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

ReMarNet: Conjoint Relation and Margin Learning for Small-Sample Image Classification

Despite achieving state-of-the-art performance, deep learning methods generally require a large amount of labeled data during training and may suffer from overfitting when the sample size is small. To ensure good generalizability of deep networks under small sample sizes, learning discriminative features is crucial. To this end, several loss functions have been proposed to encourage large intra-class compactness and inter-class separability. In this paper, we propose to enhance the discriminative power of features from a new perspective by introducing a novel neural network termed Relation-and-Margin learning Network (ReMarNet). Our method assembles two networks of different backbones so as to learn the features that can perform excellently in both of the aforementioned two classification mechanisms. Specifically, a relation network is used to learn the features that can support classification based on the similarity between a sample and a class prototype; at the meantime, a fully connected network with the cross entropy loss is used for classification via the decision boundary. Experiments on four image datasets demonstrate that our approach is effective in learning discriminative features from a small set of labeled samples and achieves competitive performance against state-of-the-art methods. Codes are available at https://github.com/liyunyu08/ReMarNet.Comment: IEEE TCSVT 202

Urinary biomarkers associated with podocyte injury in lupus nephritis

The most prevalent and devastating form of organ damage in systemic lupus erythematosus (SLE) is lupus nephritis (LN). LN is characterized by glomerular injury, inflammation, cell proliferation, and necrosis, leading to podocyte injury and tubular epithelial cell damage. Assays for urine biomarkers have demonstrated significant promise in the early detection of LN, evaluation of disease activity, and tracking of reaction to therapy. This is because they are non-invasive, allow for frequent monitoring and easy self-collection, transport and storage. Podocyte injury is believed to be a essential factor in LN. The extent and type of podocyte injury could be connected to the severity of proteinuria, making podocyte-derived cellular debris and injury-related urinary proteins potential markers for the diagnosis and monitoring of LN. This article focuses on studies examining urinary biomarkers associated with podocyte injury in LN, offering fresh perspectives on the application of biomarkers in the early detection and management of LN

Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

<p>Abstract</p> <p>Objective</p> <p>Very little information is known about the toxic effects of cadmium on somatic cells in mammalian testis. The objective of this study is to explore the toxicity of cadmium on piglet Sertoli cells.</p> <p>Methods</p> <p>Sertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet Sertoli cells were identified by oil red O staining and Fas ligand (FasL) expression as assayed by immunocytochemistry and expression of transferrin and androgen binding protein by RT-PCR. Sertoli cells were cultured in DMEM/F12 supplemented with 10% fetal calf serum in the absence or presence of various concentrations of cadmium chloride, or treatment with p38 MAPK inhibitor SB202190 and with cadmium chloride exposure. Apoptotic cells in seminiferous tubules of piglets were also performed using TUNEL assay in vivo.</p> <p>Results</p> <p>Cadmium chloride inhibited the proliferation of Piglet Sertoli cells as shown by MTT assay, and it increased malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) activity. Inhibitor SB202190 alleviated the proliferation inhibition of cadmium on piglet Sertoli cells. Comet assay revealed that cadmium chloride caused DNA damage of Piglet Sertoli cells and resulted in cell apoptosis as assayed by flow cytometry. The in vivo study confirmed that cadmium induced cell apoptosis in seminiferous tubules of piglets. Transmission electronic microscopy showed abnormal and apoptotic ultrastructure in Piglet Sertoli cells treated with cadmium chloride compared to the control.</p> <p>Conclusion</p> <p>cadmium has obvious adverse effects on the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis, and aberrant morphology. This study thus offers novel insights into the toxicology of cadmium on male reproduction.</p

Regulation of enteric nervous system via sacral nerve stimulation in opioid-induced constipated rats

ObjectivesSacral nerve stimulation (SNS) has been employed for treating constipation. However, its mechanisms involving enteric nervous system (ENS) and motility are largely unknown. In this study, we investigated the possible ENS involvement of SNS in treating Loperamide-induced constipation in rats.MethodsExperiment-1 was designed to study the effects of acute SNS on whole colon transit time (CTT). In experiment-2, we induced constipation by Loperamide and then applied daily SNS or sham-SNS for 1 week. Choline acetyltransferase (ChAT), nitric oxide synthase (nNOS), and PGP9.5 in colon tissue were examined at the end of the study. Moreover, survival factors such as phosphorylated AKT (p-AKT) and Glial cell-derived neurotrophic factor (GDNF) were measures by immunohistochemistry (IHC) and western blot (WB).Key results(1) SNS with one set of parameters shortened CTT starting at 90 min after phenol red administration (p &lt; 0.05). (2) While Loperamide induced slow transit constipation with a significant reduction in fecal pellet number and feces wet weight, daily SNS for a week resolved constipation. (3) Moreover, SNS was able to shorten whole gut transit time comparing to sham-SNS (p = 0.01). (4) Loperamide reduced the number of PGP9.5 and ChAT positive cells, and downregulated ChAT protein expression and upregulated nNOS protein expression, whereas these detrimental effects were significantly reversed by SNS. (5) Furthermore, SNS increased expressions of both GDNF and p-AKT in colon tissue. (6) Vagal activity was reduced following Loperamide (p &lt; 0.01); yet SNS normalized vagal activity.ConclusionSNS with appropriate parameters improves opioid-induced constipation and reversed the detrimental effects of Loperamide on enteric neurons possibly via the GDNF-PI3K/Akt pathway.GRAPHICAL ABSTRAC

DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

On activation, naive T cells grow in size and enter cell cycle to mount immune response. How the fundamental processes of T-cell growth and cell cycle entry are regulated is poorly understood. Here we report that DCAF1 (Ddb1–cullin4-associated-factor 1) is essential for these processes. The deletion of DCAF1 in T cells impairs their peripheral homeostasis. DCAF1 is upregulated on T-cell receptor activation and critical for activation-induced T-cell growth, cell cycle entry and proliferation. In addition, DCAF1 is required for T-cell expansion and function during anti-viral and autoimmune responses in vivo. DCAF1 deletion leads to a drastic stabilization of p53 protein, which can be attributed to a requirement of DCAF1 for MDM2-mediated p53 poly-ubiquitination. Importantly, p53 deletion rescues the cell cycle entry defect but not the growth defect of DCAF1-deficient cells. Therefore, DCAF1 is vital for T-cell function through p53-dependent and -independent mechanisms