occur in the simulation analysis of single point cutting process when only the finite element method (FEM) is used. The abrasive-grain is modeled with finite element while the target workpiece is modeled by SPH particles. The simulation results revealed that normal and tangential forces in UAG are smaller compared to those in conventional grinding (CG) without ultrasonic vibration. The scratch profiles shows that the cutting path appears to be sinusoidal when ultrasonic vibration is introduced in grinding process, which leads to a higher material removal rate than that without ultrasonic vibration.

This paper aims to develop an alternative novel technique for the high efficiency and ultrafine surface finishing of fused silica glass. A semi-fixed abrasive tool named MCF (magnetic compound fluid) wheel is produced by distributing a certain volume of MCF slurry uniformly over the whole circumference surface of ring-shaped permanent magnets. An experimental rig is constructed in house followed by experimental investigations involving effects of the MCF wheel construction and process parameters on the material removal and work-surface roughness. As a result, the performance of the developed MCF wheel in the surface finishing of fused silica glass has been confirmed, and the appropriate wheel construction and process parameters have been determined in terms of the material removal rate, the flatness of polishing area and the surface roughness, showing an extremely smooth work-surface with surface roughness of Ra0.92nm has been achieved successfully in the current work.

Gelatin has been broadly utilized in the food, pharmaceutical, photographic, cosmetic and packaging industries, and there is also huge potential for novel applications of gelatin in the fields of biotechnology and biomedicine. In the present study, we extracted gelatin from fish processing waste, i.e., scale of tilapia, by a combined method of extrusion-pretreatment and hot water extraction. The extrusion-pretreatment process increases the extraction yield of gelatin. Three gelatins (FS2: preconditioning with double-distilled water (ddH2O) before extrusion, FS12: preconditioning with citric acid solution before extrusion, FS14: preconditioning with acetic acid solution before extrusion) were obtained and all of them enhanced cell adhesion, cell growth, and wound healing in HaCaT cells and protected HaCaT cells from H2O2-induced cellular damage. Among FS2, FS12, and FS14, FS12 exhibited the most pronounced enhancement of cell adhesion, cell growth, and wound healing in HaCaT cells, and thus it may have potential as an effective natural raw material in cell therapies for cutaneous wounds and for reducing H2O2-induced oxidative damage of cells. In additional experiments, it was found that phosphorylations of Akt and mTOR are involved in the signaling pathway activated by FS2, FS12, and FS14 in HaCaT cells.

Independent studies have shown that in node negative breast cancer patients less than 71 years, the proliferation marker mitotic activity index (MAI) is the strongest, most well reproducible prognosticator and chemotherapy success predictor. The MAI overshadows the prognostic value of tubule formation, nuclear atypia and thereby grade. An often used crude mitotic impression is much less prognostic than the MAI; strict adherence to the MAI protocol is therefore important. The prognostic value of the MAI is age dependent: although patients with a MAIor = 10 always have a poor prognosis irrespective of age, a low MAI (10) loses its favourable prognostic association in women70 years. PPH3 counts are prognostically stronger than the MAI, and markers such as Cyclin-B and E2FR are promising, but must be validated. Compared with commercial prognostic gene expression signatures, the MAI is at least as strong prognostically, has far fewer false positive results and as such should be included as an independent feature in any node negative breast cancer pathology report.

BACKGROUND Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles. Progression-free survival (PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score). Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC. TRIAL REGISTRATION ClinicalTrials.gov. (Identifier: NCT01780181).

Background Traditional Chinese medicine (TCM) is a widely applied complementary therapy for cancer patients. It can reduce the chemical drugs induced toxic effects to improve the quality of life (QOL). This study applies the highest quality of clinical trial methodology to examine the role of TCM in improving QOL of postoperative non-small-cell lung cancer patients. Methods and design This study is a multi-center, randomized, placebo-controlled, double-blind trial. Four hundred eighty patients will be recruited into seven different research centers in China. These patients that meet the inclusion criteria will be randomized into either a treatment group or a placebo group. Each group will receive treatments of 3-weekly chemotherapy with TCM or placebo for four cycles. The primary outcome will involve the evaluation of QOL and the secondary outcome assessments will include two-year disease-free survival rate and disease-free survival. Other efficacy assessments are changes of TCM symptoms and toxicity. Side effects and safety profile of the therapy would be evaluated at the same time. The investigators expect that TCM therapy combined with chemotherapy is superior to chemotherapy solely in terms of QOL improvement and disease-free survival extension. "Intention-to-treat" analysis will include all randomized participants. Discussion The results from the clinical trial will provide evidence for the effectiveness of chemotherapy combined with or without TCM in QOL of postoperative NSCLC patients. Trial registration Clinical Trials.gov (Identifier: NCT01441752).