Fe-Doped Ni2P/NiSe2 Composite Catalysts for Urea Oxidation Reaction (UOR) for Energy-Saving Hydrogen Production by UOR-Assisted Water Splitting.

The development of efficient urea oxidation reaction (UOR) catalysts helps UOR replace the oxygen evolution reaction (OER) in hydrogen production from water electrolysis. Here, we prepared Fe-doped Ni2P/NiSe2 composite catalyst (Fe-Ni2P/NiSe2-12) by using phosphating-selenizating and acid etching to increase the intrinsic activity and active areas. Spectral characterization and theoretical calculations demonstrated that electrons flowed through the Ni-P-Fe-interface-Ni-Se-Fe, thus conferring high UOR activity to Fe-Ni2P/NiSe2-12, which only needed 1.39 V vs RHE to produce the current density of 100 mA cm-2. Remarkably, this potential was 164 mV lower than that required for the OER under the same conditions. Furthermore, EIS demonstrated that UOR driven by the Fe-Ni2P/NiSe2-12 exhibited faster interfacial reactions, charge transfer, and current response compared to OER. Consequently, the Fe-Ni2P/NiSe2-12 catalyst can effectively prevent competition with OER and NSOR, making it suitable for efficient hydrogen production in UOR-assisted water electrolysis. Notably, when water electrolysis is operated at a current density of 40 mA cm-2, this UOR-assisted system can achieve a decrease of 140 mV in the potential compared to traditional water electrolysis. This study presents a novel strategy for UOR-assisted water splitting for energy-saving hydrogen production.

Co/Co3O4 Heterojunctions Encased in Porous N-Doped Carbon Nanocapsules for High-Performance Cathode of Rechargeable Zinc-Air Batteries.

A long-term goal of rechargeable zinc-air batteries (ZABs) has always been to design bifunctional electrocatalysts that are robust, effective, and affordable for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). It has become a feasible method to construct metal/metal oxide interfaces to achieve superior electrocatalytic performance for ORR and OER by enhanced charge transfer. In this study, Co/Co3O4 heterojunctions were successfully prepared and encased in porous N-doped mesoporous carbon (Co/Co3O4@NC) via a simple condensation-carbonization-etching method. The extensive specific surface area of Co/Co3O4@NC facilitates effective interaction between the electrolyte and the catalyst, thereby enabling sufficient exposure of active sites for the ORR and the OER, consequently enhancing the rate of transport of active species. The well-designed Co/Co3O4@NC delivers superior ORR catalytic activity with a half-wave potential of 0.82 V (vs RHE) and a low overpotential of 347 mV at 10 mA cm-2 for OER in alkaline solution. The power density of Co/Co3O4@NC-based alkaline aqueous ZAB (156.5 mW cm-2) is superior to the commercial Pt/C + IrO2-based alkaline aqueous ZAB, and the cycling stability of ZAB is up to 220 h. In addition, Co/Co3O4@NC-based ZAB shows a high power density (50.1 mW cm-2). The construction of metal/metal oxide heterojunction encased in N-doped mesoporous carbon provides a novel route for the design of bifunctional electrocatalysts for high-performance ZABs.

Recent progress in the synthesis of transition metal nitride catalysts and their applications in electrocatalysis.

Transition metal nitrides (TMNs) have become excellent substitutes for precious metals such as Pt and Ir in the field of electrocatalysis because of their excellent electrocatalytic performance, high conductivity, good corrosion resistance and stability. As we all know, the commonly utilized carbon-based materials corrode easily during electrocatalysis, which will lead to catalyst falling off and agglomeration. Compared with carbon-based materials, TMNs have stronger corrosion resistance and higher stability. In the metal nitrides, a variety of chemical bonds (metal bond, ionic bond and covalent bond) coexist, among which the ionic bond between metal atoms and nitrogen atoms can make the d-band shrink and narrow, which leads to TMNs having characteristics similar to precious metals in the electrocatalytic process; thus, they can be used as a substitute for precious metal catalysts. In this paper, the synthesis method and catalytic principle of transition metal nitrides and their applications in the fields of hydrogen evolution reaction (HER), oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are discussed, and the shortcomings of TMNs as a catalyst, the challenges faced in catalyst research and the developments and prospects for the future are pointed out.

Modulation Strategies for the Preparation of High-Performance Catalysts for Urea Oxidation Reaction and Their Applications.

Compared with the traditional electrolysis of water to produce hydrogen, urea-assisted electrolysis of water to produce hydrogen has significant advantages and has received extensive attention from researchers. Unfortunately, urea oxidation reaction (UOR) involves a complex six-electron transfer process leading to high overpotential, which forces researchers to develop high-performance UOR catalysts to drive the development of urea-assisted water splitting. Based on the UOR mechanism and extensive literature research, this review summarizes the strategies for preparing highly efficient UOR catalysts. First, the UOR mechanism is introduced and the characteristics of excellent UOR catalysts are pointed out. Aiming at this, the following modulation strategies are proposed to improve the catalytic performance based on summarizing various literature: 1) Accelerating the active phase formation to reduce initial potential; 2) Creating double active sites to trigger a new UOR mechanism; 3) Accelerating urea adsorption and promoting C─N bond cleavage to ensure the effective conduct of UOR; 4) Promoting the desorption of CO2 to improve stability and prevent catalyst poisoning; 5) Promoting electron transfer to overcome the inherent slow dynamics of UOR; 6) Increasing active sites or active surface area. Then, the application of UOR in electrochemical devices is summarized. Finally, the current deficiencies and future directions are discussed.

Recent advances in the synthesis and electrocatalytic application of MXene materials.

MXenes are a class of two-dimensional materials with a graphene-like structure, which have excellent optical, biological, thermodynamic, electrical and magnetic properties. Due to the diversity resulting from the combination of transition metals and C/N, the MXene family has expanded to more than 30 members and been applied in many fields with broad application prospects. Among their applications, electrocatalytic applications have achieved many breakthroughs. Therefore, in this review, we summarize the reports on the preparation of MXenes and their application in electrocatalysis published in the last five years and describe the two main methods for the preparation of MXenes, i.e., bottom-up and top to bottom synthesis. Different methods may change the structure or surface termination of MXenes, and accordingly affect their electrocatalytic performance. Furthermore, we highlight the application of MXenes in the electrocatalytic hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO2RR), nitrogen reduction reaction (NRR), and multi-functionalization. It can be concluded that the electrocatalytic properties of MXenes can be modified by changing the type of functional groups or doping. Also, MXenes can be compounded with other materials to produce electronic coupling and improve the catalytic activity and stability of the resulting composites. In addition, Mo2C and Ti3C2 are two types of MXene materials that have been widely studied in the field of electrocatalysis. At present, research on the synthesis of MXenes is focused on carbides, whereas research on nitrides is rare, and there are no synthesis methods meeting the requirements of green, safety, high efficiency and industrialization simultaneously. Therefore, it is very important to explore environmentally friendly industrial production routes and devote more research efforts to the synthesis of MXene nitrides.

Current Status and Challenges of Aptamers Screening and Optimization.

BACKGROUND: Aptamers, consisting of single-stranded DNA or RNA, have secondary and tertiary structures which could bind specifically to target molecules. They are characterized by strong specificity, high affinity, low molecular weight, and low immunogenicity; therefore, the current research focuses on their potential as a targeted drug carrier, a diagnostic probe for diseases, or as a direct therapeutic drug. OBJECTIVE: In this review, how to improve the success rate of adaptor screening and the optimization after screening is described. RESULTS: For aptamer screening, an efficient selection strategy is needed. In this article, by analyzing key aspects of SELEX such as initial library design, screening procedures, truncation and modification after screening, a comprehensive analysis of each step that might meet obstacles in SELEX is provided. CONCLUSION: Aptamers, which possess the specificity and affinity with the target, can serve as targeted drug carriers or biosensors for diagnosing a disease. If the problems in the screening process in cell-SELEX technology, truncation, and modification after screening are solved, it will have a broader range of applications.

Mechanism of Xiaoer Chiqiao Qingre Granules in clearing heat and removing food stagnation in suckling rats with fever and food accumulation based on metabolomics / 中国中药杂志

Children's fever is often accompanied by food accumulation. Traditional Chinese medicine believes that removing food stagnation while clearing heat of children can effectively avoid heat damage. To systematically evaluate the efficacy of Xiaoer Chiqiao Qingre Granules(XRCQ) in clearing heat and removing food accumulation and explore its potential mechanism, this study combined suckling SD rats fed with high-sugar and high-fat diet with injection of carrageenan to induce rat model of fever and food accumulation. This study provided references for the study on the pharmacodynamics and mechanism of XRCQ. The results showed that XRCQ effectively reduced the rectal temperature of suckling rats, improved the inflammatory environment such as the content of interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ(IFN-γ), white blood cells, and monocytes. XRCQ also effectively repaired intestinal injury and enhanced intestinal propulsion function. According to the confirmation of its efficacy of clearing heat, the thermolytic mechanism of XRCQ was further explored by non-targeted and targeted metabolomics methods based on LTQ-Orbitrap MS/MS and UPLC-QQQ-MS/MS. Non-target metabolomics analysis of brain tissue samples was performed by QI software combined with SIMCA-P software, and 22 endogenous metabolites that could be significantly regulated were screened out. MetaboAnalyst pathway enrichment results showed that the intervention mechanism was mainly focused on tyrosine metabolism, tricarboxylic acid cycle, inositol phosphate metabolism, and other pathways. At the same time, the results of targeted metabolomics of brain tissue samples showed that XRCQ changed the vitality of digestive system, and inhibited abnormal energy metabolism and inflammatory response, playing a role in clearing heat and removing food stagnation from multiple levels.

Aerobic exercise regulates FGF21 and NLRP3 inflammasome-mediated pyroptosis and inhibits atherosclerosis in mice.

Fibroblast growth factor 21 (FGF21), a known risk factor for atherosclerosis, is readily regulated by exercise, and it can inhibit NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. However, it is not clear whether aerobic exercise inhibits atherosclerosis via these pathways. Eight-week-old apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet were randomly divided into 1-h post-exercise (EX-1h), 24-h post-exercise (EX-24h), and sedentary (SED) groups. C57BL/6J wild-type mice fed normal chow served as controls (WT group). Mice in the EX-1h and EX-24h groups were subjected to treadmill exercise training for 12 weeks. Aerobic exercise reduced body weight; blood glucose, lipid, and inflammation levels; and aortic plaque area proportion. Aerobic exercise increased the sensitivity of FGF21 by upregulating the expression of the downstream receptor adiponectin (ApN); the serum FGF21 level after exercise increased initially, and then decreased. Aerobic exercise downregulated the expression of NLRP3 inflammasome-mediated pyroptosis-related markers in the aorta, and FGF21 may participate in the above process. Meanwhile, the liver may be the tissue source of serum FGF21 during aerobic exercise. In conclusion, aerobic exercise may inhibit atherogenesis by regulating FGF21 and NLRP3 inflammasome-mediated pyroptosis. Our study provides new information on the atherosclerosis-preventing mechanism of aerobic exercise.

Nurses' knowledge, attitudes, and willingness to practice hospice care: An analysis of influencing factors.

BACKGROUND: Hospice care is a multidisciplinary approach that focused on patients' quality of life, and nurses allocate more of their time with patients and patients' families than those nurses working in other disciplines. Nurses' knowledge of and attitudes toward hospice care can affect the quality of hospice care. At present, China's hospice care institutions are suffering from an obvious shortage of nursing staff. Since clinical nurses are the main force behind the future provision of hospice care, their knowledge of, attitudes and willingness to practice can greatly promoted the growth of hospice care, however, available data on clinical nurses' willingness to practice hospice care are limited. METHODS: A cross-sectional descriptive study design was employed to collect data from 1833 nurses working in tertiary or secondary general hospitals in Guangxi, China. We examined nurses' demographic characteristics and scores on the Chinese version of the hospice care knowledge scale, the Chinese version of the Bradley Attitude Assessment Questionnaire, and a brief quiz concerning their willingness to practice hospice care in the future. Descriptive, single factor, multiple regression analyses and logistic regression analyses were used for data analysis. RESULTS: Nurses displayed moderate mean scores for both knowledge of and attitudes, and only 505 (27.5%) nurses expressed their willingness to practice hospice care, 1329 (72.5%) of nurses sampled expressed their unwillingness or uncertainty. Multivariate regression analyses showed that education, professional qualification, monthly income, whether they had been trained in hospice care, and willingness to practice hospice care were the main influencing factors of knowledge; education, whether they lived with someone aged >60 years, and whether they had been trained in hospice care were main factors influencing attitudes. Additionally, logistic regression analyses showed that hospice care knowledge, whether they had been trained in hospice care, and whether they had clinical experience affected the nurses' willingness to practice hospice care. CONCLUSION: This study highlighted a knowledge gap and moderate attitudes toward hospice care among nurses, and most nurses did not prefer to practice hospice care. Having been trained in hospice care was the main common factor of nurses' knowledge of, attitudes toward, and willingness to practice hospice care in the future, indicating the necessity to provide nurses with more targeted hospice care training.

The miR-23b/27b/24-1 Cluster Inhibits Hepatic Fibrosis by Inactivating Hepatic Stellate Cells.

BACKGROUND & AIMS: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-ß (TGF-ß) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis. METHODS: Experimental fibrosis was studied in carbon tetrachloride (CCl4)-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means. RESULTS: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-ß2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-ß signaling pathway by down-regulation of TGF-ß2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-ß signaling increased ECM degradation. CONCLUSIONS: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.

Vaccination status, acceptance, and knowledge toward a COVID-19 vaccine among healthcare workers: a cross-sectional survey in China.

Healthcare workers (HCWs) are considered both a high-risk population regarding infections and effective vaccine recommenders whose willingness to be vaccinated is the key to herd immunity. However, the vaccination status, acceptance, and knowledge of the 2019 coronavirus disease (COVID-19) vaccine among HCWs remain unknown. Therefore, we conducted an online survey regarding the above among HCWs in China after the vaccine was made available. Questionnaires returned by 1,779 HCWs were analyzed. Among these participants, 34.9% were vaccinated, 93.9% expressed their willingness to receive the COVID-19 vaccine, and vaccine knowledge level was high (89.2%). A bivariate analysis found that participants with a college degree, low level of knowledge, non-exposure to COVID-19 status, and those who are females or nurses have a lower vaccination rate, while participants who are married, with a monthly income of more than 5,000 yuan, and low knowledge levels are less willing to be vaccinated. A multivariate analysis found that participants with a high (OR = 7.042, 95% CI = 4.0918-12.120) or medium (OR = 3.709, 95% CI = 2.072-6.640) knowledge level about COVID-19 vaccines were more willing to be vaccinated. Participants were less likely to accept a COVID-19 vaccine if they were married (OR = 0.503, 95% CI = 0.310-0.815). In summary, Chinese HCWs have a strong willingness to be vaccinated and a high level of knowledge. Measures, such as targeted education for HCWs with low willingness and low level of knowledge, open vaccine review procedures, increased government trust, reduced vaccine costs, and provide vaccination guarantee policies, may improve the vaccination coverage of the at-risk group.

Analysis of key genes and related transcription factors in liver fibrosis based on bioinformatic technology.

OBJECTIVE: To analyze differentially expressed genes (DEGs) related to liver fibrosis, and clarify the key genes and the possible targets in the progression of liver fibrosis. METHODS: Using microarray datasets, GSE38199 was extracted from Gene Expression Omnibus (GEO), and a bioinformatics method was performed to find DEGs and transcription factors related to liver fibrosis. RESULTS: A total of 58 DEGs were screened out according to GEO2R online analysis tool, which included 49 up-regulated and 9 down-regulated genes. These DEGs were mainly involved in formation with the extracellular region and extracellular exosome through gene ontology (GO) enrichment analysis. Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis showed that DEGs mainly participated in the PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, and metabolic pathways. Based on the results of the Protein-Protein Interaction (PPI) network and Molecular Complex Detection (MCODE) analysis, 9 key genes (COL1A1, FBN1, BGN, COL6A3, MMP2, FBLN5, LUM, PDGFRB, LOXL1) were screened out. A total of 30 transcription factors were found according to these 9 key genes, of which 4 transcription factors (Stat3, Trp53, NF-κB1, Sp1) were enriched. CONCLUSION: Stat3, Trp53, NF-κB1, and Sp1 were all related to the development of liver fibrosis, and FBLN5 might be a target for liver fibrosis.

Interaction of non­parenchymal hepatocytes in the process of hepatic fibrosis (Review).

Hepatic fibrosis (HF) is the process of fibrous scar formation caused by chronic liver injury of different etiologies. Previous studies have hypothesized that the activation of hepatic stellate cells (HSCs) is the central process in HF. The interaction between HSCs and surrounding cells is also crucial. Additionally, hepatic sinusoids capillarization, inflammation, angiogenesis and fibrosis develop during HF. The process involves multiple cell types that are highly connected and work in unison to maintain the homeostasis of the hepatic microenvironment, which serves a key role in the initiation and progression of HF. The current review provides novel insight into the intercellular interaction among liver sinusoidal endothelial cells, HSCs and Kupffer cells, as well as the hepatic microenvironment in the development of HF.

A case report of polyglandular syndrome induced by programmed death-1 inhibitor and literature review / 中华内分泌代谢杂志

We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

Analysis of clinical trials of dermatological drugs in China, 2020 / 中华皮肤科杂志

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Identification of chemical constituents of Xiaoer Chiqiao Qingre Granules based on UHPLC-LTQ-Orbitrap-MS/MS and network pharmacology analysis / 中国中药杂志

This study aimed to qualitatively analyze the chemical components in Xiaoer Chiqiao Qingre Granules(XRCQ) by UHPLC-LTQ-Orbitrap-MS/MS and identify its material basis. The absorbed components in plasma were combined for exploring the potential action mechanism by integrated network pharmacology. ACQUITY UPLC HSS T3(2.1 mm×100 mm, 1.8 μm) column and mobile phase system of 0.1% formic acid solution(A)-acetonitrile(B) were used for gradient elution, followed by high resolution liquid chromatography-mass spectrometry in both positive and negative ion scanning modes. According to the precise relative molecular mass and MS/MS fragment ions, a total of 124 chemical components were identified in XRCQ by the comparison with references and literature reports, among which 29 compounds were completely confirmed by comparison with reference substances. Then, the main absorbed components of XRCQ in plasma were also analyzed and clarified by UHPLC-LTQ-Orbitrap-MS/MS. BATMAN-TCM and SwissTargetPrediction were used for target prediction of absorbed components in plasma. Following the plotting of association network with Cytoscape 3.8.2, the core targets were subjected to GO and KEGG pathway enrichment analysis and a component-target-pathway network was constructed. A total of eight main targets of XRCQ against fever in children were obtained together with eight absorbed components in plasma, including glycyrhydinic acid, hesperidin, emodin, reticuline, daidzein, magnolignan C, magnolignan A, and magnolaldehyde D. It was inferred that XRCQ might improve alimentary system abnormality, inflammatory response, oxidative stress, and endocrine disorder through tumor necrosis factor, PI3 K-AKT, and other signaling pathways. The present study comprehensively expounded the chemical profiles of XRCQ and the main absorbed components in plasma and predicted the potential mechanism of XRCQ based on integrated network pharmacology, which has provided certain theoretical reference for the clinical application of XRCQ.

Up-regulation of microRNA-496 suppresses proliferation, invasion, migration and in vivo tumorigenicity of human osteosarcoma cells by targeting eIF4E.

Osteosarcoma is an aggressive bone tumor characterized by a high level of genetic instability and recurring DNA deletions and amplifications. This study aims to investigate how microRNA-496 (miR-496) affects proliferation, invasion, and migration of human osteosarcoma (OS) cells and in vivo tumorigenicity by targeting eukaryotic translation initiation factor 4E (eIF4E). Microarray-based gene expression profiling involving OS was used in order to identify differentially expressed genes. After that, the interaction between miR-496 expression and OS patients' survival rate was determined. The expression pattern of miR-496 and eIF4E was determined in OS tissues and cells, and their potential relationship was further analyzed by using the dual luciferase reporter gene assay. With the purpose of identifying the functional role miR-496 in OS, cell proliferation, migration, and invasion were measured in cells treated with miR-496 mimic or inhibitor. A nude mouse model was constructed in order to investigate the regulatory effects of miR-496 on tumor growth in vivo by regulating eIF4E. OS cells exhibited a down-regulated expression of miR-496 and an up-regulated expression of eIF4E. miR-496 expression was positively correlated to OS patients' survival rate. Bioinformatics analysis suggested eIF4E would be a direct target of miR-496, and the expression of eIF4E was inhibited by overexpression of miR-496. miR-496 elevation was found to exert suppressive effects on OS cell proliferation, migration and invasion in vitro and tumor growth in vivo, with the effects being reversed using miR-496 depletion. Altogether, the above findings support a conclusion that miR-496 could work as a tumor suppressor in OS through down-regulation of eIF4E. This study may provide a novel target for treatment of OS.

CDK4/6 inhibition versus mTOR blockade as second-line strategy in postmenopausal patients with hormone receptor-positive advanced breast cancer: A network meta-analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (palbociclib and abemaciclib) and mammalian target of rapamycin (mTOR) inhibitors (everolimus) are effective agents for restoring endocrine sensitivity in patients with advanced breast cancer progression on prior aromatase inhibitors. We conducted a network meta-analysis to compare these treatments in terms of progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). METHODS: The PubMed and Embase databases were searched for relevant publications between January 2000 and June 2018. Treatments were ranked based on a network meta-analysis. Ranking was determined by P-score. A random-effect model was used when heterogeneity was detected; otherwise, a fixed-effect model was used. RESULTS: Six trials comprising 4063 patients formed the comparison network. Compared with everolimus plus exemestane, the combinations of palbociclib or abemaciclib with fulvestrant showed similar efficacies in PFS and no differences in ORR. For the CBR, palbociclib demonstrated improvement, while abemaciclib did not. Incidences of severe adverse events did not significantly differ. A total of 29%, 15.9%, and 4% of patients discontinued everolimus, abemaciclib, and palbociclib, respectively, due to toxicity. CONCLUSION: These results suggest similar efficacies between CDK4/6 inhibition and mTOR blockade; however, CDK4/6 inhibitors were associated with favorable toxicity profiles.

Effect of consolidation chemotherapy following definitive chemoradiotherapy in patients with esophageal squamous cell cancer.

Definitive chemoradiotherapy (dCRT) is a treatment option for patients with localized esophageal squamous cell carcinoma (ESCC). We investigated consolidation chemotherapy (CCT) in patients with ESCC who attained clinical complete response after dCRT. Between January 2009 and December 2012, medical records of ESCC patients treated with dCRT were retrospectively reviewed, and those who attained CCR were identified. Progression-free survival and overall survival rates were estimated by the Kaplan-Meier method. The Cox regression model was used to determine prognostic factors. Of the 522 patients treated with dCRT, 209 patients achieved CCR, with 67 receiving consolidation chemotherapy (the CCT group) and 142 receiving dCRT alone (the control group). CCT did not prolong progression-free survival (33.0 vs 18.0 months, P = 0.07, HR = 0.70, 95% CI, 0.48-1.04); however, CCT improved the median overall survival (53.4 vs 27.0 months, P = 0.04, HR = 0.67, 95% CI, 0.44-0.99) compared with dCRT alone. CCT remained a favorable prognostic factor for overall survival in a multivariate analysis (HR = 0.59, P = 0.02); however, a propensity score analysis failed to show an additional overall survival benefit with CCT. In the present analysis, CCT did not improve progression-free survival but may have extended overall survival in ESCC patients who achieved complete clinical response after dCRT.

Fulvestrant plus targeted agents versus fulvestrant alone for treatment of hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy: a meta-analysis of randomized controlled trials.

To compare the addition of targeted agents to fulvestrant with fulvestrant alone in hormone-receptor positive advanced breast cancer progressed on previous endocrine therapy; a meta-analysis of all relevant randomized controlled trials was performed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for relevant publications reporting randomized controlled trials between January 2000 and June 2016. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were assessed. Eight trials with a total of 2,470 patients were included in this meta-analysis. Compared with fulvestrant alone, combination therapy improved PFS (HR = 0.79; 95% CI 0.72-0.87; P = 0.00), increased ORR (RR = 1.70; 95% CI 1.30-2.21; P = 0.00), and showed a trend of increase in DCR (RR = 1.27; 95% CI 0.96-1.69, P = 0.09). In network analysis, only CD4/6 and PI3K/m-TOR inhibitors showed significant treatment effects with a P-score of 0.9999 and 0.7615, respectively. Patients treated with combination therapy developed more grade 3 or greater toxic effects (RR = 1.24; 95% CI 1.13-1.36; P = 0.00). Combining targeted agents with fulvestrant showed benefit but with increased toxicity in patients with advanced breast cancer compared with fulvestrant alone. Biomarkers for treatment optimization are lacking. The CD4/6 and PI3K/m-TOR pathways merit further investigation.