This study investigates the role of Annexin A1 (ANXA1) in regulating T cell function and its implications in bone marrow adiposity in aplastic anaemia (AA). Utilizing single-cell sequencing analysis, we compared bone marrow tissues from AA patients and healthy individuals, focusing on T cell subgroups and their impact on bone marrow pathology. Our findings reveal a significant activation of CD8+ T cells in AA, driven by reduced ANXA1 expression. This heightened T cell activity promotes adipogenesis in bone marrow-derived mesenchymal stem cells via IFN-γ secretion. Overexpression of ANXA1 was found to suppress this process, suggesting its therapeutic potential in AA treatment. The study highlights ANXA1 as a crucial regulator in the AA-associated immune microenvironment and bone marrow adiposity. KEY POINTS: This study found that ANXA1 is significantly downregulated in AA and provides detailed insights into its critical role in the disease. The study demonstrates the excessive activation of CD8+ T cells in the progression of AA. The research shows that the overexpression of ANXA1 can effectively inhibit the activation of CD8+ T cells. The study confirms that overexpression of ANXA1 reduces the secretion of the cytokine IFN-γ, decreases adipogenesis in bone marrow-derived mesenchymal stem cells and may improve AA symptoms. This research provides new molecular targets for the treatment of AA.

Aplastic anemia (AA) is a debilitating hematological disorder characterized by bone marrow failure. Recent advancements in mesenchymal stem cell (MSC) research have highlighted potential therapeutic avenues, particularly through the modulation of cellular pathways influenced by novel agents like Irisin. This study investigates Irisin's effects on MSCs in the context of AA using advanced techniques such as single-cell sequencing and spatial transcriptomics. Irisin administration in AA model mice significantly altered gene expression in MSCs, particularly affecting 935 genes associated with the Hippo signaling pathway, notably the MST1/2-YAP axis. These changes were linked to decreased adipogenic differentiation and enhanced mitochondrial membrane system homeostasis. In vitro experiments supported these findings, showing Irisin's capability to inhibit the MST1/2-YAP signaling pathway and suppress adipogenesis in bone marrow stem cells (BMSCs). Corresponding in vivo studies demonstrated that Irisin treatment not only downregulated Mst1 and Mst2 but also upregulated Yap expression. Importantly, these molecular alterations led to reduced bone marrow adiposity and improved hematopoietic function in AA mice, showcasing Irisin's potential as an effective treatment option. The study underscores the critical role of the MST1/2-YAP pathway in mediating Irisin's therapeutic effects, suggesting promising strategies for AA management through targeted MSC pathway modulation.

Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune dysregulated T cells-mediated destruction of BM haemopoietic stem cells (HPSC). The objective of this study was to investigate potential therapeutic effect of irisin, a molecule involved in adipose tissue transition, on AA mouse model. Our results showed that the concentration of irisin in serum was lower in AA patients than in healthy controls, suggesting a role of irisin in the pathogenesis of AA. In the AA mice, irisin administration prolonged the survival rate, prevented or attenuated peripheral pancytopenia, and preserved HPSC in the BM. Moreover, irisin also markedly reduced BM adipogenesis. In vitro results showed that irisin increased both cell proliferation and colony numbers of HPSC. Furthermore, our results demonstrated that irisin upregulated the expression of mitochondrial ATPase Inhibitory Factor 1 (IF1) in HPSC, inhibited the activation of mitochondrial fission protein (DRP1) and enhanced aerobic glycolysis. Taken together, our findings indicate novel roles of irisin in the pathogenesis of AA, and in the protection of HPSC through stimulation of proliferation and regulation of mitochondria function, which provides a proof-of-concept for the application of irisin in AA therapy.

RATIONALE:Broncholithiasis is a rare disease and is characterized by calcification in the tracheobronchial tree. This disease has a predilection in the adult and occurrence is rare in children. Considering its infrequency, we report a rare clinical case, with the aim of sharing our experience during the diagnosis and treatment procedures.PATIENT CONCERNS:We report a 9-year- and 6-month-old girl who complained of chronic cough and recurrent wheeze for 2 months.DIAGNOSIS:Bronchialithiasis were found under bronchoscope. Pathologic examination revealed aspergillosis.INTERVENTIONS:The stone and surrounding granulation tissue were removed using a bronchoscope and the patient was treated with antifungal therapy.OUTCOMES:The patient was in good general health without any clinical symptoms during the follow-up period.LESSONS:Pulmonary Aspergillus infection can cause bronchiolithiasis. Stones were removed under bronchoscope, and anti-Aspergillus therapy was effective.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

Previously, the main treatment options for tracheoesophageal fistula included surgery and conservative treatment. Herein, we report a child suffering from severe tracheoesophageal fistula due to button battery ingestion. The child relapsed soon after a repair surgery. Then, he was endotracheally implanted with a fully-covered metallic stent combined with a jejunal tube feeding. He recovered soon and the stent was removed five months later. The fistula was healed with no relapse during a 25-month follow-up. Therefore, endotracheal implantation of fully-covered metallic stent is an alternative treatment for tracheoesophageal fistula due to button battery ingestion, especially in cases with severe respiratory disorders.

Objective To discuss the effect of electronic bronchoscopy comprehensive therapy in the diagnosis and treatment of glottis and subglottic stenosis after intubation in children.Methods The records of 28 children diagnosed as glottis and subglottic stenosis after intubation by bronchoscopy in Qilu Children's Hospital of Shandong University from January 2012 to January 2015 were reviewed.They all had the neck and chest CT,bronchoscopic diagnostics,and received comprehensive treatment of laser,forceps,balloon angioplasty under electronic bronchoscopy,preoperative and postoperative evaluation was performed according to the improvement of respiratory status and endoscopic findings.All patients were followed up for 6-12 months.Results These 28 children were successfully extubated,and inspiratory dyspnea,hoarseness,and other symptoms were improved,endoscopic narrowest part was widened by 6-12 months of follow-up,including 17 cases reached clinical cure,about 6 times per patient;7 cases were successfully extubated and still in follow-up currently;2 cases of neonatal infants were extubated successfully,but they had vocal congestion,edema,glottis narrow fissure without special intervention,and were under clinical observation currently;2 cases gave up treatment because of the other problems.All patients had no serious bleeding,respiratory insufficiency or other complications.Conclusions Electronic bronchoscopic comprehensive treatment is an effective and safe method to treat glottis and subglottic stenosis after intubation in children.

Objective To describe the role of medical thoracoscopy in the diagnosis and treatment of pleural diseases in children.Methods Thoracoscopy procedures had been carried out in 9 patients with recurrent pleurisy and pleural effusion who were hospitalized in Department of Pulmonary,Intervention Qilu Children's Hospital of Shandong University from no vember 2013 to June 2015.Pleural biopsy was performed under direct visual guidance to obtain tissues,and pleural adhesion and cellulose exudation had been cleaned out in 7 cases.Results Six cases of the 9 patients had been diagnosed with tuberculous pleurisy.Pleural tumor and infectious diseases had been exclused in 1 case with biateral pleural and pericardial effusion,thickened heart capsule was found in the operation,then continuous cardiac ultrasound examination confirmed the diagnosis of constrictive pericarditis after the medical thoracoscopy procedure.The clinical symptoms were controlled in 1 case of lung abscess and empyema after cleaning out the pus moss and necrotic tissue with anti-infective therapy,the pleural adhesion was reduced.One case with empyema was converted to thoracic surgery as combined with severe pleural adhesion.Medium bleeding was found in 1 case during the procedure.Minor pneumothorax and subcutaneous emphysema occurred in 1 case after operation.There were no severe complications in the other 7 patients.Conclusions As a modern intervention technique of diagnosis and treatment of respiratory system disease,thoracoscopy is a safe and effective technique for pediatric patients.

Objective To discuss the diagnosis,curative effect evaluation of infantile subglottic hemangioma through bronchoscopy,and oral Propranolol curative effect.Methods Twenty-four cases of subglottic hemangioma were retrospectively analyzed from April 2012 to March 2015 in Shandong University Qilu Children's Hospital,all cases were diagnosised by neck enhanced CT or magnetic resonance,receiving oral Propranolol treatment.Starting dose was 0.5 mg/(kg · d),3 times per day,monitored in terms of blood pressure,blood sugar and heart rate,etc.with no bad reaction after 3 days of dosage,increased to 2.0 mg/(kg · d),6 days later to maintain the dose for at least 6 months,with bronchoscopy follow-up visit on a regular basis.All the children received 3 to 15 months of follow-up.Results Clear diagnosis of subglottic hemangioma was made in 24 cases who received oral Propranolol treatment,and after 5-7 days symptoms such as laryngeal stridor and dyspnea were relieved to different extent.Under the bronchoscope tumors could be observed to shrink.After 6 months of oral Propranolol,11 cases of tumors had completely faded,13 cases of tumors had significantly reduced,laryngeal stridor and breathing difficulties were relieved.One patient with parotid gland hemangioma was also improved,3 cases had mild bradycardia during hospital treatment,but during hospitalization and after discharge low blood pressure,hypoglycemia and other side effects were not observed.Conclusions Bronchoscopy in the diagnosis and treatment of infantile subglottic hemangioma plays an important role in the judgment of curative effect as it is both safe and reliable.Taking oral Propranolol can help to shrink tumors in a short period of time,improve the symptoms of respiratory tract obstruction,with distinct curative effect and little side effect.

目的 探讨支气管镜下电凝治疗儿科气道管腔内肉芽形成、纤维组织增生导致气道狭窄及咽喉部占位性病变压迫气道引起通气不畅的疗效和安全性.方法 对2009年9月至2011年6月山东大学齐鲁儿童医院呼吸介入科收治的12例气道内增生病变患儿,其中支气管异物后气道内增生3例、支气管内膜结核菌感染引起黏膜肉芽生长阻塞气道所致肺不张2例、气管插管后气管黏膜纤维组织增生导致气管狭窄出现呼吸困难5例、舌根部囊肿压迫会厌致会厌抬起受限而引起呼吸困难2例.实施支气管镜下电凝治疗.分别于术前和最后1次电凝治疗后对病变部位进行支气管镜下评估,胸部CT及肺功能检查,对肺不张及通气功能进行评价.结果 12例患儿分别接受电凝治疗(共13次),其中显效11例、有效1例,有效率100％,未见并发症发生.结论 支气管镜下电凝治疗对于异物、感染后肉芽组织生长阻塞气道形成的肺不张、气管插管后气道内膜纤维组织增生性气管狭窄以及咽喉部占位性病变压迫气道形成的呼吸困难,是快速、有效的治疗方法,但手术操作有风险,需经技术培训.

Objective To discuss the effect of electric coagulation through bronchoscopy in diagnosis and treatment of congenital vallecular cyst in children.Method Ten cases of congenital vallecular cyst in the study with age ranged from 21 days to 4 years and 10 months were treated with electric coagulation through bronchoscopy.The therapeutic effect was evaluated by endoscopic and clinical manifestation.And all the patients were followed-up for 6-12 months.Result All the patients obtained 3-5 times electric coagulation.After the operation,the cyst decreased in size,epiglottis softening was subsided,uplift uncompression,dyspnea and laryngeal stridor were improved obviously.After follow-up periods of 6-12 months,no capsule wall were left,and the activity of the epiglottis resumed.No severe complication was found in any patient.Conclusion Electric coagulation through bronchoscopy is a simple,effective and safe method to treat congenital vallecular cyst in children.

Objective To discuss the effect and security of balloon dilatation using a bronchoscope in the management of benign tracheobronchial stenosis.Methods A total of 156 child patients with proximal benign tracheobronchial stenosis were managed by balloon using the flexible electronic bronchoscope.Of these patients,146 were with pneumonia,4 patients with tuberculosis infection,1 patient with granulation tissue by airway extraneous material,5 patients after tracheal intubation.Results The 156 patients obtained 1-3 times of balloon dilatation.In these patients,the curative effects of 139 patients were excellent,12 patients effective,and 5 patients invalid.In 139 excellent patients,the airway average diameter in narrow segmental bronchus was increased and the ventilatory capacity of closed lung was increased above two-thirds in 134 patients and the dyspneic respiration with main bronchus stenosis disappeared in 5 excellent patients.In 12 effective patients,the ventilatory capacity of closed lung was increased from one-third to two-thirds after therapy with balloon dilatation.In 5 invalid patients,the ventilatory capacity of closed lung was not changed,although the partial airway stenosis was removed.So,the total effect rate was 96.8% after therapy with balloon dilatation.After follow-up periods of 1-6 months,the airway dilated by balloon did not become narrow again and closed lung did not appear again through chest X-ray or CT.No severe complication was found in any patient.Conclusion Airway plasty with high pressure balloon dilatation using flexible electronic bronchoscope is an effective,safe,simple and rapid method for treatment of proximal benign tracheobronchial stenosis in child.

OBJECTIVE:To analyze the effect and safety of bronchoscopic cryosurgery in children with lower airway stenosis caused by granulation and fiber hyperplasia.METHOD:Twenty-two patients had undergone bronchoscopic examination and cryosurgery, 18 patients with atelectasis caused by Mycoplasma pneumoniae pneumonia, 2 patients with endobronchial tuberculosis (EBTB), 1 patient with atelectasis caused by granulation tissue after bronchial foreign body, and 1 case who had severe dyspnea, with tracheal stenosis after long-term endotracheal intubation during surgery for heart disease. All the patients under went bronchoscopic cryosurgery for several times, 1 case with severe tracheal stenosis was operated by electric coagulation before cryosurgery. Before and after the treatment, all the patients were evaluated based on clinical symptoms, tracheal lumen by bronchoscopy, chest CT for atelectasis and pulmonary function for tracheal stenosis.RESULT:The patients were treated with cryosurgery for 1-4 times. Sixteen cases were markedly improved, clinical symptoms disappeared completely, no granulation and fiber hyperplasia were found during bronchoscopy, and all the atelectasis were cured. After the treatment, the bronchial lumen diameter of the patient with tracheal stenosis was increased from 2 mm to about 5 mm, the tidal volume increased from 3.0 ml/kg to 8.8 ml/kg. Five cases were effectively improved, the clinical symptoms also disappeared, during bronchoscopy and bronchial alveolar lavage (BAL), no granulation and fiber hyperplasia were found, but some distal bronchial tubes were atresia or narrowed, the lumen was patent, the atelectasis recovered partially. In 1 case the treatment was ineffective, as the clinical symptoms and granulation disappeared, but because almost all distal bronchi were atresia or narrow, the lumen was not patent during BAL, there was no change on chest CT. The total effective rate was 21/22 (95.5%). No severe complications occurred during and after the procedures. All the patient were followed up for 1 - 12 months, no case had recurrence.CONCLUSION:Treatment with bronchoscopic cryosurgery is a safe and effective methods to tracheal stenosis caused by granulation tissue and fiber hyperplasia in children.

OBJECTIVE:To evaluate the effect of bronchoalveolar lavage (BAL) through bronchoscopy in diagnosis and treatment of accidental inhalation of liquid and powdery foreign bodies in children.METHOD:Twenty-one cases of accidental inhalation were classified into the following 4 groups according to the materials inhaled: 3 cases inhaled the lipidic material; 2 cases inhaled chemical material; 15 cases inhaled hydrosoluble materials; 1 case inhaled powdery material. Eighteen cases were hospitalized within 3 days after the accidents, which included 16 cases treated within 1 day in hospital. And 3 cases were hospitalized 3 days after the accident. After hospitalization, all patients were immediately treated with direct aspiration and lavage clearance method through bronchoscopy. The inhaled foreign materials were cleared as soon as possible, which reduced the absorption, stimulation and infection of respiratory mucosa. The therapeutic effect was evaluated by endoscopic findings, clinical manifestation, laboratory examination and chest imaging. At the same time, decision was made on the second BAL and the prognosis was estimated.RESULT:Twenty-one cases had dyspnea of certain degree. The bronchial mucous membrane of all the 21 cases showed hyperemia, edema and exudate attached. Lavage fluid looked like broth and contained much of the inhaled material. After two to five times treatment, 18 cases were cured (86%), but 3 cases died (14%). One of these 3 cases fell into an oil well, 1 into mosquito repellent solution, another into manure pit. The patients who could not survive had severe airway obstruction, which was difficult to clean and made the problem deteriorated progressively. One of the patients was sent to a hospital 3 days after the accident and another case developed fungal infection, pneumothorax and finally respiratory failure.CONCLUSION:BAL through bronchoscopy is necessary for children who accidentally inhaled liquid and powdery materials. This treatment is safe and effective in diagnosis and treatment of such problems in children. The effect of treatment is influenced by types of inhaled material, the time of lavage clearance through bronchoscopy, and certain complications, such as infection etc.

OBJECTIVE:To assess the efficacy and safety of balloon dilatation through flexible bronchoscopy in the management of inflammatory stenosis of grade 4-5 bronchus.METHOD:Thirty patients with inflammatory bronchial stenosis caused by mycoplasmal pneumonia complicated with pulmonary atelectasis were treated with balloon dilatation through fiberoptic bronchoscopy. Before the procedure and after the last operation, therapeutic effect on pulmonary atelectasis were evaluated with CT and all of the patients were followed-up for 1 - 6 months.RESULT:One to three operations were required to achieve satisfactory dilatation. After balloon dilatation, the average airway diameter increased obviously and the farther airways were opened after the therapy with irrigation. In 25 of 30 cases satisfactory immediate effects were obtained, a narrow airway diameter above expansion significantly increased as compared with preoperative diameter. In 5 children treated with balloon dilatation, the stenosis could not be improved significantly. In 3 patients with hyperplasia of granulation tissue, cryotherapy had to be applied. The operations were ineffective in the other two patients whose course of disease exceeded 3 months. After follow-up periods of 1 - 6 months, chest CT manifestation of expanded sites was improved in 28 patients and atelectasis disappeared. No severe complication was found in any patients.CONCLUSION:Bronchoplasty by balloon dilatation through flexible fiberoptic bronchoscopy is a simple, effective and safe method to treat childhood tracheobronchial stenosis after pulmonary infections.