Value of biotargeted drugs in airway mucus therapy of asthma / 中国临床药理学与治疗学

Airway mucus plug is a common phenotype in asthma that increases the risk of acute asthma attacks by causing aggravation of airflow obstruction. Given its important role in asthma, treatment targeting airway mucus plugs may be a strategy to control asthma progression and prevent fatal asthma exacerbations. Previous studies have shown that acidosophils and T2 type inflammation are related with the formation of mucus plugs, and biotargeted drugs targeting the above pathways may be effective in the treatment of airway mucus plugs.

Mechanism and treatment of mucous hypersecretion in chronic obstructive pulmonary disease / 中国临床药理学与治疗学

Airway mucus hypersecretion is one of the important pathophysiological and clinical manifestations of chronic obstructive pulmonary disease. It has been reported in the literature that COPD patients with chronic airway mucus hypersecretion have more frequent acute exacerbations, more severe lung function decline, and higher hospitalizations and mortality. Therefore, it is particularly critical to understand the pathogenesis of hypersecretion of mucus in chronic obstructive pulmonary disease and find out effective treatment. This article focuses on the structure, significance of airway mucus and the mechanism of hypersecretion of mucus in chronic obstructive pulmonary disease (COPD). In addition, we also summarized drug and non-drug therapy for chronic airway mucus hypersecretion in this article. Drug therapy includes traditional drug therapy, some new targeted drug therapy for pathogenesis and traditional Chinese medicine therapy, and non-drug therapy includes smoking cessation, physical therapy and bronchos-copy therapy. We hope that it will provide new ideas and directions for the treatment of mucus hypersecretion in COPD patients.

Pathogenesis of Airway Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.

Mucus-penetrating nonviral gene vaccine processed in the epithelium for inducing advanced vaginal mucosal immune responses

Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females. Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells (ECs), which represent the main technical difficulties for vaccine development, reside in the harsh, acidic human vaginal environment. Different from frequently employed viral vectors, two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses. Differing design concepts include the charge-reversal property (DRLS) to mimic a virus that uses any cells as factories, as well as the addition of a hyaluronic acid coating (HA/RLS) to directly target dendritic cells (DCs). With a suitable size and electrostatic neutrality, these two nanoparticles penetrate a mucus hydrogel with similar diffusivity. The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo. Therefore it induced more robust mucosal, cellular, and humoral immune responses. Moreover, the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA (naked), indicating timely protection against pathogens at the mucus layer. These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.

Yifei Jianpi recipe improves cigarette smoke-induced inflammatory injury and mucus hypersecretion in human bronchial epithelial cells by inhibiting the TLR4/NF-κB signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the mechanism of Yifei Jianpi recipe for improving cigarette smoke- induced inflammatory injury and mucus hypersecretion in cultured human bronchial epithelial cells.@*METHODS@#Serum samples were collected from 40 SD rats treated with Yifei Jianpi recipe (n=20) or normal saline (n=20) by gavage. Cultured human bronchial epithelial 16HBE cells were stimulated with an aqueous cigarette smoke extract (CSE), followed by treatment with the collected serum at different dilutions. The optimal concentration and treatment time of CSE and the medicated serum for cell treatment were determined with CCK-8 assay. The expressions of TLR4, NF-κB, MUC5AC, MUC7, and muc8 at both the mRNA and protein levels in the treated cells were examined with RT- qPCR and Western blotting, and the effects of TLR4 gene silencing and overexpression on their expressions were assessed. The expressions of TNF-α, IL-1 β, IL-6 and IL-8 in the cells were detected using ELISA.@*RESULTS@#At the optimal concentration of 20%, treatment with the medicated serum for 24 h significantly lowered the mRNA and protein expressions of TLR4, NF- κB, MUC5AC, MUC7, and MUC8 in CSE- exposed 16HBE cells, and these effects were further enhanced by TLR4 silencing in the cells. In 16HBE cells with TLR4 overexpression, the expressions of TLR4, NF-κB, MUC5AC, MUC7, and MUC8 were significantly increased after CSE exposure and were lowered following treatment with the medicated serum (P < 0.05). The medicated serum also significantly lowered the levels of TNF-α, IL-1β, IL-6 and IL-8 in CSE-exposed 16HBE cells (P < 0.05).@*CONCLUSIONS@#In the 16HBE cell model of chronic obstructive pulmonary disease (COPD), treatment with Yifei Jianpi recipe-medicated serum improves inflammation and mucus hypersecretion possibly by reducing MUC secretion and inhibiting the TLR4/NF-κB signaling pathway.

Recent progress in application of nanovaccines for enhancing mucosal immune responses

Mucosal vaccines that stimulate both mucosal and systemic immune responses are desirable, as they could prevent the invading pathogens at their initial infection sites in a convenient and user-friendly way. Nanovaccines are receiving increasing attention for mucosal vaccination due to their merits in overcoming mucosal immune barriers and in enhancing immunogenicity of the encapsulated antigens. Herein, we summarized several nanovaccine strategies that have been reported for enhancing mucosal immune responses, including designing nanovaccines that have superior mucoadhesion and mucus penetration capacity, designing nanovaccines with better targeting efficiency to M cells or antigen-presenting cells, and co-delivering adjuvants by using nanovaccines. The reported applications of mucosal nanovaccines were also briefly discussed, including prevention of infectious diseases, and treatment of tumors and autoimmune diseases. Future research progresses in mucosal nanovaccines may promote the clinical translation and application of mucosal vaccines.

Versatile flexible micelles integrating mucosal penetration and intestinal targeting for effectively oral delivery of paclitaxel

The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.

Effects of recombinant human interferon α2a suppository on levels of inflammatory factors in cervical mucus of HPV-infected patients / 中国生物制品学杂志

@#Objective To investigate the effects of recombinant human interferon α2a(rhIFNα2a) suppository on the levels of inflammatory factors in the cervical mucus of patients infected with human papillomavirus(HPV).Methods A total of60 HPV-positive patients admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from March to August in 2022 were selected as study objects,and then divided into observation and control groups,30 cases for each group,according to the random number table method.The observation group was given rhIFNα2a suppository therapy by vaginal medication,once every other day,continuous 10 times a month as a course of treatment,and 3 consecutive courses of treatment.The control group did not use drugs.The cervical secretions were collected and the levels of IL-1β,IL-2R,IL-6,IL-8,IL-10 and tumor necrosis factor-α(TNF-α) were measured by chemiluminescence assay.Results After 3 months of treatment,the levels inflammatory factors IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group were significantly lower than those in the control group(t=-2.717,-2.686,-3.178 and-3.25,respectively,each P <0.05).Compared with before treatment,the levels of IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group also decreased significantly(t=5.934,4.092,6.495 and 3.287,respectively,each P <0.01),while in the control group,only the level of IL-8 in cervical mucus was significantly different(t=2.345,P=0.024).Conclusion rhIFNα2a suppository can reduce the level of inflammatory factors in cervical mucus,attenuate the inflammatory response and accelerate the clearance of HPV.

Influence of airway mucus plugs on patients with bronchial asthma and its management / 中华健康管理学杂志

Objective:To explore the influence of airway mucus plugs on patients with bronchial asthma and its management.Methods:In this cross-sectional study, from January 2020 to June 2022, 100 patients who were diagnosed with asthma and underwent chest CT examination in the Outpatient Department of Peking University Third Hospital were included. The chest CT results and medical history, pulmonary function, fractional exhaled nitric oxide (FeNO), blood routine, total allergen IgE, Aspergillus fumigatus M3 allergen-specific IgE antibody test results were collected. According to the results of chest CT, the asthma patients were divided into group with mucus plugs and those without mucus plugs. Distribution of airway mucus plugs and the mucus plug scores based on lung segments were calculated. The relationships of mucus plugs with medical history, pulmonary function [These included before and after the bronchodilation test, forced vital capacity percent of predicted value (FVC%pred), forced expiratory volume in one second percent of predicted value (FEV 1%pred), FEV 1/FVC, peak expiratory flow percent of predicted value (PEF%pred), maximal mid-expiratory flow percent of predicted value (MMEF%pred), maximal expiratory flow at 25%, 50%, 75% of vital capacity remaining percent of predicted value (MEF 25%pred, MEF 50%pred, MEF 75%pred)], FeNO, and peripheral blood eosinophil (Eos) counts were analyzed. The logistic regression model was used to analyze whether airway mucus plug was a risk factor for asthma exacerbation, and the corresponding intervention strategies were explored. Results:Among the 100 patients with asthma, 24 cases were in the mucus plug group and 76 cases were in the non-mucus plug group. The distribution of mucus plug was more common in the lower lungs (30.53% and 9.16% in the lower and upper lobe of left lung, respectively; 29.01%, 14.50% and 16.80% in the lower, middle and upper lobe of right lung, respectively). The average score of mucus plug was (4.42±3.12) points. The body mass index (BMI), the number of visits to a doctor due to asthma exacerbations, FeNO, peripheral blood Eos counts in the mucus plug group were higher than those in the non-mucus plug group [(24.95±4.34) vs (23.22±2.91) kg/m 2, 0(0, 1) vs 0(0, 0), 97(37, 169) vs 31(18, 59) ppb (1 ppb=1×10 -9), 0.41(0.15, 0.70) vs 0.18(0.09, 0.37)×10 9/L](all P<0.05), and FVC%pred, FEV 1%pred, FEV 1/FVC, PEF%pred, MEF 50%pred, MEF 25%pred, MMEF%pred, MEF 75%pred were lower than those in the non-mucus plug group [(87.49±19.32)% vs (97.34±14.24)%, (76.49±19.58)% vs (91.07±18.33)%, (72.44±10.91)% vs (79.48±8.13)%, (82.36±24.46)% vs (93.83±18.27)%, (53.03±24.81)% vs (75.75±27.15)%, (46.47±22.92)% vs (64.09±25.90)%, (50.28±23.73)% vs (74.53±26.80)%, (71.30±27.55)% vs (89.92±26.82)%] (all P<0.05). In the group with mucus plug, the airway mucus plug score was positively correlated with the patient′s body weight and the number of peripheral blood Eos counts at enrollment ( r=0.413, 0.478; all P<0.05), and negatively correlated with FVC%pred and FEV 1%pred ( r=-0.576, -0.465; all P<0.05). Logistic regression analysis showed that airway mucus plug score was a risk factor for acute asthma attack ( OR=1.269, 95% CI: 1.031-1.562; P=0.024). Conclusions:Asthma patients have a high incidence of airway mucus plug, which is related to the level of Eos inflammation and body size. Airway mucus plugs can promote airflow obstruction and acute exacerbation of asthma. In clinical practice, appropriate asthma management policies can be formulated for airway mucus plugs to delay the progression of asthma and reduce the number of acute attacks.

Virulence associated characteristics and drug resistance of Klebsiella pneumoniae isolated from patients living in Zhongjiang county of Sichuan province / 中国基层医药

Objective:To investigate the distribution characteristics of virulence-related phenotypes/genotype, capsular serotype, drug resistance phenotypes, and sequence typing (ST) of Klebsiella pneumoniae in patients living in Zhongjiang county, improve clinical understanding, and provide evidence for the prevention and control of bacterial drug resistance and clinical rational drug use. Methods:The data of 135 strains of Klebsiella pneumoniae isolated from patients who received treatment in Zhongjiang County People's Hospital from July to December 2019 were retrospectively analyzed. Bacterial identification and drug sensitivity testing were performed using the WalkAway-40Plus automated microbiology system. Strains with a high viscosity phenotype were identified using wire drawing experiments. Hypervirulence-associated capsular serotype and virulence genes were verified by polymerase chain reaction. ST of Klebsiella pneumoniae strain was identified using multilocus sequence typing. Results:Strains with a high viscosity phenotype were identified in 50.4% of the 135 strains. 54.1%, 54.8%, and 54.1% of the strains were positive for virulence genes iucA, iroN, rmpA. The proportion of strains with capsular Serotype K1 or K2 was 11.9% and 15.6%, respectively. A total of 65 kinds of ST were identified, with ST23 and ST37 being the most common, accounting for 11.1% and 6.7%, respectively. The resistance rate of the strains to 16 kinds of antibiotics was 0.0%-25.2%, and the resistance rate to Carbapenem antibiotics, Amikacin, and Tigecycline was less than 1%. The positive rate of virulence gene of strains with a high viscosity phenotype was significantly higher than that of strains without a high viscosity phenotype ( P < 0.001), and its resistance rate to Cephalosporin was significantly lower in strains with a high viscosity phenotype than that in strains without a high viscosity phenotype ( P < 0.001). Conclusion:Klebsiella pneumoniae in Zhongjiang County is characterized by "high virulence and low drug resistance". It is necessary to continuously monitor the changes in the virulence and drug resistance of Klebsiella pneumoniae in Zhongjiang County, Sichuan Province, and be alert to the rapid dissemination of highly virulent strains.

Exploration on the TCM pathogenesis of hypersecretion of airway mucus in children base on the theory of water-liquid metabolism and triple energizer membranous system / 国际中医中药杂志

The pathological position of hypersecretion of airway mucus is in airway mucosa. Modern TCM theory believes that the airway mucosa belongs to the triple energizer membranous system of TCM, and the airway mucus is a part of TCM water-liquid system. Based on the TCM physiological characteristics of children, this article explored the pathogenesis of airway mucus hypersecretion in children, and believed that the airway mucus hypersecretion was the result of the disorder of water-liquid metabolism in TCM, which was closely related to the function of qi transformation of triple energizer membranous system. Failure of qi transformation in triple energizer is the core pathogenesis of hypersecretion of airway mucus in children. The deficiency of yang qi in children leads to the disorganization of vaporization in triple energizer, which leads to the insufficiency of movement and transformation function, the failure of water and qi in water, the stop of water and water accumulation, the abnormity of water and grain. The disorder of water-liquid metabolism leads to the occurrence of high airway mucus secretion in children.

Vaginal Electrical Impedance Detects the Fertile Window in Healthy Women: a Pilot Study / La Impedancia Eléctrica Vaginal Detecta la Ventana Fértil en Mujeres Sanas: un Estudio Piloto

ABSTRACT This work analyzes the electrical impedance (EI) measurement of cervical mucus (CM) using a device to determine the fertile window. In this prospective and longitudinal study, fourteen healthy women aged 18 to 44 were enrolled to evaluate three menstrual cycles. EI was measured through a medical device inserted into the vagina for two minutes daily. Patients were monitored by urine luteinizing hormone (LH) strip, blood collection, and vaginal ultrasound to visualize the dominant follicle. Finally, the predictive EI capacity was validated by the receiver operating characteristic (ROC) of anovulatory vs. ovulatory impedances. The peak of LH was 35.7 (±4.5) mUI/ml and the dominant follicle size was 15.45 mm (±0.559). There were statistical differences in EI measurements between the follicular and luteal phases vs. the ovulation phase (p<0.0361 and p<0.0160). After data normalization, an area under the ROC curve (AUC) of 0.713 (P value= 0.0253), a Youden J index of 0.4545Ω, a sensitivity of 63.6%, and a specificity of 81.8% were found. Low EI in the ovulatory period belongs to the LH ovulatory peak and follicular release. EI can be used for ovulation monitoring, birth control, or promoting pregnancy as a safe and innocuous method.

RESUMEN Este trabajo analiza la medición de la impedancia eléctrica (IE) del moco cervical (MC) mediante un dispositivo para determinar la ventana fértil. En este estudio prospectivo y longitudinal, se incluyeron 14 mujeres sanas de 18 a 44 años para evaluar tres ciclos menstruales. La IE se midió a través de un dispositivo médico colocado en la vagina durante dos minutos diarios. Las pacientes fueron monitoreadas con una tira de hormona luteinizante (LH) en orina, recolección de sangre y ultrasonido vaginal para visualizar el folículo dominante. Finalmente, la capacidad predictiva de IE fue validada por la curva ROC (receiver operating characteristic) de impedancias anovulatorias vs. ovulatorias. El pico de LH fue de 35.7(±4.5) mUI/ml; el folículo de tamaño dominante fue de 15.45 mm (±0.559). Se encontraron diferencias estadísticas para la medición de la IE de las fases folicular y lútea versus la fase de ovulación (p<0.0361 y p<0.0160). Después de la normalización de los datos, se encontró un área bajo la curva ROC (AUC) de 0.713 (valor de P = 0.0253), un índice de Youden J de 0.4545 Ω, sensibilidad del 63.6 % y especificidad del 81.8 %. La IE baja en el período ovulatorio que pertenece al pico ovulatorio de LH y liberación folicular. La IE se puede utilizar para el control de la ovulación, el control de la natalidad o la promoción del embarazo como método seguro e inocuo.

Utilización de ventilación percusiva intrapulmonar como terapia de higiene bronquial mecánica en pacientes pediátricos críticos / Use of Intrapulmonary Percussive Ventilation as Mechanical Bronchial Hygiene Therapy in Critical Pediatric Patients

La ventilación percusiva intrapulmonar (VPI) es una técnica de higiene bronquial mecánica (THBM) de alta frecuencia, que favorece la movilización de secreciones y es considerada como alternativa para la resolución de atelectasias. Estudio de serie de casos, prospectivo, observacional y descriptivo que se llevó a cabo entre el 1 de agosto del 2019 y el 31 de diciembre del 2019. Se incluyeron todos los pacientes menores de 18 años, con soporte ventilatorio que recibieron al menos una sesión de VPI dentro de terapia intensiva. El objetivo primario de nuestro estudio es describir las características de la población en la que se utilizó un equipo domiciliario de VPI como THBM en la UCIP. De manera secundaria describiremos la metodología de implementación del dispositivo y sus resultados. Resultados: Se incluyeron 18 pacientes y se realizaron 48 sesiones de VPI. El principal motivo para la realización de VPI fue el diagnóstico de atelectasia (83,3%). El tratamiento se realizó tanto en pacientes con VMI (ventilación mecánica invasiva) (55,6%) como en pacientes con soporte no invasivo (44,4%), ya sea VMNI (ventilación mecánica no invasiva) o CNAF (cánula nasal de alto flujo). En el 53,3% de los pacientes, se evidenció resolución radiográfica de la atelectasia, entre los cuales, el 75% solo requirió entre una y dos sesiones para resolverlas. No se observaron complicaciones graves. Conclusión: Este estudio permite describir la población en la cual se implementa VPI a la vez que presenta una herramienta que podría ser de utilidad para la resolución de atelectasias.

Intrapulmonary percussive ventilation (IPV) is a high-frequency mechanical bronchial hygiene technique (MBHT) that favors secretion clearance and is considered an alterna tive to the resolution of atelectasis. This is a prospective, observational and descriptive case series study conducted be tween August 1st, 2019 and December 31st, 2019. The study included patients younger than 18 years on ventilatory support who received at least one session of IPV in the intensive care unit. The primary objective of our study was to describe the characteristics of the population in whom we used a home IPV device as MBHT in the PICU. On a secondary level, we will describe the methodology for using this device and its results. Results: 18 patients were included; 48 IPV sessions were done. The main reason for doing IPV was the atelectasis diagnosis (83.3%). The treatment was carried out both in patients on IMV (invasive mechanical ventilation) (55.6%) and in patients with non-invasive support (44.4%), whether it was NIMV (non-invasive mechanical ventilation) or HFNC (high-flow nasal cannula). 53.3% of the patients showed radiographic resolution of atelectasis, where 75% only required between one and two sessions to resolve it. No severe complications were observed. Conclusion: This study allows us to describe the population receiving IPV and presents a tool that could be useful for the resolution of atelectasis.

Use of Intrapulmonary Percussive Ventilation as Mechanical Bronchial Hygiene Therapy in Critical Pediatric Patients / Utilización de ventilación percusiva intrapulmonar como terapia de higiene bronquial mecánica en pacientes pediátricos críticos

ABSTRACT Intrapulmonary percussive ventilation (IPV) is a high-frequency mechanical bronchial hygiene technique (MBHT) that favors secretion clearance and is considered an alternative to the resolution of atelectasis. This is a prospective, observational and descriptive case series study conducted between August 1st, 2019 and December 31st, 2019. The study included patients younger than 18 years on ventilatory support who received at least one session of IPV in the intensive care unit. The primary objective of our study was to describe the characteristics of the population in whom we used a home IPV device as MBHT in the PICU. On a secondary level, we will describe the methodology for using this device and its results. Results: 18 patients were included; 48 IPV sessions were done. The main reason for doing IPV was the atelectasis diagnosis (83.3%). The treatment was carried out both in patients on IMV (invasive mechanical ventilation) (55.6%) and in patients with non-invasive support (44.4%), whether it was NIMV (non-invasive mechanical ventilation) or HFNC (high-flow nasal cannula). 53.3% of the patients showed radiographic resolution of atelectasis, where 75% only required between one and two sessions to resolve it. No severe complications were observed. Conclusion: This study allows us to describe the population receiving IPV and presents a tool that could be useful for the resolution of atelectasis.

RESUMEN La ventilación percusiva intrapulmonar (VPI) es una técnica de higiene bronquial mecánica (THBM) de alta frecuencia, que favorece la movilización de secreciones y es considerada como alternativa para la resolución de atelectasias. Estudio de serie de casos, prospectivo, observacional y descriptivo que se llevó a cabo entre el 1 de agosto del 2019 y el 31 de diciembre del 2019. Se incluyeron todos los pacientes menores de 18 años, con soporte ventilatorio que recibieron al menos una sesión de VPI dentro de terapia intensiva. El objetivo primario de nuestro estudio es describir las características de la población en la que se utilizó un equipo domiciliario de VPI como THBM en la UCIP. De manera secundaria describiremos la metodología de implementación del dispositivo y sus resultados. Resultados: Se incluyeron 18 pacientes y se realizaron 48 sesiones de VPI. El principal motivo para la realización de VPI fue el diagnóstico de atelectasia (83,3%). El tratamiento se realizó tanto en pacientes con VMI (ventilación mecánica invasiva) (55,6%) como en pacientes con soporte no invasivo (44,4%), ya sea VMNI (ventilación mecánica no invasiva) o CNAF (cánula nasal de alto flujo). En el 53,3% de los pacientes, se evidenció resolución radiográfica de la atelectasia, entre los cuales, el 75% solo requirió entre una y dos sesiones para resolverlas. No se observaron complicaciones graves. Conclusión: Este estudio permite describir la población en la cual se implementa VPI a la vez que presenta una herramienta que podría ser de utilidad para la resolución de atelectasias.

Fenômeno de extravasamento de muco: relato de dois casos clínicos / The mucous retention phenomenom: tho clinical cases report

O fenômeno de extravasamento de muco, também referido como mucocele, é uma lesão comum da mucosa oral resultante da ruptura de um ducto da glândula salivar com extravasamento da mucina. O principal fator etiológico é o trauma local. A localização mais comum é o lábio inferior, mas outros locais podem ser afetados. Existe a necessidade de diagnóstico diferencial uma vez que, pelo aspecto clínico e localização, as mucoceles assemelham-se a outras lesões que afetam a boca. Diante desse cenário, o objetivo deste trabalho foi relatar dois casos clínicos de fenômeno de extravasamento de muco (mucocele), evidenciando suas características clínicas, histopatológicas, tratamento e prognóstico. Acredita-se que o conhecimento das principais características dessa condição patológica possa auxiliar o clínico na adoção dos principais procedimentos na avaliação, conduta e tratamento desses pacientes.

The mucous retention phenomenon, also called as oral mucocele, is a common lesion of the oral mucosa resulting from the rupture of a salivary gland duct. The main etiological factor is local trauma. The most common location is the lower lip, but other locations can be affected. Differential diagnosis is important because mucoceles resemble other oral lesions. Thus, the aim of the present study was to report two cases of mucocele, demonstrating its clinical and histopathological characteristics, treatment and prognosis.. It is believed that knowledge of the main characteristics of this lesions can help the clinician in carrying out the main procedures in the evaluation, conduct and treatment of these patients.

Effect of Yifei Huatan Decoction on Relieving Airway Hyperviscosity in Asthmatic Rats with Spleen Deficiency Syndrome and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the effect of Yifei Huatan decoction on relieving airway hyperviscosity in asthmatic rats with spleen deficiency syndrome and its mechanism. MethodFifty-five SPF level SD rats at 8-9 week of age were used to induce asthma with spleen deficiency syndrome by animal modeling of traditional Chinese medicine combined with asthma of western medicine. After successful modeling， the rats were divided into model group， dexamethasone group， low， medium， and high-dose Yifei Huatan decoction groups by random number table method， and 11 clean SD rats at 8-9 week of age were recorded as a normal group. Rats in the dexamethasone group were given 0.087 5 mg kg-1 dexamethasone acetate by gavage. Rats in the low， medium， and high-dose Yifei Huatan decoction groups were given 0.8， 1.6， 3.2 g kg-1 Yifei Huatan decoction liquid extract by gavage， respectively. Rats in the model group and the normal group were given 10 mL kg-1 distilled water. The medicine were given once per day for 8 w， and the general situation of each group was observed. The levels of interleukin-4 （IL-4）， IL-13， and interferon-γ （IFN-γ） in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. The pathological changes in lung tissues of rats were observed by hematoxylin-eosin （HE） staining. Alcian blue-periodic acid Schiff （AB-PAS） staining was used to detect the hyperplasia of airway goblet cells and mucus secretion in rats. The mRNA expressions of transforming growth factor-β1 （TGF-β1）， Smad2， Smad3， mucin 5AC （MUC5AC）， and mucin 5B （MUC5B） in the lung tissues of rats were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B in the lung tissues of rats were detected by Western blot. ResultAs compared with the normal group， rats in the model group showed the symptoms of spleen deficiency syndrome， such as decreased body weight， muscle emaciation， decreased food intake， increased water intake， increased anal temperature， tiredness， and decreased swimming endurance， accompanied by dyspnea symptoms such as wheezing and nodding. As compared with the normal group， IL-4 and IL-13 levels in the BALF of the model group were significantly increased （P<0.01）， while the IFN-γ level was significantly decreased （P<0.01）. In the model group， a large number of inflammatory cells were observed in the mucosa and submucosa of the airway， and the smooth muscle of the trachea was significantly thickened. The hyperplasia， deformation， and exfoliation of various epithelial cells were observed in the mucosa， and the pathological scores of lung tissue increased significantly （P<0.01） in the model group. A large number of goblet cells were observed in the airway with the formation of plenty of mucous thrombus in the model group， and the positive relative staining area of airway， and mRNA and protein expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B were significantly increased （P<0.01）. As compared with the model group， IL-4 and IL-13 levels in BALF of the dexamethasone group and the Yifei Huatan decoction groups decreased， while the IFN-γ level increased. The inflammatory cell infiltration in airway mucosa and submucosa， the thickening of tracheal smooth muscle， the hyperplasia， deformation， and exfoliation of epithelial cells in mucosa were gradually decreased， and the pathological scores of lung tissues decreased significantly （P<0.01） in the dexamethasone group and the Yifei Huatan decoction groups. Goblet cell proliferation gradually decreased， and the positive relative staining area of airway， and mRNA and protein relative expressions of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B decreased with statistically significant difference （P<0.05， P<0.01）. There was no significant difference in the above indexes in the dexamethasone group and the Yifei Huatan decoction low-dose group. The above indexes were dose-dependent in the low， medium， and high-dose Yifei Huatan decoction groups. ConclusionYifei Huatan decoction reduces airway hyperviscosity in asthmatic rats with spleen deficiency syndrome， which may be related to the inhibition of TGF-β1， Smad2， Smad3， MUC5AC， and MUC5B expressions， down-regulation of IL-4 and IL-13 levels， and up-regulation of IFN-γ level.

Effect of Bufei Yishen Prescription on Airway Mucus Hypersecretion and Notch3 and HES1 Expression in Lung Tissues of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1 （HES1） in rats with chronic obstructive pulmonary disease （COPD） and to explore its action mechanism. MethodForty-eight SD rats were randomly divided into the control group， model group， Bufei Yishen prescription group， and aminophylline （APL） group，with 12 rats in each group. The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks， and the corresponding drugs （3.7 g·kg-1·d-1 Bufei Yishen prescription and 54 mg·kg-1·d-1 APL） were administered by gavage during the next eight weeks. After the last administration at week 20， the lung tissue was sampled for observing the pathological changes and the rat lung function was detected. The tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and mucoprotein 5AC （MUC5AC） in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues were assayed. ResultCompared with the control group， the model group exhibited significantly weakened pulmonary function （P<0.05，P<0.01）， reduced average number of alveoli （P<0.01）， elevated mean linear intercept （P<0.01）， and up-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and Notch3， HES1， and MUC5AC mRNA and protein expression in lung tissue （P<0.05，P<0.01）. Compared with the model group， Bufei Yishen prescription and APL remarkably enhanced pulmonary function， alleviated its pathological injury （P<0.05，P<0.01）， and down-regulated TNF-α， IL-6， and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3， HES1， and MUC5AC in lung tissues （P<0.05，P<0.01）. ConclusionThe mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.

Research progress of delivery strategies related mucus barrier in mucosal drug delivery / 药学学报

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

Bufei Yishen formula attenuates cigarette smoke extract-induced airway mucus hypersecretion by regulating Notch signaling pathway / 中华危重病急救医学

Objective:To explore the mechanism of Bufei Yishen formula (BYF) on attenuating cigarette smoke extract (CSE)-induced airway mucus hypersecretion by regulating Notch signaling pathway.Methods:The human airway epithelial cell 16HBE was cultured in vitro, and the cells in logarithmic growth phase were used for the experiments. ① Intervention condition screening experiment: the 16HBE cells were grouped, methylthiazolyldiphenyl-tetrazolium (MTT) method and enzyme-linked immunosorbent assay (ELISA) were used to detect the effects of different concentrations of CSE (2.5%, 5%, 10%, 20%, 40%), different concentrations of BYF drug-containing serum (5%, 10%, 20%, 40%), and different concentrations of Notch signal pathway blocker DAPT (5, 10, 20, 40 μmol/L) on cell activity and secretion of mucin 5AC (MUC5AC) levels. In addition, a blank control group was set up to screen out the best conditions for preparing CSE-induced cell mucus hypersecretion model and BYF and DAPT intervention. ② Intervention experiment: the 16HBE cells were divided into four groups. The blank control group was not given any treatment; the 16HBE cells were induced by 10% CSE for 24 hours to prepare mucus hypersecretion model in the CSE model group; the cells in the CSE+BYF group and CSE+DAPT group were given 10% BYF or 20 μmol/L DAPT, respectively, for intervention at the same time for 24 hours. Real-time fluorescent quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expressions of MUC5AC, Notch3 and hairy and enhancer of split 1 (HES1) in the cells. Western blotting was used to detect the protein expressions of Notch3 and HES1 in the cells. Results:① Results of the screening experiment of intervention conditions: compared with the blank control group, 10% CSE induction for 24 hours was the best condition for establishing cell mucus hypersecretion model that neither affected cell viability nor increased the secretion of MUC5AC; while 10% BYF and 20 μmol/L DAPT was the optimal intervention condition. ② Intervention experiment results: compared with the blank control group, the mRNA expressions of MUC5AC, Notch3, and HES1 and the protein expressions of Notch3 and HES1 in the CSE model group were significantly increased, indicating that CSE activated Notch3 and HES1 signal activation and induced 16HBE cells to secrete mucus protein. Compared with the CSE model group, BYF and DAPT could significantly down-regulate the mRNA and protein expressions of MUC5AC, Notch3, and HES1 in cells [MUC5AC mRNA (2 -ΔΔCT): 1.03±0.13, 0.96±0.05 vs. 1.35±0.07, Notch3 mRNA (2 -ΔΔCT): 1.10±0.14, 1.10±0.02 vs. 1.31±0.15, HES1 mRNA (2 -ΔΔCT): 1.26±0.10, 1.14±0.15 vs. 1.45±0.08, Notch3 protein (Notch3/GAPDH): 0.10±0.03, 0.16±0.03 vs. 0.31±0.09, HES1 protein (HES1/GAPDH): 0.37±0.06, 0.34±0.08 vs. 0.50±0.05, all P < 0.05]. Conclusion:The mechanism of BYF attenuating mucus hypersecretion of 16HBE cells induced by CSE was associated with the inhibition of Notch signaling pathway activation.