Correlation between PIK3CA mutation and clinicopathological features and prognosis of breast cancer / 基础医学与临床

Objective To find the correlation between phosphatidylinositol kinase-3 catalytic subunit A gene(PIK3CA)mutation and pathological features as well as clinical prognosis of breast cancer.Methods The patho-logical data of 181 patients diagnosed with invasive breast cancer from January 2018 to January 2020 were collected.The estrogen receptor(ER),progestogen receptor(PR),human epidermal growth factor receptor-2(HER2),Ki67 were examined by immuno-histochemistry(IHC).Mutation of exon 9 and exon 20 of PIK3CA were examined by quantitative real-time PCR(qPCR).Results Among 181 cases of invasive breast cancer,70 cases had PIK3CA mutation with 31 cases(44.28%)showed exon 9 mutations and 39 cases(55.71%)showed exon 20 mutations.The difference between PIK3CA mutation and their distribution in molecular typing of breast cancer was statistically significant(P＜0.05).The expression of PIK3CA mutation in breast cancer with different Ki67 expression was sig-nificantly different(P＜0.05).There were 34 cases(48.57%)showed PIK3CA mutations in the HR+/HER2 group and 36 cases(51.43%)of non HR+/HER2 group mutations.There was a statistically significant difference in the distribution of PIK3CA mutations between 2 groups(P＜0.05).The death rate of PIK3CA mutation cases was higher than that of PIK3CA wild type cases(P＜0.05).Conclusions PIK3CA mutation is associated with molecular typ-ing,Ki67 increment index and prognosis of breast cancer.Detection of PIK3CA mutation provides potential support to the development of precise treatment of breast cancer patients.

Fluorescence Sensor for Zearalenone Detection Based on Oxidized Single-walled Carbon Nanohorns/N-doped Carbon Quantum Dots-aptamer.

Zearalenone (ZEN), a resorcinolactone toxin, which has been a potential threat to agricultural production and human health. In this study, a sample and rapid fluorescence sensor was established for the detection of ZEN, which is based on the fluorescence properties of N-doped carbon dots-aptamer (NCDs-apt) and the quenching ability of oxidized single-walled carbon nanohorns (oxSWCNHs). NCDs synthesized by one-step hydrothermal method were connected with ZEN-aptamer (ZEN-apt), and oxSWCNHs were added to quench the fluorescence of NCDs-apt. Therefore, an oxSWCNHs/NCDs-apt aptasensor based on fluorescence "on-off" for the determination of ZEN in food was formed. Under optimum conditions, the limit of detection (LOD) of this method was 18 ng/mL and the linear range was 20 ~ 100 ng/mL. The possible interfering substances were investigated, and the results showed excellent selectivity. The recoveries were in the range of 99.5%~114.3%, and the relative standard deviations (RSDs) were not more than 6.5%, which demonstrated that this aptasensor was successfully applied for the detection of ZEN in food samples with satisfactory result.

Vortex-assisted dispersive liquid-liquid microextraction based on the hydrophobic deep eutectic solvent-based ferrofluid for extraction and detection of myclobutanil.

A vortex-assisted dispersive liquid-liquid microextraction (VA-DLLME) procedure using hydrophobic deep eutectic solvent-based ferrofluid (HDES-FF) as an extractant was established. The developed sample preparation method coupled with high-performance liquid chromatography-diode array detector (HPLC-DAD) was applied to the pretreatment and determination of myclobutanil (MYC) in fruit juice. Hydrophobic deep eutectic solvent, synthesized by n-decanoic acid and DL-menthol, was as a carrier and combined with magnetic nanoparticles (Fe3O4@OA) to form HDES-FF as an extractant with high extraction capacity. The synthesized materials were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), and vibrating sample magnetometer (VSM). Parameters affecting extraction efficiency were optimized using single-factor experiments and Box-Behnken design via response surface methodology (BBD-RSM). Parallel tests were performed three times under the optimal conditions predicted by the model, yielding an actual mean recovery of 94.77% with RSD of 2.7% (n = 3) and an enrichment factor of 41.8 ± 0.98 (mean value ± SD, n = 3). Under the optimal conditions, the linear range was 1.0-100.0 µg·mL-1; the limit of detection (LOD) and limit of quantification (LOQ) were 0.25 and 0.80 µg·mL-1, respectively. The average spiked recoveries in the samples ranged from 98.2 to 100.5% with intra-day relative standard deviations (RSDs) of 1.2-3.5% (n = 3) and inter-day RSDs of 1.1-3.8% (n = 3). Finally, the method was successfully applied to the determination of MYC antimicrobial agent in different fruit juice samples. The proposed HDES-FF-VA-DLLME/HPLC-DAD method was verified to widely apply to the extraction of triazole fungicides.

Polylactic-co-glycolic acid-based nanoparticles modified with peptides and other linkers cross the blood-brain barrier for targeted drug delivery.

Because of the blood-brain barrier, only a limited fraction of drugs can penetrate the brain. As a result, there is a need to take larger doses of the drug, which may result in numerous undesirable side effects. Over the past few decades, a plethora of research has been conducted to address this issue. In recent years, the field of nanomedicine research has reported promising findings. Currently, numerous types of polylactic-co-glycolic acid-based drug-delivery systems are being studied, and great progress has been made in the modification of their surfaces with a variety of ligands. In this review, the authors highlight the preparation of polylactic-co-glycolic acid-based nanoparticles and single- and dual-targeted peptide modifications for site-specific drug delivery into the brain.

The blood­brain barrier prevents many drugs used to treat brain diseases from having clinical effects. To solve this issue, some promising findings have been reported in the field of nanomedicine research, which will be introduced in this article as possible effective methods for the treatment of brain diseases. This review will focus on the nature of the polylactic-co-glycolic acid polymers involved in the preparation of desired targeted nanocarriers, the synthesis methods for achieving the drug loaded system and the choice and preparation of the targeting agents.

Cell Membrane Biomimetic Nanoparticles with Potential in Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is to blame for about 60% of dementia cases worldwide. The blood-brain barrier (BBB) prevents many medications for AD from having clinical therapeutic effects that can be used to treat the affected area. Many researchers have turned their attention to cell membrane biomimetic nanoparticles (NPs) to solve this situation. Among them, NPs can extend the half-life of drugs in the body as the "core" of the wrapped drug, and the cell membrane acts as the "shell" of the wrapped NPs to functionalize the NPs, which can further improve the delivery efficiency of nano-drug delivery systems. Researchers are learning that cell membrane biomimetic NPs can circumvent the BBB's restriction, prevent harm to the body's immune system, extend the period that NPs spend in circulation, and have good biocompatibility and cytotoxicity, which increases efficacy of drug release. This review summarized the detailed production process and features of core NPs and further introduced the extraction methods of cell membrane and fusion methods of cell membrane biomimetic NPs. In addition, the targeting peptides for modifying biomimetic NPs to target the BBB to demonstrate the broad prospects of cell membrane biomimetic NPs drug delivery systems were summarized.

Analysis Methods of Common Herbicides in Biological Material and Research Progress / 法医学杂志

Herbicides are a kind of chemical or biological agents that can effectively destroy or inhibit weed growth. Because of the widespread and frequent use of herbicides, herbicide poisonings have often been reported. At present, the main species reported to have caused poisoning are paraquat, diquat, glyphosate, and glufosinate. The main instrumental analysis method is LC-MS. This paper reviews the research progress on analysis methods of common herbicides in biological material and their application, summarizes the sample pretreatment and instrumental analysis situation of qualitative and quantitative analysis of herbicides in biological material, and collects test data of actual poisoning cases, to provide reference for clinical diagnosis and treatment and forensic identification of herbicide poisoning.

Metabolism of New Psychoactive Substances 4F-MDMB-BUTINACA in Zebrafish / 法医学杂志

Objective To study the metabolic transformation pathways of 4F-MDMB-BUTINACA in vivo by establishing zebrafish models. Methods Six adult zebrafish were randomly divided into blank control group and experimental group, with three fish in each group. After the zebrafish in the experimental group were exposed to 1 μg/mL 4F-MDMB-BUTINACA for 24 h, they were transferred to clean water and cleaned three times, then pretreated for instrumental analysis. The zebrafish in blank control group were not exposed to 4F-MDMB-BUTINACA. Mass spectrometry and structural analysis of 4F-MDMB-BUTINACA and its metabolites were conducted by liquid chromatography-high resolution mass spectrometry and Mass Frontier software. Results A total of twenty-six metabolites of 4F-MDMB-BUTINACA were identified in zebrafish, including eighteen phase Ⅰ metabolites and eight phase Ⅱ metabolites. The main metabolic pathways of phase Ⅰ metabolites of 4F-MDMB-BUTINACA in zebrafish were ester hydrolysis, N-dealkylation, oxidative defluorination and hydroxylation, while the main metabolic pathway of phase Ⅱ metabolites was glucuronidation. Conclusion Metabolite Md24 （ester hydrolysis） and Md25 （ester hydrolysis combined with dehydrogenation） would be recommended to be potentially good biomarkers for abuse of 4F-MDMB-BUTINACA.

Formulation regularity and thinking of adjuvant sleep-improving Chinese medicinal health products / 中国中药杂志

To summarize and analyze the current adjuvant sleep-improving Chinese medicinal health products,this study retrieved the information on health products with the sleep-improving effect published by the Department of Special Food Safety Supervision and Management,State Administration for Market Regulation( SMAR),which was statistically analyzed with Microsoft Excel and TCMISS for the characteristics of formulations. A total of 435 sleep-improving health products were collected,including 344 ones containing Chinese herbal medicines. Among them,413 health products were not suitable for adolescents,neither 194 for pregnant women. Ten Chinese herbal medicines showed a frequency of use ≥40,with 1 095 times( 73. 1%) in use. Through unsupervised hierarchical entropy-based clustering of the above Chinese herbal medicines of health products( degree of support of 45 and confidence coefficient of0. 7),12 new formulas were obtained. The composition of Chinese herbal medicines was consistent with the principles of improving sleep in traditional Chinese medicine( TCM) theories,i. e.,replenishing the heart and spleen,nourishing blood,calming the nerves,nourishing Yin,reducing internal heat,communicating the heart and kidney,replenishing Qi,relieving convulsions,clearing heat,resolving phlegm,regulating the middle warmer,soothing the liver,relieving heat,and calming the heart. According to TCM theories,syndrome differentiation was performed based on the existing sleep-improving health products,followed by data mining and analysis according to the formulation regularity,aiming to provide new ideas for the development of new Chinese medicinal health products. In particular,attention should be attached to the requirements of special populations to provide a basis for follow-up studies,exert the advantages of TCM,and lay a foundation for Chinese medicinal health products to service the public.

Effect of Açaí oil, alcohol extract and water extract on temperature tendency and metabolic level of mice with deficiency-feat and deficiency-cold / 中国中药杂志

To investigate the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the temperature tendency animal behavior and intrinsic biochemical indexes, such ascyclic nucleotides and metabolic level, in mice with deficiency-heat and deficiency-cold syndrome, in order to study the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling. KM mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given thyroid tablet solution(160 mg·kg~(-1)), the mice in deficiency-cold group were given hydrocortisone solution(25 mg·kg~(-1)) through gastric perfusion every afternoon for 14 days, and each administration group was given the corresponding drug. The temperature tendency, cyclic nucleotides and metabolic level of animals were measured after the experiment. The Açaí alcohol extract was consistent with the Açaí powder, with a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinnamomi Cortex, with a regulatory effect on the deficiency-cold model mice. In this study, based on the parable theory of traditional Chinese medicine's properties and tastes, property of alcohol extract of Açaí was cool, while the property of oil and water extract were warm, the alcohol extract of Açaí was the material basis of Açaí cold medicine by the methods of homogeneous comparison and heterogeneous disproval.

Study on material basis of Açaí cold drug based on neuro-endocrine-immune network / 中国中药杂志

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.