Andrographolide restores steroid sensitivity to block LPS/IFNγ-induced IL-27 and airway hyper-responsiveness in mice

OBJECTIVE Steroid-resistant airway hyper-responsiveness(AHR)has been proposed to be related to the activation of innate host defense pathways such as those induced by LPS,IFN-γ,and LPS/IFN-γ-stimulated essential mediator IL-27.We investigated whether andrographolide,apreviously demonstrated anti-inflammatory bioactive molecule extracted from the plant Andrographis paniculata,could restore steroid sensitivity to block LPS/IFN-γ-induced IL-27 production and AHR viaits anti-oxidative property.METHODS Mouse macrophage cell line Raw264.7,mouse primary pulmonary monocyte/macrophage,and BALB/c mouse were treated with LPS/IFN-γ,in the presence and absence of increasing doses of dexamethasone and/or andrographolide.mRNA and protein levels of IL-27 in vitro and in vivo were examined,and mouse AHR was assessed.RESULTS Dexamethasone alone failed to inhibit LPS/IFN-γ-induced IL-27 and AHR in mice.Andrographolide significantly facilitated the suppressive effect of dexamethasone on LPS/IFN-γ-induced IL-27 level in macrophage cell line and primary monocyte/macrophage,mouse bronchoalveolar lavage fluid and lung tissue,and furthermore on the incurring AHR.LPS/IFN-γdid not impede nuclear translocation of glucocorticoid receptors but diminishthe protein level of histone deacetylase-2(HDAC2),an essential epigenetic enzymeresponsible for steroid anti-inflammatory action.Andrographolide at low doses(5μmol·L-1 in vitro;1mg·kg-1,ip in vivo)restored nuclear HDAC2 protein levels both in cells and in mouse lungs,possibly via suppression of PI3K/Akt signaling pathway and up-regulation of the anti-oxidative transcription factor Nrf-2level.CONCLUSION Our data suggest that andrographolide may resensitize steroid action on blocking LPS/IFN-γ-induced IL-27 and resultant AHR by restoring HDAC2 level.

Factors influencing the continuity of evidence-based practice in perioperative airway management for elderly patients with fractures:A qualitative study

BACKGROUND More and more evidence-based practices are emerging,but researchers mostly focus on short-term effects,resulting in evidence-based practices not being applied in the clinic in the long term.In this study,we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic.AIM To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures.METHODS This study was qualitative research.Nine nurses who implemented evidencebased practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects.Semi-structured interviews were conducted with them,and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model.RESULTS Three main themes and ten subthemes were identified:Process aspects(benefits to patients,benefits to nurses,lack of follow-up,complex processes);staff aspects(insufficient human resources,inadequate training and education,lack of leadership support);and organizational environment aspects(inadequate infrastructure,poor patient compliance,poor doctor cooperation).CONCLUSION Human resources,training and education,leadership support,infrastructure,and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

Clinical and pathological characteristics and expression of related molecules in patients with airway disseminated lung adenocarcinoma

Objective:Lung adenocarcinoma exhibits diverse genetic and morphological backgrounds,in addition to considerable differences in clinical pathology and molecular biological characteristics.Among these,the phenomenon of spread through air space(STAS),a distinct mode of lung cancer infiltration,has rarely been reported.Therefore,this study aimed to explore the relationship between STAS tumor cells and the clinical and molecular characteristics of patients with lung adenocarcinoma,as well as their impact on prognosis.Methods:This study included 147 patients who were diagnosed with lung adenocarcinoma at the Inner Mongolia Autonomous Region Cancer Institute between January 2014 and December 2017.Surgical resection specimens were retrospectively analyzed.Using univariate and multivariate Cox analyses,we assessed the association between STAS and the clinicopathological features and molecular characteristics of patients with lung adenocarcinoma.Furthermore,we investigated the effects on patient prognosis.In addition,we developed a column–line plot prediction model and performed internal validation.Results:Patients with positive STAS had a significantly higher proportion of tumors with a diameter≥2 cm,with infiltration around the pleura,blood vessels,and nerves,and a pathological stage>IIB than in STAS-negative patients(P<0.05).Cox multivariate survival analysis revealed that clinical stage,STAS status,tumor size,and visceral pleural invasion were independent prognostic factors influencing the 5-year progression-free survival in patients with lung adenocarcinoma.The predictive values and P values from the Hosmer-Lemeshow test were 0.8 and 0.2,respectively,indicating no statistical difference.Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.884 and 0.872 for the training and validation groups,respectively.The nomogram model exhibited the best fit with a value of 192.09.Conclusions:Clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis are independent prognostic factors for patients with STAS-positive lung adenocarcinoma.The nomogrambased on the clinical stage,pleural invasion,vascular invasion,peripheral nerve invasion,tumor size,and necrosis showed good accuracy,differentiation,and clinical practicality.

Research on the Application of Evidence-Based Quality Control Circle to Improve the Implementation Rate of Airway Management Measures in Adult Critically Ill Patients

Objective: To explore the effect of evidence-based quality control circle (QCC) in improving the implementation rate of airway management measures in adult critically ill patients. Methods: Based on the Joanna Briggs Institute (JBI) evidence-based health care model, the best evidence of airway management in adult critically ill patients was obtained and applied to the clinic. Results: The total implementation rate of airway management measures in adult critically ill patients increased from 23.62% before the implementation of quality control circle to 88.82%, and the pulmonary infection rate in critically ill patients decreased from 42.31% to 21.74%, with statistical significance between the two groups (P 0.05). Conclusion: Evidence-based quality control circle activities can standardize the practice standards of airway management in critically ill patients, reduce the occurrence of patients’ airway related complications, and improve clinical outcomes.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Continuous positive airway pressure for treating hypoxemia due to pulmonary vein injury:A case report

BACKGROUND Vascular injury during thoracoscopic surgery for esophageal cancer is a rare but life-threatening complication that can lead to severe hypotension and hypoxemia.Anesthesiologists need to provide rapid and effective treatment to save patients'lives.CASE SUMMARY A 54-year-old male patient was scheduled to undergo a thoracoscopic-assisted radical resection of esophageal cancer through the upper abdomen and right chest.While dissociating the esophagus from the carina through the right chest,unexpected profuse bleeding occurred from a suspected pulmonary vascular hemorrhage.While the surgeon attempted to achieve hemostasis,the patient developed severe hypoxemia.The anesthesiologist implemented continuous positive airway pressure(CPAP)using a bronchial blocker(BB),which effectively improved the patient’s oxygenation and the operation was completed success-fully.CONCLUSION CPAP using a BB can resolve severe hypoxemia caused by accidental injury of the left inferior pulmonary vein during surgery.

Airway ultrasound for patients anticipated to have a difficult airway:Perspective for personalized medicine

Airway ultrasound allows for precise airway evaluation,particularly for assessing the difficult airway and the potential for front of neck access.Many studies have shown that identification of the cricothyroid membrane by airway ultrasound is more accurate than digital palpation.However,no reports to date have provided clinical evidence that ultrasound identification of the cricothyroid membrane increases the success rate of cricothyroidotomy.This is a narrative review which describes patients with difficult airways for whom airway ultrasound may have been useful for clinical decision making.The role of airway ultrasound for the evaluation of difficult airways is summarized and an approach to the use of ultrasound for airway management is proposed.The goal of this review is to present practical applications of airway ultrasound for patients predicted to have a difficult airway and who undergo cricothyroidotomy.

Laryngeal mask airway bougie ultrasonography guided intubation in a morbidly obese patient with diffi cult airway

Airway management of morbidly obese patients is challenging due to inherent anatomical and physiological variations.[1]The frequent association of compromised hemodynamics,hypoxemia,or acidosis in an emergency department(ED)setting adds to the difficulty of the procedure.Rapid airway management position(RAMP),awake fiber-optic guided intubation,use of intubating laryngeal mask airway(ILMA),and video-laryngoscope are a few techniques that have been described to tackle difficult airways in these patients.[2]Studies have shown that the availability of fi ber-optic scopes(3%–60%),videolaryngoscopes(39%–88%),and laryngeal mask airways(LMA)(65%–83%)varies in different ED settings.[3,4]Furthermore,a lack of adequate training and the need for time-bound resuscitation make implementation of the above techniques challenging.

Difficult airway due to cervical haemorrhage caused by spontaneous rupture of a parathyroid adenoma: A case report

BACKGROUND Cervical haemorrhage due to spontaneous rupture of a parathyroid adenoma is a rare complication that may cause life-threatening acute airway compromise.CASE SUMMARY A 64-year-old woman was admitted to the hospital 1 day after the onset of right neck enlargement, local tenderness, head-turning difficulty, pharyngeal pain, and mild dyspnoea. Repeat routine blood testing showed a rapid decrease in the haemoglobin concentration, indicating active bleeding. Enhanced computed tomography images showed neck haemorrhage and a ruptured right parathyroid adenoma. The plan was to perform emergency neck exploration, haemorrhage removal, and right inferior parathyroidectomy under general anaesthesia. The patient was administered 50 mg of intravenous propofol, and the glottis was successfully visualised on video laryngoscopy. However, after the administration of a muscle relaxant, the glottis was no longer visible and the patient had a difficult airway that prevented mask ventilation and endotracheal intubation. Fortunately, an experienced anaesthesiologist successfully intubated the patient under video laryngoscopy after an emergency laryngeal mask placement. Postoperative pathology showed a parathyroid adenoma with marked bleeding and cystic changes. The patient recovered well without complications.CONCLUSION Airway management is very important in patients with cervical haemorrhage. After the administration of muscle relaxants, the loss of oropharyngeal support can cause acute airway obstruction.Therefore, muscle relaxants should be administered with caution. Anaesthesiologists should pay careful attention to airway management and have alternative airway devices and tracheotomy equipment available.

Anesthesia management in a pediatric patient with complicatedly difficult airway:A case report

BACKGROUND Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce.In addition to relatively more difficulties in the technique of endotracheal intubation,the time for manipulation is restricted compared to adults.Securing the airways safely and avoiding the occurrence of hypoxemia in these patients are of significance.CASE SUMMARY A 9-year-old boy with spastic cerebral palsy,severe malnutrition,thoracic scoliosis,thoracic and airway malformation,laryngomalacia,pneumonia,and epilepsy faced the risk of anesthesia during palliative surgery.After a thorough preoperative evaluation,a detailed scheme for anesthesia and a series of intu-bation tools were prepared by a team of anesthesiologists.Awake fiberoptic intubation is the widely accepted strategy for patients with anticipated difficult airways.Given the age and medical condition of the patient,we kept him sedated with spontaneous breathing during endotracheal intubation.The endotracheal intubation was completed on the second attempt after the failure of the first effort.Fortunately,the surgery was successful without postoperative complications.CONCLUSION Dealing with difficult airways in the pediatric population,proper sedation allows time to intubate without interrupting spontaneous breathing.The appropriate endotracheal intubation method based on the patient’s unique characteristics is the key factor in successful management of these rare cases.

Comparison of emergency surgical cricothyroidotomy and percutaneous cricothyroidotomy by experienced airway providers in an obese,in vivo porcine hemorrhage airway model

Background: Emergency front-of-neck airway(eFONA) is a life-saving procedure in “cannot intubate, cannot oxygenate”(CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique “percutaneous cricothyroidotomy”(n=6) or scalpelbougie-tube technique “surgical cricothyroidotomy”(n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median(interquartile range, IQR) times to secure airway were 109(IQR 71–130) s and 298(IQR 128–360) s(P=0.0152), arterial blood saturation(SaO2) were 74.7(IQR 46.6–84.2)% and 7.9(IQR 4.1–15.6)%(P=0.0167), PaO_(2) were 7.0(IQR 4.7–7.7) kPa and 2.0(IQR 1.1–2.9) kPa(P=0.0667), and times of cardiac arrest(proxy survival) were 137–233 s, 190(IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six(33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5(IQR 7.5–21.3), did not influence time to secure airway.Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.

Experimental study on the regulation effect of Qiaoqin Qingfei agent on cough variant asthma based on airway neurogenic inflammation

Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.

针对性气道护理对重症监护室患者舒适度与呼吸机相关性肺炎的影响

目的探讨针对性气道护理模式在重症监护室(ICU)患者中的应用效果。方法选择2021年1月—2022年12月医院120例ICU患者,按组间基线资料可比的原则将其分为对照组和观察组,每组60例。对照组予以常规护理,观察组采用针对性气道护理。观察两组患者护理干预前、护理干预5 d后的呼吸状况及舒适度,比较其康复进程、导管堵塞情况及呼吸机相关性肺炎(VAP)发生情况。结果观察组患者护理干预5 d后的PaO_(2)水平高于对照组,组间比较差异有统计学意义(P<0.05)。PaCO_(2)水平低于对照组,组间比较差异有统计学意义(P<0.05)。观察组患者护理干预5 d后的Kolcaba舒适状况量表(GCQ)评分高于对照组,差异有统计学意义(P<0.05)。观察组患者机械通气时间及ICU治疗时间分别为6.50±1.08 d和7.84±1.50 d,短于对照组的7.22±1.36 d和8.68±1.74 d,差异有统计学意义(P<0.05);观察组患者机械通气期间的导管堵塞程度较对照组轻,且VAP发生率低于对照组,差异均有统计学意义(P<0.05)。结论针对性气道护理模式可改善ICU患者呼吸状况及舒适度,缩短康复进程,并可减轻患者机械通气治疗期间导管堵塞程度,降低VAP发生率。

视频喉镜结合综合困难气道训练考核系统在急诊规范化培训住院医师气管插管培训中的应用研究

目的探讨视频喉镜结合综合困难气道训练考核系统在急诊规范化培训住院医师气管插管培训中的应用效果。方法选择2022年1月—2023年6月在首都医科大学宣武医院急诊科轮转的住院医师58人,随机分为对照组(n=28)和试验组(n=30)。对照组应用直接喉镜结合综合困难气道训练考核系统进行气管插管技能培训,试验组应用视频喉镜结合综合困难气道训练考核系统进行气管插管技能培训。培训结束后对两组住院医师进行气管插管技能考核,内容包括正常气道和困难气道的气管插管,分别比较两组住院医师气管插管时间、一次性插管成功率、喉镜对门齿的压力、气管插管位置正确率的区别。另外,分别对两组住院医师进行教学满意度问卷调查。结果普通气道气管插管中,试验组与对照组喉镜对门齿的压力和气管插管位置正确率的差异无统计学意义(P>0.05);一次性插管成功率试验组大于对照组,气管插管时间试验组小于对照组(均P<0.05)。在困难气道气管插管中,试验组的一次性插管成功率和气管插管位置正确率大于对照组(P<0.05),插管时间和喉镜对门齿的压力明显小于对照组(P<0.05)。调查问卷自评显示,试验组对气管插管自信心和学习兴趣大于对照组(P<0.05),满意度和技能评分两组差异无统计学意义(P>0.05)。结论应用视频喉镜结合综合困难气道训练考核系统对急诊规范化培训住院医师进行气管插管培训可以提高气管插管成功率,减少对门齿的损伤,提高住院医师的学习兴趣。

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice

Objective The function of Bcl-6 in T follicular helper(Tfh)cell maturation is indispensable,and Tfh cells play a pivotal role in asthma.This study investigated the impact of Bcl-6 on asthmatic traits.Methods The microscopic pathological alterations,airway resistance(AR),and lung compliance(LC)were determined in asthmatic mice and Bcl-6 interference mice.The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry,RT-qPCR,and Western blotting,respectively.The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF)were determined.Results Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone(DXM).Asthmatic mice exhibited an increased AR and a decreased LC,while Bcl-6 siRNA or DXM mitigated these changes.The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice,and they significantly decreased after Bcl-6 inhibition or DXM treatment.RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice,and it decreased following Bcl-6 inhibition or DXM treatment.The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend.In asthmatic mice,the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF,but not with the IgG1 levels.Conclusion The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression,which effectively hinders Tfh cell differentiation,ultimately resulting in a concurrent reduction in IgE production.

川陈皮素对慢性阻塞性肺疾病模型大鼠气道黏液高分泌的抑制作用及其分子机制

目的:探讨川陈皮素(NOB)对慢性阻塞性肺疾病(COPD)大鼠气道黏液高分泌的影响,阐明其对内质网应激(ERS)信号通路调控的分子机制。方法:按随机数字表法将45只SD大鼠随机分为对照组、模型组、NOB组、ERS抑制剂4-苯基丁酸(4-PBA)组和NOB+4-PBA组,每组9只。除对照组外,其他各组大鼠均采用烟熏联合气道内注入脂多糖(LPS)建立COPD大鼠模型,建模成功后给予相应药物(50 mg·kg^(-1)·d^(-1)Nob或0.35 g·kg^(-1)·d^(-1)4-PBA)干预,每天1次,连续干预4周。完成药物干预后,采用小动物呼吸机和血气分析仪检测各组大鼠肺功能指标[肺动态顺应性(Cdyn)和气道阻力(RL)]和动脉血气指标[血二氧化碳分压(PaCO_(2))和动脉血氧分压(PaO_(2))];苏木精-伊红(HE)染色法观察各组大鼠肺组织杯状细胞增生情况;酶联免疫吸附测定(ELISA)法检测各组大鼠肺泡灌洗液(BALF)中气道杯状细胞内黏蛋白5AC(MUC5AC)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平;实时荧光定量PCR(RT-qPCR)法检测各组大鼠肺组织中MUC5AC mRNA表达水平;Western blotting法检测各组大鼠肺组织MUC5AC和ERS相关蛋白肌醇依赖酶1α(IRE1α)、转录激活因子6(ATF6)、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)及葡萄糖调节蛋白78(GRP78)表达水平。结果:与对照组比较,模型组大鼠肺气道杯状细胞大量增生,Cdyn和PaO_(2)水平明显降低(P<0.05),而RL和PaCO_(2)水平明显升高(P<0.05),BALF中MUC5AC、IL-1β、TNF-α和IL-6水平及肺组织中MUC5AC、IRE1α、ATF6、CHOP以及GRP78蛋白表达水平明显升高(P<0.05);与模型组比较,NOB组、4-PBA组和NOB+4-PBA组大鼠肺功能、动脉血气指标以及肺气道杯状细胞增殖情况均有明显缓解,且BALF中IL-1β、TNF-α和IL-6水平及肺组织中MUC5AC、IRE1α、ATF6、CHOP以及GRP78蛋白表达水平均明显降低(P<0.05),而NOB+4-PBA组大鼠的缓解效果最佳。结论:NOB能有效缓解COPD大鼠肺气道黏液高分泌情况,其作用机制可能与抑制ERS介导的MUC5AC高表达有关。

芪桂五物汤对支气管哮喘患者症状改善、气道重塑及免疫平衡的影响

目的:观察并探讨芪桂五物汤对支气管哮喘患者症状改善、气道重塑及免疫平衡的影响。方法:选取2021年10月—2023年3月太仓市中医医院收治的80例支气管哮喘患者,按照单双数抽签法将其平均分为两组,即对照组(40例)和观察组(40例)。入院后,对照组给予常规方法治疗,观察组除常规治疗外再给予芪桂五物汤治疗。比较两组治疗效果、气道重塑指标、血清免疫因子水平及肺通气功能指标。结果:观察组的治疗总有效率高于对照组,差异有统计学意义(P<0.05)。治疗前,两组气道重塑指标比较,差异均无统计学意义(P>0.05);治疗后,两组的气道重塑指标水平均较治疗前有降低,相较于对照组,观察组降低更为显著(P<0.05)。治疗前,两组血清免疫因子水平比较,差异均无统计学意义(P>0.05);治疗后,两组γ干扰素(IFN-γ)、白介素-4(IL-4)均较治疗前有所改善,相较于对照组,观察组改善更为显著(P<0.05)。治疗前,两组肺通气功能指标比较,差异均无统计学意义(P>0.05);治疗后,两组肺通气功能指标水平均较治疗前有所提高,相较于对照组,观察组提高更为显著(P<0.05)。结论:芪桂五物汤不仅可以明显改善支气管哮喘患者的临床症状,还能改善患者的气道重塑、血清免疫因子水平及肺功能指标,对支气管哮喘患者的治疗效果显著。

吴茱萸碱对哮喘模型大鼠炎症及上皮细胞凋亡的影响及机制

目的 探究吴茱萸碱对哮喘模型大鼠炎症反应及上皮细胞凋亡的影响及潜在机制。方法 将SD大鼠分为对照组、模型组、吴茱萸碱低剂量组(10 mg/kg)、吴茱萸碱高剂量组(20 mg/kg)、地塞米松组(阳性对照,0.5 mg/kg)、表皮细胞生长因子(EGF)组[丝裂原活化蛋白激酶(MAPK)激活剂,10μg]、吴茱萸碱高剂量+EGF组(20 mg/kg吴茱萸碱+10μg EGF),每组10只。除对照组外,其余各组大鼠以10%卵白蛋白(OVA)-氢氧化铝混合液3点注射致敏联合2%OVA雾化液吸入激发的方式建立哮喘模型。检测各组大鼠支气管肺泡灌洗液(BALF)中的炎症细胞(巨噬细胞、淋巴细胞)数,观察大鼠肺组织的病理变化,检测大鼠肺组织中气道上皮细胞凋亡情况、血清炎症因子(肿瘤坏死因子α、白细胞介素6、白细胞介素4)水平、通路相关蛋白[p38 MAPK、磷酸化p38MAPK(p-p38 MAPK)、信号转导及转录激活因子1(STAT1)]及凋亡相关蛋白[B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)]的表达水平。结果 与对照组比较,模型组大鼠肺组织可见支气管黏膜水肿、肺泡间隔增厚和大量炎症细胞浸润,炎症细胞数显著增多;气道上皮细胞凋亡率、炎症因子水平、p-38 MAPK/p-38 MAPK和Bax、STAT1蛋白表达水平均显著升高,Bcl-2蛋白表达水平和Bcl-2/Bax均显著降低(P<0.05)。与模型组比较,吴茱萸碱低、高剂量组和地塞米松组大鼠肺组织病理改变均有不同程度缓解,上述各指标均显著逆转,而EGF组上述指标的变化趋势则相反(P<0.05);EGF能显著减弱高剂量吴茱萸碱对哮喘大鼠炎症反应的改善作用(P<0.05)。结论 吴茱萸碱可减轻哮喘大鼠炎症反应并减少气道上皮细胞凋亡,其作用机制可能与抑制p38 MAPK/STAT1信号通路有关。

五虎汤抑制miRNA以改善病毒诱发的哮喘气道炎症

目的探讨微小核糖核酸-144(microRNA-144,miRNA-144)对呼吸道合胞病毒(respiratory syncytial virus,RSV)引起哮喘的模型小鼠出现气道炎症反应过程中的免疫调节和五虎汤的治疗干预作用。方法将40只SPF级雄性C57小鼠随机分为空白组、模型组、五虎汤组、西药组,每组10只,除空白组外,其余各组小鼠用RSV鼻腔滴入,复合鸡卵清蛋白(ovalbumin,OVA)腹腔注射诱发哮喘小鼠模型;五虎汤组灌胃五虎汤,西药组灌胃利巴韦林+生理盐水,模型组灌胃等容积生理盐水,空白组灌胃等容积生理盐水,每天1次,连续1周。实验结束后,比较各组小鼠一般情况;使用DSI Buxco PFT肺功能检测系统检测小鼠肺功能残气量与肺总量比(RV/TLC)以检测小鼠气流受限的程度;分别用HE、Masson、PAS染色方法染色观察各组肺组织病理学改变;ELISA法检测肺泡灌洗液(BALF)中白介素(IL)-10、IL-17、肿瘤坏死因子α(TNF-α)和TGF-β的含量;qPCR法检测miRNA-144表达。结果与空白组比较,模型组小鼠呼吸道症状明显,肺功能RV/TLC升高,提示气流受限,肺组织炎症损伤加重,BALF中炎症因子IL-10、IL-17、TNF-α和TGF-β改变,miRNA-144表达上调(P<0.05);与模型组比较,五虎汤组、西药组均可缓解哮喘小鼠呼吸道症状、肺功能通气受限及肺组织炎症浸润等,同时miRNA-144下降,BALF中IL-10、IL-17、TNF-α和TGF-β的含量改变(P<0.05)。结论五虎汤可能通过降低miRNA-144的表达,调节Th1/Th2介导的炎症反应,达到改善RSV诱发哮喘模型小鼠的气道炎症的效果。