Introduction Fibrosing interstitial lung diseases (F-ILD) affect substantial patient populations with significant mortality and socioeconomic burden. Approximately one-third of patients with F-ILD develop a progressive fibrosing phenotype with poor outcomes. Current monitoring methods, including pulmonary function testing and high-resolution CT (HRCT), often lag behind increases in fibrotic activity, limiting early risk identification and optimal treatment timing. Fibroblast activation protein (FAP) imaging can capture fibrotic activity at the pathological level. This study aims to evaluate the incremental value of ⁹⁹ᵐTc-FAPI single-photon emission CT (SPECT)/CT for early warning of disease progression in F-ILD and develop a predictive model integrating fibroblast activation protein inhibitor (FAPI) quantitative parameters with clinical variables. Methods and analysis This prospective, single-centre, observational cohort study will recruit 380 adult patients with confirmed F-ILD diagnoses from December 2024 to June 2027, with 12-month follow-up. Comprehensive baseline evaluation includes pulmonary function testing, 6-min walk test, laboratory investigations and ⁹⁹ᵐTc-FAPI SPECT/CT imaging. Follow-up visits at 3, 6 and 12 months will assess clinical outcomes. The primary outcome is disease progression within 12 months, defined as ≥5% forced vital capacity decline, ≥10% diffusing capacity of the lungs for carbon monoxide decline, increased fibrosis on HRCT, acute exacerbation or death. Cox proportional hazards regression models will be used for predictive model construction, with internal validation using bootstrap resampling and temporal split methods. Ethics and dissemination The study protocol has been approved by the Ethics Committee of Fujian Provincial Hospital (K2024-11-010) and will be conducted according to the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications and academic conference presentations. De-identified individual participant data will be available upon reasonable request after primary publication. Trial registration number Chinese Clinical Trial Registry ChiCTR2400093808.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the development of benign tumors and lesions in multiple organ systems. The syndrome arises from heterozygous mutations in either TSC1 or TSC2. In this study, we identified a family with a TSC1 c.363 + 668G > C mutation exhibiting diverse clinical phenotypes. The proband and affected family members exhibited multifocal nodular pneumocyte hyperplasia (MMPH), renal hamartomas, bone marrow hyperplasia, and pulmonary lymphangioleiomyomatosis (LAM), with genetic co-segregation analysis confirming the association between the mutation and the clinical phenotype. Genetic co-segregation analysis demonstrated that the TSC1 c.363 + 668G > C mutation was consistently associated with the observed clinical features in this family. Using first-generation Sanger sequencing, we identified a heterozygous splicing variation located in intron 5 of TSC1 (NM_000368.5). In vitro cell and family Minigene results show that TSC1 c.363 + 668G > C mutation can lead to abnormal retention of 92 bp intron sequence in different positions, which may be related to the alternative splicing phenomenon that the same gene produces different splicing variants in different tissues or development stages. The 3D protein structure analysis using Chimera revealed that the mutation site was located at the 363rd base, within the intron between the 121st and 122nd amino acids. This mutation resulted in the insertion of a 92-base sequence, causing a frameshift that led to premature termination of the TSC1 protein after the translation of 26 amino acids. Additionally, the 121st amino acid was altered from lysine to asparagine, significantly shortening the mutated TSC1 protein. These findings provide critical experimental evidence supporting the potential pathogenic mechanism of the TSC1 c.363 + 668G > C mutation. Future research should focus on validating this splicing abnormality in patient-derived cells or tissues and investigating its impact on protein expression and functional activity to better understand its role in disease progression.Clinical trial number: K2024-09-144.

IntroductionThe homeostasis of the microbiome in lower respiratory tract is crucial in sustaining normal physiological functions of the lung. Different pulmonary diseases display varying degrees of microbiome imbalance; however, the specific variability and clinical significance of their microbiomes remain largely unexplored.MethodsIn this study, we delineated the pathogen spectrum and commensal microorganisms in the lower respiratory tract of various pulmonary diseases using metagenomic sequencing. We analyzed the disparities and commonalities of the microbial features and examined their correlation with disease characteristics.ResultsWe observed distinct pathogen profiles and a diversity in lower airway microbiome in patients diagnosed with cancer, interstitial lung disease, bronchiectasis, common pneumonia, Nontuberculous mycobacteria (NTM) pneumonia, and severe pneumonia.DiscussionThis study illustrates the utility of Metagenomic Next-generation Sequencing (mNGS) in identifying pathogens and analyzing the lower respiratory microbiome, which is important for understanding the microbiological aspect of pulmonary diseases and essential for their early and precise diagnosis.

Abstract This study aimed to develop and validate prediction models to estimate the risk of death and intensive care unit admission in COVID-19 inpatients. All RT-PCR-confirmed adult COVID-19 inpatients admitted to Fujian Provincial Hospital from October 2022 to April 2023 were considered. Elastic Net Regression was used to derive the risk prediction models. Potential risk factors were considered, which included demographic characteristics, clinical symptoms, comorbidities, laboratory results, treatment process, prognosis. A total of 1906 inpatients were included finally by inclusion/exclusion criteria and were divided into derivation and test cohorts in a ratio of 8:2, where 1526 (80%) samples were used to develop prediction models under a repeated cross-validation framework and the remaining 380 (20%) samples were used for performance evaluation. Overall performance, discrimination and calibration were evaluated in the validation set and test cohort and quantified by accuracy, scaled Brier score (SbrS), the area under the ROC curve (AUROC), and Spiegelhalter-Z statistics. The models performed well, with high levels of discrimination (AUROCICU [95%CI]: 0.858 [0.803,0.899]; AUROCdeath [95%CI]: 0.906 [0.850,0.948]); and good calibrations (Spiegelhalter-Z ICU : − 0.821 (p-value: 0.412); Spiegelhalter-Z death : 0.173) in the test set. We developed and validated prediction models to help clinicians identify high risk patients for death and ICU admission after COVID-19 infection.

Background Primary ciliary dyskinesia (PCD) is an autosomal recessive hereditary disease characterized by recurrent respiratory infections. In clinical manifestations, DNAH5 (NM_001361.3) is one of the recessive pathogenic genes. Primary familial brain calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcification in the basal ganglia and other brain regions. PFBC can be inherited in an autosomal dominant or recessive manner. A family with PCD caused by a DNAH5 compound heterozygous variant and PFBC caused by a MYORG homozygous variant was analyzed. Methods In this study, we recruited three generations of Han families with primary ciliary dyskinesia combined with primary familial brain calcification. Their clinical phenotype data were collected, next-generation sequencing was performed to screen suspected pathogenic mutations in the proband and segregation analysis of families was carried out by Sanger sequencing. The mutant and wild-type plasmids were constructed and transfected into HEK293T cells instantaneously, and splicing patterns were detected by Minigene splicing assay. The structure and function of mutations were analyzed by bioinformatics analysis. Results The clinical phenotypes of the proband (II10) and his sister (II8) were bronchiectasis, recurrent pulmonary infection, multiple symmetric calcifications of bilateral globus pallidus and cerebellar dentate nucleus, paranasal sinusitis in the whole group, and electron microscopy of bronchial mucosa showed that the ciliary axoneme was defective. There was also total visceral inversion in II10 but not in II8. A novel splice variant C.13,338 + 5G > C and a frameshift variant C.4314delT (p. Asn1438lysfs *10) were found in the DNAH5 gene in proband (II10) and II8. c.347_348dupCTGGCCTTCCGC homozygous insertion variation was found in the MYORG of the proband. The two pathogenic genes were co-segregated in the family. Minigene showed that DNAH5 c.13,338 + 5G > C has two abnormal splicing modes: One is that part of the intron bases where the mutation site located is translated, resulting in early translation termination of DNAH5; The other is the mutation resulting in the deletion of exon76. Conclusions The newly identified DNAH5 splicing mutation c.13,338 + 5G > C is involved in the pathogenesis of PCD in the family, and forms a compound heterozygote with the pathogenic variant DNAH5 c.4314delT lead to the pathogenesis of PCD.

Documented radiological and physiological anomalies among coronavirus disease 2019 survivors necessitate prompt recognition of residual pulmonary parenchymal abnormalities for effective management of chronic pulmonary consequences. This study aimed to devise a predictive model to identify patients at risk of such abnormalities post-COVID-19. Our prognostic model was derived from a dual-center retrospective cohort comprising 501 hospitalized COVID-19 cases from July 2022 to March 2023. Of these, 240 patients underwent Chest CT scans three months post-infection. A predictive model was developed using stepwise regression based on the Akaike Information Criterion, incorporating clinical and laboratory parameters. The model was trained and validated on a split dataset, revealing a 33.3% incidence of pulmonary abnormalities. It achieved strong discriminatory power in the training set (area under the curve: 0.885, 95% confidence interval 0.832-0.938), with excellent calibration and decision curve analysis suggesting substantial net benefits across various threshold settings. We have successfully developed a reliable prognostic tool, complemented by a user-friendly nomogram, to estimate the probability of residual pulmonary parenchymal abnormalities three months post-COVID-19 infection. This model, demonstrating high performance, holds promise for guiding clinical interventions and improving the management of COVID-19-related pulmonary sequela.

A 50-year-old female patient, presenting with a past history of Reynaud's syndrome, xerostomia and xerophthalmia, was admitted to Fujian Provincial Hospital because of coughing for 10 days and left anterior chest pain for 1 day. Chest imaging showed multiple nodules and masses, and diffuse cystic lesions in both lungs. Based on the differential diagnosis of multiple pulmonary masses and diffuse cystic lesions respectively, autoantibodies, radionuclide dynamic imaging of the parotid, positron emission tomography-CT, CT-guided percutaneous transthoracic needle biopsy, and other examinations were performed. The diagnosis of diffuse large B-cell lymphoma stage ⅣA (lung, parotid gland) and Sjögren's syndrome was confirmed. By analyzing the imaging features and pathogenesis in detail, the diffuse cystic lesions of both lungs were considered to be related to lymphocytic interstitial pneumonia caused by Sjögren's syndrome. The pulmonary space-occupying lesions in the lungs were significantly absorbed after RCHOP regimen for lymphoma.

目的 探讨肺纤维化小鼠自噬活性改变对NLRP3炎性体活化的影响.方法 将32只雄性SFP级C57BL/6小鼠随机分为对照组(A组)、实验组(B组、C组、D组),每组各8只小鼠.实验组B组、C组、D组雾化吸入剂量为35 mg/kg博来霉素(BLM),并分别在给药后第7天、第14天、第28天处死,A组雾化吸入相同容积生理盐水,并在给药后第28天处死.HE染色观察小鼠肺组织病理改变;Masson染色计算肺组织胶原纤维沉积;蛋白免疫印迹法(Western blot)检测肺组织p62、Beclin1、NLRP3、Caspase-1、Notch1的表达水平.结果 HE染色结果显示,A组小鼠肺组织肺泡结构基本正常,未见明显纤维化;B组、C组、D组小鼠肺组织纤维化程度逐渐加重,可见纤维化病灶逐渐扩大,肺间质纤维组织增生.Masson染色显示,肺间质有少许蓝色染色区域.B组、C组、D组,蓝色染色区域依次增加,肺间质蓝色染色区域面积差异有统计学意义(P＜0.05).Western blot结果显示,A组p62相对表达量低于各实验组,实验组B、C、D组之间差异有统计学意义(P＜0.05);A组Beclin1表达量高于各实验组,实验组B、C、D组之间差异有统计学意义(P＜0.05);A组NLRP3、Caspase-1、Notch1表达量均低于实验组,差异均有统计学意义(P＜0.05).实验组B、C、D组中NLRP3、Caspase-1、Notch1之间的表达量差异均有统计学意义(P＜0.05).结论 自噬抑制和NLRP3炎性小体激活在小鼠肺纤维化中扮演重要角色;自噬活性降低,Notch1信号通路活化后导致NLRP3炎性小体激活,其可能是小鼠肺纤维化逐渐加重的机制之一.

Objective: To explore the effects of ipratropium bromide combined with non-invasive ventilation for patients with both chronic obstructive pulmonary disease (COPD) and respiratory failure. Methods: A total of 110 patients with both COPD and respiratory failure who were admitted to our hospital from April 2018 to August 2019 were enrolled in this study; of which 52 patients were treated with a noninvasive ventilator as Group A, and the rest were treated with ipratropium bromide combined with noninvasive ventilation as Group B. The two groups were compared for blood gas indexes, pulmonary function, and treatment efficacy, and adverse reactions. Results: After treatment, Group B showed better blood gas indexes and pulmonary function than Group A (both P < 0.05), and Group B also showed significantly lower levels of inflammatory factors than Group A (P < 0.05). In addition, the efficacy and life quality of Group B were better than those of Group A, and adverse reactions of Group B were less than those of Group A (all P < 0.05). Conclusion: Ipratropium bromide combined with noninvasive ventilation is effective in the treatment of patients with both COPD and respiratory failure.

Objective: As a traditional herbal medicine extracted from the seeds of Brucea javanica, Brucea javanica oil (BJO) has been clinically used to treat wart, chronic gastroenteritis and a variety of malignant tumors, including gastrointestinal cancer and lung cancer. We have recently reported the anti-tumor role and possible molecular mechanisms of BJO in treatment of lung cancer. However, it remains elusive whether BJO also has an anti-inflammatory effect. Methods: The pneumonia-related inflammatory factors of macrophages under LPS treatment were investigated by real-time PCR and ELISA assays. LPS-induced acute pneumonia rat model was established. Hematoxylin and eosin (HE) examination was performed to detect histopathological changes in the lung tissues. Real-time PCR and ELISA assays were also used to detect the pneumonia-related inflammatory factors in lung tissues. Results: LPS-induced expression and secretion of pneumonia-related inflammatory factors (TNF-alpha, IL-1 beta, IL-6 and IL-8) were significantly suppressed by BJO in a concentration-dependent manner in RAW264.7 cells. However, BJO did not affect cell proliferation and survival rate. Further mechanistic studies revealed that BJO down-regulated the phosphorylation of I kappa B and p65, thereby inhibiting NF-kappa B pathway of macrophages and exerting its anti-inflammatory function. Western blot analysis showed that the phosphorylation levels of I kappa B and p65 were significantly up-regulated while the protein level of I kappa B was inhibited upon LPS stimulation in RAW264.7 cells and in lung tissue. Notably, LPS stimulation levels of I kappa B and p65 were effectively reversed under BJO co-treatment. The expression level of p65 was not influenced by LPS and BJO treatment. HE staining results showed that BJO can reduce the infiltration of inflammatory cells in lung. Conclusion: BJO can reduce the level of inflammatory factors in lung tissue, which provides a theoretical basis for BJO emulsion as an adjuvant therapy for pneumonia.

Rhabdomyolysis syndrome is a clinical emergency that can cause disturbance of the internal environment and even acute renal failure.Rhabdomyolysis caused by viral infection is rare.This paper reported a case of COVID-19 who developed lower extremity muscle pain with soya urine during the progression of the disease and was clinically diagnozed with rhabdomyolysis syndrome.Through the analysis of clinical diagnosis and treatment data, clinicians will improve the alertness in the early recognition and diagnosis of this syndrome.

病历摘要患者男,42岁,个体经营户,主因"胸闷1个月,咳嗽、咳痰10d"于2020年7月10日入院.患者1个月前无明显诱因出现胸闷,位于左胸前,伴气促,深呼吸后好转,无胸痛、咯血,无发热,无夜间盗汗.10d前出现咳嗽,咳少许白痰,就诊当地医院.查胸部CT示双肺弥漫性病变,轻度脂肪肝.予"头孢他啶、莫西沙星"抗感染、"氨溴索"化痰等治疗,症状好转.为进一步明确肺部病变性质转诊我院.自发病以来体重无明显变化.既往确诊"2型糖尿病"10d.吸烟20年,每日2包,未戒烟.无酗酒史.家族中无类似及肿瘤疾病者.

患者男，25岁，因“胸痛9 d，加重1 d”入院，胸部影像学提示双肺多发以上肺为主的磨玻璃结节，数天内影像学变化快，原磨玻璃影渐变实，且病灶范围增多。以“双肺多发磨玻璃结节、类结节影”作为鉴别切入点，完善病原学检查、气管镜、经皮肺穿刺活检、胸腔镜下肺活检等，最终病理证实为结节病。使用糖皮质激素治疗2个月后病灶明显吸收。

目的 探讨重症鹦鹉热衣原体肺炎患者的临床特点及宏基因二代测序(mNGS)在其病原学诊断中的应用.方法 收集2019年11月-2021年2月住院的重症鹦鹉热衣原体肺炎患者9例,男性5例,女性4例,年龄中位数67岁.回顾性分析患者的病历资料,描述其临床表现、实验室检查、影像学特点、mNGS病原学结果及治疗过程.结果 9例中,4例发病前接触过鸟类或禽类.临床表现主要为高热、咳嗽、呼吸困难、乏力、肌肉酸痛;白细胞计数正常或轻度升高,中性粒细胞比例和降钙素原明显升高,部分患者出现肝、肾功能异常;胸部CT检查主要表现为单侧或双侧肺叶斑片状实变影.所有患者均进行mNGS检测,均检出鹦鹉热衣原体核酸序列,予多西环素单药或联用莫西沙星为基础的治疗,均痊愈.结论 鹦鹉热衣原体肺炎发病率低,但病情危重,对疑似病例应尽早完善mNGS检测,及时启动以四环素类药物为基础的治疗方案.

目的 骨髓增生异常综合征是起源于造血干细胞的一组异质性髓系克隆性疾病,常因临床表现非特异性导致漏诊或误诊.本文通过报道1例以咳嗽、咳痰、气促、发热等呼吸道症状为首发伴嗜酸性粒细胞增多及贫血的骨髓增生异常综合征患者,对其临床诊治资料进行分析,以提高临床医师对本病早期识别与诊断的警惕.

Objective: To evaluate the diagnostic efficiency of different methods in detecting COVID-19.Methods: PubMed, Web of Science and Embase databases were searched for identifing eligible articles. All data were calculated utilizing Meta Disc 1.4, Revman 5.3.2 and Stata 12. The diagnostic efficiency was assessed via these indicators including summary sensitivity and specificity, positive likelihood ratio (PLR), negative LR (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic curve (sROC) and calculate the AUC. Results: 18 articles (3648 cases) were included. EPlex: pooled sensitivity was 0.94; specificity 1.0; PLR 90.91; NLR 0.07; DOR 1409.49; AUC=0.9979, Q*=0.9840. Panther Fusion: pooled sensitivity was 0.99; specificity 0.98; PLR 42.46; NLR 0.02; DOR 2300.38; AUC=0.9970, Q*=0.9799. Simplexa: pooled sensitivity was 1.0; specificity 0.97; PLR 26.67; NLR 0.01; DOR 3100.93; AUC=0.9970, Q*=0.9800. Cobas®: pooled sensitivity was 0.99; specificity 0.96; PLR 37.82; NLR 0.02; DOR 3754.05; AUC=0.9973, Q*=0.9810. RT-LAMP: pooled sensitivity was 0.98; specificity 0.99; PLR 36.22; NLR 0.04; DOR 751.24; AUC=0.9905, Q*=0.9596. Xpert Xpress: pooled sensitivity was 0.99; specificity 0.97; PLR 27.44; NLR 0.01; DOR 3488.15; AUC=0.9977, Q*=0.9829.Conclusions: These methods (ePlex, Panther Fusion, Simplexa, Cobas®, RT-LAMP and Xpert Xpress) bear higher sensitivity and specificity, and might be efficient methods complement to the gold standard.

Objective To investigate the mechanism of cigarette smoke extract (CSE) inducing apoptosis of pulmonary artery endothelial cells (HPAECs), especially focus on the role of NLRP3(NLR family pyrin domain protein 3) inflammasome. Methods After transfection with NLRP3 siRNA and NC siRNA, HPAECs from experimental group and control group were stimulated by 10% CSE for 12 h, annexin V/PI flow method was used to detect the apoptosis of the two groups of cells before and after CSE stimulation. Cultured HPAECs were further divided into four groups:control group, CSE group (10% CSE solution was added), NAC+CSE group (10 mmol/L NAC pretreatment for 1 h and then 10% CSE culture solution) and NAC group (10 mmol/L NAC treatment for 1 h). After 12 h culture, intracellular reactive oxygen species(ROS) were detected by DCFH-DA fluorescent probe. The expression of NLRP3 and caspase-1 was determined by Western blot. Results After CSE stimulation, the survival rate of HPAECs in siNC group decreased, and the apoptosis was significantly increased as compared with that before CSE stimulation (P＜0.05). After CSE stimulation, the apoptosis rate of siNLRP3 group decreased compared with that after the same CSE stimulation in siNC group (P＜0.05).The intracellular ROS level in the CSE group was significantly increased as compared with that in the control group, which in the NAC+CSE group was decreased compared with that in the CSE group (P＜0.05). In the CSE group, NLRP3 and caspase-1 were significantly increased compared with the control group, while the expression of NLRP3 and caspase-1 in NAC+CSE group was lower than that in CSE group (P＜0.05). Conclusions CSE could induce apoptosis of HPAECs accompanied by increased NLRP3 inflammatory corpuscle expression. Silencing of NLRP3 protein expression can inhibit the apoptotic effect of CSE on HPAEC.

Abstract Objective Aimed to summarize the characteristics of chest CT imaging in Chinese hospitalized patients with Coronavirus Disease 2019 (COVID-19) to provide reliable evidence for further guiding clinical routine. Methods PubMed, Embase and Web of Science databases were searched to identify relevant articles involving the features of chest CT imaging in Chinese patients with COVID-19. All data were analyzed utilizing R i386 4.0.0 software. Random-effects models were employed to calculate pooled mean differences. Results 19 retrospective studies (1332 cases) were included. The results demonstrated that the combined proportion of ground-glass opacities (GGO) was 0.79 (95% CI 0.68, 0.89), consolidation was 0.34 (95% CI 0.23, 0.47); mixed GGO and consolidation was 0.46 (95% CI 0.37; 0.56); air bronchogram sign was 0.41 (95% CI 0.26; 0.55); crazy paving pattern was 0.32 (95% CI 0.17, 0.47); interlobular septal thickening was 0.55 (95% CI 0.42, 0.67); reticulation was 0.30 (95% CI 0.12, 0.48); bronchial wall thickening was 0.24 (95% CI 0.11, 0.40); vascular enlargement was 0.74 (95% CI 0.64, 0.86); subpleural linear opacity was 0.28 (95% CI 0.12, 0.48); intrathoracic lymph node enlargement was 0.03 (95% CI 0.00, 0.07); pleural effusions was 0.03 (95% CI 0.02, 0.06). The distribution in lung: the combined proportion of central was 0.05 (95% CI 0.01, 0.11); peripheral was 0.74 (95% CI 0.62, 0.84); peripheral involving central was 0.38 (95% CI 0.19, 0.75); diffuse was 0.19 (95% CI 0.06, 0.32); unifocal involvement was 0.09 (95% CI 0.05, 0.14); multifocal involvement was 0.57 (95% CI 0.48, 0.68); unilateral was 0.16 (95% CI 0.10, 0.23); bilateral was 0.83 (95% CI 0.78, 0.89); The combined proportion of lobes involved (> 2) was 0.70 (95% CI 0.61, 0.78); lobes involved (≦ 2) was 0.35 (95% CI 0.26, 0.44). Conclusion GGO, vascular enlargement, interlobular septal thickening more frequently occurred in patients with COVID-19, which distribution features were peripheral, bilateral, involved lobes > 2. Therefore, based on chest CT features of COVID-19 mentioned, it might be a promising means for identifying COVID-19.

目的 探讨大鼠间质性肺炎Ⅱ型肺泡上皮细胞自噬活性的变化及其机制.方法 将16只Wistar雄性大鼠随机数字分为对照组(A组)和实验组(B组),每组8只.实验组雾化吸入博来霉素,对照组雾化吸入等量生理盐水.所有大鼠于28 d处死,收集各组肺组织标本.苏木精-伊红染色(HE)观察肺组织病理改变;Masson三色染色法观察肺组织胶原纤维生成情况;采用免疫黏附法分离Ⅱ型肺泡上皮细胞后,采用蛋白质免疫印迹法(Western blot)检测-平滑肌肌动蛋白(α-SMA)、泛素结合蛋白p62、自噬微管相关蛋白轻链3(LC3 Ⅰ/Ⅱ)、磷酸化的蛋白激酶B(p-Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)及其磷酸化形式p-mTOR的表达变化.结果 1)HE染色显示,A组大鼠肺组织呈正常表现,未见肺泡炎及纤维化改变;B组肺实质呈大片融合实变,其间有少量巨噬细胞、中性粒细胞等炎性细胞浸润,成纤维细胞增多,肺泡间隔明显增厚,可见胶原沉积.2)Masson染色显示,A和B组蓝色区域面积分别为(12.12±1.61) mm2、(23.73±4.20) mm2,B组蓝色面积大于A组,差异有统计学意义(P＜0.05));A组蓝色区域主要集中在气管或血管周围,肺间质只有少量散在的点状着色,B组蓝色区域除气管和血管周围外,肺间质也可见大量蓝色着色区,呈片絮状.3)Westernblot结果显示,B组铲SMA蛋白相对表达量高于A组;B组p62蛋白相对表达量高于A组;B组LC3Ⅱ/Ⅰ比值低于A组;B组p-Akt和p-mTOR相对表达量均高于A组,差异均有统计学意义(均P＜0.05);A组和B组mTOR蛋白相对表达量差异无统计学意义(P＞0.05).结论 大鼠间质性肺炎Ⅱ型肺泡上皮细胞出现细胞自噬活性抑制,Akt/mTOR信号通路激活是其可能的机制之一.

目的 评估多索茶碱联合沙美特罗/氟替卡松在稳定期中重度慢性阻塞性肺疾病(COPD)治疗中的安全性和有效性.方法 将符合GOLD指南诊断标准的75例稳定期的中重度COPD患者随机分成3组,分别接受沙美特罗/氟替卡松(50/250 μg)+多索茶碱(A组)、沙美特罗/氟替卡松(50/500 μg)+维生素B6(B组)、沙美特罗/氟替卡松(50/250μg)+维生素B6(C组)治疗6个月.分别于治疗前、治疗后3、6个月,动态监测患者FEV1、FVC及6 min步行距离的变化.结果 与治疗前相比,3组FEV1、FVC及6 min步行距离得到显著提高(P＜0.05),尤其是A、B组,但组间差异无统计学意义;与治疗后3个月相比,同组患者治疗后6个月的肺功能指标有所下降,但差异无统计学意义(P＞0.05).组间对比显示,A组治疗后6个月FEV1明显优于C组(P＜0.05);不论是治疗后3或6个月,A、B组的FVC、6min步行距离较C组均有所改善,但差异无统计学意义(P＞0.05).结论 稳定期中重度以上COPD患者,在联合使用长效β2受体激动剂和吸入糖皮质激素的基础上,加用多索茶碱安全、有效并可减少吸入糖皮质激素的用量.