Clinical efficacy and safety of Kanglaite injection, adjuvant cemcitabine and cisplatin chemotherapy for advanced non-small-cell lung cancer: A systematic review and meta-analysis

Purpose: To investigate the effectiveness and safety of the combination of Kanglaite injection (KLTi) and gemcitabine and cisplatin (GP) chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods: PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wan-Fang, CBM, and CQVIP were comprehensively searched from January 2010 till November 2020. Randomized controlled trials (RCTs) of KLTi plus GP in the treatment of NSCLC were selected and assessed for inclusion. Review Manager 5.3 software was used for meta-analysis.Results: Twenty-five RCTs on advanced NSCLC examined the inclusion criteria. The meta-analysis showed that compared with GP chemotherapy alone, KLTi plus GP chemotherapy significantly improved objective response rate (ORR) (RR = 1.36, 95% CI 1.23-1.51, p < 0.00001), disease control rate (DCR) (RR = 1.17, 95% CI 1.11 - 1.23, p < 0.00001), and reduced adverse drug reactions(ADRs) such as hair loss (RR = 0.60, 95% CI 0.47 - 0.76, p < 0.0001), gastrointestinal reaction (RR = 0.68, 95% CI 0.62 - 0.75, p < 0.00001), impairment of liver and kidney function (RR = 0.65, 95% CI 0.53 - 0.80, p < 0.001), nervous system damage (RR = 0.42, 95% CI 0.26 - 0.69, p = 0.0005), myelosuppression (I-II phase) (RR = 0.79, 95 % CI 0.66 - 0.95, p = 0.01), myelosuppression (III-IV phase) (RR = 0.44, 95 % CI0.27 - 0.72, p = 0.001), anemia (RR = 0.74, 95 % CI 0.60 - 0.91, p = 0.006), leukopenia (RR = 0.78, 95% CI 0.69, 0.87, p < 0.0001), thrombocytopenia (RR = 0.59, 95 % CI 0.49, 0.72, p < 0.00001), hypochromia (RR = 0.74, 95% CI 0.59, 0.92, p = 0.008).Conclusion: KLTi adjuvant GP chemotherapy reduces adverse effects in patients with advanced NSCLC. Thus, KLTi might be an effective and safe intervention for NSCLC&nbsp

Lower-order compensation chain threshold-reduction technique for multi-stage voltage multipliers

This paper presents a novel threshold-compensation technique for multi-stage voltage multipliers employed in low power applications such as passive and autonomous wireless sensing nodes (WSNs) powered by energy harvesters. The proposed threshold-reduction technique enables a topological design methodology which, through an optimum control of the trade-off among transistor conductivity and leakage losses, is aimed at maximizing the voltage conversion efficiency (VCE) for a given ac input signal and physical chip area occupation. The conducted simulations positively assert the validity of the proposed design methodology, emphasizing the exploitable design space yielded by the transistor connection scheme in the voltage multiplier chain. An experimental validation and comparison of threshold-compensation techniques was performed, adopting 2N5247 N-channel junction field effect transistors (JFETs) for the realization of the voltage multiplier prototypes. The attained measurements clearly support the effectiveness of the proposed threshold-reduction approach, which can significantly reduce the chip area occupation for a given target output performance and ac input signal

Microbial metabolites are involved in tumorigenesis and development by regulating immune responses

The human microbiota is symbiotic with the host and can create a variety of metabolites. Under normal conditions, microbial metabolites can regulate host immune function and eliminate abnormal cells in a timely manner. However, when metabolite production is abnormal, the host immune system might be unable to identify and get rid of tumor cells at the early stage of carcinogenesis, which results in tumor development. The mechanisms by which intestinal microbial metabolites, including short-chain fatty acids (SCFAs), microbial tryptophan catabolites (MTCs), polyamines (PAs), hydrogen sulfide, and secondary bile acids, are involved in tumorigenesis and development by regulating immune responses are summarized in this review. SCFAs and MTCs can prevent cancer by altering the expression of enzymes and epigenetic modifications in both immune cells and intestinal epithelial cells. MTCs can also stimulate immune cell receptors to inhibit the growth and metastasis of the host cancer. SCFAs, MTCs, bacterial hydrogen sulfide and secondary bile acids can control mucosal immunity to influence the occurrence and growth of tumors. Additionally, SCFAs, MTCs, PAs and bacterial hydrogen sulfide can also affect the anti-tumor immune response in tumor therapy by regulating the function of immune cells. Microbial metabolites have a good application prospect in the clinical diagnosis and treatment of tumors, and our review provides a good basis for related research

Mapping Functional Brain Activation Using [14C]-Iodoantipyrine in Male Serotonin Transporter Knockout Mice

Contains fulltext : 183592.PDF (publisher's version ) (Open Access

Fixperts : models, learning and social contexts

Fixperts is a learner-centred, creative-problem-solving and project-based learning programme. In a Fixperts project, participants (Fixperts) team-up with an insight provider (Fix Partner) to identify a daily problem in the Fix Partner’s life that becomes the focus of a project aimed at delivering a solution or Fix. This paper introduces four pedagogic models developed via delivery of Fixperts projects at leading international design universities. It presents four approaches to the challenge of moving from the Person, to the Problem, to the Fix. These four models – Primary, Partnership, Community, Public - represent the evolution of the Fixperts framework to better enable the development of students as confident and empathetic socially-led designers. Fixperts builds competencies which are predicted to become essential to an ability to thrive in our increasingly uncertain future

The role of the SGK3/TOPK signaling pathway in the transition from acute kidney injury to chronic kidney disease

Introduction: Profibrotic phenotype of renal tubular epithelial cells (TECs) featured with epithelial to mesenchymal transition (EMT) and profibrotic factors secretion, and aberrant accumulation of CD206+ M2 macrophages are the key points in the transition from acute kidney injury (AKI) to chronic kidney disease (CKD). Nevertheless, the underlying mechanisms involved remain incompletely understood. Serum and glucocorticoid-inducible kinase (SGK) is a serine/threonine protein kinase, required for intestinal nutrient transport and ion channels modulation. T-LAK-cell-originated protein kinase (TOPK) is a member of the mitogen activated protein kinase family, linked to cell cycle regulation. However, little is known about their roles in AKI-CKD transition.Methods: In this study, three models were constructed in C57BL/6 mice: low dose and multiple intraperitoneal injection of cisplatin, 5/6 nephrectomy and unilateral ureteral obstruction model. Rat renal tubular epithelial cells (NRK-52E) were dealt with cisplatin to induce profibrotic phenotype, while a mouse monocytic cell line (RAW264.7) were cultured with cisplatin or TGF-β1 to induce M1 or M2 macrophage polarization respectively. And co-cultured NRK-52E and RAW264.7 through transwell plate to explore the interaction between them. The expression of SGK3 and TOPK phosphorylation were detected by immunohistochemistry, immunofluorescence and western blot analysis.Results:In vivo, the expression of SGK3 and p-TOPK were gradually inhibited in TECs, but enhanced in CD206+ M2 macrophages. In vitro, SGK3 inhibition aggravated epithelial to mesenchymal transition through reducing the phosphorylation state of TOPK, and controlling TGF-β1 synthesis and secretion in TECs. However, SGK3/TOPK axis activation promoted CD206+ M2 macrophage polarization, which caused kidney fibrosis by mediating macrophage to myofibroblast transition (MMT). When co-cultured, the TGF-β1 from profibrotic TECs evoked CD206+ M2 macrophage polarization and MMT, which could be attenuated by SGK3/TOPK axis inhibition in macrophages. Conversely, SGK3/TOPK signaling pathway activation in TECs could reverse CD206+ M2 macrophages aggravated EMT.Discussion: We revealed for the first time that SGK3 regulated TOPK phosphorylation to mediate TECs profibrotic phenotype, macrophage plasticity and the crosstalk between TECs and macrophages during AKI-CKD transition. Our results demonstrated the inverse effect of SGK3/TOPK signaling pathway in profibrotic TECs and CD206+ M2 macrophages polarization during the AKI-CKD transition

Identification of the toxin components of Rhizoctonia solani AG1-IA and its destructive effect on plant cell membrane structure

Rice sheath blight is a fungal disease caused mainly by Rhizoctonia solani AG1-IA. Toxins are a major pathogenic factor of R. solani, and some studies have reported their toxin components; however, there is no unified conclusion. In this study, we reported the toxin components and their targets that play a role in R. solani AG1-IA. First, toxins produced by R. solani AG1-IA were examined. Several important phytotoxins, including benzoic acid (BZA), 5-hydroxymethyl-2-furanic aid (HFA), and catechol (CAT), were identified by comparative analysis of secondary metabolites from AG1-IA, AG1-IB, and healthy rice. Follow-up studies have shown that the toxin components of this fungus can rapidly disintegrate the biofilm structure while maintaining the content of host plant membrane components, thereby affecting the organelles, which may also explain the lack of varieties highly resistant to sheath blight

Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery

The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300∼700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features

Vitamin E stabilizes iron and mitochondrial metabolism in pulmonary fibrosis

Introduction: Pulmonary fibrosis (PF) is a fatal chronic lung disease that causes structural damage and decreased lung function and has a poor prognosis. Currently, there is no medicine that can truly cure PF. Vitamin E (VE) is a group of natural antioxidants with anticancer and antimutagenic properties. There have been a few reports about the attenuation of PF by VE in experimental animals, but the molecular mechanisms are not fully understood.Methods: Bleomycin-induced PF (BLM-PF) mouse model, and cultured mouse primary lung fibroblasts and MLE 12 cells were utilized. Pathological examination of lung sections, immunoblotting, immunofluorescent staining, and real-time PCR were conducted in this study.Results: We confirmed that VE significantly delayed the progression of BLM-PF and increased the survival rates of experimental mice with PF. VE suppressed the pathological activation and fibrotic differentiation of lung fibroblasts and epithelial-mesenchymal transition and alleviated the inflammatory response in BLM-induced fibrotic lungs and pulmonary epithelial cells in vitro. Importantly, VE reduced BLM-induced ferritin expression in fibrotic lungs, whereas VE did not exhibit iron chelation properties in fibroblasts or epithelial cells in vitro. Furthermore, VE protected against mitochondrial dysmorphology and normalized mitochondrial protein expression in BLM-PF lungs. Consistently, VE suppressed apoptosis in BLM-PF lungs and pulmonary epithelial cells in vitro.Discussion: Collectively, VE markedly inhibited BLM-induced PF through a complex mechanism, including improving iron metabolism and mitochondrial structure and function, mitigating inflammation, and decreasing the fibrotic functions of fibroblasts and epithelial cells. Therefore, VE presents a highly potential therapeutic against PF due to its multiple protective effects with few side effects