Presentation of the ATLETAS DA VOZ™ Conditioning Program

Objectives: To present a simple form of vocal and breathing conditioning for voice professionals based on concepts from vocal science. The vocal conditioning program called Voice Athletes Conditioning uses the principles of exercise physiology to gradually improve vocal and respiratory overload to achieve endurance, power, and flexibility. Methods: Due to our personal experience with high voice users, we synthesized a vocal conditioning program (AVCP) that combines voice science, exercise physiology, sports science and physical therapy principles. This is an 8-week program of daily vocal and breathing exercises with overload enhancement each week using different types of breathing devices and semi-occluded vocal tract exercises, designed and developed according to the specific requirements and performance of the voice professional. Reflections: Professional voice users often experience episodes of vocal fatigue that can directly affect their performance and vocal health. As with physical training for athletes, voice exercises can also contribute to improving vocal conditioning, preventing voice disorders, as well as helping to obtain better performance, greater tolerance to fatigue and shorter recovery time. Conclusions: AVCP is an approach that considers the principles of muscle training aimed objectively at the respiratory and vocal muscles, carried out with a variety of breathing devices and specific vocal exercises in search of greater performance time, less physiological stress, and shorter recovery time in the professional use of the voice.

Objetivos: Presentar una forma sencilla de acondicionamiento vocal y respiratorio para profesionales de la voz, basada en conceptos de la ciencia vocal. El programa de acondicionamiento vocal denominado Voice Athletes Conditioning utiliza los principios de la fisiología del ejercicio para mejorar gradualmente la sobrecarga vocal y respiratoria, con el fin de lograr resistencia, potencia y flexibilidad. Métodos: Debido a nuestra experiencia personal con usuarios de voz aguda, sintetizamos un programa de acondicionamiento vocal (AVCP) que combina principios de la ciencia de la voz, la fisiología del ejercicio, las ciencias del deporte y la fisioterapia. Se trata de un programa de 8 semanas de ejercicios vocales y respiratorios diarios con realce de sobrecarga cada semana utilizando diferentes tipos de dispositivos respiratorios y ejercicios semioclusivos del tracto vocal, diseñado y desarrollado de acuerdo con los requerimientos específicos y el rendimiento del profesional de la voz. Reflexiones: Los usuarios profesionales de la voz experimentan a menudo episodios de fatiga vocal que pueden afectar directamente su rendimiento y salud vocal. Al igual que ocurre con el entrenamiento físico de los deportistas, los ejercicios vocales también pueden contribuir a mejorar el acondicionamiento vocal, prevenir trastornos de la voz, además de ayudar a obtener un mejor rendimiento, una mayor tolerancia a la fatiga y un menor tiempo de recuperación. Conclusiones: El AVCP es un enfoque que considera los principios del entrenamiento muscular dirigido objetivamente a la musculatura respiratoria y vocal, realizado con diversos aparatos respiratorios y ejercicios vocales específicos en busca de un mayor tiempo de actuación, menor estrés fisiológico y menor tiempo de recuperación en el uso profesional de la voz.

Screening of essential oils against oxacillin - resistant Staphylococcus aureus strains isolated from bovine mastitis / Screening de aceites esenciales frente a Staphylococcus aureus oxacilino - resistentes extraidos de aislados de mastitis bovina

Bovine mastitis is a disease wi th far - reaching consequences for the dairy industry. Staphylococcus aureus is a pathogen that is especially resistant to antibiotics. The objective of this study was to evaluate the antimicrobial activity of the essential oils Lippia citriodora (Lam.), Thy mus vulgaris (L), and a mixture of the essential oils Lippia citriodora and Thymus vulgaris (50/50 v/v), against isolates of oxacillin - resistant Staphylococcus aureus (n=15) of positive cases of bovine mastitis. For the statistical analysis, the IBM SPSS s tatistical package was used. The mixture of essential oils ( Lippia citriodora and Thymus vulgaris (50/50 v/v)) obtained the most significant antimicrobial activity in relation to pure essential oils. It is therefore concluded that the mixture of these oils boosts their antimicrobial activity ( p <0.05). The minimum inhibitory and bactericidal concentration of this mixture for the total isolations was 12 µL/L and 25 µL/mL, respectively.

La mastitis bovina es una enfermedad de gran impacto para la industria lechera. El Staphylococcus aureus es uno de los principales patógenos, especialmente aquellos resistentes a los antibióticos. El objetivo de este estudio fue evaluar la actividad antimicrobiana de los aceites esenciales de Lippia citriodora (Lam.), Thymus vulgaris (L), y una mezcla de aceites esenciales de Lippia citriodora y Thymus vulgaris (50/50 v/v), frente a aislamientos clínicos de Staph ylococcus aureus oxacilino - resistentes (n=15) de mastitis bovina. Se utilizó p rograma estadístico IBM SPSS y se concluyó la diferencia significativa a un p <0.05. La mezcla de aceites esenciales ( Lippia citriodora y Thymus vulgaris (50/50 v/v)), obtuvo la m ayor actividad antimicrobiana en relación a los aceites esenciales puros, se concluye que la mezcla de estos aceites potencia su actividad antimicrobiana ( p <0.019). La concentración mínima inhibitoria y bactericida de esta mezcla fue del 12 µL/mL y 25 µL/m L, respectivamente, y puede ser una alternativa terapéutica.

Cambios en Mecánica Respiratoria en Usuarios Pediátricos en Ventilación Mecánica Post Cirugía de Cardiopatía Congénita Sometidos a Kinesiología Respiratoria versus Succión Endotraqueal. Revisión Estructurada / Changes in Respiratory Mechanics in Pediatric Users on Mechanical Ventilation Post Congenital Heart Disease Surgery Undergoing Respiratory Kinesiology versus Endotracheal Suction. Structured Review

Introducción. Las cardiopatías congénitas (CC) en Chile corresponden a la segunda causa de muerte en menores de 1 año, requiriendo cirugías paliativas y/o correctivas el 65% de estas. En el post operatorio frecuentemente se utiliza ventilación mecánica invasiva (VM) y succión endotraqueal (SET) para remover secreciones. Sin embargo, la kinesiología respiratoria (KTR) ha mostrado mejoras significativas en la distensibilidad toracopulmonar (Cest) y resistencia de vía aérea (Rva) en otros grupos de usuarios pediátricos y adultos en VM. Objetivo. Comparar los cambios en la Cest y Rva en usuarios pediátricos en VM post cirugía de cardiopatía congénita (CCC) sometidos a KTR versus SET exclusiva. Métodos. Revisión sistemática de estudios publicados en bases de datos PUBMED, PeDro, Scielo y Google Scholar que comparan el uso de KTR ó SET sobre los cambios en mecánica ventilatoria en usuarios pediátricos en VM post cirugía de cardiopatía congénita, limitados a inglés, español y portugués, excluyendo a sujetos con traqueostomía o con oxigenación por membrana extracorpórea. Se utilizó guía PRISMA para la selección de artículos. Se revisaron 397 artículos y se seleccionó 1 artículo extra de los artículos sugeridos. Se eliminó 1 artículo por duplicidad. Por títulos y resúmenes se seleccionaron 2 artículos, los cuales al leer el texto completo fueron retirados debido a que la población no correspondía a cardiópatas. Resultados. El final de artículos seleccionados fue de 0 artículos, debido a lo cual se removió el operador Booleano "NOT", y se removió la población de cardiopatías. De este modo quedaron 2 artículos seleccionados para la revisión cualitativa final donde se compara KTR versus SET, y KTR en kinesiólogos especialistas y no especialistas, mostrando ambos aumento en la Cest y disminución de la Rva a favor de la KTR, hasta los 30 minutos post intervención. Conclusiones. No se encontraron artículos que demuestren cambios en Cest y Rva con el uso de KTR + SET versus SET exclusiva, en usuarios pediátricos ventilados posterior a CCC. Con la remoción de filtros seleccionamos 2 artículos que demuestran aumento de Cest y disminución de Rva en sujetos pediátricos en VM, uno comparando con SET, y por grupos de especialistas y no especialistas en respiratorio. Se sugieren estudios primarios para evaluar los efectos de esta intervención en esta población.

Introduction. Congenital heart diseases (CHD) are the second general cause for children death under 1 year. In Chile, approximately 65% CHD need surgery, could was palliative or corrective. In the postoperative period, invasive mechanical ventilation (MV) is frequently used as a life support method, but it is associated with complications. Tracheal suction (SET) is regularly used to remove secretions; however, respiratory chest physiotherapy (KTR) has shown significant improvements in thoraco-pulmonary compliance and airway resistance in other groups of pediatrics and adult's users in MV. Objetive. to compare changes in thoraco-pulmonary compliance and airway resistance in pediatric subjects under mechanical ventilation after congenital heart disease surgery comparing chest physiotherapy and exclusive tracheal suction. Methods. systematic review of studies published in PUBMED, PeDro, Scielo and Google Scholar databases who compares KTR or SET use on changes in ventilatory mechanics in pediatric users under MV after congenital heart disease surgery, limited to English, Spanish and Portuguese languages, excluding user with tracheostomy or extracorporeal membrane of oxygenation. It was use the PRISMA guide to articles selection. A search was carried out, with a total of 397 articles reviewed (English: PubMed = 3, PeDro = 8, Scholar = 383; Spanish: Scholar = 3, Scielo = 0; and Portuguese: Scielo = 0). One extra article was selected from the suggested articles, and 1 article was eliminated due to duplication. By titles and abstracts, 2 articles were selected, but the population did not correspond to heart disease. Results. the final selected articles were 0 articles. By this reason, it were removed: Boolean operator "NOT", and congenital heart disease population. Thus, 2 articles were selected for the final qualitative review where it was compares KTR versus SET, and KTR by specialist and non-specialist. Both articles shown improvement in compliance and resistance until 30 minutes post intervention. The CC population was in a 40 to 60% range in both studies. Conclusions. it was no found articles that demonstrate changes in compliance and resistance in the airway with the use of KTR + SET versus exclusive SET in pediatric users after CCC connected to MV. After filter remotion, we found 2 studies shown improves in increase compliance and reduce resistance in pediatric user in MV, ones comparing with SET, and the other one comparing between specialists in respiratory pediatric physiotherapy and not specialists. It suggests to made primary clinical studies about this intervention in CC population.

Resistencia a los inhibidores de la integrasa en niños con el virus de la inmunodeficiencia humana por transmisión vertical: primeros casos en Uruguay / Resistance to integrase inhibitors in children with vertically-transmitted human immunodeficiency virus: First cases in Uruguay

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.

Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.

High fat diet- induced obesity decreases ErbB receptors expression in liver and adipose tissue in C57BL/6 mice

Neuregulins (NRGs) are a family of signaling proteins that bind to receptor tyrosine kinases of the ErbB family (ErbB2 to ErbB4), which can homo- or heterodimerize depending on their structural features and cell type. Many studies have proposed that decreased NRG levels are a common characteristic of obesity. In liver and adipose tissue, the increase in NRG expression has protective effects against obesity. However, it is still unknown whether ErbBs expression is altered in this pathology. We hypothesized that high fat diet-induced obesity downregulates ErbB receptors expression in obese mice compared to normal weight mice. Males C57BL/6 mice (n=6-7 for each group) were fed for 12 weeks and divided into: (i) control diet (CD; 10%-kcal fat, 20%-kcal protein, 70%-kcal carbohydrates), and (ii) high fat diet (HFD; 60%-kcal fat, 20%-kcal protein, 20%-kcal carbohydrates). General parameters and ErbBs expression (qPCR, immunohistochemistry and Western blot) were evaluated. We observed a significant increase in final body weight (47%), adipose tissue to body weight ratio (244%) and HOMA-IR (69%), among other parameters, in obese mice. In HFD group significantly decreased ErbB2 (48%) and ErbB3 (66%) mRNA levels in liver (no change in ErbB4), and ErbB2 (43%), ErbB3 (76%) and ErbB4 (35%) in adipose tissue, compared to CD. Furthermore, ErbB2 and ErbB3 protein levels decreased significantly in HFD group compared to the CD in liver. Therefore, our results suggest that HFD-induced obesity significantly decreases ErbBs expression in liver and adipose tissue in this murine model, that may be associated with alterations in the NRG pathway in obese mice.

Las neuregulinas (NRGs) son una familia de proteínas de señalización que se unen a receptores tirosina quinasas de la familia ErbB (ErbB2 a ErbB4), que pueden homo- o heterodimerizar dependiendo de sus características estructurales y del tipo celular. Estudios han propuesto que la disminución de los niveles de NRG es una característica común de la obesidad. En el hígado y el tejido adiposo (TA), el aumento de la expresión de NRG tiene efectos protectores contra la obesidad. Sin embargo, aún se desconoce si la expresión de ErbBs está alterada en esta patología. Nuestra hipótesis es que la obesidad inducida por una dieta alta en grasas (DAG) disminuye la expresión de los ErbB en ratones obesos. Ratones machos C57BL/6 (n=6-7 para c/grupo) fueron alimentados durante 12 semanas y divididos en: (i) dieta control (DC; 10%-kcal grasa, 20%-kcal proteína, 70%-kcal carbohidratos), y (ii) DAG (60%-kcal grasa, 20%-kcal proteína, 20%-kcal carbohidratos). Se evaluaron los parámetros generales y la expresión de ErbBs (qPCR, inmunohistoquímica y Western blot). Observamos un aumento significativo del peso corporal final (47%), de la relación tejido adiposo/peso corporal (244%) y del HOMA-IR (69%), entre otros parámetros, en ratones obesos. En este grupo disminuyó significativamente los niveles de ARNm de ErbB2 (48%) y ErbB3 (66%) en el hígado (sin cambios en ErbB4), y de ErbB2 (43%), ErbB3 (76%) y ErbB4 (35%) en el TA. Además, los niveles de proteína ErbB2 y ErbB3 disminuyeron significativamente, en comparación con el grupo DC en el hígado. Nuestros resultados sugieren que la obesidad inducida por DAG disminuye significativamente la expresión de ErbBs en el hígado y el TA, que puede estar asociado con alteraciones en la vía NRG en ratones obesos.

Analysis of Healthcare-associated Infections before and during the COVID-19 pandemic in a Colombian hospital

Introduction: Healthcare-associated infections pose a significant challenge, contributing to hospital morbidity and mortality. Objective: To describe the behavior of Healthcare Associated Infections before and during the pandemic reported to a high-complexity health institution in Colombia. Material and Methods: In our retrospective observational study on Healthcare-Associated Infections (HAIs), we analyzed data from all in-patients diagnosed with HAIs between 2018 and 2020. This included clinical, demographic, microbiological, and microbial susceptibility information collected from the Committee on Nosocomial Infections' prospective database. Data from 391 isolates were obtained using Whonet software for antimicrobial resistance surveillance. Results: We found 504 cases of HAIs (2018-2020) with an overall in-hospital infection rate of 2.55/1000 patient-days. The median age for pediatric patients was 5 years, and for adults, 56 years, with 57% male. The leading admission diagnoses were oncologic disease complications (31%). Bacteremia had a 30-day mortality rate of 13%, predominantly catheter-associated (37%). Gram-negative bacilli, notably Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa, represented 58% cases of HAI. Discussion: The critical need for specific interventions and antimicrobial management to control HAIs, especially given the challenges posed by the COVID-19 pandemic, is highlighted. Conclusions: This is the first report on HAIs incidence at a tertiary hospital in Bucaramanga, Santander (Colombia). Bacteremia was predominant; 75% of HAIs patients had comorbidities. Gram-negative bacilli prevailed; a notable rise in ICU respiratory infections occurred during the 2020 COVID-19 pandemic. Resistance to cephalosporins and carbapenems was prevalent.

Tracing probiotic producing bacterial species from gut of buffalo (Bubalus bubalis), South-East-Asia / Rastreando espécies bacterianas produtoras de probióticos de intestino de búfalo (Bubalus bubalis), sudeste da Ásia

Due to extensive application of antibiotics as growth promoters in animal feed, antimicrobial resistance has been increased. To overcome this challenge, rumen microbiologists search for new probiotics to improve the rate of livestock production. The present study was aimed to isolate and evaluate breed-specific lactic acid bacteria (LAB) as potential animal probiotics. The current study was conducted during 10 months from July 2020 to April 2021, in which a total of n=12 strains were isolated from different samples including milk, rumen, and feces of Nilli Ravi Buffaloes. These isolates were evaluated for their antimicrobial potential against common animal pathogens (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). All the isolates were identified using 16S rRNA gene sequencing and the phylogenetic analyses inferred that these strains showed close relations to the species of various genera; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis, and Lactococcus lactis. NMCC-Ru2 has exhibited the enormous potential of antimicrobial activity, 28 mm, for Salmonella typhimurium;23 mm for Listeria monocytogenes 21 mm for E.coil. Highest resistance was seen in NMCC-Ru2 agasint test antbiotic, like 25.5 mm for Tetracycline. Overall results revesl that the probiotic profile of isolates was achieved using standard criteria, particularly with animal probiotic properties

Devido à extensa aplicação de antibióticos como promotores de crescimento na alimentação animal, a resistência aos antimicrobianos aumentou. Para superar esse desafio, os microbiologistas do rúmen buscam novos probióticos para melhorar a produtividade do gado. O presente estudo teve como objetivo isolar e avaliar bactérias lácticas específicas de raças (BAL) como potenciais probióticos animais. 12 cepas foram isoladas de diferentes amostras, incluindo leite, rúmen e fezes de búfalos Nilli Ravi. Esses isolados foram avaliados quanto ao seu potencial antimicrobiano contra patógenos animais comuns (Bacillus spp., E. coli, Staphylococcus aureus, Salmonella spp., Listeria spp.). Todos os isolados foram identificados por meio do sequenciamento do gene 16S rRNA e as análises filogenéticas inferiram que essas cepas apresentaram estreita relação com as espécies de vários gêneros; Enterococcus lactis, Pediococcus pentosaceus, Bacillus subtilis, Weissella cibaria, Weissella soli, Bacillus tequilensis, Weissella bombi, Bacillus licheniformis, Lactococcus lactis, Bacillus megaterium, Lactobacillus ruminis e Lactococcus lactis. O perfil probiótico dos isolados foi obtido usando critérios padrão, particularmente com propriedades probióticas animais.

Impact of Folic Acid on the Resistance of Non-small Cell Lung Cancer Cells to Osimertinib by Regulating Methylation of DUSP1 / 中国肺癌杂志

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.

The role of jasmonic acid in stress resistance of plants: a review / 生物工程学报

Jasmonic acid (JA), a plant endogenously synthesized lipid hormone, plays an important role in response to stress. This manuscript summarized the biosynthesis and metabolism of JA and its related regulatory mechanisms, as well as the signal transduction of JA. The mechanism and regulatory network of JA in plant response to biotic and abiotic stresses were systematically reviewed, with the latest advances highlighted. In addition, this review summarized the signal crosstalk between JA and other hormones in regulating plant resistance to various stresses. Finally, the problems to be solved in the study of plant stress resistance mediated by JA were discussed, and the application of new molecular biological technologies in regulating JA signaling to enhance crop resistance was prospected, with the aim to facilitate future research and application of plant stress resistance.

Research advances in second-line therapies for hepatocellular carcinoma after resistance to targeted therapy combined with immunotherapy / 临床肝胆病杂志

In recent years， clinical studies on targeted therapy and immunotherapy for advanced hepatocellular carcinoma used alone or in combination have provided abundant evidence on efficacy and safety for the selection of first-line therapies. However， no consensus has been reached on the selection of second-line therapies in various clinical guidelines for hepatocellular carcinoma， which is caused by the fact that existing evidence is limited to the options after failure of sorafenib and that there is still a lack of high-level evidence for new first-line therapies such as second-line therapies after resistance to targeted therapy and immunotherapy for hepatocellular carcinoma. This article reviews the results of current clinical trials and summarizes the studies on second-line therapies for hepatocellular carcinoma after resistance to first-line targeted therapy and immunotherapy for hepatocellular carcinoma based on the different mechanisms of action of drugs， as well as the research advances in recent years. For hepatocellular carcinoma patients with resistance to first-line targeted therapy and immunotherapy， targeted combination therapy and dual-immune therapy are expected to improve treatment outcome and survival， and more prospective clinical studies are needed in the future to provide effective and safe treatment regimens for hepatocellular carcinoma patients with resistance to targeted therapy and immunotherapy.

Research advances in monoclonal antibodies for treatment of drug resistance in inflammatory bowel disease / 中国生物制品学杂志

@#Inflammatory bowel disease(IBD)is a complex inflammatory disease mediated by immunity that is treated with the goal of maintaining disease remission and preventing recurrence. With the deep study of the molecular mechanism of the occurrence and development of IBD,many related target molecules have been found,and the monoclonal antibodies of corresponding targets have been used to treat the disease,while the drug resistance phenomenon generated during treatment has seriously affected the treatment effect. In this paper,monoclonal antibodies such as infliximab were reviewed for the treatment of IBD resistance,with a view to understanding its possible mechanisms and exploring effective treatments and preventive measures

Isolation and identification of Lactobacillus paracasei and Bacillus subtilis in goose feces / 中国生物制品学杂志

@#Objective To isolate and identify Lactobacillus paracasei and Bacillus subtilis from feces of northern white geese.Methods Lactobacillus paracasei and Bacillus subtilis,numbered S00834-8 and IS00439-2 respectively,were isolated from feces of 30 52-week-old northern white geese and cultured in specific medium,and identified by 16S DNA sequencing. The two strains were cultured for different time duration(0,2,4,6,8,10,12,14,16,18,20,22,24,36 and 48 h),at different temperature(34,36,37,38 and 40 ℃)and pH(5. 5,6. 0,6. 5,7. 0,7. 5 and 8. 0). The growth characteristics of the strains were evaluated according to the A600values measured by UV-Vis spectrophotometer. At the same time,the acid and bile salt tolerance(pH 2. 0,2. 5,3. 0,3. 5 and 7. 0,bile salt concentration 0,0. 3%,0. 5%,1. 0% and 1. 5%)and the antibiotic tolerance were tested. Results The strains S00834-8 and IS00439-2 were Lactobacillus paracasei subspecies tolerance H and Bacillus subtilis KA9,respectively. The strain S00834-8 cultured under the optimum condition of the culture medium with pH 6. 0,at 37 ℃,for 12 h,had good bile resistance and gastric acid resistance,which was moderately susceptible to piperacillin,norfloxacin,amikacin,gentamicin and tetracycline,and susceptible to levofloxacin,streptomycin and chloramphenicol. The strain IS00439-2 best cultured in the culture medium with pH 7. 5,at 36 ℃,for 8 h,showed good bile resistance and gastric acid resistance,which was moderately sensitive to levofloxacin and tetracycline,while sensitive to piperacillin,norfloxacin,streptomycin and chloramphenicol. Conclusion Goose-derived Lactobacillus paracasei subspecies tolerance H and Bacillus subtilis KA9 have good acid resistance and bile salt resistance,which are expected to be candidate strains for goose-derived microecological preparations.

Influence factors of bone mineral density and its correlation with insulin resistance in obese children in Qianjiang area / 公共卫生与预防医学

Objective To explore the influencing factors of bone mineral density (BMD) in obese children in Qianjiang area and analyze the correlation between BMD and insulin resistance. Methods The data on pediatric cases from the outpatient department of Jianghan Oilfield General Hospital in Qianjiang from January 2018 to December 2022 were collected. A total of 183 obese children who met the inclusion and exclusion criteria were included in the study and selected in the observation group. A total of 352 children undergoing physical examination during the same period were selected as the control group. Results The body mass, waist circumference, waist to hip ratio, and BMI of obese children were significantly higher than those of the control group (P<0.001). Biochemical indexes including FBG, FINS, Home-IR, ALP, and LDL-C in obese children were significantly higher than those in the control group (P<0.05), while bone mineral density, Ca, P, sOC and HDL-C were significantly lower than those in the control group (P<0.001). The bone mineral density of obese children was significantly correlated with their exercise intensity, sunshine exposure duration, sitting time, intake of milk and dairy products, intake of sweets, supplementation of trace elements, BMI, Home-IR, and sex (all P<0.05). BMI, Home-IR, sex, exercise intensity, and sunshine exposure length were independent risk factors affecting bone mineral density of obese children (all P<0.05). Bone mineral density was negatively correlated with BMI and Home-IR (P=0.028 and0.017, respectively), and positive correlation with exercise intensity and sunlight exposure (P=0.033). Conclusion BMD of obese children in Qianjiang area is affected by gender, body mass index, diet, vitamin intake, and physical activity, and is negatively correlated with insulin resistance. Home-IR can be used as a reference for screening BMD of obese children.

Primary drug resistance among HIV-1 patients in Hubei Province in 2020-2022 / 公共卫生与预防医学

Objective To investigate the prevalence of primary drug resistance among HIV-1 patients in Hubei Province from 2020 to 2022, and to provide corresponding basis and data support for HIV antiviral therapy (ART) in Hubei Province. Methods During 2020-2022, plasma samples of HIV-1 infected patients before ART were collected., Patients’ demographic data and baseline laboratory test data were also collected. HIV-1 pol region was amplified by in-house method for sub-type typing and drug-resistant mutation site analysis. Results The pol gene sequence was successfully amplified in 242 of 285 cases, with a success rate of 84.9%. CRF07_BC was the predominant HIV-1 sub-type, accounting for 47.11% (114/242), followed by CRF01_AE, accounting for 25.21% (61/242), sub-type B, accounting for 14.16% (35/242), and CRF55_01B, accounting for 4.13% (10/242). The primary resistance rate was 6.20% (15/242). The mutation site of nucleoside reverse transcriptase inhibitors (NRTIs) was mainly M184V, and the mutation sites of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were mainly E138A/G/EG and V179E. These different mutation sites led to different degrees of drug resistance to 12 drugs. The incidence of drug resistance mutation of CRF55_01B sub-type was significantly higher than that of other sub-types. Conclusion The primary drug resistance rate of HIV-1 infected patients is at a slightly high level in Hubei Province, and close monitoring of primary drug resistance and mutation sites should be strengthened before ART, especially for CRF55_01B sub-type.

Research hotspots and trends of tigecycline drug resistance: A study based on CiteSpace / 公共卫生与预防医学

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Synthesis and antibacterial activity evaluation of octapeptin derivatives / 药学学报

Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Analysis on risk factors of clopidogrel resistance in patients with ischemic stroke / 药学实践杂志

Objective To investigate the risk factors of drug resistance in patients with ischemic stroke by clopidogrel therapy and provide references for promoting clinical individualized drug therapy. Methods A total of 202 inpatients diagnosed with ischemic stroke were admitted and given dual anti-treatment (aspirin+clopidogrel). CYP2C19 genotype was detected by microarray hybridization during hospitalization, and CYP2C19 gene polymorphisms were classified into fast metabolism group, medium metabolism group and slow metabolism group according to the type of drug metabolism. Patients were tested for platelet inhibition induced by adenosine diphosphate (ADP) according to thromboelastographic (TEG) on 7~14 d of drug administration. ADP <30% was classified as clopidogrel drug resistance group and ADP ≥30% as non-resistance group. Logistic regression analysis was used to study the risk factors for the development of clopidogrel resistance. Results Among 202 patients with ischemic stroke, 87 were in the resistant group and 115 in the non-resistant group. The proportion of patients with clopidogrel resistance combined with diabetes and the level of white blood cell count were higher than that in the non-resistant group, and the differences were statistically significant (P<0.05).The proportion of patients with clopidogrel resistance in the CYP2C19 intermediate metabolism group was significantly higher than that in the fast metabolism group, and the rate of platelet inhibition was also significantly lower than that in the fast metabolism group, all with statistically significant differences (P<0.05). Conclusion Combined diabetes mellitus, high white blood cell count levels and CYP2C19 mid-metabolic phenotype are independent risk factors for the development of clopidogrel resistance in patients with ischemic stroke.

Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism / 中国药房

OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome （PCOS） and its mechanism. METHODS One hundred and twenty-six female rats were randomly separated into blank group， PCOS group， poria acid low-dose group （8.33 mg/kg）， pachymic acid high-dose group （33.32 mg/kg）， ethinylestradiol cyproterone group （positive control group， 0.34 mg/kg）， recombinant rat high mobility group protein B1 protein （rHMGB1） group （8 μg/kg）， and poria acid high dose+rHMGB1 group （33.32 mg/kg poria acid+8 μg/kg rHMGB1）， with 18 rats in each group. Except for the blank group， the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling， administration was performed once a day for 4 weeks. After medication， the fasting blood glucose and fasting insulin levels， and insulin resistance index （HOMA-IR） were measured in rats； the levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH） and testosterone （T） in rat serum， and the levels of interleukin-1β （IL-1β） and tumor necrosis factor- α （TNF- α） in ovarian tissue were detected； ovarian coefficients of rats were calculated； the pathological changes of ovarian tissue were observed； the expressions of HMGB1， receptor for advanced glycosylation elaine_ tanghong@sina.com end product （RAGE） and phosphorylated nuclear factor κB p65 （p-NF-κB p65） proteins were determined in ovarian tissue of rats. RESULTS Compared with the blank group， the pathological injury of ovarian tissue of rats in the PCOS group was serious， the levels of fasting blood glucose and fasting insulin， HOMA-IR and ovarian coefficient were increased， the levels of serum LH and T were increased， while the levels of FSH were decreased； the levels of IL-1β and TNF-α， the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were increased， with statistical significance （P＜0.05）. Compared with the PCOS group， pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group， and fasting blood glucose， fasting insulin levels， HOMA-IR and ovarian coefficient were decreased； serum LH and T levels were decreased， while FSH levels were increased； the levels of IL-1β and TNF-α and the expressions of HMGB1， RAGE and p-NF-κB p65 protein in ovarian tissue were decreased， with statistical significance （P＜0.05）. The trend of corresponding indexes in rHMGB1 group was opposite to the above （P＜0.05）. Compared with poria acid high-dose group， the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group （P＜0.05）. CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/ RAGE pathway.

Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Mechanism Exploration of TG Regulating PI3K/Akt to Improve Insulin Resistance in Liver of T2DM Rats Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangzhi pills on the improvement of insulin resistance （IR） in the liver with type 2 diabetes （T2DM） by regulating phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway based on differential genes and its possible molecular mechanism. MethodT2DM rat models were prepared by high fat （HFD） diet combined with streptozotocin （STZ） intraperitoneal injection. The experiment was divided into blank group， model group， metformin hydrochloride group （0.18 g·kg-1）， Tangzhi pills high （1.08 g·kg-1）， medium （0.54 g·kg-1） and low （0.27 g·kg-1） dose groups. Rat serum， liver， and pancreatic tissue were collected， and the pathological tissue of the liver and pancreas was observed using hematoxylin-eosin （HE） staining. The fasting blood glucose level （FBG） was detected， and oral glucose tolerance （OGTT） tests were conducted. Enzyme-linked immunosorbent assay （ELISA） was used to detect fasting serum insulin （FINS） and glycated hemoglobin （GHb） levels in rats. IR homeostasis model index （HOMA-IR）， β cellular homeostasis index （HOMA-β）， and insulin sensitivity index （ISI） were calculated. Biochemical methods were used to determine the levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL-C）， and high-density lipoprotein （HDL-C） in rat serum. Transcriptomics obtained differentially expressed mRNA from liver tissue and enriched differentially expressed pathways. Real-time reverse transcriptase polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of cyclic adenylate responsive element binding protein 3-like protein 2 antibody （CREB3l2）， B-lymphocyte tumor 2 （Bcl-2）， Toll-like receptor 2 （TLR2）， cyclin-dependent kinase inhibitor 1A （CDNK1A）， and DNA damage induced transcription factor 4-like protein （DDIT4） in liver tissue. Western blot was used to detect the protein expression of phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， glucose transporter 4 （GLUT4）， insulin receptor （INSR）， and insulin receptor substrate 2 （IRS2）. ResultThe pharmacodynamic experiment results showed that compared with model group， Tangzhi pills groups repaired liver and pancreatic tissue to varying degrees， reduced blood sugar （P<0.01）， and promoted a decrease in serum FINS， GHb， and HOMA-IR （P<0.05， P<0.01）. In addition， HOMA-β and ISI increased （P<0.05， P<0.01）. The levels of TC， TG， and LDL-C decreased （P<0.05， P<0.01）， while the levels of HDL-C increased （P<0.05， P<0.01）. The transcriptomics experimental results confirmed that the PI3K/Akt signaling pathway was significantly expressed in both the blank group and model group， as well as in the high-dose Tangzhi pills group and model group. CDNK1A， DDIT4， CREB3l2， Bcl-2， and TLR2 were significantly differentially expressed mRNA during TG intervention in T2DM. Compared with the model group， the protein expression of p-PI3K， p-Akt， GLUT4， INSR， and IRS2 increased in all Tangzhi pills groups （P<0.01）. The mRNA expression of CREB3l2， Bcl-2， and TLR2 increased （P<0.01）， while that of CDNK1A and DDIT4 decreased （P<0.01）. ConclusionTangzhi pills may regulate the PI3K/Akt signaling pathway based on the differential mRNA expression of CREB3l2， Bcl-2， TLR2， CDNK1A， and DDIT4， thereby improving IR in the liver with T2DM.