The Role and Therapeutic Potential of Non-coding RNAs in Resistance to EGFR-TKIs targeted therapy for Non-small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, of which non-small cell lung cancer (NSCLC) is the most common type, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are widely used for the treatment of NSCLC. EGFR-TKIs are known to develop a drug-resistant response after a certain number of cycles of dosing, and how to alleviate or even reverse EGFR-TKI resistance is an urgent problem at present. This review focuses on the role of ncRNAs in the resistance of NSCLC to EGFR-TKIs and the potential mechanisms underlying the development of NSCLC resistance to EGFR-TKIs. NcRNAs are involved in NSCLC resistance to EGFR-TKIs by mediating cellular drug efflux, epithelial-mesenchymal transition, apoptosis, autophagy, and EGFR mutation. ncRNAs play a crucial role in NSCLC resistance to EGFR-TKIs. Hopefully, the results will provide some guidance and help for the treatment and prognosis of NSCLC.

Peptide-based Nanomaterials: Self-assembly and Applications.

The self-assembly behavior of polypeptides is common in nature. Compared with monopeptides, polypeptide-based self-assembled nanomaterials with ordered structures have good thermal stability, mechanical stability, semi-conductivity, piezoelectric and optical properties. In recent years, the self-assembly of polypeptides has become a hot topic in the material science and biomedical field. By reasonably adjusting the molecular structure of the polypeptide and changing the external environment of the polypeptide, the polypeptide can be self-assembled or triggered by non-covalent bonding forces such as hydrogen bond, hydrophobicity, and π - π accumulation to form specific polypeptide assemblies such as nanoparticles, hydrogels, nanofibers, and micelles. Due to good biocompatibility and controllable degradability, polypeptide-based self-assembled nanomaterials have been widely used in the fields of nanotechnology, imaging technology, biosensor, and biomedical science. As a new drug delivery system, the polypeptide-drug conjugate has the advantages of low toxicity, high efficiency, enhanced drug stability, and avoiding side effects. This paper reviews the research progress of polypeptide-drug self-assembly nanostructure in recent years. Several structural models of polypeptide self-assembly technology and the mechanism of polypeptide self-assembly are introduced. Then the assembly form of polypeptide-drug self-assembly and the application of selfassembly compound therapy is described.

Analysis of Tumor Immune Microenvironment Based on Bulk RNA-sequencing Data and Its Application / 肿瘤防治研究

Cancer immunotherapy is one of the most promising biological therapies. The dynamic changes of the immune microenvironment of heterogeneous tumors are critical factors in determining the interaction and therapeutic efficacy between tumor and immune microenvironment. Therefore, quantitative analysis of its constituent cells, related genes, and phenotypes in real time is of great importance. The methods used to analyze tumor immune microenvironment include immunohistochemistry, flow cytometry and so on. With the development of next-generation sequencing technology, transcriptome RNA sequencing data analysis has become one of the important methods to determine the composition of tumor immune microenvironment. This article focuses on the common methods of bulk RNA sequencing data analysis and related research progress.

T cell immunotherapy mediated by dual-affinity aptamer targeted liposome / 药学学报

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Novel strategies for promoting tumor penetration of anticancer nanomedicines / 药学学报

There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.

Visual analysis of research hotspots and frontiers on randomized controlled trials of acupuncture and moxibustion in the past 10 years / 中国针灸

Retrieved the literature on randomized controlled trials (RCT) of acupuncture and moxibustion from 2011 to 2020 in the Web of Science (WOS) database, and explored research hotspots and frontiers in the field of acupuncture and moxibustion by visually analyze to countries, institutions, authors, keywords, cited literature, etc. using CiteSpace V5.6.R2. A total of 1147 articles were included. China has the largest number of publications, and the top 3 publications are Beijing University of Chinese Medicine, Capital Medical University and Kyung Hee University. The hot research interventions in acupuncture and moxibustion include acupuncture, electroacupuncture, and bee acupuncture. The hot research topics include nerve regeneration, spasms, nausea, pain, obesity, cancer, etc. The research frontiers include acupuncture analgesia, diversification of acupuncture and its clinical effects, brain effects of acupuncture and acupuncture clinical mechanisms. It is believed that the cooperation between countries and institutions should be strengthened in the future, and deeper research should be carried out on the research content that is both hot spot and frontier.

Synthesis and fluorescence properties of two dendritic molecules based on naphthalimide and triphenylamine.

Artificial light-harvesting systems have attracted great interest in biological photosynthesis and photo-voltaic devices areas due to their unique structures, easy purification, low-cost, and convenient processing abilities. Here, two dendritic molecules based on triphenylamine and naphthalimide have been designed and synthesized, their structures were confirmed by 1 H NMR, ESI-MS, and high resolution mass spectrometry. In these molecules, triphenylamine units perform as the electron donor moiety, and naphthalimide units perform as the electron acceptor. The obvious quenched fluorescence intensity and considerably shortened lifetime of the dendritic molecules combined with the molecular frontier orbital energy levels proved that the dendritic molecules not only are good candidates as hole-transporting materials but also are two excellent photo-induced electron transfer materials. Therefore, it is believed that these dendritic molecules have potential application value in photo-voltaic devices.

Rhodiola crenulata extract decreases fatty acid oxidation and autophagy to ameliorate pulmonary arterial hypertension by targeting inhibiton of acylcarnitine in rats / 中国天然药物

Pulmonary arterial hypertension (PAH) is a devastating pulmonary circulation disease lacking high-efficiency therapeutics. The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata, a well-known traditional chinese medicine with cardiopulmonary protection capacity, on PAH by exploiting functional lipidomics. The rat model with PAH was successfully established for first, following Rhodiola crenulata water extract (RCE) treatment, then analysis of chemical constituents of RCE was performed, additional morphologic, hemodynamic, echocardiographic measurements were examined, further targeted lipidomics assay was performed to identify differential lipidomes, at last accordingly mechanism assay was done by combining qRT-PCR, Western blot and ELISA. Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls, mostly assigned to acylcarnitines, phosphatidylcholines, sphingomyelin associated with the PAH development. Excitingly, RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH. Furthermore, RCE was observed to reduce autophagy, confirmed by significantly inhibited PPARγ, LC3B, ATG7 and upregulated p62, and inactivated LKB1-AMPK signal pathway. Notably, we accurately identified the constituents in RCE, and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy. Altogether, RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH. This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.

Dietary supplementation with pioglitazone hydrochloride improves intramuscular fat, fatty acid profile, and antioxidant ability of thigh muscle in yellow-feathered chickens.

BACKGROUND: Muscle fat content and fatty acid composition play an important role in poultry flavor and taste. To investigate the effects of pioglitazone hydrochloride (PGZ) on growth performance and thigh muscle quality in yellow-feathered chickens, 360 female chickens were randomly divided into three groups and treated with three doses of PGZ (0, 7.5, and 15 mg kg-1 ) for 28 days. Each group had six replicates of 20 chickens. RESULTS: The results showed that dietary supplementation with 15 mg kg-1 PGZ increased average daily feed intake (ADFI) and the average daily gain (ADG) from 0 to 14 days. Furthermore, the triglyceride (TG) level was decreased by 15 mg kg-1 PGZ, whereas the eviscerated yield was increased. The relative weight of the heart and kidneys showed a linear increase with dietary PGZ supplementation, and the drip loss of the thigh muscle was significantly decreased by 15 mg kg-1 PGZ supplementation. Moreover, a* value, intramuscular fat (IMF), and polyunsaturated fatty acids (PUFAs) showed a linear increase, and pH24 h and drip loss showed a quadratic influence with the levels of PGZ supplementation. In particular, the PUFA proportion was increased by 7.63% and 9.14% in the 7.5 mg kg-1 PGZ and 15 mg kg-1 PGZ groups, respectively. Additionally, 15 mg kg-1 of PGZ increased the total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX ) activity. CONCLUSION: In summary, 15 mg kg-1 PGZ has substantial effects on growth performance and meat quality, particularly by decreasing drip loss and increasing IMF content, PUFA proportions, and antioxidant ability. © 2019 Society of Chemical Industry.

Dietary supplementation with pioglitazone hydrochloride and chromium methionine manipulates lipid metabolism with related genes to improve the intramuscular fat and fatty acid profile of yellow-feathered chickens.

BACKGROUND: Intramuscular fat (IMF) and polyunsaturated fatty acids (PUFAs) have been thought to play a crucial role in improving meat quality. Considering the ability of pioglitazone hydrochloride (PGZ) to deposit fat, and the anti-stress capability of chromium methionine (CrMet), we combined these compounds to produce higher quality meat in poultry. A total of 3000 female chickens were divided into four groups (five replicates, each with 150 chickens): control, control plus15 mg·kg-1 PGZ, control plus 200 µg·kg-1 CrMet, and control plus15 mg·kg-1 PGZ plus 200 µg·kg-1 CrMet. The experiment lasted for 28 days. RESULTS: Compared to the control group and the PGZ group, the average daily gain (ADG) was significantly increased in the PGZ plus CrMet group, whereas the feed-to-gain ratio (F/G) was decreased from 0 to 14 days. Meanwhile, the redness value of breast muscle and IMF of thigh muscle increased in the PGZ plus CrMet group compared with the control group and these detections in the PGZ plus CrMet group exhibited highest value among the four groups. The cooking loss decreased in the breast muscle and thigh muscle after PGZ combined with CrMet in diets. The percentages of C16:1, C18:2n-6 and PUFAs increased in the PGZ plus CrMet group. The mRNA abundance of peroxisome proliferator activated receptor (PPAR) γ, PPAR coactivator 1 α, and fatty acid binding protein 3 was significantly enhanced with PGZ plus CrMet supplementation. CONCLUSION: Collectively, dietary supplementation with PGZ plus CrMet improved growth performance and meat quality by decreasing the cooking loss and increasing the IMF and PUFA levels. © 2019 Society of Chemical Industry.

Research status and prospects on adenosine receptor mechanism of acupuncture for myocardial ischemia / 中国针灸

The relationship between adenosine receptor (AdoR) and myocardial ischemia (MI), effect of acupuncture for MI and action mechanism of acupuncture improving MI by regulating AdoR are summarized. The existing researches have preliminarily reflected that the improvement of MI treated with acupuncture may be achieved by influencing the expression of AdoR. However, there are still some limitations, e.g. most of the research regimens are single-acupoint, the research results are not entirely consistent and the interaction of AdoRs are ignored, all these need to be further verified and supplemented.

Rapid and visual detection for hypochlorite of an AIE enhanced fluorescence probe.

In this paper, a new 'turn-on' fluorescence probe for the rapid, sensitive, and visual detection of hypochlorite is reported. The push-pull type trianiline-tricyanofuran-based fluorescent probe was prepared using a condensation reaction between tricyanofuran and the thiophene-trianiline derivative that had high quantum yields and showed aggregation-induced emission enhanced properties. Upon exposure to hypochlorite, prominent fluorescence enhancement of the probe was observed via the release of the fluorophore from the probe. The probe showed a ratiometric absorption change at 315 nm and 575 nm. Importantly, the probe showed an excellent detection limit for hypochlorite at 1.2 × 10-7  M in solution and it was successfully applied for monitoring hypochlorite in waste water by test strip. This work reports a new fluorescence analytical sensing method for hypochlorite that has potential practical value in environmental monitoring and biological discrimination.

Two-channel near-infrared fluorescence Ag+ ion sensing of a new star-shaped dendrimer.

A new near-infrared fluorescence sensor PDI-PD for Ag+ ions was successfully prepared and its structure characterized by 1 H nuclear magnetic resonance (NMR), 13 C NMR and high-resolution mass spectrometry; matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (HRMS MALDI-TOF). The probe exhibited rapid, sensitive, and selective two-channel fluorescence responses towards Ag+ ions and protons. The probe has a marked high binding affinity and high sensitivity for Ag+ , with a detection limit of 1.4 × 10-6  M. An approximately five-fold enhanced core emission at 784 nm was attributed to fluorescence resonance energy transfer (FRET). The enhanced core emission of the probe with Ag+ ions based on photo-induced electron transfer and FRET is discussed. In addition, the probe presented a visible colour change. All experimental results demonstrated that PDI-PD is an efficient tool for the selective, sensitive and rapid detection of Ag+ ions and protons using two-channel fluorescence responses.

Synthesis and Application of A Flavone-based Fluorescent Probe for Detection of Hydrazine / 分析化学

A fluorescence enhancement probe (ZY8) for the detection of N2H4was designed and synthesized by employing 3-hydroxyflavone as a fluorophore,and its spectral properties had been investigated. The results showed that ZY8 had relatively good selectivity and specificity to N2H4in Tris-HCl-ethanol solution (9:1, V/V, pH 7.40). The fluorescent intensity of ZY8 exhibited good linear relationship with concentration of N2H4in the concentration range of 1.6×10-7mol/L-6.2×10-5mol/L,and its detection limit was estimated to be 1. 6×10-7mol/L. ZY8 itself had weak fluorescence, upon addition of N2H4, an approximate 9-fold fluorescence enhancement was observed, and the color of the solution changed from light grayish green to bright grass-green at UV light of 365 nm. So ZY8 might be used to the visual recognition of N2H4. ZY8 could detect N2H4in near-physiological pH range, and it had fast response and strong anti-interference ability. Moreover,ZY8 could be loaded as test paper for naked-eye detection of N2H4at mmol/L level in water solution,and it was also applied in the determination of N2H4in various water samples by the standard addition recovery experiments, with the recovery ratio ranged from 96.0% to 104.2% %, and RSD of all< 4%. The results of this study demonstrated that ZY8 had potential application to the detection of N2H4in the monitoring of environmental pollution.

The Relationship between Japanese Encephalitis and Environmental Factors in China Explored Using National Surveillance Data / 生物医学与环境科学（英文）

Japanese encephalitis (JE) is a serious public health issue. This study was undertaken to better understand the relationship between JE distribution and environmental factors in China. JE data from 2005 to 2010 were retrieved from National Notifiable Disease Report System. ArcGIS, remote sensing techniques, and R software was used to exhibit and explore the relationship between JE distribution and environmental factors. Our results indicated that JE cases were mostly concentrated in warm-temperate, semitropical and tropical zones with annual precipitation > 400 mm; Broad-leaved evergreen forest, shrubs, paddy field, irrigated land, dryland, evergreen coniferous forest, and shrubland were risk factors for JE occurrence, and the former five were risk factors for counties with high JE incidence. These findings will inform the effective allocation of limited health resources such as intensive vaccination, surveillance and training in areas with high environmental risk factors.

[Correlation studies in goats about the membrane thickness and pressure of the maxillary and frontal sinuses].

OBJECTIVE: This study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane. METHODS: The membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected. RESULTS: The top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03 ± 65.97), (461.33 ± 91.37), (216.90 ± 46.47) µm. The pressure were (260.08 ± 80.12), (306.90 ± 94.37), (121.72 ± 31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P < 0.05). The mean differences in membrane pressure were also statistically significant (P < 0.05). CONCLUSION: The membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane.

Correlation studies in goats about the membrane thickness and pressure of the maxillary and frontal sinuses / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aimed to explore the differences of membrane thickness and pressure on the paranasal sinus membrane in goats and analyze their causes. The results can provide theoretical basis and guidance for the issues of the maxillary sinus floor augmentation related to the membrane.</p><p><b>METHODS</b>The membrane was cut into two sizes from every sinus membrane. The membrane was fixed in formalin to obtain tissue specimens for the membrane thickness study and pressure study. The correlation between the two parameters was then analyzed, and appropriate statistical methods and software were selected.</p><p><b>RESULTS</b>The top of maxillary sinus, the bottom of maxillary sinus and the frontal sinus membrane thickness were (410.03 ± 65.97), (461.33 ± 91.37), (216.90 ± 46.47) µm. The pressure were (260.08 ± 80.12), (306.90 ± 94.37), (121.72 ± 31.72) kPa. The mean differences of the membrane thickness between the top of the maxillary sinus and the frontal sinus, bottom and frontal, and top and bottom were statistically significant (P < 0.05). The mean differences in membrane pressure were also statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>The membrane thickness and pressure of the top and bottom of the maxillary sinus are higher than those of the frontal sinus membrane. However, the thickness and pressure of the bottom membrane are slightly higher than those of the top membrane. Pressure and membrane thickness are positively correlated in the sinus membrane.</p>

Advanced research on characteristics of the classical subtype of human glioblastoma / 实用肿瘤学杂志

Glioblastoma(GBM)is one of the most common primary intracranial tumor that has high de-gree of malignancy ,invasive ability and a fatal prognosis .In recent years ,with the development of modern technol-ogy in biomedical sciences ,the understanding on GBM has developed gradually from pathological diagnosis to mo -lecular classifications ,which is based on the molecular characteristics of genetic signatures .Based on gene expres-sion and DNA methylation patterns , primary glioblastoma is divided into four subtypes , including the classical , neural,proneural and mesenchymal .These molecular classifications are closely relevant to the biological charac-teristics of glioblastoma .This review briefly introduces the molecular classifications of primary glioblastoma , but mainly focuses on the changes of the major genetic EGFR ,PTEN and PI3K,CDKN2A in the classical subtype of GBM,and discusses the treatment strategies for primary glioblastoma .

Two Fe3(µ3-S)2(CO)8 clusters with terminal N-heterocyclic carbenes.

The title compounds with terminal N-heterocyclic carbenes, namely octacarbonyl(imidazolidinylidene-κC(2))di-µ3-sulfido-triiron(II)(2 Fe-Fe), [Fe3(C3H6N2)(µ3-S)2(CO)8], (I), and octacarbonyl(1-methylimidazo[1,5-a]pyridin-3-ylidene-κC(3))di-µ3-sulfido-triiron(II)(2 Fe-Fe), [Fe3(C8H8N2)(µ3-S)2(CO)8], (II), have been synthesized. Each compound contains two Fe-Fe bonds and two S atoms above and below a triiron triangle. One of the eight carbonyl ligands deviates significantly from linearity. In (I), dimers generated by an N-H···S hydrogen bond are linked into [001] double chains by a second N-H···S hydrogen bond. These chains are packed by a C-H···O hydrogen bond to yield [101] sheets. In (II), dimers generated by an N-H···S hydrogen bond are linked by C-H···O hydrogen bonds to form [111] double chains.

Research progress on pharmacogenomics of antiretroviral drugs / 中国药理学通报

AIDS has become a global disease,and a variety of drugs are used in the treatment of AIDS ,but the interindividual variabilities in efficacy and toxicity remain important limitations for the use of these drugs.Studies have shown genetic polymor-phism is the main reason for interindividual variabilities of drug reaction.In recent years,scholars focused on the pharmacog-enomics of anti-AIDS drugs and found that genetic polymor-phisms,in large part,determine the interindividual variabilities of the responese of these drugs.This paper reviews the research progress on pharmacogenomics of the four types of anti-AIDS drugs commonly used in China,including nucleoside reverse transcriptase inhibitors (NRTIs),non-nucleoside reverse tran-scriptase inhibitors (NNRTIs),protease inhibitors (PIs)and integrase inhibitors (raltegravir).