Interface Engineering of MOF-Derived Co3O4@CNT and CoS2@CNT Anodes with Long Cycle Life and High-Rate Properties in Lithium/Sodium-Ion Batteries.

Metal-organic framework materials can be converted into carbon-based nanoporous materials by pyrolysis, which have a wide range of applications in energy storage. Here, we design special interface engineering to combine the carbon skeleton and nitrogen-doped carbon nanotubes (CNTs) with the transition metal compounds (TMCs) well, which mitigates the bulk effect of the TMCs and improves the conductivity of the electrodes. Zeolitic imidazolate framework-67 is used as a precursor to form a carbon skeleton and a large number of nitrogen-doped CNTs by pyrolysis followed by the in situ formation of Co3O4 and CoS2, and finally, Co3O4@CNTs and CoS2@CNTs are synthesized. The obtained anode electrodes exhibit a long cycle life and high-rate properties. In lithium-ion batteries (LIBs), Co3O4@CNTs have a high capacity of 581 mAh g-1 at a high current of 5 A g-1, and their reversible capacity is still 1037.6 mAh g-1 after 200 cycles at 1 A g-1. In sodium-ion batteries (SIBs), CoS2@CNTs have a capacity of 859.9 mAh g-1 at 0.1 A g-1 and can be retained at 801.2 mAh g-1 after 50 cycles. The unique interface engineering and excellent electrochemical properties make them ideal anode materials for high-rate, long-life LIBs and SIBs.

The molecular mechanism of polysaccharides in combating major depressive disorder: A comprehensive review.

Major depressive disorder (MDD) is a complex psychiatric condition with diverse etiological factors. Typical pathological features include decreased cerebral cortex, subcortical structures, and grey matter volumes, as well as monoamine transmitter dysregulation. Although medications exist to treat MDD, unmet needs persist due to limited efficacy, induced side effects, and relapse upon drug withdrawal. Polysaccharides offer promising new therapies for MDD, demonstrating antidepressant effects with minimal side effects and multiple targets. These include neurotransmitter, neurotrophin, neuroinflammation, hypothalamic-pituitary-adrenal axis, mitochondrial function, oxidative stress, and intestinal flora regulation. This review explores the latest advancements in understanding the pharmacological actions and mechanisms of polysaccharides in treating major depression. We discuss the impact of polysaccharides' diverse structures and properties on their pharmacological actions, aiming to inspire new research directions and facilitate the discovery of novel anti-depressive drugs.

Deciphering the Olefin Isomerization-Polymerization Paradox of Palladium(II) Diimine Catalysts: Discovery of Simultaneous and Independent Pathways of Olefin Isomerization and Living Polymerization.

This work elucidates a long-standing unexplained paradox commonly observed within the polymerization of α-olefin using palladium (Pd)(II)-diimine catalysts, in which isomerization and living polymerization of α-olefins are both observed. With a classical mechanistic understanding of these complexes, this behavior is often dismissed and interpreted as experimental error. Herein, we present a comprehensive mechanistic investigation into this phenomenon that supports the existence of a novel mechanistic pathway for Pd(II)-diimine complexes. Part one of the mechanistic study lays the foundation of the proposed mechanism, in which neutral Pd(II)-diimine complexes were found to exhibit a moderate to good catalytic activity for olefin isomerization of α-olefins despite the established notion that catalyst activation is required. Extensive experimental and computational studies reveal the possibility of a partial dissociation of the diimine ligand, which frees up one coordination site and enables coordination-insertion. This finding is significant as the coexistence of two reactive coordination sites at the palladium center becomes a valid proposal for the activated cationic Pd(II)-diimine complexes. In part two, we examined and validated the simultaneously observed α-olefin isomerization and living polymerization using the cationic Pd(II)-diimine catalyst, which supports the presence of two independent reaction pathways of isomerization and polymerization, respectively. Moreover, the addition of a strong Lewis acid, such as AlCl3, accelerates the ligand dissociation and the consequential isomerization as it weakens the palladium-nitrogen bond through competitive binding. In part three, Lewis acid-triggered olefin isomerization-polymerization is employed to prepare living olefinic block copolymers and further synthesize novel polyolefin-polar block copolymers with unique architectures, distinct levels of branching, crystallinity, and polar functionality in a one-pot manner.

Phytochemistry and pharmacology of Armeniacae semen Amarum: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Armeniacae Semen Amarum (Prunus armeniaca L. var. ansu Maxim., Ku xingren, bitter almond, ASA) is an important medicine in Traditional Chinese Medicine (TCM). It is widely used because of its remarkable curative effect in relieving cough and asthma, moistening intestines and defecating. AIM OF THE REVIEW: This review aims to enlighten the deeper knowledge about ASA, giving a comprehensive overview of its traditional uses, phytochemistry, pharmacology and toxicology for future investigation of plant-based drugs and therapeutic applications. MATERIALS AND METHODS: The databases used are Web of Science, PubMed, Baidu academic, Google academic, CNKI, Wanfang and VIP . In addition, detailed information on ASA was obtained from relevant monographs such as Chinese Pharmacopoeia. RESULTS: The active components of ASA mainly include amygdalin, bitter almond oil, essential oil, protein, vitamin, trace elements and carbohydrates. The pharmacological studies have shown that ASA has beneficial effects such as antitussive, antiasthmatic, anti-inflammatory, analgesic, antioxidant, antitumour, cardioprotective, antifibrotic, immune regulatory, bowel relaxation, insecticidal, etc. CONCLUSIONS: Many reports have been published on ASA's various active ingredients and biological uses. However, only a few reviews on its phytoconstituents and pharmacological uses. In addition, the exploration and development of ASA in other fields also deserve more attention in future research.

Escin alleviates stress-induced intestinal dysfunction to protect brain injury by regulating the gut-brain axis in ischemic stroke rats.

Hyperactivity of HPA axis results in intestinal dysfunction, which may play a role in brain injury caused by ischemic stroke (IS). Escin shows a neuroprotective effect but it may not penetrate blood brain barrier (BBB). Previous work in our laboratory showed that escin ameliorated intestinal injury in animals. The aim of this study is to investigate whether escin attenuates brain injury by improving intestinal dysfunction in middle cerebral artery occlusion (MCAO) rats, to mimic IS. MCAO rats and lipopolysaccharides (LPS)-induced Caco-2 cells were used to evaluate the effects of escin in vivo and in vitro. The results showed that escin could not penetrate BBB but reduced brain infarct volume, improved neurological function, inhibited neuroinflammation, ameliorated intestinal dysfunction and tissue integrity by increasing the expression of the tight junction protein in vivo and in vitro. Escin reduced the increased corticosterone and endotoxin level in blood of MCAO rats, regulated GR/p38 MAPK/NF-κB signaling pathway in ileal tissue and LPS/TLR4/NF-κB signaling pathway in ischemic brain tissue. These findings suggest that escin could attenuate ischemic brain injury by improving intestinal dysfunction, and it may be a promising way to protect brain injury by protecting intestine, instead of targeting the brain directly after IS.

A review of the botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality of Anemarrhena asphodeloides Bunge.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizomes of Anemarrhena asphodeloides Bunge., belonging to the family Liliaceae, are named 'Zhi-mu' according to traditional Chinese medicine theory. It is a medicinal plant that has long been used as a tonic agent in various ethnomedicinal systems in East Asia, especially in China, and also for treating arthralgia, hematochezia, tidal fever, night sweats, cough, dry mouth and tongue, hemoptysis, etc. THE ARM OF THE REVIEW: The review aims to provide a systematic overview of botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides and to explore the future therapeutic potential and scientific potential of this plant. MATERIALS AND METHODS: A comprehensive literature search was performed on Anemarrhena asphodeloides using scientific databases including Web of Science, PubMed, Google Scholar, CNKI, Elsevier, SpringerLink, ACS publications, ancient books, Doctoral and master's Theses. Collected data from different sources was comprehensively summarised for botany, ethnopharmacology, phytochemistry, pharmacology, toxicology and quality control of Anemarrhena asphodeloides. RESULTS: A comprehensive analysis of the literature as mentioned above confirmed that the ethnomedical uses of Anemarrhena asphodeloides had a history of thousands of years in eastern Asian countries. Two hundred sixty-nine compounds have been identified from Anemarrhena asphodeloides, including steroidal saponins, flavonoids, phenylpropanoids, alkaloids, steroids, organic acids, polysaccharides, benzophenones and other ingredients. Studies have shown that the extracts and compounds from Anemarrhena asphodeloides have extensive pharmacological activities, such as nervous system activity, antitumour, anti-inflammatory, antidiabetic, antiosteoporotic, antiallergic, antiplatelet aggregation, antimicrobial, antiviral, anti-ageing, hair growth promoting, preventing cell damage, etc. Evaluating the quality and toxicity of Anemarrhena asphodeloides is essential to confirm its safe use in humans. CONCLUSION: Anemarrhena asphodeloides is widely used in traditional medicine and have diverse chemical constituents with obvious biological activities. Nevertheless, more studies should be carried out in animals and humans to evaluate the cellular and molecular mechanisms involved in its biological activity and confirm its safe use.

Advances in extraction methods, chemical constituents, pharmacological activities, molecular targets and toxicology of volatile oil from Acorus calamus var. angustatus Besser.

Acorus calamus var. angustatus Besser (ATT) is a traditional herb with a long medicinal history. The volatile oil of ATT (VOA) does possess many pharmacological activities. It can restore the vitality of the brain, nervous system and myocardial cells. It is used to treat various central system, cardiovascular and cerebrovascular diseases. It also showed antibacterial and antioxidant activity. Many studies have explored the benefits of VOA scientifically. This paper reviews the extraction methods, chemical components, pharmacological activities and toxicology of VOA. The molecular mechanism of VOA was elucidated. This paper will serve as a comprehensive resource for further carrying the VOA on improving its medicinal value and clinical use.

Comprehensive metabolism study of Tangeretin in rat plasma, urine and faeces using ultra-high performance liquid chromatography-Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry.

BACKGROUND: Tangeretin, present in citrus fruits, is a polymethoxy flavone with extensive pharmacological effects. It has been widely used in the clinic, but there were no detailed studies on the in vivo metabolism of tangeretin. OBJECTIVE: This study aimed to establish a rapid and effective strategy to identify the metabolites of tangeretin and evaluate the biotransformation pathways of tangeretin in rats. METHODS: The ultra-high performance liquid chromatography (UHPLC) equipped with a Q-Exactive Orbitrap mass spectrometer was used to identify the metabolites of tangeretin in plasma, urine and faeces of rats after intragastric administration. Based on high-resolution extracted ion chromatograms (HREICs) and parallel reaction monitoring mode (PRM), metabolites of tangeretin were identified by comparing the accurate mass, chromatographic retention times, diagnostic product ions (DPIs) and neutral loss fragments (NLFs) with those of tangeretin reference standard. Isomers were distinguished by ClogP values. RESULTS: An efficient and integrated strategy was established for the comprehensive screening and characterizing of tangeretin metabolites through Rapid Profiling. Based on this strategy, a total of 52 metabolites were detected and identified, among which 25 metabolites were found in rat plasma, while 48 and 16 metabolites were characterized from rat urine and faeces, respectively. These metabolites were produced by demethylation, demethoxylation, hydroxylation, methoxylation, glucuronidation, glycosylation, sulfation, and their composite reactions. Interestingly, tangeretin is easy to lose methyl in vivo and becomes an intermediate product, and then other phase I and phase II reactions occur. Moreover, the characteristic fragmentation pathways of tangeretin were summarized for the subsequent metabolite identification. CONCLUSION: The analytical method based on UHPLC-Q-Exactive mass spectrometer has the ability to quickly clarify unknown metabolism. And the the comprehensive metabolism study of tangeretin provided an overall metabolic profile, which will be of great scientific basis for further studies on tangeretin in determining its pharmacokinetics, the bioactivity of the metabolites, and clinical applications.

Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats.

Herb-drug interactions are vital in effectively managing type-2-diabetes complications. Puerarin is a natural isoflavonoid in the Pueraria genus, and its pharmacological activities, including antidiabetic activity, are well established. The similar modes of action of puerarin and metformin in diabetic models suggest their positive pharmacodynamic interactions. This study investigated this in streptozotocin/nicotinamide-induced type-2 diabetic rats. Puerarin at doses of 80 mg/kg, 120 mg/kg and 160 mg/kg improved the activity of metformin in reversing hyperglycaemia, dysregulated lipid profiles, dysfunction of the liver, kidney, and pancreas, and inflammation. The treatment with either puerarin (high dose, 160 mg/kg intraperitoneally) or metformin (100 mg/kg intraperitoneally) did not bring the dysregulated biomarkers to normal levels in 4 weeks. By contrast, the combination of puerarin (160 mg/kg) and metformin (100 mg/kg) did. This study is the first to report scientific evidence for the positive pharmacodynamic interactions between puerarin and metformin.

Recent advances in nutritional composition, phytochemistry, bioactive, and potential applications of Syzygium aromaticum L. (Myrtaceae).

Syzygium aromaticum is an aromatic plant native to Indonesia, and introduced to tropical regions worldwide. As an ingredient in perfumes, lotions, and food preservation, it is widely used in the food and cosmetic industries. Also, it is used to treat toothache, ulcers, type 2 diabetes, etc. A variety of nutrients such as amino acids, proteins, fatty acids, and vitamins are found in S. aromaticum. In addition to eugenol, isoeugenol, eugenol acetate, ß-caryophyllene and α-humulene are the main chemical constituents. The chemical constituents of S. aromaticum exhibit a wide range of bioactivities, such as antioxidant, antitumor, hypoglycemic, immunomodulatory, analgesic, neuroprotective, anti-obesity, antiulcer, etc. This review aims to comprehend the information on its taxonomy and botany, nutritional composition, chemical composition, bioactivities and their mechanisms, toxicity, and potential applications. This review will be a comprehensive scientific resource for those interested in pursuing further research to explore its value in food.

The chemistry and efficacy benefits of polysaccharides from Atractylodes macrocephala Koidz.

Atractylodes macrocephala Koidz (AM), traditional Chinese medicine (TCM) with many medicinal values, has a long usage history in China and other oriental countries. The phytochemical investigation revealed the presence of volatile oils, polysaccharides, lactones, flavonoids, and others. The polysaccharides from AM are important medicinal components, mainly composed of glucose (Glc), galactose (Gal), rhamnose (Rha), arabinose (Ara), mannose (Man), galacturonic acid (GalA) and xylose (Xyl). It also showed valuable bioactivities, such as immunomodulatory, antitumour, gastroprotective and intestinal health-promoting, hepatoprotective, hypoglycaemic as well as other activities. At the same time, based on its special structure and pharmacological activity, it can also be used as immune adjuvant, natural plant supplement and vaccine adjuvant. The aim of this review is to summarize and critically analyze up-to-data on the chemical compositions, biological activities and applications of polysaccharide from AM based on scientific literatures in recent years.

A review on the advances in the extraction methods and structure elucidation of Poria cocos polysaccharide and its pharmacological activities and drug carrier applications.

Poria cocos polysaccharide (PCP) is one of the main active components of Poria cocos that is extensively used in the world. PCP can be divided into intro-polysaccharides and exopolysaccharides. PCP is mainly composed of glucose, galactose and mannose. There are many methods to exact PCP, and methods can affect its yield. PCP and its derivatives exhibit diverse biological functions such as antitumour, antioxidant, anti-inflammatory, immune-regulatory, hepatoprotective, etc. There is the potential application of PCP as drug carriers. The review provides a comprehensive summary of the latest extraction and purification methods of PCP, its chemistry, synthesis of PCP derivates, their pharmacological activities and their applications as drug carriers. This review provides comprehensive information on PCP, which can be used as the basis for further research on PCP and its derivates.

Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis.

Background: Pheretima aspergillum (common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract. Methods: The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool. Results: A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects via inhibiting the transforming growth factor beta 1 (TGF-ß1, SMD = -3.16, 95% CI: -4.18, -2.14, p < .00001) and alpha-smooth muscle actin (α-SMA: SMD = -2.57, 95% CI: -3.47, -1.66, p < .00001). Conclusion: Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19.

Lung alveolar type-II (AT-II) cells produce pulmonary surfactant (PS), consisting of proteins and lipids. The lipids in PS are primarily responsible for reducing the air-fluid surface tension inside the alveoli of the lungs and to prevent atelectasis. The proteins are of two types: hydrophilic and hydrophobic. Hydrophilic surfactants are primarily responsible for opsonisation, thereby protecting the lungs from microbial and environmental contaminants. Hydrophobic surfactants are primarily responsible for respiratory function. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the lungs through ACE-2 receptors on lungs and replicates in AT-II cells leading to the etiology of Coronavirus disease - 2019 (COVID-19). The SARS-CoV-2 virus damages the AT-II cells and results in decreased production of PS. The clinical symptoms of acute respiratory distress syndrome (ARDS) in COVID-19 patients are like those of neonatal respiratory distress syndrome (NRDS). The PS treatment is first-line treatment option for NRDS and found to be well tolerated in ARDS patients with inconclusive efficacy. Over the past 70°years, a lot of research is underway to produce natural/synthetic PS and developing systems for delivering PS directly to the lungs, in addition to finding the association between PS levels and respiratory illnesses. In the present COVID-19 pandemic situation, the scientific community all over the world is searching for the effective therapeutic options to improve the clinical outcomes. With a strong scientific and evidence-based background on role of PS in lung homeostasis and infection, few clinical trials were initiated to evaluate the functions of PS in COVID-19. Here, we connect the data on PS with reference to pulmonary physiology and infection with its possible therapeutic benefit in COVID-19 patients.

A nomogram-based immune-serum scoring system predicts overall survival in patients with lung adenocarcinoma.

OBJECTIVE: The immunoscore, which is used to quantify immune infiltrates, has greater relative prognostic value than tumor, node, and metastasis (TNM) stage and might serve as a new system for classification of colorectal cancer. However, a comparable immunoscore for predicting lung adenocarcinoma (LUAD) prognosis is currently lacking. METHODS: We analyzed the expression of 18 immune features by immunohistochemistry in 171 specimens. The relationship of immune marker expression and clinicopathologic factors to the overall survival (OS) was analyzed with the Kaplan-Meier method. A nomogram was developed by using the optimal features selected by least absolute shrinkage and selection operator (LASSO) regression in the training cohort (n = 111) and evaluated in the validation cohort (n = 60). RESULTS: The indicators integrated in the nomogram were TNM stage, neuron-specific enolase, carcino-embryonic antigen, CD8center of tumor (CT), CD8invasive margin (IM), FoxP3CT, and CD45ROCT. The calibration curve showed prominent agreement between the observed 2- and 5-year OS and that predicted by the nomogram. To simplify the nomogram, we developed a new immune-serum scoring system (I-SSS) based on the points awarded for each factor in the nomogram. Our I-SSS was able to stratify same-stage patients into different risk subgroups. The combination of I-SSS and TNM stage had better prognostic value than the TNM stage alone. CONCLUSIONS: Our new I-SSS can accurately and individually predict LUAD prognosis and may be used to supplement prognostication based on the TNM stage.

A comprehensive review on Pueraria: Insights on its chemistry and medicinal value.

Pueraria species are listed in the Chinese Pharmacopeia and are being used for the treatment of various health ailments and in protecting health. Puerarin, a chemotaxonomic marker of Pueraria, received investigational drug status for the treatment of alcohol abuse and listed in DRUGBANK database. The purpose of this review is to provide insights on health benefits of Pueraria, its bioactive constituents and molecular mechanisms. The information is retrieved from various databases. The most investigated plant part is tuber and the major bioactive constituents are isoflavones. The Pueraria is reported to possess a lots of health benefits on brain, liver, heart, kidney, bone, stomach, muscle, skin, and reproductive system. Pueraria also shown beneficial effects in postmenopausal women. In this review, the scientific information on Pueraria reported until May 2020 were analysed and summarized logically to appreciate its health benefits and to identify research gaps.

Sorting and gene mutation verification of circulating tumor cells of lung cancer with epidermal growth factor receptor peptide lipid magnetic spheres.

BACKGROUND: This study aimed to identify an efficient, simple, and specific method of detecting mutations in the epidermal growth factor receptor (EGFR) gene in isolated lung cancer circulating tumor cells (CTCs) and to improve the ability to obtain tumor tissue clinically. METHODS: EGFR peptide lipid magnetic spheres (EG-P-LMB) were prepared by reverse evaporation, and characterization and cell capture efficiency assessed. The peripheral blood samples of 30 lung cancer patients were isolated and identified with the EG-P-LMB using 20 healthy volunteers as controls. Finally, the isolated CTCs were tested for EGFR gene mutations, and the tissue samples selected for comparison. RESULTS: The prepared magnetic spheres had a smaller particle size and higher stability according to the particle size potential test. Their morphology was homogeneous by atomic force observation, and the UV test showed that there were peptides on the surface. The separation efficiency of EG-P-LMB was greater than 90% in PBS and greater than 80% in the blood simulation system. Compared with the tissue sample results, the positive rate of EGFR gene mutations was 94%. The CTC test results of 27 patients were consistent with the tissue test results of the corresponding patients, and the consistency with the tissue comparison test results was 90% (27/30). CONCLUSIONS: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: EG-P-LMB can effectively capture CTCs in the peripheral blood of patients with lung cancer. CTC detection can accurately identify mutations in the EGFR gene and improve the ability to obtain tumor tissue in clinical practice. WHAT THIS STUDY ADDS: This study added EGFR peptide lipid magnetic spheres to capture CTCs in the blood. Genetic testing was performed and compared with tissues. It solves the problem of clinically difficult tumor tissue sampling.

Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer.

OBJECTIVE: Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively. RESULTS: Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243-1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283-1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers. CONCLUSIONS: Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

MiR-193a-3p is an Important Tumour Suppressor in Lung Cancer and Directly Targets KRAS.

BACKGROUND/AIMS: MicroRNAs (miRNAs) have emerged as major regulators of tumour development and progression in non-small cell lung cancer (NSCLC). However, the role of miR-193a-3p in NSCLC is still unclear. METHODS: Quantitative RT-PCR was used to detect miR-193a-3p expression levels in NSCLC tumour tissues. CCK8, EdU and cell migration assays were performed to analyse the biological functions of miR-193a-3p in NSCLC cells. Luciferase reporter assays were used to validate the bioinformatics-predicted target genes of miR-193a-3p. Western blotting and RNA/DNA interference carried out to evaluate the association between miR-193a-3p and KRAS. RESULTS: miR-193a-3p expression was decreased in the NSCLC tumour tissues. We investigated the biological effects of miR-193a-3p both in vivo and in vitro and found that enforced expression of miR-193a-3p inhibited tumour formation and suppressed cell proliferation and cell migration. KRAS was found to be a potential target of miR-193a-3p, and dual luciferase reporter assays showed that miR-193a-3p directly binds to the 3'-untranslated region (3'-UTR) of KRAS mRNA. In addition, we found that changing the expression of KRAS had the opposite results to those induced by miR-193a-3p in the NSCLC cells. Importantly, simultaneous overexpression of miR-193a-3p and KRAS could counteract the effects of both on cellular functions. CONCLUSION: These findings highlight an important role for miR-193a-3p as a tumour suppressor in NSCLC pathogenesis via the regulation of KRAS expression.

Prognostic value of number of negative lymph node in patients with stage II and IIIa non-small cell lung cancer.

BACKGROUND: The definitive validation evidence of the implications of lymph node metastases regarding the survival of Non-Small Cell Lung Cancer (NSCLC) patients is lacking. We aimed to evaluate the prognostic impact of several lymph node metastases-associated risk factors including Number of Negative Lymph Node (NLN) and risk-stratify NSCLC patients into subsets with different prognosis. METHOD: A total of 482 patients with N1 and N2 NSCLC were included in this study. The prognostic importance of a set of risk factors was examined by univariate and multivariate analysis. The cut-off points and 5 years survival rates were calculated to test the best grouping system to stratify the patients with difference outcome. RESULTS: Our analysis indicated that both Ratio of the Metastatic Lymph nodes (RML) and Number of Negative Lymph Node (NLN) were associated with overall survival (OS) and disease free survival (DFS). RML percentage 20% and 55%, and NLN counts 10 and 30 were proved as the optimal cut-off points to predict OS by classifying patients into 3 groups, respectively. RML and NLN actually are more powerful in predicting survival outcome for male patients compared to female patients. Stratified survival analyses using combined factors indicated that the 5-year survival rate (5-YSR) is high in RML I + NLN I/III subgroup (5-YSR = 57.1% and 43.3%) and low in RML III + NLN II/III subgroup (5-YSR = 0.0 % each). CONCLUSIONS: NLN is a strong prognostic factor for OS and DFS of stage II/IIIa NSCLC patients, and provides a useful classification scheme for NSCLC patients when combined with RML.