Effects of diisononyl phthalate on lipid metabolism in HepG2 cells / 环境与职业医学

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L−1). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L−1), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L−1 after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L−1, respectively (P<0.05). After exposure to 30 mmol·L−1 and 100 mmol·L−1 DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L−1 DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L−1 group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L−1 DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L−1 and 100 mmol·L−1 can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.

Synthesis and antibacterial activities of phosphonate derivatives containing aminothiazoloxime fragment / 药学学报

Based on the principle of molecular hybridization, fifteen compounds were designed and synthesized through the combination of aminothiazoloxime and phosphonate fragment. The results showed that these compounds had better inhibitory effects on the tested bacteria. In particular, the activities of compounds Ⅲf and Ⅲi against S. aureus, E. coli, methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FREC) were the most significant, the minimal inhibitory concentration (MIC) of Ⅲf was 1, 8, 4, 16 μg·mL-1 respectively, and the MIC of Ⅲi was 4, 4, 16, 8 μg·mL-1 respectively, which were slightly lower than that of the control drug oxacillin, and their anti-E. coli, MRSA and FREC activities were superior to that of the control drug oxacillin. Their activities to S. aureus were close to that of oxacillin, and to E. coli, MRSA and FREC were superior to that of oxacillin, which is worthy of further study.

Kinase modulators approved by FDA in 2022 / 药学学报

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

Synthesis and biological activities of chlorin e6-based conjugate of fluorouracil as dual-mode antitumor photosensitizer / 药学实践杂志

Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 171- and 152 cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, 1H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.

Methodology for the Development of Clinical Practice Guidelines for Chinese Patent Medicine（Part 4）： Evidence Retrieval and Evaluation / 中医杂志

The retrieval and evaluation of evidence is the basis for the development of clinical practice guidelines for Chinese patent medicine. As traditional Chinese medicine has a different development trajectory and utilization characteristics from modern medicine， there is certain differences in terms of evidence composition， retrieval and integration.This paper discussed multi-source body of evidence on Chinese patent medicine based on modern evidence-based medicine and ancient medical literature， and summarized the retrieval strategy as well as the possible problems and solving methods. For different types of evidence on Chinese patent medicine， the corresponding evaluation tools have been recommended， and the order to integrate the evidence based on the quality of the evidence from high to low is suggested. Finally， a multi-source based evidence retrieval-evaluation-integration scheme for Chinese patent medicine has been formed， which will provide a methodological reference for practitioners in the development of clinical practice guidelines for Chinese patent medicine.

Ecological and biological patterns of stream fish studies from the Piracicaba-CapivariJundiaí Basin (PCJ Basin, SP) assessed through a systematic review / Padrões ecológicos e biológicos de estudos de peixes de riachos da Bacia PiracicabaCapivari-Jundiaí (Bacia PCJ, SP) avaliados por meio de uma revisão sistemática

Tropical streams are among the most threatened ecosystems in the world. As such, studies carried out and compiled over spatial and temporal scales can provide useful information to examine patterns of species diversity and threats to their survival. Here we conducted a systematic review of published research on biological and ecological aspects of stream fish fauna found in the Piracicaba-Capivari-Jundiaí Basin, an industrial watershed of São Paulo State. We aimed to detect main patterns, trends and gaps in studies related to species composition, distribution, spatial and temporal scales, as well as in the covered topics. Results were related to main land uses, biomes and Conservation Units. A constant increase in published articles occurred from 2003 until 2016 with an average of 1.8 articles/year. Twenty-six publications were considered for the present study, reporting on fish samples obtained in 67 sites and resulting in 89 species. A high proportion of studies were concentrated in the Corumbataí sub-basin, and rarefaction curves indicated that stream fish richness in the PCJ Basin may be considerably higher than that shown by the actual numbers. Basin studies were unevenly distributed and did do not include such highly preserved areas as the Camanducaia, Jaguari and Jundiaí sub-basins. We emphasize the importance of further surveys in these regions, as well as in high priority conservation areas, which may lead to new insights for developing appropriate conservation strategies for this basin.

Riachos tropicais estão entre os ecossistemas mais ameaçados do mundo e a compilação de estudos temporais e espaciais pode fornecer informações úteis para examinar padrões de diversidade de espécies e ameaças nesses sistemas. Realizamos uma revisão sistemática das pesquisas publicadas sobre aspectos biológicos e ecológicos da ictiofauna de riachos da bacia do Piracicaba-Capivari-Jundiaí, uma bacia industrial do Estado de São Paulo. O objetivo foi detectar os principais padrões, tendências e lacunas em estudos relacionados à composição, distribuição de espécies, escalas espaciais, temporais e temas abordados. Os resultados foram relacionados aos principais usos do solo, biomas e Unidades de Conservação. Foi verificado um aumento constante de artigos entre 2003 e 2016, com média de 1,8 artigos/ano. Vinte e seis publicações foram consideradas para o estudo, que indicaram 67 locais amostrados, e o registro de 89 espécies. Uma alta proporção deles concentrou-se na sub-bacia de Corumbataí e curvas de rarefação indicaram que a riqueza de peixes de riacho na bacia do PCJ deve ser consideravelmente maior do que os números atuais. A distribuição desigual de estudos na bacia, que não inclui áreas altamente preservadas como as sub-bacias de Camanducaia, Jaguari e Jundiaí, enfatiza a necessidade de se obter mais informações nessas regiões, bem como em áreas de conservação de alta prioridade. Novas abordagens relacionadas a conceitos e teorias ecológicas em estudos futuros poderão fornecer informações que ajudem a desenvolver estratégias de conservação adequadas para esta bacia.

Keratinase mediated fabrication and partial characterization of gold nanoparticles and its antibacterial potential

Keratinase is mainly involved in recycling of keratin waste. Of late, researchers extended its application to nanotechnology. In the present study, we have made an attempt to fabricate and characterize gold nanoparticles using crude keratinase enzyme from Serratia ficaria and also study their biological application, particularly antibacterial activity. The formation of gold nanoparticles (AuNPs) was first verified by UV-Visible Spectroscopy. FTIR spectra confirmed the presence of responsible secondary metabolites for stabilization of nanoparticles. The morphological characteristics and particle size of synthesized nanoparticles were analyzed. The AuNPs showed significant antibacterial activity against Klebsiella pneumonia, Bacillus cereus and Staphylococcus aureus. The highest radical scavenging activity, 60.62% for AuNPs was observed at 500 µg/mL. Results of this study reveals significance of keratinase application in nano-based biological applications.

Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil

Abstract Remifentanil is a modern fentanyl analogue with ultrashort-action granted by an esterase-labile methyl propanoate chain. Here, we present the development of a continuous flow methodology for the key N-alkylation step of remifentanil preparation in a biphasic, "slug-flow" regime. We screened parameters under microwave-assisted reactions, translated conditions to flow settings, and obtained remifentanil under 15-min residence time in a 1-mL microreactor, with a space-time yield of 89 mg/mL·h and 94% yield.

Effective interventions for the promotion of breastfeeding and healthy complementary feeding in the context of Primary Health Care / Intervenções efetivas para a promoção da amamentação e da alimentação complementar saudável no contexto da Atenção Primária à Saúde

Abstract Objective: To develop a rapid review on effective actions for the promotion of breastfeeding and healthy complementary feeding in primary health care and to summarize a list of actions and their elements for implementation. Data source: The review included systematic reviews on the effectiveness of interventions to promote breastfeeding and/or healthy complementary feeding for mothers and other caregivers, and/or professionals who work with this population, in comparison with any usual approach or none. Data synthesis: A total of 32 systematic reviews were included in the evidence synthesis. Ten types of interventions were evaluated in systematic reviews on promotion of breastfeeding and four types of interventions on promotion of healthy complementary feeding. The synthesis allowed six aspects to be discussed, and these must be considered to increase the chances of interventions' impact: type of intervention, target audience, timing of intervention, actors that can implement it, strategies and methods of intervention, and intensity of intervention. Conclusions: It was possible to assemble a list of actions whose effectiveness has already been demonstrated, providing elements for local adaptations. Evidence is expected to support and strengthen the implementation of programs aimed at promoting breastfeeding and complementary feeding in primary health care.

Resumo Objetivo: Desenvolver uma revisão rápida sobre intervenções efetivas para a promoção do aleitamento materno e da alimentação complementar saudável na Atenção Primária à Saúde e sintetizar um cardápio de ações e seus elementos para implementação. Fontes de dados: Foram incluídas revisões sistemáticas que avaliaram a efetividade de intervenções para promoção do aleitamento materno e/ou alimentação complementar saudável com mães e outros cuidadores e/ou profissionais que atuam com essa população em comparação com qualquer abordagem usual ou nenhuma. Síntese dos dados: Na síntese das evidências, foram incluídas 32 revisões sistemáticas. Nas revisões sistemáticas, foram avaliados dez tipos de intervenções no tema "promoção do aleitamento materno" e quatro tipos de intervenções no tema "promoção da alimentação complementar saudável". A síntese dos resultados permitiu discutir seis aspectos da implementação que devem ser considerados para aumentar as chances de impacto das intervenções: tipo de intervenção, público-alvo, momento da intervenção, atores que podem implementar, estratégias e métodos para conduzir a intervenção, e intensidade da intervenção. Conclusões: Os resultados permitiram apresentar um cardápio de ações cuja efetividade já foi demonstrada, fornecendo elementos para adaptações locais. Espera-se que as evidências apresentadas possam apoiar e fortalecer a implementação de programas de promoção do aleitamento materno e da alimentação complementar saudável na Atenção Primária à Saúde.

Comensalidade, câncer e sobrevivência: uma metassíntese qualitativa sobre experiências alimentares de pacientes após o diagnóstico de câncer / Commensality, cancer and survival: A qualitative meta-synthesis of patients' food experiences after cancer diagnosis

Resumo Objetivo Compreender as experiências e as práticas alimentares a partir do diagnóstico de câncer. Método: Trata-se de uma pesquisa bibliográfica, do tipo metassíntese qualitativa. Utilizou-se a diretriz ENTREQ como protocolo, tendo como pergunta norteadora: "Quais são as experiências e as práticas alimentares de indivíduos após o diagnóstico de câncer?". A busca foi realizada nas bases de dados Lilacs, Pubmed, Embase e Food Science and Techonology, a partir da combinação de palavras-chave relacionadas à alimentação e nutrição, ao adoecimento por câncer e à pesquisa qualitativa, publicados entre 2015 e 2020, em português, inglês e espanhol. Método Foram encontrados 414 artigos e excluídos 396, após leitura dos títulos e resumos. Além dos 18 artigos potenciais, foram incluídos cinco artigos de outras fontes, totalizando 23. Foram identificadas três categorias empíricas: ruptura da trajetória alimentar e estratégias de adaptação; reconstrução da identidade; e vicissitudes da comensalidade. Conclusões As perdas relacionadas à alimentação impactam na existencialidade do ser, na expressão da identidade e nas relações sociais, podendo levar ao isolamento e a desritualização da alimentação. As mudanças físicas podem levar a distúrbios de imagem corporal e sofrimento psíquico. Em decorrência dos sintomas de impacto nutricional, a família é o suporte emocional para reorganização da alimentação.

Abstract Objective To understand the experiences and eating practices from the diagnosis of cancer. Method This is a bibliographic research, of the qualitative meta-synthesis type, using the ENTREQ guideline as a protocol, with the guiding question: "What are the experiences and eating practices of individuals after being diagnosed with cancer?". The search was carried out in the Lilacs, Pubmed, Embase and Food Science and Techonology databases based on the combination of keywords related to food and nutrition, illness from cancer and qualitative research, published between 2015 and 2020, in Portuguese, English and Spanish. Results 414 articles were found and 396 were excluded after reading the titles and abstracts. In addition to the 18 potential articles, 5 articles from other sources were included, totaling 23. Three empirical categories were identified: disruption of the food trajectory and adaptation strategies; reconstruction of identity; and vicissitudes of commensality. Conclusions Losses related to food impact the existentiality of being, the expression of identity and social relationships, which can lead to the isolation and de-ritualization of food. Physical changes can lead to body image disorders and psychological distress. Due to the symptoms of nutritional impact, the family is the emotional support for the reorganization of food.

Solriamfetol impurities:Synthesis,characterization,and analytical method(UPLC-UV)validation / 药物分析学报

Given that impurities may affect the quality and safety of drug products,impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol,which is used to treat excessive daytime sleepiness.Although the high-performance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities,their synthesis,structure elucidation,and chromatographic determination have not been reported yet.To bridge this gap,we herein identified,synthesized,and isolated eight process-related solriamfetol impurities,characterized them using spectroscopic and chromatographic tech-niques,and proposed plausible mechanisms of their formation.Moreover,we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection,revealing that its selectivity,linearity,accuracy,precision,and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.Thus,the developed method was concluded to be suitable for the routine analysis of solriamfetol substances.

Psychological experiences in adolescents with non-suicidal self-injury behavior： a qualitative Meta-synthesis / 四川精神卫生

BackgroundNon-suicidal self-injury （NSSI） is a serious global public health issue and an important risk factor for suicide attempts and completed suicide. The incidence of NSSI among adolescents in China is 27.4%. Therefore， it is critical to address NSSI and prevent its progression into more severe mental health conditions. ObjectiveTo systematically evaluate the psychological experiences and needs of adolescents with NSSI behavior， so as to provide references for formulating targeted intervention strategies for this demographic. MethodsA computer search was conducted across a total of eleven databases， including Cochrane Library， Embase， PubMed， PsycINFO， Web of Science， CINAHL， Medline， CNKI， Wanfang， VIP and CBM， to gather qualitative research on the psychological experiences and needs of adolescents with NSSI behavior. The search extended from the establishment of these databases up to March， 2023. The Australian Joanna Briggs Institute （JBI） qualitative research quality evaluation tools were used to evaluate the included literature， and a Meta-synthesis method was used to integrate the results. ResultsA total of 11 studies were included， yielding 46 research findings. Similar findings were consolidated into 10 new categories， ultimately resulting in 5 synthesized outcomes， including interpersonal conflict， academic pressure and self-reflective struggles， self-injurious behaviors intertwined with inner emotions， the power of love to overcome helplessness， and adjustment and seeking positive coping strategies. ConclusionAdolescents often have experienced negative life events before NSSI behaviors， with notable conflicts in interpersonal relationships， academic pressures and family education. Following NSSI behavior， they undergo various psychological experiences， such as transient feelings of relief， dependence and guilt. In addition， they crave guidance and assistance from professionals to cope with negative emotions.［Funded by Social Psychological Service and Crisis Intervention in 2022 （number， LZXL-202213）］

The stereoselective synthesis of privileged epimer of C-10 carba artemisinins and the effect of substituted groups with different acid-base properties on the antimalarial activity / 药学学报

Artemisinin is a sesquiterpene lactone natural product that contains an endoperoxide bond. Artemisinin has various biological activities including antimalarial, anti-tumor, antiviral and anti-fibrotic activity. Owing to the poor pharmacokinetic properties of artemisinin, its derivatives are currently used in clinic and frequently reported in literature. Although numerous derivatives of artemisinin have been reported, no study has been carried out yet to study the effect of substituted groups with different acid-base property on the antimalarial activity. Among these derivatives, the C-10 carbon artemisinin derivatives are often reported, and their corresponding 10β epimer show much better antimalarial activity than 10α epimer with large-sized substitute. However, there is currently no stereoselective synthesis to efficiently prepare the privileged 10β epimer of C-10 carba artemisinin. To address these two scientific questions, we herein first report an optimized method to stereoselectively synthesize the 10β epimer of C-10 carba artemisinin (98∶2 d.r.). Second, we employed the optimized method to synthesize a series of C-10 carba artemisinin derivatives with different acid-base properties. The antimalarial examination indicated that those derivatives with neutral groups or basic group of short chain showed similar antimalarial activity as dihydroartemisinin (DHA). The acidic group could dramatically decrease the antimalarial effect and was more than 22-fold less effective than DHA or the neutral ones. This study will shed light on the development of new generation of artemisinin derivatives with potent activity.

Synthesis and antifungal evaluation of chalcone derivatives combined with fluconazole against drug-resistant Candida albicans / 中国药科大学学报

@#Chalcone is a common scaffold in natural products with optimal properties and biological activities.In this study, we designed and prepared eight new coumarin-chalcone derivatives (5a-5h), and confirmed their structures by 1H NMR and 13C NMR. Their in vitro antifungal activity combined with fluconazole (FLC) against drug-resistant Candida albicans was tested by microdilution method.The results indicated that most chalcone derivatives showed good antifungal activity against drug resistant Candida albicans with FLC, particularly with compound 5g displaying better antifungal activity (MIC50 = 5.60 μg/mL) than FLC (MIC50 = 200 μg/mL) when combined with FLC, so, these derivatives could be used as synergists of antifungal drugs.

Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors / 药学学报

To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.

Research progress of bio-metal organic frameworks in drug delivery system / 中国药科大学学报

@#In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

Design, synthesis and antifungal activity of novel triazoles containing propyl side chains / 药学实践杂志

Objective To study the antifungal activity of a new series of triazole compounds with n-propyl side chain and disubstituted benzyl structure. Methods Eleven target compounds were designed and synthesized. The structures were confirmed by 1H NMR, and some compounds were confirmed by 13C NMR or HRMS. Three fungal strains were selected as experimental strains, and the antifungal activity was tested in vitro according to the standardized antifungal sensitivity test method recommended by National Committee for Clinical Laboratory Standards (NCCLS). Results Compound B11 showed better activity against candida albicans SC5314 than fluconazole and was comparable to posaconazole; Compounds B10, B11 and B4 showed better activity against cryptococcus neoformanis H99 than fluconazole, while compounds B2, B3, B5, B6 and B7 showed similar activity to fluconazole against cryptococcus neoformanis H99; while all compounds showed poor activity against aspergillus fumigatus. Conclusion Some of the target compounds with n-propyl side chain and disubstituted benzyl group structure had certain antifungal activity and could be identified as potential lead antifungal drugs.

Design, synthesis and antidiabetic activity studies of purine derivatives / 药学学报

Based our previous work, twelve purine derivatives were designed and synthesized as dual modulators of GPR119 and DPP-4by conjugating the GPR119 activating and DPP-4 inhibiting fragments with the position 6 and 9 of purine core via an approach of merged pharmacophores. Compound 11, bearing 2-fluoro-4-methylsulphonyl anilide and cyanopyrrolidine moieties, exhibited the most potent GPR119 agonistic activities (EC50 = 0.33 μmol·L-1, IA = 71.1%) and DPP-4 inhibitory (58.4% inhibition at 10 μmol·L-1, 21.2% inhibition at 1 μmol·L-1) activities in the in vitro antidiabetic study. Subsequently, we performed studies on structure activity relationships and molecular docking to guide the further drug design.

Nurses′ experience and reality dilemma in advance care planning:a qualitative meta-synthesis / 中国实用护理杂志

Objective:To systematically evaluate and integrate the qualitative research of the practical experience and practical difficulties of advance care planning (ACP), so as to provide a reference for subsequent clinical nurses to better carry out ACP.Methods:PubMed, Web of Science, Embase, Cochrane Library, CINAHL, CNKI, Wanfang, VIP, Chinese Biomedical Literature Database were collected the qualitative research on the practical experience and practical difficulties of nurses′advance care planing, and the search time was the database establishment until August 1, 2022. Literature quality evaluation was conducted by the Joanna Briggs Institute (JBI) (2016), and the results were summarized using Meta integration method.Results:A total of 13 studies were included, and 39 studies were summarized into 11 new categories, forming 4 integrated results: nurses′ cognition of ACP practice, emotional experience of nurses′ ACP practice, personal factors that hinder ACP practice, and external environmental factors that hinder ACP practice.Conclusions:In ACP practice, nurses should be actively guided to have positive cognitive and emotional experience to improve their competence in ACP practice. At the same time, government departments should be united to support, integrate hospitals, society and other forces to formulate coping strategies against obstacles, so as to promote the development and practice of ACP.

Meta synthesis of qualitative research on male participation in traumatic childbirth experience / 中国实用护理杂志

Objective:To systematically review the qualitative research on male participation in traumatic childbirth experience, and to provide reference for promoting and improving the physical and mental health and paternity experience of expectant fathers.Methods:Qualitative research on male participation in traumatic childbirth experience published in databases of PubMed, Embase, Web of Science, Spring Link, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM) and Wanfang Database were searched from the establishment of the database to June 2022. The quality of literature was evaluated by the quality evaluation standard of Australian JBI Evidence-based Health Care Center, and the pooled integration method in Meta integration was used to integrate the results.Results:A total of 12 articles were included, and 51 main research results were extracted, which were further summarized into 10 categories, and 4 integrated results were formed: men had prominent negative emotional experience; men lack decision-making participation and communication with medical staff during traumatic childbirth; the impact of traumatic childbirth experience on men; perception and coping after traumatic childbirth.Conclusions:Medical staff should pay attention to the emotional experience of men participating in traumatic childbirth, meet their decision-making information needs in the process of accompanying delivery, identify negative emotions in time after delivery and provide help and support, strengthen the family-centered perinatal health service model, promote the physical and mental health of expectant fathers, and improve the family well-being.