RESUMEN
OBJECTIVES: In this study, we describe the patterns of antibiotic prescription for neonates based on World Health Organization's (WHO) Essential Medicines List Access, Watch, and Reserve (AWaRe), and the Management of Antibiotic Classification (MAC) Guidelines in China. METHODS: One-day point-prevalence surveys (PPS) on antimicrobial prescriptions were conducted on behalf of hospitalized neonates in China from September 1 and November 30, annually from 2017 to 2019. RESULTS: Data was collected for a total of 2674 neonatal patients from 15 hospitals in 9 provinces across China of which 1520 were newborns who received at least one antibiotic agent. A total of 1943 antibiotic prescriptions were included in the analysis. The most commonly prescribed antibiotic was meropenem (11.8%). The most common reason for prescribing antibiotic to neonates was pneumonia (44.2%). There were 419 (21.6%), 1343 (69.1%) and 6 (0.3%) antibiotic prescriptions in the Access, Watch and Reserve groups, respectively. According to MAC Guidelines in China, there were 1090 (56.1%) antibiotic agents in the Restricted and 414 (21.3%) in the Special group. CONCLUSION: Broad-spectrum antibiotics included in the Watch and Special groups were likely to be overused in Chinese neonates.
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Antibacterianos , Prescripciones de Medicamentos , Humanos , Recién Nacido , Prevalencia , Encuestas de Atención de la Salud , Antibacterianos/uso terapéutico , China/epidemiologíaRESUMEN
Over the past decade, immunotherapies have brought about significant changes in how we approach the treatment of various solid tumors and blood-related cancers. However, the effectiveness of checkpoint blockade therapy has been constrained to a rate of under 30â¯%. A significant challenge in the realm of tumor immunotherapy revolves around comprehending the mechanisms through which regulatory T (Treg) cells induce immunosuppression. We have recently discovered that USP22 (ubiquitin-specific peptidase 22) a deubiquitinating enzyme that is increased in various tumors, is an oncogene and controls Treg immune suppressive activity for tumor evasion, providing a rationale for USP22 targeting to achieve both onco- and immuno-therapeutic efficacies. Herein, we identified the traditional Chinese secoiridoid compound gentiopicroside as a USP22 inhibitor. Gentiopicroside treatment decreased the forkhead box P3 (Foxp3) expression, which subsequently reduced Treg immune suppressive activity. Treatment of cancer cells by gentiopicroside resulted in an increase in histone 2B monoubiquitination (H2Bub) in a USP22-dependent manner and a decrease in programmed cell death ligand 1 (PD-L1) expression, both of which are known as USP22-specific substrates. Docking and molecular dynamic simulation revealed that gentiopicroside stably binds to USP22 catalytic pocket, supporting that gentiopicroside is a USP22 inhibitor. Importantly, administration of gentiopicroside to mice significantly inhibited the growth of syngenetic lung adenocarcinoma. Further analysis of intratumoral immune cells revealed a dramatic increase CD8+ T cell production of IFN-γ and granzyme B (GZMB), confirming that gentiopicroside enhances antitumor immunity. Our study revealed that gentiopicroside is a USP22-specific inhibitor with potent antitumor therapeutic potentials.
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Inmunoterapia , Glucósidos Iridoides , Linfocitos T Reguladores , Ubiquitina Tiolesterasa , Glucósidos Iridoides/farmacología , Humanos , Animales , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Inmunoterapia/métodos , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/antagonistas & inhibidores , Ratones , Línea Celular Tumoral , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Factores de Transcripción ForkheadRESUMEN
BACKGROUND: We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD). DESIGN AND METHODS: This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR. RESULTS: A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively. CONCLUSION: LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD.
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Proteína C-Reactiva , Aneurisma Coronario , Síndrome Mucocutáneo Linfonodular , Humanos , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/diagnóstico , Estudios Retrospectivos , Masculino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Femenino , Preescolar , Lactante , Aneurisma Coronario/etiología , Aneurisma Coronario/inmunología , Niño , Linfocitos/inmunología , Vasos Coronarios/patología , Biomarcadores/sangre , Curva ROCRESUMEN
Objectives: Use of Broad-spectrum antibiotics is related closely to increasing antimicrobial resistance. Reports on antibiotic prescriptions for Chinese children were rare. We described the prescribing patterns of antibiotic prescriptions for Chinese children from 2017 to 2019 based on the Anatomical Therapeutic Chemical Classification (ATC classification); the Access, Watch, and Reserve (AWaRe) classification from the World Health Organization (WHO), and the Management of Antibiotic Classification in China. Methods: A 1-day point-prevalence survey (PPSs) on antibiotics prescribing for Chinese children was conducted in hospitalized children from 17 centers in 10 Chinese provinces from 1 September 2017 to 30 November 2019. Results: A total of 4,982 antibiotic prescriptions for Chinese children were included in the analysis. There were 76 types of antibiotic agents in total, 22 (28.9%) of which accounted for 90% of all antibiotic prescriptions. The top-three antibiotics prescribed for children were azithromycin (684, 13.7%), ceftriaxone (508, 10.2%) and latamoxef (403, 8.1%). Third-generation cephalosporins (1,913, 38.4%) were the most commonly prescribed antibiotic classes. On the basis of the AWaRe classification, the Watch group antibiotics accounted for 76.3% and Access group antibiotics accounted for 12.1% of all antibiotic prescriptions. On the basis of the China classification, we showed that 26.5% of antibiotic prescriptions were in the Unrestricted group, 53.6% in the Restricted group, and 14.5% in the Special group. Conclusion: The proportion of antibiotics included in the Watch group and the Special group was high in children in China. The AWaRe classification and China classification for antibiotic prescriptions could be used to supply detailed data for antibiotic stewardship as a simple metric.
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Sulfiredoxin (Srx) is a newly discovered antioxidant enzyme playing a role in the catalytic reduction of oxidative modifications. Srx is overexpressed in a variety of cancers. It may promote carcinogenesis as well as tumor progression. In this study, we report for the first time that Srx expression might be positively associated with the development of gastric cancer and tumor malignancy. Immunohistochemistry showed that, compared to normal tissues (42%, 20/47), Srx expression in gastric tumors (85%, 40/47) was much more common (chi-square test, p<0.01). In addition, the staining of Srx was stronger in poorly differentiated gastric cancer than in well-differentiated gastric cancer. Western blotting showed that, in the gastric tumor cell line BGC823, the Srx protein was upregulated in response to H2O2 treatment, although it was inadequate to counteract the increased oxidative stress, as indicated by the gradually increasing level of malondialdehyde (MDA). In addition, Srx expression, MDA levels, and ROS levels in BGC823 cells were markedly inhibited upon treatment with diallyl trisulfide (DATS), a major constituent of garlic oil with proven anticancer effects. These results suggest that Srx may be an oxidative stress marker. Antioxidation may account for the anticancer potential of garlic.
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Compuestos Alílicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genética , Neoplasias Gástricas/tratamiento farmacológico , Sulfuros/farmacología , Compuestos Alílicos/química , Antioxidantes/química , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ajo/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/toxicidad , Malondialdehído/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Sulfuros/químicaRESUMEN
BACKGROUND: Human beta-defensin-3 (HBD(3)) is an epithelial peptide that has been demonstrated to have a salt-insensitive broad spectrum of potent antimicrobial activity. Expressing antimicrobial peptides in Escherichia coli (E. coli) is very difficult for it can result in death of the bacterial host cells. Our aim was to establish a prokaryotic system expressing soluble HBD(3) protein and demonstrate the antimicrobial activity of the expressed protein. We then studied whether the host cells would activate the suicide pathways. METHODS: We first cloned the complementary DNA coding for the mature chain of HBD(3), inserted it into the vector PGEX-KG then transformed E. coli BL21 (DE3) with the appropriate recombinant plasmid. After induction with 0.5 mmol/L isopropyl-1-thio-beta-D-galactopyranoside (IPTG) the transformed E. coli produced a recombinant glutathione S-transferase and HBD(3) (GST-HBD(3)) fusion protein. The fusion protein was treated with thrombin to produce pure HBD(3) protein then the antimicrobial activity of HBD(3) was evaluated in a liquid microdilution assay. RESULTS: The fusion protein GST-HBD(3) was efficiently cleaved by thrombin and yielded HBD(3) that had anti-staphylococcus aureus activity with a minimal inhibitory concentration level of 12.5 microg/ml. The E. coli strain expressing the recombinant protein did not grow slower than the empty vector strain. CONCLUSION: Active HBD(3) in E. coli by expressing the recombinant protein GST-HBD(3) could be produced, and suicide did not occur in the E. coli strain expressing the recombinant protein.
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Escherichia coli/crecimiento & desarrollo , beta-Defensinas/metabolismo , beta-Defensinas/farmacología , Secuencia de Aminoácidos , ADN Complementario/química , ADN Complementario/genética , Electroforesis en Gel de Poliacrilamida , Escherichia coli/genética , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Humanos , Datos de Secuencia Molecular , Plásmidos/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Staphylococcus aureus/efectos de los fármacos , Trombina/metabolismo , beta-Defensinas/genéticaRESUMEN
BACKGROUND: Recent studies indicate that increased expression of glyoxalase I (GLO1) could result in epileptic seizures; thus, this study further explored the association of GLO1 with epilepsy from the perspective of molecular genetics. MATERIAL AND METHODS: GLO1 single nucleotide polymorphisms (SNPs; rs1130534, rs4746 and rs1049346) were investigated in cohort I (the initial samples: 249 cases and 289 controls). A replication study designed to confirm the positive findings in cohort I was performed in cohorts II (the additional samples: 130 cases and 191 controls) and I+II. RESULTS: In cohorts I, II and I+II, the CC genotype at rs1049346 T>C exerts a protective effect against both late-onset epilepsy (odds ratio [OR]=2.437, p=0.013; OR=2.844, p=0.008; OR=2.645, p=0.000, q=0.003, respectively) and drug-resistant epilepsy (DRE) (OR=2.985, p=0.020; OR=2.943, p=0.014; OR=3.049, p=0.001, q=0.006, respectively). Further analyses in cohort I+II indicate that the presence of the TAC/AAT haplotypes (rs1130534-rs4746-rs1049346) may be used as a marker of predisposition to/protection against DRE (p=0.002, q=0.010; p=0.000, q=0.002, respectively). CONCLUSIONS: This study is the first to demonstrate that the GLO1 SNPs are significantly associated with epilepsy. In particular, the rs1049346 T>C SNPs are potentially useful for risk assessment of late-onset epilepsy and DRE.