High-risk clones of ESBL-producing Klebsiella pneumoniae colonizing ICU patients in Natal, northeastern Brazil / Clones de alto risco de Klebsiella pneumoniae produtores de ESBL colonizando pacientes de UTI em Natal, Nordeste do Brasil / Clones de alto riesgo de Klebsiella pneumoniae productores de BLEE que colonizan pacientes de UCI en Natal, noreste de Brasil

Background and objectives: colonization by extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae in Intensive Care Unit (ICU) patients is considered a risk factor for infections, and poses as a source of spreading these strains in hospital facilities. This study aimed to perform the genetic characterization of ESBL-producing K. pneumoniae isolates recovered from surveillance swabs in an ICU in northeastern Brazil. Methods: the isolates were recovered between 2018-2019 from the nasal, axillary, and rectal sites of 24 patients admitted to the ICU. Bacterial identification was performed by traditional biochemical tests. Antimicrobial susceptibility was assessed by disk diffusion, and ESBL phenotype was detected by double-disc synergy test. Polymerase chain reaction (PCR) for blaCTX-M, blaSHV, and blaTEM genes, PFGE, and MLST were carried out in representative isolates. Results: a total of 27 isolates were recovered from 18 patients (75%). The ESBL production was detected in 85% of isolates. Resistance to ciprofloxacin, sulfamethoxazole/trimethoprim and most of the ß-lactams tested was recurrent, except for carbapenems. The blaSHV, blaTEM, and blaCTX-M genes were found in high frequency, and the CTX-M-(1, 2 and 9) groups were identified. Seven sequence types (ST11, ST14, ST17, ST395, ST709, ST855, and ST3827) were described, most of them considered high-risk. Conclusion: these findings emphasize the potential threat of well-established high-risk clones in an ICU, and highlight the importance of monitoring these clones to prevent infections.(AU)

Justificativa e objetivos: a colonização por Klebsiella pneumoniae produtora de ß-lactamase de espectro estendido (ESBL) em pacientes de Unidade de Terapia Intensiva (UTI) é considerada um fator de risco para infecções, e representa uma fonte de disseminação dessas cepas em instalações hospitalares. Este estudo objetivou realizar a caracterização genética de isolados de K. pneumoniae produtores de ESBL recuperados de swabs de vigilância em uma UTI no Nordeste do Brasil. Métodos: os isolados foram recuperados entre 2018-2019 dos sítios nasal, axilar e retal de 24 pacientes internados na UTI. A identificação bacteriana foi realizada por testes bioquímicos tradicionais. A suscetibilidade antimicrobiana foi avaliada por disco-difusão, e o fenótipo ESBL foi detectado pelo teste de sinergia de duplo-disco. Polymerase chain reaction (PCR) para os genes blaCTX-M, blaSHV e blaTEM, PFGE e MLST foram realizados em isolados representativos. Resultados: foram recuperados 27 isolados de 18 pacientes (75%). A produção de ESBL foi detectada em 85% dos isolados. A resistência à ciprofloxacina, sulfametoxazol/trimetoprima e à maioria dos ß-lactâmicos testados foi recorrente, exceto para os carbapenêmicos. Os genes blaSHV, blaTEM e blaCTX-M foram encontrados em alta frequência, e os grupos CTX-M-(1, 2 e 9) foram identificados. Sete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 e ST3827) foram descritos, a maioria deles considerados de alto risco. Conclusão: esses achados enfatizam a ameaça potencial de clones de alto risco bem estabelecidos em uma UTI, e destacam a importância do monitoramento desses clones para prevenir infecções.(AU)

Justificación y objetivos: la colonización por Klebsiella pneumoniae productora de ß-lactamasas de espectro extendido (BLEE) en pacientes de Unidades de Cuidados Intensivos (UCI) se considera un factor de riesgo para infecciones, y se presenta como una fuente de propagación de estas cepas en instalaciones hospitalarias. Este estudio tuvo como objetivo realizar la caracterización genética de aislamientos de K. pneumoniae productores de BLEE recuperados de hisopos de vigilancia en una UCI en el noreste de Brasil. Métodos: los aislamientos se recuperaron entre 2018-2019 de sitios nasales, axilares y rectales de 24 pacientes ingresados en la UCI. La identificación bacteriana se realizó mediante pruebas bioquímicas tradicionales. La susceptibilidad antimicrobiana se evaluó mediante difusión en disco, y el fenotipo BLEE se detectó mediante la prueba de sinergia de doble-disco. La polymerase chain reaction (PCR) para los genes blaCTX-M, blaSHV y blaTEM, PFGE y MLST se llevaron a cabo en aislamientos representativos. Resultados: se recuperaron 27 aislamientos de 18 pacientes (75%). La producción de ESBL se detectó en 85% de los aislamientos. La resistencia a ciprofloxacino, sulfametoxazol/trimetoprima y a la mayoría de los ß-lactámicos evaluados fue recurrente, excepto a los carbapenémicos. Los genes blaSHV, blaTEM y blaCTX-M se encontraron en alta frecuencia, y se identificaron los grupos CTX-M-(1, 2 y 9). Se describieron siete sequence types (ST11, ST14, ST17, ST395, ST709, ST855 y ST3827), la mayoría consideradas de alto riesgo. Conclusión: estos hallazgos enfatizan la amenaza potencial de los clones de alto riesgo bien establecidos en una UCI, y resaltan la importancia de monitorear estos clones para prevenir infecciones.(AU)

Recent Research Progress on CircRNA in Hematological Malignancies--Review / 中国实验血液学杂志

Most hematological tumors have high-grade malignancy and low cure rate, requiring new molecular markers for detection and evaluation. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed-loop structures, which participate in gene transcription and translation by binding to microRNAs and proteins. In recent years, with the deepening research on circRNAs, circRNAs have been found to play an important role in hematological malignancies. In this review, the latest research progress on the function and molecular mechanism of circRNAs in hematological malignancies was systematically summarized, and it was found that circRNAs may be potential new biomarkers and therapeutic targets in hematological malignancies.

IMPACTO-MR: um estudo brasileiro de plataforma nacional para avaliar infecções e multirresistência em unidades de terapia intensiva / IMPACTO-MR: a Brazilian nationwide platform study to assess infections and multidrug resistance in intensive care units

RESUMO Objetivo: Descrever o IMPACTO-MR, um estudo brasileiro de plataforma nacional em unidades de terapia intensiva focado no impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Métodos: Descrevemos a plataforma IMPACTO-MR, seu desenvolvimento, critérios para seleção das unidades de terapia intensiva, caracterização da coleta de dados, objetivos e projetos de pesquisa futuros a serem realizados na plataforma. Resultados: Os dados principais foram coletados por meio do Epimed Monitor System® e consistiram em dados demográficos, dados de comorbidades, estado funcional, escores clínicos, diagnóstico de internação e diagnósticos secundários, dados laboratoriais, clínicos e microbiológicos e suporte de órgãos durante a internação na unidade de terapia intensiva, entre outros. De outubro de 2019 a dezembro de 2020, 33.983 pacientes de 51 unidades de terapia intensiva foram incluídos no banco de dados principal. Conclusão: A plataforma IMPACTO-MR é um banco de dados clínico brasileiro de unidades de terapia intensiva focado na pesquisa do impacto das infecções por bactérias multirresistentes relacionadas à assistência à saúde. Essa plataforma fornece dados para o desenvolvimento e pesquisa de unidades de terapia intensiva individuais e ensaios clínicos observacionais e prospectivos multicêntricos.

ABSTRACT Objective: To describe the IMPACTO-MR, a Brazilian nationwide intensive care unit platform study focused on the impact of health care-associated infections due to multidrug-resistant bacteria. Methods: We described the IMPACTO-MR platform, its development, criteria for intensive care unit selection, characterization of core data collection, objectives, and future research projects to be held within the platform. Results: The core data were collected using the Epimed Monitor System® and consisted of demographic data, comorbidity data, functional status, clinical scores, admission diagnosis and secondary diagnoses, laboratory, clinical, and microbiological data, and organ support during intensive care unit stay, among others. From October 2019 to December 2020, 33,983 patients from 51 intensive care units were included in the core database. Conclusion: The IMPACTO-MR platform is a nationwide Brazilian intensive care unit clinical database focused on researching the impact of health care-associated infections due to multidrug-resistant bacteria. This platform provides data for individual intensive care unit development and research and multicenter observational and prospective trials.

Aspectos farmacológicos prácticos de las drogas para el tratamiento de la tuberculosis drogorresistente en adultos y pediatría / Practical Pharmacological Aspects of Drugs Used for the Treatment of Drug-Resistant Tuberculosis in Adults and Children

La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.

The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practi cal pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.

Practical Pharmacological Aspects of Drugs Used for the Treatment of Drug-Resistant Tuberculosis in Adults and Children / Aspectos farmacológicos prácticos de las drogas para el tratamiento de la tuberculosis drogorresistente en adultos y pediatría

ABSTRACT The emergence of resistant strains of Mycobacterium tuberculosis to multiple drugs and the difficulties of their diagnosis and treatment constitute a challenge to global public health. To face this challenge, new anti-tuberculosis drugs, such as bedaquiline, pretomanid, and delamanid, as well as replacement drugs, such as fluoroquinolones, linezolid and clofazimine, are used. Based on the evidence provided by multicenter studies, drugs associated with a better prognosis of drug-resistant tuberculosis have been discovered and, recently, a new classification has been proposed, as well as new totally oral regimens. In this review, we describe current treatment regimens and practical pharmacological aspects required when prescribing new drug-resistant tuberculosis treatment regimens.

RESUMEN La emergencia de cepas resistentes de Mycobacterium tuberculosis a múltiples drogas, las dificultades de su diagnóstico y tratamiento constituyen un desafío a la salud pública mundial. Para afrontar esta situación, se emplean nuevas drogas antituberculosis, como bedaquilina, pretomanid y delamanid, así como drogas repropuestas, como fluoroquinolonas, linezolid y clofazimina. Con base en la evidencia brindada por estudios multicéntricos, se han descubierto fármacos asociados a un mejor pronóstico de la tuberculosis drogorresistente y, recientemente, se ha propuesto una nueva clasificación, así como nuevos esquemas totalmente orales. En esta revisión, describimos los esquemas de tratamiento actuales y los aspectos farmacológicos prácticos necesarios a la hora de la prescripción de los nuevos regímenes de tratamiento de la tuberculosis drogorresistente.

Clinical and bronchoscopy characteristics of Mycoplasma pneumoniae pneumonia in children with 23S rRNA resistance gene positive in bronchoalveolar lavage fluid / 中华实用儿科临床杂志

Objective:To investigate clinical and bronchoscopy characteristics of Mycoplasma pneumoniae pneumonia in children with 23S rRNA resistance gene positive in bronchoalveolar lavage fluid(BALF), and find clinical indicators that can identify Mycoplasma pneumoniae drug resistance early.Methods:The clinical data of 61 hospita-lized children diagnosed with Mycoplasma pneumoniae pneumonia as subjects from October 2017 to June 2018 in the Department of Pediatric Respiratory Medicine of Shengjing Hospital Affiliated to China Medical University were analyzed retrospectively.Bronchoscopy was performed on each subject and the BALF was taken and used to detect the 2063 site mutation of the 23S rRNA V region gene in BALF, and they were divided into drug-resistant gene positive group and drug-resistant gene negative group.The clinical manifestations, relevant laboratory data, imaging data, and bronchoscopy findings in different load groups were compared.Statistical methods such as t test, rank sum test, χ2 test, Fisher′ s exact probability method, and multivariate Logistic regression analysis were used to analyze the data. Results:Among the 61 children, 38 cases (62.30%) were in the drug resistance gene positive group, and 23 cases (37.70%) were in the drug resistance gene negative group.There were no significant differences in gender and age between the two groups (all P>0.05). The days of hospitalization and fever in the children with positive drug resistance genes were longer than those in the negative drug resistance gene groups, and they were more likely to have refractory mycoplasma pneumoniae pneumonia(RMPP) and extra pulmonary complications, with statistically significant differences ( P<0.05), but there were no significant differences in hypoxemia ( P>0.05). There were significant differences in white blood cell(WBC), C-reactive protein(CRP), procalcitonin(PCT), D-Dimer (D-D) and interleukin-6 (IL-6) between the two groups (all P<0.05). Except that the WBC level in the drug-resistant gene-positive group was lower than that in the drug-resistant gene-negative group, the rest of the test results indicated that the drug-resistant gene-positive group was higher than the drug-resistant gene-negative group.There were no significant differences in the concentrations of serum lactate dehydrogenlase(LDH)and IL-6 in BALF ( P>0.05). In this study, Logistic regression analysis was performed on several statistically significant laboratory indicators.It was found that WBC was more sensitive to identify drug resistance genes, and the optimal critical value was 8.55×10 9/L.The specificity of D-D in identifying drug resistance genes was higher, and the optimal cut-off value was 523 μg/L.In the drug resistance gene positive group, 35 cases (92.11%) showed extensive lung consolidation/atelectasis on imaging, and the drug resistance gene negative group was 13 cases (56.52%), with statistically significant differences ( P<0.05). The drug resistance gene-positive group mainly showed mucosal erosion, necrosis, phlegm plug/plastic phlegm plug and bronchitis stenosis, with a total of 19 cases (50.00%). In the drug resistance gene negative group, the main manifestations of mucosal longitudinal wrinkle, flocculent and viscous secretions were 14 cases (60.88%), with statistically significant differences ( P<0.05). Conclusions:The point mutation of 23S rRNA V region gene is closely related to the clinical characteristics of children with Mycoplasma pneumoniae pneumonia.Children with A2063G mutation are more prone to have RMPP and extrapulmonary complications, and their imaging manifestation and bronchoscopy are more severe.The levels of leukocytes and D-D in the blood have significance for the early identification of drug resistance.The systemic excessive immune inflammatory response caused by Mycoplasma pneumoniae pneumonia with drug-resistant gene positive needs to be valued.

Clinical Analysis of Bloodstream Infection after Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).@*METHODS@#The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.@*RESULTS@#Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001).@*CONCLUSION@#The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words　　;

Eosinophilic cystitis, a rare cause of persistent haematuria in a diabetic dog / Cistite eosinofílica, uma causa rara de hematúria persistente em um cão diabético

Eosinophilic cystitis is a rare inflammatory disorder characterized by eosinophilic infiltration of entire layers of the bladder wall. The condition has been described in adults, children, and dogs. However, there are no consensus guidelines for the treatment of eosinophilic cystitis. Although human and veterinary literature reviews show some effectiveness in management with corticosteroids, antihistamines, and antibiotics, a variety of serious and frequent side effects are associated with steroid therapy. As a result, steroids are relatively contraindicated for patients with diabetes mellitus and Cushing's syndrome. A five-year-old neutered male chow-chow with controlled diabetes was referred with an 18-month history of malodorous urine, gross haematuria, and dysuria that were nonresponsive to antibiotics. The findings on general examination were unremarkable except for abdominal suprapubic discomfort. The complete blood count and biochemical profile (such as urea and creatinine) were normal except for mild peripheral eosinophilia. Although ultrasonography, bladder contrast radiography, and urine cytology findings indicated malignancy, with the presence of atypical urothelial cells, histopathology confirmed eosinophilic cystitis. Management with cyclosporine was adequate with complete remission of haematuria. This case report presents the first reported successful use of cyclosporine for the treatment of eosinophilic cystitis in a dog with diabetes.(AU)

A cistite eosinofílica é uma doença inflamatória rara caracterizada por infiltração eosinofílica de todas as camadas da parede da bexiga. Essa enfermidade já foi descrita em adultos, crianças e cães. No entanto, não há um consenso de diretrizes sobre o seu tratamento. Mesmo que as literaturas humana e veterinária mostrem alguma eficácia no manejo com corticosteroides, anti-histamínicos e antibióticos, uma variedade de efeitos colaterais graves e frequentes está associada à terapia com esteroides. Dessa forma, o uso de esteroides é relativamente contraindicado para pacientes com diabetes mellitus e síndrome de Cushing, por exemplo. Um chow-chow, macho, castrado, de cinco anos e diabético estável foi encaminhado para atendimento com histórico de urina fétida, hematúria macroscópica e disúria não responsiva a antibióticos há 18 meses. A avaliação dos parâmetros físicos estava dentro dos padrões, exceto por desconforto abdominal suprapúbico à palpação. O hemograma e o perfil bioquímico (como a ureia e a creatinina) estavam dentro da normalidade para a espécie, exceto por eosinofilia periférica leve. Embora a ultrassonografia, a radiografia contrastada da bexiga e os achados da urinálise indicassem malignidade, com a presença de células uroteliais atípicas, a histopatologia confirmou o diagnóstico definitivo de cistite eosinofílica. O manejo com ciclosporina foi satisfatório, com ausência completa da hematúria. Este relato de caso apresenta o primeiro uso documentado de ciclosporina para o tratamento de cistite eosinofílica com sucesso em um cão com diabetes.(AU)

Membrane-disruptive peptides/peptidomimetics-based therapeutics: Promising systems to combat bacteria and cancer in the drug-resistant era

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

Effects of RNA Targeting mPGES-1 on Proliferation and Apoptosis of K562/A Cells / 中山大学学报(医学科学版)

@#【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.

Research progress on the effect of pH-sensitive drug delivery systems on oral microorganisms / 口腔疾病防治

@#Microorganisms are closely related to the occurrence and development of common oral diseases. Due to the unique physiological and anatomical characteristics of the oral cavity, locally introduced antibacterial drugs cannot be maintained in the effective concentration range under the effect of saliva erosion. Therefore, to enhance the retention and bioavailability of antibacterial drugs in biofilms, some scholars designed pH sensitive drug delivery systems with the fact that the pH value of oral biofilm is lower than the physiological pH value. This article reviews the research reports of a pH-sensitive drug delivery system in the oral cavity and elaborates its application in oral diseases such as dental caries, endodontic disease, periapical disease, peri-implant diseases, and oral candidiasis. Literature review Results show that the pH-sensitive drug delivery system loaded with antibacterial drugs could be used for the control of oral microorganisms with excellent pH sensitivity and antibacterial properties, especially in the application of acid-producing bacteria such as Streptococcus mutans for the prevention and treatment of dental caries. However, the research of pH-sensitive drug delivery systems in the oral cavity is still limited to basic research,and in clinical applications, it still faces many challenges, such as a complex design and synthesis, difficulties with lasting effects and eliminating drug-resistance and persistent bacteria. Further optimization of pH sensitive systems, as well as animal experiments and in vivo studies will be the focus of future research.

The shift of the treatment strategy of gastrointestinal stromal tumor from the surgical perspective / 中华外科杂志

As tumors originated from mesenchymal tissue, gastrointestinal stromal tumors (GIST) has its own typical history. For the idea of treatment for GIST at different historical periods, the role and value of surgery for the treatment of GIST keep changing. Laparoscopy and endoscopy will have the role they deserved. With the understanding of pathogenesis of GIST, targeted chemotherapy will be more and more accurate and individualized. How to improve the overall therapeutic effect of GIST, especially for the patients with the high risk and drug-resistance, is the dilemma and challenges for the surgeons.

miR-125a-5p promotes the resistance to gefitinib in non-small cell lung carcinoma cells by targetingAPAF1 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective:ToinvestigatetheroleofmiR-125a-5pininducingthegefitinib(Gef)-resistance of non-small cell lung carcinoma (NSCLC) cells and its possible mechanism. Methods: Human NSCLC drug-resistant cell line A549/GR and NSCLC cell line A549 were chosen for this study. miR-125a-5p mimic, miR-125a-5p inhibitor, pcDNA3.1-APAF1 and empty vector pcDNA3.1 were transfected into A549/GR cells. The expression level of miR-125a-5p in cell lines was detected by qPCR. MTT, Transwell and Flow cytometry were used to detect the effects of Gef on proliferation, migration and apoptosis of cell lines, respectively. The targeting relationship between miR-125a-5p and APAF1 (apoptotic peptidase activating factor 1) was verified by Dual-luciferase reporter gene system. In addition, the expression of APAF1 protein in A549/GR cells was detected by Western blotting. The expression levels of caspase-3 and caspase-9 were assessed by colorimetry. Results: Expression level of miR-125a-5p was upregulated significantly in Gefresistant A549/GR cells (P<0.01). AndtheinfluencesofGefonA549/GRcellswereenhancedby knockdown of miR-125a-5p, including inhibiting cell proliferation and migration (all P<0.05) and inducing apoptosis (P<0.01). Dual luciferase reporter gene assay confirmed that miR-125a-5p targeted APAF1 and negatively regulated its expression. Furthermore, by targetedly downregulating APAF1, miR-125a-5p alleviated the inhibition of proliferation and migration (all P<0.05) and promotion of apoptosis (P<0.05) of A549/GR cells caused by Gef, and attenuated Gef-induced upregulation of apoptosis-related proteins caspase-3 and caspase-9 (all P<0.05). Conclusion: miR-125a-5p promotes Gef-resistance of A549/GR cells, and the underlying mechanisms are promotion of proliferation, migration and inhibition of apoptosis of non-small cell lung cancer cells by targetingAPAF1.

Retrospective analysis of colistin-resistant bacteria in a tertiary care centre in India

The incidence of carbapenem-resistant Enterobacteriaceae has been steadily rising. The morbidity, mortality and financial implications of such patients are significant. We did a retrospective analysis of the case records of 11 patients who had culture report positive for pan drug-resistant (PDR) organisms. There were total 15 isolates of PDR organisms in 11 patients. These were associated with catheter-associated urinary tract infections (7), tracheitis (4), bacteraemia (2), meningitis (1) and soft-tissue infection (1). Average APACHE II score was 23.72 (range 7-36) indicating patients with multiple co-morbidities and organ dysfunction. The average length of hospital stay was 60.72 (25-123) days. The overall mortality rate was 81.81 per cent, while PDR infection-related mortality was 18.18 per cent. Strict implementation of antibiotic stewardship programme is essential to limit use and prevent abuse of colistin.

To Study Clinico-Radiological Profile of Multi-Drug Resistant Tuberculosis Patients

Drug resistance is a threat to TB control program worldwide. Patient infected with multiple drug resistant strains are less likely to become cured. Management of resistant cases is complex and presents therapeutic limitations. Patients with multidrug resistant strains are more prone to treatment failure, progresses to more chronic forms of the disease and death. In most areas of the world, the routine use of drug susceptibility tests, let alone cultures to diagnose tuberculosis or multidrug resistant tuberculosis is beyond the scope of health care resources. According to Global Tuberculosis Report 2015, about 3.3% of newly diagnosed patients had multidrug resistant tuberculosis and 20% of previously treated Tuberculosis cases were estimated to have Multidrug resistant Tuberculosis (MDR-TB). This present study was conducted in the department of chest and TB, Government medical college, Amritsar, with an aim to study the clinico-radiological profile of patients with multidrug resistant tuberculosis. Methods: A prospective study was conducted at the Chest and TB hospital, Amritsar which included 100 diagnosed patients of Multidrug Resistant Tuberculosis. Clinicoradiological profile of these patients was determined. Results: Out of 100 study population, maximum number of patients belonged to the age group of 21-30 years i.e. 26% followed by 22% in the age group of <20 years. Most common symptom was cough with expectoration which was present in 94 (94%) patients. 97 (97%) patients were having previous history of ATT, 3 (3%) patients were not having any previous history of ATT. On radiology unilateral disease was present in 48 (48%) patients, bilateral disease present in 52 (52%) patients. Parenchymal infiltration was present in 79 (79%) patients. Cavitation was present in 23 (23%), Fibrocavitary disease was present in 37 (37%) study subjects. Previous history of ATT had significant association with extent of lesion on chest x- ray (p < 0.05). Conclusion: clinico-radiological characteristics should always be determined where appropriately administered drugs have not achieved necessary drug levels to deal with all the population of mycobacteria, to timely modify and strengthen the national programs, and evaluation of trends in drug resistance pattern.

Effect of matrine on sensitivity of A549/DDP cells to cisplatin by inhibiting microRNA-192 / 中草药

Objective: To investigate the effect of matrine on increasing the sensitivity of A549/DDP cells to cisplatin by regulating microRNAs. Methods: Data mining was performed on a microarray dataset (accession ID: GSE43249) from GEO database using bioinformatics analysis. Then microRNAs which related to the sensitivity of A549 cells to cisplatin were selected as candidate microRNAs. A549 and A549/DDP cells were cultured in vitro. The expression changes of candidate microRNAs were confirmed by qRT-PCR. The effect of matrine on the level of candidate microRNAs was also determined by qRT-PCR in A549/DDP cells. The level of microRNA-192 (miR-192) in A549/DDP cells was up-regulated by transfecting sequence of miR-192mimic. The CCK-8 assay was used to observe the effect of matrine and (or) miR-192 up-regulation on the sensitivity of A549/DDP cells to cisplatin. Results: Data mining Results: showed that there were 11 microRNAs with significant changes in A549/DDP cells compared with cisplatin-sensitive A549 cells (P < 0.05). The changes of miR-192 and miR-194 expression were confirmed in vitro. Compared with untreated A549/DDP cells, matrine treatment reduced the level of miR-192 in A549/DDP cells (P < 0.05). Matrine treatment increased the sensitivity of A549/DDP cells to cisplatin. Up-regulation of miR-192 could antagonize this effect and induce the resistance of A549 cells to cisplatin. Conclusion: Matrine may increase the sensitivity of A549 cells to cisplatin by inhibiting miR-192.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.

Current status and progress of the treatment of acute promyelocytic leukemia / 白血病·淋巴瘤

Acute promyelocytic leukemia (APL) is a special type of acute leukemia. The cure rate of APL has been significantly improved in the past decades due to the use of anthracyclines, all-trans retinoic acid and arsenic. Modern stratified treatment of APL further enhances the therapeutic efficacy and reduces the treatment-related toxicity. This article reviews the history of all-trans retinoic acid and arsenic into clinical application, and the characteristics of disease, treatment status of all-trans retinoic acid and arsenic, treatment mechanism and drug resistance mechanism in APL are introduced.

Genetic characteristics of highly pathogenic avian influenza A(H5N6) virus in Suzhou City / 中华疾病控制杂志

Objective To analyze host adaptability and drug resistance variation of highly pathogenic avian influenza (HPAI) A(H5N6) viruses obtained from outbreaks in Suzhou City. Methods Real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay was used for influenza virus detection in pharynx or anus swabs of dead birds and suspected cases. Full genome of H5N6 positive samples were sequenced by using Sanger method. Hemagglutinin (HA) and neuramidinase (NA) phylogenetic trees were constructed by MEGA software. Results A child was laboratory confirmed to have A(H5N6) viruses infection in November 2018. A outbreak of avian flu in poultry in W district during the Spring Festival was laboratory confirmed as a A(H5N6) epidemic situation. Avian-origin H5N6 viruses possessed D198N and Q226H resistance mutations. The homology of HA and NA genes of Suzhou strains were 98.01%-100.0% and 98.16%-100.0%, respectively. These H5N6 strains belonged to 2.3.4.4 H5 clad. Multiple basic amino acid at the cleavage site of HA implied the highly pathogenic characteristics of Suzhou H5N6 strains. Conclusion H5N6 is a kind of malti-sourse reassortment virus, which is still evolving. Multiple loci of Suzhou H5N6 strains of this epidemic were identified to have drifted. The prevalence of drug-resistant mutations should be closely monitored in order to timely take effective measures to prevent serious damage to public health and poultry production industries.

Analysis of antimicrobial resistance and staphylococcal cassette chromosome mec ( SCCmec ) in 99 Staphylococcus epidermidis strains isolated from early pregnancy cervical swabs and external environ-ment / 中华微生物学和免疫学杂志

Objective To analyze the antimicrobial resistance, distribution of resistance genes and staphylococcal cassette chromosome mec ( SCCmec) in 99 strains of mecA gene-positive Staphylococcus epi-dermidis strains isolated from early pregnancy cervical swabs and external environment in Beijing Chaoyang District from 2015 to 2016. Methods Kirby-Bauer disk diffusion method was performed to detect the sus-ceptibility of the 99 Staphylococcus epidermidis strains to cefoxitin. Microbroth dilution method was used to test their susceptibility to vancomycin, daptomycin, penicillin, erythromycin, compound sulfamethoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol. PCR was used to detect drug re-sistance genes of ermA, ermB, ermC, msrA, norA1, norA2, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM and to analyze the SCCmec types ofⅠ, Ⅱ, Ⅲ, Ⅳa, Ⅳb, Ⅳc, Ⅳd and Ⅴ. The results were compared with those of capillary electrophoresis. SPSS was used for data analysis. Results All of the 99 mecA-positive Staphylococcus epidermidis strains were sensitive to vancomycin and 93. 94％ of them were sensitive to datomycin. The resistance rates to penicillin, erythromycin, cefoxitin, compound sulfame-thoxazole, tetracycline, ciprofloxacin, clindamycin, gentamicin and chloramphenicol were 97. 98％, 85. 86％, 79. 80％, 52. 54％, 27. 27％, 43. 43％, 36. 36％, 23. 23％ and 11. 11％. The strains that car-ried the genes of norA1, norA2, ermA, ermB, ermC, msrA, sul1, sul2, sul3, aac(6')/aph(2″), ant(4', 4″), ant(6) and tetM accounted for 100％, 93. 94％, 0. 00％, 3. 03％, 17. 17％, 57. 58％, 50. 51％, 12. 12％, 4. 04％, 30. 30％, 8. 08％, 4. 04％ and 25. 26％, respectively. Among the 99 strains, 5. 05％, 0％, 43. 43％, 10. 10％, 0. 00％, 3. 03％, 3. 03％ and 19. 19％ belonged to SCCmecⅠ, Ⅱ, Ⅲ, Ⅳa,Ⅳb,Ⅳc,Ⅳd andⅤ, respectively, and 4. 04％ (4/99) were positive to two SCCmec types. The types of 12. 12％ (12/99) of the strains were unidentified. Conclusions All of the 99 strains of mecA-positive Staphylococcus epidermidis were sensitive to vancomycin. Among them, the strains carrying multidrug resist-ance genes accounted for 89. 90％. The main mechanisms of resistance to macrolides, sulfonamides and ami-noglycosides in local strains were related to the resistance genes of msrA, sul1 and aac ( 6')/aph ( 2″) . SCCmec Ⅲ was the prevalent type. There were 88. 37％ of SCCmec Ⅲ type strains and 75％ of unknown type strains carrying multiple resistance genes. Apart from that, the isolated strains of other SCCmecⅢtypes all carried multiple resistance genes.