Non‐small cell lung cancer in China Chen, Peixin; Liu, Yunhuan; Wen, Yaokai ...
Cancer communications,
October 2022, Letnik:
42, Številka:
10
Journal Article
Recenzirano
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In China, lung cancer is a primary cancer type with high incidence and mortality. Risk factors for lung cancer include tobacco use, family history, radiation exposure, and the presence of chronic ...lung diseases. Most early‐stage non‐small cell lung cancer (NSCLC) patients miss the optimal timing for treatment due to the lack of clinical presentations. Population‐based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China. The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC, thus prolonging survival in patients with positive drivers. In the exploration of immune escape mechanisms, programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitor monotherapy and PD‐1/PD‐L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China. In the Chinese Society of Clinical Oncology's guidelines for NSCLC, maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy. Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC. In this review, we summarized recent advances in NSCLC in China in terms of epidemiology, biology, molecular pathology, pathogenesis, screening, diagnosis, targeted therapy, and immunotherapy.
Ochratoxin A (OTA), frequently existing in the food and feeds, could induce immunotoxicity. Porcine circovirus type 2 (PCV2), as a primary causative agent of porcine circovirus–associated disease, ...also could induce immunosuppression. However, it is still unknown whether PCV2 infection impacts OTA-induced immunotoxicity. The pigs and porcine alveolar macrophages (PAMs) were used as the model in the present experiment. The results in vivo indicated that PCV2 infection exacerbated OTA-induced immunotoxicity, NF-κB p65 phosphorylation, and TLR4 and MyD88 mRNA and protein expression in spleen. The results in vitro showed that OTA at 7.0 and 9.0 μM decreased cell viability and increased LDH release of PAMs without PCV2 infection. However, with PCV2 infection, OTA at 5.0, 7.0 and 9.0 μM significantly decreased cell viability and increased LDH release compared with absence of PCV2 infection. In addition, OTA at 5.0 and 7.0 μM significantly increased Annexin V/PI-positive rate, apoptosis of nuclear, γ-H2AX foci, IL-1α and TNF-α expression in PAMs with PCV2 infection compared with absence of PCV2 infection. In addition, PCV2 infection enhanced OTA-induced TLR4 and MyD88 mRNA and protein expression and NF-κB p65 phosphorylation. Knockdown of TLR4 alleviated the exacerbating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage in PAMs. These results indicated that PCV2 infection aggravated OTA-induced immunotoxicity and reduced the dose of OTA-induced immunotoxicity via TLR4/NF-κB p65 signaling pathway, which could provide basis for establishing limits for OTA.
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•PCV2 infection aggravated OTA-induced immunotoxicity in pigs and PAMs.•PCV2 infection aggravated OTA-induced TLR4/ NF-κB p65 signaling pathway in pigs and PAMs.•TLR4-siRNA eliminated the aggravating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage.•PCV2 infection aggravated OTA-induced immunotoxicity by promoting TLR/NF-κB p65 signaling pathway.
SUMMARY
Morphological phylogenetic analyses suggest that scalidophorans (priapulids, loriciferans, and kinorhynchs) and nematoids (nematodes and nematomorphs) form the ecdysozoan clade Cycloneuralia, ...which is a sister group to panarthropods. It has been proposed that extant priapulids and Cambrian priapulid‐like scalidophorans, because of their conserved evolution, have the potential to illuminate the ancestral morphology, ecology, and developmental biology of highly derived ecdysozoans such as nematods and arthropods. As such, Cambrian fossils, particularly Markuelia and possibly olivooids, can inform the early evolution of scalidophorans, cycloneuralians, and ecdysozoans. However, the scalidophoran Markuelia is known exclusively as embryo fossils, and the olivooids have been alternatively interpreted as cnidarians or cycloneuralians. Here, we describe a post‐embryonic scalidophoran fossil Eopriapulites sphinx new genus and species, which represents the oldest known scalidophoran, from the early Cambrian Period (∼535 Ma) in South China. E. sphinx is similar to modern scalidophorans in having an introvert armed with hollow scalids, a collar with coronal scalids, and a pharynx with pharyngeal teeth, but its scalids and pharyngeal teeth are arranged in a hexaradial pattern. Phylogenetically resolved as a stem‐group scalidophoran, E. sphinx shares a hexaradial pattern with the hexaradial arrangement of certain anatomical structures in kinorhynchs, loriciferans, nematoids, and Cambrian fossils such as Eolympia pediculata, which could also be a scalidophoran. Thus, the bodyplan of ancestral cycloneuralians may have had a component of hexaradial symmetry (i.e., some but not necessarily all anatomical parts are hexaradially arranged). If panarthropods are nested within paraphyletic cycloneuralians, as several molecular phylogenetic analyses suggest, the ancestral ecdysozoans may have been a legless worm possibly with a component of hexaradial symmetry.
Selenizing Astragalus polysaccharides (sAPS) were prepared by nitric acid–sodium selenite method. Effect of sAPS on carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanisms were ...investigated in the rat. Forty male Wistar rats were divided into five equal groups as follows: control group; CCl4 group; CCl4+Astragalus polysaccharides group; CCl4+sodium selenite group and CCl4+selenizing Astragalus polysaccharides group. The results showed that sAPS significantly decreased the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase in the serum, malondialdehyde and hydroxyproline content in liver (P<0.01), and increased the levels of total protein, total antioxidant capacity, glutathione peroxidase, and superoxide dismutase in liver of rats induced by CCl4. In addition, expression levels of antioxidant-related genes (GPX1, SOD1, and Nrf2) were significantly increased following supplementation of the sAPS (P<0.01). Furthermore, sAPS effectively ameliorated CCl4 induced hepatic necrosis and inflammation, and it also reduced the expression levels of proinflammatory cytokines including TNF-α, IL-6, COX-2 and NFκB (P<0.01). Moreover, sAPS significantly decreased the expression levels of α-smooth muscle actin, collagen 1, TGF-β1, but increased the Bcl-2/Bax mRNA ratio in rats administered CCl4 (P<0.01). Taken together, it could be concluded that sAPS could increase the activities of Astragalus polysaccharides and sodium selenite to protect the liver from damage by attenuating hepatic inflammation, oxidative stress, fibrogenesis, and induces apoptosis and cell cycle arrest in hepatic stellate cells.
•Selenizing Astragalus polysaccharides (sAPS) were prepared by nitric acid–sodium selenite method.•The combined effect of sAPS could improve the activities of APS, and Selenium on CCl4 induces liver injury in rats.•sAPS ameliorate liver damage by reducing inflammation, oxidative stress, and inhibit hepatic stellate cell proliferation.
Morphology-based phylogenetic analyses support the monophyly of the Scalidophora (Kinorhyncha, Loricifera, Priapulida) and Nematoida (Nematoda, Nematomorpha), together constituting the monophyletic ...Cycloneuralia that is the sister group of the Panarthropoda. Kinorhynchs are unique among living cycloneuralians in having a segmented body with repeated cuticular plates, longitudinal muscles, dorsoventral muscles, and ganglia. Molecular clock estimates suggest that kinorhynchs may have diverged in the Ediacaran Period. Remarkably, no kinorhynch fossils have been discovered, in sharp contrast to priapulids and loriciferans that are represented by numerous Cambrian fossils. Here we describe several early Cambrian (~535 million years old) kinorhynch-like fossils, including the new species Eokinorhynchus rarus and two unnamed but related forms. E. rarus has characteristic scalidophoran features, including an introvert with pentaradially arranged hollow scalids. Its trunk bears at least 20 annuli each consisting of numerous small rectangular plates, and is armored with five pairs of large and bilaterally placed sclerites. Its trunk annuli are reminiscent of the epidermis segments of kinorhynchs. A phylogenetic analysis resolves E. rarus as a stem-group kinorhynch. Thus, the fossil record confirms that all three scalidophoran phyla diverged no later than the Cambrian Period.
The mechanism of action of Batroxobin included the decomposition of the fibrinogen to fibrin degradation products (FDPs) and D-dimer and mobilization of endothelial cells to release endogenous nt-PA ...and to promote thrombolysis. This review aims to summarize current study findings about batroxobin on correcting cerebral arterial, venous, and peripheral vascular diseases, to explore the mechanism of batroxobin on anti-thrombosis process.
A thorough literature search was conducted utilizing the PubMed Central (PMC) and EMBASE databases to identify studies up to June 2021. Data from clinical studies and animal experiments about batroxobin were extracted, integrated and analyzed based on Cochrane handbook for systematic reviews of interventions approach and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P), including the condition of subjects, the usage and dosage, research observation index and main findings.
A total of 62 studies were enrolled in this systematic review, including 26 clinical studies and 36 animal experiments. The 26 clinical studies involved 873 patients with arterial ischemic events, 92 cases with cerebral venous thrombosis, 13 cases with cerebral cortical vein thrombosis, and 1,049 cases with peripheral vascular diseases. These patients included 452 males and 392 females aged 65.6 ± 5.53 years. The results revealed that batroxobin had broad effects, including improving clinical prognosis (
= 12), preventing thrombosis (
= 7), promoting thrombolysis (
= 6), and improving vascular cognitive dysfunction (
= 1). The effects of batroxobin on reducing neuronal apoptosis (
= 8),relieving cellular edema (
= 4), improving spatial memory (
= 3), and promoting thrombolysis (
= 13) were concluded in animal experiments. The predominant mechanisms explored in animal experiments involved promoting depolymerization of fibrinogen polymers (
= 6), regulating the expression of related molecules (
= 9); such as intercellular adhesion molecule, heat shock proteins, tumor necrosis factor), reducing oxidative stress (
= 5), and reducing inflammation response (
= 4).
Batroxobin can correct both arterial and venous ischemic diseases by promoting depolymerization of fibrinogen polymers, regulating the expression of related molecules, reducing oxidative stress, and reducing the inflammation response.
Some rare microscopic cycloneuralians are present in the Cambrian of South China, represented by Eopriapulites and Eokinorhynchus (both early Cambrian), fossil embryos of Markuelia (middle to late ...Cambrian), and palaeoscolecids (early to late Cambrian). Among them, palaeoscolecids are relatively diverse and abundant. Here, we describe new material of three-dimensionally phosphatized and microscopic cycloneuralians from the Paibian Stage of Wangcun Lagerstätte, western Hunan, South China. New material includes fossil embryos assignable to Markuelia sp., two other types of fossil embryos, and three species of palaeoscolecids, including Dispinoscolex decorus Duan, Dong, and Donoghue, 2012, Schistoscolex hunanensis Duan, Dong, and Donoghue, 2012, and Austroscolex sinensis new species. The palaeoscolecid fragments differ mainly in size and armor of the trunk annuli. Since Eokinorhynchus and Eopriapulites occurred the earliest among the Cambrian cycloneuralians, it is proposed here that: (1) cycloneuralians originated in the Cambrian Fortunian small shelly faunas rather than in the early Cambrian macrobenthos, (2) ancestral cycloneuralians may have simple trunk armor, and (3) Eopriapulites represents an ancestral cycloneuralian.
A wide variety of scalidophoran worms have been found in the Cambrian Fortunian in recent years, suggesting that scalidophorans diversified during this age. Here, we report new scalidophoran material ...obtained from the 2nd member of the Kuanchuanpu Formation (Fortunian Stage) in Zhangjiagou Lagerstätte, Xixiang County, Shaanxi Province, South China. Three indeterminate forms of scalidophoran worms are described in detail. The morphology of these worms differs from that of any coeval worms and may represent new taxa. However, because these fossils are fragmented and lack detailed information on the arrangement pattern of introvert scalids, they are named here in open nomenclature. This study enriches the diversity of the earliest scalidophorans to 7 genera and species and 10 indeterminate forms. Based on the new fossils, Fortunian scalidophoran worms can be divided into three categories: (1) worms with microannuli; (2) worms with macroannuli; and (3) worms without annuli.
Microscopic medusozoans from the Cambrian Fortunian stage of South China are well known for their exceptionally preserved embryos and elongated tubes. However, additional details of their morphology ...remain unclear. This paper describes new medusozoan fossils showing the whole apical complement and covering the morphological integrity of
Qinscyphus
. The apical part of
Qinscyphus
is considered to be soft during early ontogeny, and the inverted pentagonal pyramid may gradually form with growth and development. This discovery of the apical complement of
Qinscyphus
is novel and essential to complement the external morphology of early medusozoan fossils. More importantly, the new specimens have different annuli with triangular thickenings, providing a more comprehensive view on the developmental sequence of
Qinscyphus
. Therefore, this work allows a better understanding of early medusozoans ecology and evolution.
Fortunian scalidophoran worms have shown high diversity, with 7 genera and species and 10 indeterminate forms. Current studies have mainly focused on morphology as well as early evolution, and ...studies on ontogeny have not been carried out due to the limited number of specimens. Here, we report new material of an Orsten-type preserved Indeterminate Form 3 from the Zhangjiagou section. Collected specimens of Indeterminate Form 3 with different annulus widths indicate the presence of several ontogenetic stages. We found newly formed sclerites on the annulus of Indeterminate Form 3 at different ontogenetic stages, suggesting that the sclerites of Indeterminate Form 3 become more numerous in addition to increasing in size during growth. The size of the large sclerites may also increase as the worms grow, however, their number may not change.
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