Clinical characteristics and risk factors for primary Sjögren's syndrome complicated with pulmonary arterial hypertension. / åŽŸå‘æ€§å¹²ç‡¥ç»¼åˆå¾åˆå¹¶è‚ºåŠ¨è„‰é«˜åŽ‹çš„ä¸´åºŠç‰¹å¾å’Œå±é™©å› ç´ .

OBJECTIVES: Primary Sjögren's syndrome (pSS) is involved in pulmonary tissue. Pulmonary arterial hypertension (PAH) is one of the pulmonary complications caused by pSS. This study aims to investigate the clinical characteristics and risk factors for pSS complicated with PAH. METHODS: We retrospectively analyzed 165 patients in the Second Xiangya Hospital of Central South University. They were divided into a pSS-PAH group (n=86) and a pSS group (n=79) according to pulmonary artery pressure detected by color doppler echocardiography. The clinical characteristics, laboratory test indexes, and risk factors were compared between the 2 groups. RESULTS: Among 165 patients with pSS, 86 patients (52.12%) had PAH. Females were 79 (91.90%) patients in the pSS-PAH group, more than males. The patients in the pSS-PAH group were older than those in the pSS group (all P<0.05). The incidence of keratoconjunctivitis, alopecia, Raynaud's phenomenon, cough, chest tightness, shortness of breath, and dry skin was higher (all P<0.05), and the incidence of pulmonary infection, pulmonary cystic degeneration, respiratory failure, osteoporosis, arteriosclerosis, and hypertension were higher in the pSS-PAH group than those in the pSS group (all P<0.05). The laboratory indicators of pulmonary artery diameter, right atrium diameter, right ventricular contractile diameter and pulmonary artery systolic pressure were higher in the pSS-PAH group than those in the pSS group (all P<0.05), and the positive rates of anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody were higher (all P<0.05). The incidence of restrictive ventilatory dysfunction and decreased lung diffusion volume in the pSS-PAH group was higher than that in the pSS group (both P<0.05). Advanced age (OR=1.094, 95% CI 1.053 to 1.137, P<0.001), concomitant keratoconjunctivitis (OR=2.075, 95% CI 1.054 to 4.088, P=0.035), hair loss (OR=2.655, 95% CI 1.368 to 5.152, P=0.004), dry skin (OR=2.696, 95% CI 1.364 to 5.332, P=0.004), high pulmonary artery systolic pressure (OR=1.185, 95% CI 1.125 to 1.248, P<0.001), respiratory failure (OR=2.279, 95% CI 1.137 to 4.570, P=0.020), osteoporosis (OR=2.087, 95% CI 1.025 to 4.248, P=0.043), atherosclerosis (OR=2.251, 95% CI 1.146 to 4.423, P=0.018), hypertension (OR=2.370, 95% CI 1.190 to 4.718, P=0.014), the increased antinuclear antibody (OR=2.155, 95% CI 1.094 to 4.245, P=0.026), the increased anti-SSA antibody (OR=2.565, 95% CI 1.292 to 5.091, P=0.007), the increased anti-RO-52 antibody (OR=2.623, 95% CI 1.278 to 5.383, P=0.009), and the decreased lung dispersion (OR=2.602, 95% CI 1.386 to 4.884, P=0.003), were all risk factors for PAH in pSS patients. CONCLUSIONS: The incidence of pSS-PAH is high in this study. The advanced age, elevated pulmonary artery systolic pressure, concomitant keratoconjunctivitis, alopecia, dry skin, respiratory failure, osteoporosis, arteriosclerosis, and hypertension, increased anti-nuclear antibody, anti-SSA antibody, and anti-Ro-52 antibody, and decreased pulmonary dispersion suggest that the risk of PAH is significantly increased in patients with pSS.

Clinical characteristics and risk factors of patients with eosinophilic fasciitis associated with pleural effusion.

To investigate the risk factors of eosinophilic fasciitis (EF) associated with pleural effusion (PE). A retrospective analysis was performed on 22 patients with EF diagnosed by skin biopsy in our hospital, and they were divided into EF-PE and EF according to chest computed tomography examination. The clinical characteristics, clinical manifestations, comorbidities and laboratory test indicators of the two groups were collected and compared, and the risk factors for occurring PE in patients with EF were determined by multivariate logistic regression analysis. Among 22 patients with EF, 8 had PE. The age, course of disease, incidence of fever, weight loss, cough and shortness of breath, pulmonary infection, hypothyroidism, hydronephrosis and kidney stone, swelling rate of small vascular endothelial cells, consolidation shadows, C-reactive protein and thyroid stimulating hormone in EF-PE group were higher than those in EF group, while free triiodothyronine and thyroxine were lower than those in EF group. Age, fever, shortness of breath, C-reactive protein, ESR, thyroid stimulating hormone, pulmonary infection, hypothyroidism, hydronephrosis, kidney stones, swollen small vascular endothelial cells and chest CT consolidation shadows were identified as risk factors for happening PE in patients with EF, while free triiodothyronine and free thyroxine were identified as protective factors against PE in patients with EF. The incidence of EF-PE was 36.36% in this study. Advanced age, high C-reactive protein, ESR, thyroid stimulating hormone, incidence of fever, shortness of breath, pulmonary infection, hydronephrosis, kidney stones, swollen small vascular endothelial cells, chest CT consolidation shadows, and low free triiodothyronine and thyroxine suggest that patients with EF are significantly at increased risk of PE.

Clinical characteristics of IgG4-related disease with lung involvement in 14 patients. / 14例累及肺部的IgG4ç›¸å ³æ€§ç–¾ç— çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Immunoglobulin G4-related diseases (IgG4-RD) is a rare autoimmune disease, and there is no specific diagnostic test for patients with lung involvement yet. This study aims to summarize the clinical characteristics of IgG4-RD with lung involvement and improve the understanding and diagnosis of this disease. METHODS: All patients diagnosed with IgG4-RD in the Second Xiangya Hospital from December 2014 to February 2022 were re-diagnosed according to the recommendations of Chinese Expert Consensus on the Diagnosis and Treatment of IGG4-Related Diseases in 2021. The clinical data of 14 IgG4-RD patients with pulmonary abnormalities were collected and analyzed. RESULTS: Among the 14 patients, 11 were males and 3 were females, and the median age of diagnosis was 66 (22-82) years old. Six cases had respiratory symptoms such as cough, sputum and short breath. Extrapulmonary involvement was the most common in the glands of head and neck (6/14), followed by pancreas and bile duct (4/14). Elevated serum IgG4 level was found in all patients, and most (11/14) were accompanied by abnormal inflammatory markers. Patients' pulmonary imaging findings were diverse, the most common performances were mediastinal/hilar lymphadenopathy (12/14), followed by multiple pulmonary nodules (9/14), patchy density enhancement (7/14) and the increased broncho vascular bundles (6/14). Lung biopsy was performed in 9 patients, their pathology results showed lymphoplasmic cell infiltration, 5 cases of them had interstitial fibrosis, 2 cases with phlebitis, and extrapulmonary biopsy was performed in 8 patients. Immunohistochemical results of all the patients showed that the number of IgG4+ plasma cells was more than 10 per high magnification, and the ratio of IgG4/IgG was more than 40%. For treatment, 12 patients received hormone therapy, and 5 patients combined immunosuppressive therapy with hormone. 10 patients were in remission after treatment, while 2 patients were progressed. CONCLUSIONS: IgG4-RD with lung involvement is rare and has no specific clinical manifestation. Its pulmonary imaging is diverse. Diagnosis for it should combine with serum IgG4 level and pathological examination. Glucocorticoid is the first line treatment, and combination with immunosuppressant can help prevent disease recurrence.

Different clinical characteristics of current smokers and former smokers with asthma: a cross-sectional study of adult asthma patients in China.

Smoking is a trigger for asthma, which has led to an increase in asthma incidence in China. In smokers, asthma management starts with smoking cessation. Data on predictors of smoking cessation in Chinese patients with asthma are scarce. The objective of this study was to find the differences in clinical characteristics between current smokers and former smokers with asthma in order to identify factors associated with smoking cessation. Eligible adults with diagnosed asthma and smoking from the hospital outpatient clinics (n = 2312) were enrolled and underwent a clinical evaluation, asthma control test (ACT), and pulmonary function test. Information on demographic and sociological data, lung function, laboratory tests, ACT and asthma control questionnaire (ACQ) scores was recorded. Patients were divided into a current smokers group and a former smokers group based on whether they had quit smoking. Logistic regression analysis was used to analyze the factors associated with smoking cessation. Of all patients with asthma, 34.6% were smokers and 65.4% were former smokers, and the mean age was 54.5 ± 11.5 years. Compared with current smokers, the former smokers were older, had longer duration of asthma, had higher ICS dose, had more partially controlled and uncontrolled asthma, had more pack-years, had smoked for longer, and had worse asthma control. The logistic regression model showed that smoking cessation was positively correlated with age, female sex, pack-years, years of smoking, partially controlled asthma, uncontrolled asthma, and body mass index (BMI), but was negatively correlated with ACT, FEV1, FEV1%predicted, and widowed status. More than 30% of asthma patients in the study were still smoking. Among those who quit smoking, many quit late, often not realizing they need to quit until they have significant breathing difficulties. The related factors of smoking cessation identified in this study indicate that there are still differences between continuing smokers and former smokers, and these factors should be focused on in asthma smoking cessation interventions to improve the prognosis of patients with asthma.

IL-33/ST2 mediating systemic inflammation and neuroinflammation through NF-kB participated in the neurocognitive impairment in obstructive sleep apnea.

Increasing evidence has noted that neuroinflammation contributes to the pathological processes of cognitive impairment of obstructive sleep apnea (OSA) patients. Interleukin (IL) -33/suppression of tumorigenicity 2 (ST2) signaling pathway plays well-defined roles in the inflammatory progression. The study aims to elucidate whether IL-33/ST2 signaling pathway plays a role in the cognitive dysfunction in patients with OSA via regulating neuroinflammation. We found that compared with control subjects, patients with OSA showed significantly elevated IL-33, ST2 and p65 nuclear factor-kappa B (NF-κB) levels in peripheral blood mononuclear cells (PBMCs) and inflammatory cytokines IL-6, IL-8 in serum, which were positively correlated with disease severity. Meanwhile, OSA patients exhibited a decline in Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, suggesting mild cognitive impairment. Continuous positive airway pressure (CPAP) treatment for 12 weeks significantly decreased the expression of IL-33, ST2, p65NF-κB, IL-6 and IL-8, as well as improved cognitive function of OSA patients. Moreover, the IL-33/ST2 signaling was closely correlated with sleep respiratory parameters and cognitive dysfunction. To further explore the underlying mechanism of IL-33/ST2 signaling pathway, we stimulated human microglial clone 3 (HMC3) cells with lipopolysaccharide (LPS) to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to an increase in IL-33 and ST2 expression in a dose- dependent manner, along with an increased secretion of IL-6 and IL-8. Functional experiments showed that knockdown of IL-33 ameliorated LPS-induced neuroinflammation via suppressing NF-κB signaling. Overall, current findings suggest that IL-33/ST2 signaling participated in the cognitive impairment of OSA patients by promoting neuroinflammation via activating NF-κB signaling. These results may provide a novel therapeutic target for treating OSA- associated cognitive dysfunction.

Role of epigenetic abnormalities and intervention in obstructive sleep apnea target organs.

ABSTRACT: Obstructive sleep apnea (OSA) is a common condition that has considerable impacts on human health. Epigenetics has become a rapidly developing and exciting area in biology, and it is defined as heritable alterations in gene expression and has regulatory effects on disease progression. However, the published literature that is integrating both of them is not sufficient. The purpose of this article is to explore the relationship between OSA and epigenetics and to offer better diagnostic methods and treatment options. Epigenetic modifications mainly manifest as post-translational modifications in DNA and histone proteins and regulation of non-coding RNAs. Chronic intermittent hypoxia-mediated epigenetic alterations are involved in the progression of OSA and diverse multiorgan injuries, including cardiovascular disease, metabolic disorders, pulmonary hypertension, neural dysfunction, and even tumors. This article provides deeper insights into the disease mechanism of OSA and potential applications of targeted diagnosis, treatment, and prognosis in OSA complications.

Clinical characteristics of eosinophilic granulomatosis with polyangiitis involving the lung in 13 patients. / 13ä¾‹ç´¯åŠè‚ºéƒ¨çš„å—œé ¸æ€§è‚‰èŠ½è‚¿æ€§å¤šè¡€ç®¡ç‚Žçš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis, which often starts with respiratory symptoms such as asthma, and it is difficult to make early clinical diagnosis.This study aims to improve the therapeutic level of EGPA with lung involvement via analyzing the clinical characteristics, diagnosis, and treatment . METHODS: We retrospectively analyzed the clinical data of 13 EGPA patients with lung involvement who were diagnosed from February 1, 2014 to July 31, 2021 in the Second Xiangya Hospital, Central South University. RESULTS: The ratio of male to female in 13 patients was 7꞉6. The patients were diagnosed at median age 52 (46-68) years old and 6 had been diagnosed as "bronchial asthma". Pulmonary clinical manifestations mainly included cough, expectoration, wheezing, and shortness of breath; while extra-pulmonary manifestations mainly included rash and subcutaneous mass, fever, limb numbness, muscle and joint pain, abdominal pain, etc. Peripheral blood tests of all patients showed that 11 patients had eosinophils ≥10%, 10 had elevated inflammatory indicators, and 3 were anti-neutrophil cytoplasmic antibody (ANCA) positive. The major lung imaging features were patches or strips of increased density, multiple nodules, bronchiectasis, bronchial wall thickening, exudation, mediastinal lymph nodes, and so on. Eight patients had sinusitis and 9 with abnormal electromyography. Extravascular eosinophil infiltration was found in 9 patients. Six patients with lung biopsy showed eosinophil, lymphocyte, and plasma cell infiltration, 3 patients were involved in small blood vessels, and 1 had granuloma. Pulmonary function tests were performed in 7 patients, 5 of them showed different degrees of pulmonary ventilation dysfunction, and 4 of them had diffusion dysfunction. Almost all patients respond well to glucocorticoid and immunosuppressant. CONCLUSIONS: EGPA is rare in clinical, often involving multiple systems with great harm and may combine with asthmatic manifestations. Pulmonary involvement is relatively common. However, due to insufficient recognition of this disease and huge heterogeneity of pulmonary imaging manifestations, misdiagnosis and missed diagnosis are easy to occur. Relevant laboratory, imaging, and biopsy examination should be performed as early as possible with comprehensive consideration of extrapulmonary involvement. Early identification has great significance to improve the diagnosis rate and prognosis of diseases.

Primary pulmonary artery sarcoma complicated with pulmonary embolism and pulmonary tuberculosis: A case report and literature review. / åŽŸå‘æ€§è‚ºåŠ¨è„‰è‚‰ç˜¤å¹¶è‚ºæ “å¡žã€è‚ºç»“æ ¸æ‚£è€ 1ä¾‹æŠ¥é“å¹¶æ–‡çŒ®å¤ä¹ .

A case of primary pulmonary artery sarcoma (PPAS) complicated with pulmonary embolism and pulmonary tuberculosis is reported. This patient, a 48-year old woman, was diagnosed as pulmonary tuberculosis at the initial stage of the disease, whose condition was improved after anti-tuberculosis treatment, and was finally diagnosed as PPAS combined with pulmonary embolism due to recurrence of the symptoms. PPAS is a very rare malignant tumor originating from the inner or subintima of the pulmonary artery. The clinical manifestations of PPAS have no obvious specificity which can be dyspnea, chest pain, cough, hemoptysis, and so on. Enhanced CT, enhanced MRI, and positron emission computed tomography (PET/CT) is beneficial to the differential diagnosis of PPAS, but definitive diagnosis needs intravascular biopsy or surgical biopsy. Because PPAS often presents as pulmonary embolism, patients with PPAS were often misdiagnosed as pulmonary embolism, resulting in delayed diagnosis and treatment. There are few reports of PPAS presenting as pulmonary embolism complicated with pulmonary tuberculosis at home and abroad, which is also easy to be misdiagnosed. The disease has a high degree of malignancy, which is short of effective treatment at the late stage, with short survival time and poor prognosis. Therefore, attention to the various clinical manifestations of PPAS and early diagnosis and treatment are crucial to the prognosis of PPAS patients.

Clinical analysis for 15 patients with pulmonary Langerhans cell histiocytosis and literature review. / 15ä¾‹æˆäººè‚ºæœ—æ ¼æ±‰æ–¯ç»†èƒžç»„ç»‡ç»†èƒžå¢žç”Ÿç—‡ä¸´åºŠåˆ†æžåŠæ–‡çŒ®å›žé¡¾.

OBJECTIVES: Pulmonary Langerhans cell histiocytosis (PLCH) is a clonal disease, characterized by proliferation of Langerhans cells that derived from bone marrow infiltrating the lungs and other organs. Due to the rarity of the disease, the current understanding of the disease is insufficient, often misdiagnosed or missed diagnosis. This study aims to raise clinicians' awareness for this disease via summarizing the clinical characteristics, imaging features, and treatment of PLCH. METHODS: We retrospectively analyzed clinical and follow-up data of 15 hospitalized cases of PLCH from September 2012 to June 2021 in the Second Xiangya Hospital of Central South University. RESULTS: The age of 15 patients (9 men and 6 women, with a sex ratio of 3 to 2) was 21-52 (median 33) years. Among them, 8 had a history of smoking and 5 suffered spontaneous pneumothorax during disease course. There were 3 patients with single system PLCH and 12 patients with multi-system PLCH, including 7 patients with pituitary involvement, 7 patients with lymph node involvement, 6 patients with bone involvement, 5 patients with liver involvement, 2 patients with skin involvement, 2 patients with thyroid involvement, and 1 patients with thymus involvement. The clinical manifestations were varied but non-specific. Respiratory symptoms mainly included dry cough, sputum expectoration, chest pain, etc. Constitutional symptoms included fever and weight loss. Patients with multi-system involvement experienced symptoms such as polyuria-polydipsia, bone pain, and skin rash. All patients were confirmed by pathology, including 6 by lung biopsy, 3 by bone biopsy, 2 by lymph node biopsy, and 4 by liver, skin, suprasternal fossa tumor, or pituitary stalk biopsy. The most common CT findings from this cohort of patients were nodules and/or cysts and nodular and cystic shadows were found in 7 patients. Three patients presented simple multiple cystic shadows, 3 patients presented multiple nodules, and 2 patients presented with single nodules and mass shadows. Pulmonary function tests were performed in 4 patients, ventilation dysfunction was showed in 2 patients at the first visit. Pulmonary diffusion function tests were performed in 4 patients and showed a decrease in 3 patients. Smoking cessation was recommended to PLCH patients with smoking history. Ten patients received chemotherapy while 2 patients received oral glucocorticoid therapy. Among the 11 patients with the long-term follow-up, 9 were in stable condition. CONCLUSIONS: PLCH is a neoplastic disease closely related to smoking. The clinical manifestations and laboratory examination are not specific. Pneumothorax could be the first symptom which is very suggestive of the disease. Definitive diagnosis relies on histology. There is no unified treatment plan for PLCH, and individualized treatment should be carried out according to organ involvement. Early smoking cessation is essential. Chemotherapy is the main treatment for rapidly progressing PLCH involved multiple organs. All diagnosed patients can be considered for the detection of BRAFV600E gene and relevant targeted therapies have been implemented recently.

LncRNA-CCAT1/miR-152-3p is involved in CSE-induced inflammation in HBE cells via regulating ERK signaling pathway.

Emerging studies have noted that dysregulated long non-coding RNAs (lncRNAs) are implicated in the pathological processes of chronic obstructive pulmonary disease (COPD). LncRNA colon cancer-associated transcript 1 (CCAT1) plays well-defined roles in the inflammatory progression. The study aims to figure out the effect and regulatory mechanism of CCAT1 in the cigarette smoke induced inflammation in COPD. The results showed that CCAT1 was highly expressed in lung tissues of smokers with COPD compared with never-smokers without COPD. In human bronchial epithelial (HBE) cells, cigarette smoke extract (CSE) treatment led to an increase in CCAT1 expression in a dose- and time- dependent manner. Functional experiments showed that knockdown of CCAT1 amelioratedCSE-inducedinflammation. Mechanistically, CCAT1 directly targeted miR-152-3p, and miR-152-3p overexpression reversed the pro-inflammatory effects of CCAT1 on HBE cells. Subsequently, miR-152-3p was found to regulate ERK signaling pathway. PD98059, an ERK specific inhibitor, reversed miR-152-3p knockdown mediated inflammation in HBE cells. In addition, CCAT1 acted as a sponge for miR-152-3p to positively regulate ERK signaling pathway. Overall, current findings suggest that CCAT1 promoted inflammation by activating ERK signal pathway via sponging miR-152-3p in CSE-treated HBE cells. These results may provide a novel therapeutic target for alleviating cigarette smoke mediated airway inflammation.

Prohibitin Protects Pulmonary Microvascular Endothelial Cells Against Cigarette Smoke Extract-Induced Cell Apoptosis and Inflammation.

Background: Prohibitin has been identified to play roles in cell survival and apoptosis. Here, this study aimed to clarify the role of prohibitin in cigarette smoke extract (CSE)-induced endothelial cell apoptosis. Methods: The protein level of prohibitin was assessed by Western blot in lung tissues from emphysema and control mice. CSE-induced human pulmonary microvascular endothelial cells (hPMECs) were applied to mimic smoke-related cell apoptosis in vitro. Prohibitin was overexpressed in hPMECs with or without CSE. Mitochondrial function was analyzed by JC-1 staining and ATP assay kits. Oxidative stress was assessed by flow cytometry, fluorescence staining and immunocytochemistry. Apoptosis was analyzed by flow cytometry, Western blot and caspase-3 activity assays. In addition, the expression of inflammatory markers was assessed by Western blot and real-time polymerase chain reaction (PCR). The secretion of inflammatory cytokines was measured by ELISA. Results: Prohibitin was downregulated in emphysema mouse tissues compared with control experiments. Consistently, CSE inhibited both the protein and RNA levels of prohibitin in hPMECs in a dose-dependent manner. Gain-of-function experiments indicated that CSE induced collapse of mitochondrial membrane potential (MMP) and loss of ATP, while prohibitin improved mitochondrial function. CSE induced robust ROS production and oxidative DNA damage, while prohibitin decreased this damage. Upregulation of prohibitin protected the apoptosis of hPMECs from CSE. Overexpression of prohibitin significantly reduced the levels of the main proinflammatory cytokines. Finally, prohibitin inhibited nuclear factor-kappa B (NF-κB) p65 accumulation and IκBα degradation induced by CSE. Conclusion: The current findings suggest that CSE-mediated mitochondrial dysfunction, oxidative stress, cell apoptosis and inflammation in hPMECs were reduced by overexpression of prohibitin. We identified prohibitin as a novel regulator of endothelial cell apoptosis and survival in the context of CSE exposure.

Good's syndrome combined with bronchiectasis: A case report and literature review. / Good'sç»¼åˆå¾åˆå¹¶æ”¯æ°”ç®¡æ‰©å¼ 1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

A patient with thymoma associated immunodeficiency syndrome (Good's syndrome) and bronchiectasis was retrospectively analyzed. Good's syndrome is a rare condition of immunodeficiency that is characterized by thymoma and hypogammaglobulinemia. It is important to bear in mind that Good's syndrome should be included in the differential diagnosis When patients repeatedly visited for bronchiectasis or infection, we should alert to their immune state and history of thymoma. Early screening of immunological status and aggressive correction of immune deficiency are beneficial to improving the prognosis to patients with Good's syndrome.

Clinical characteristics of pulmonary alveolar proteinosis. / 肺泡蛋白沉积症的临床特征.

OBJECTIVES: Pulmonary alveolar proteinosis (PAP) is a rare disease with non-specific and various clinical manifestations, often leading to misdiagnosis. This study aims to raise the awareness of this disease via summarizing the clinical characteristics, diagnosis, and therapy of PAP. METHODS: We retrospectively analyzed clinical data of 25 hospitalized cases of PAP during 2008 and 2019 in the Department of Respiratory and Critical Care Medicine of the Second Xiangya Hospital of Central South University. RESULTS: Cough with unkown reason and dyspnea were common clinical manifastations of PAP. Five patients had a history of occupational inhalational exposure. Sixteen patients had typical image features including ground-glass opacification of alveolar spaces and thickening of the interlobular and intralobular septa, in typical shapes called crazy-paving and geographic pattern. Fourteen patients underwent pulmonary function tests, revealing a reduction in the diffusing capacity for carbon monoxide. The positive rate of transbronchial biopsy was 95%. Five patients received the whole lung lavage and the symptoms and imaging fcauters significantly relieved after five-years follow-up. CONCLUSIONS: PAP is characterized by radiographic pattern and pathology. Transbronchial lung biopsy is effective to make diagnosis of PAP. The whole lung lavage remains a efficient therapy.

Resveratrol attenuates cigarette smoke induced endothelial apoptosis by activating Notch1 signaling mediated autophagy.

BACKGROUND: Increasing evidence shows that endothelial apoptosis contributes to cigarette smoke (CS)-induced disease progression, such as chronic obstructive pulmonary disease (COPD). Our previous studies have validated Notch1 as an anti-apoptotic signaling in CS-induced endothelial apoptosis. Resveratrol (RESV) is a naturally occurring polyphenol that exhibits an anti-apoptotic activity in endothelial cells that exposed to many kinds of destructive stimulus. However, the effects of resveratrol on Notch1 signaling in CS-induced endothelial apoptosis have not yet been fully elucidated. Therefore, the aim of this study was to examine whether RESV can protect endothelial cells from CS-induced apoptosis via regulating Notch1 signaling. METHODS: Human umbilical vein endothelial cells (HUVECs) were pretreated with RESV for 2 h, followed by cotreatment with 2.5%CSE for 24 h to explore the role of RESV in CSE induced endothelial apoptosis. 3-methyladenine (3-MA) or rapamycin was used to alter autophagic levels. Lentivirus Notch1 intracellular domain (LV-N1ICD), γ-secretase inhibitor (DAPT) and Notch1 siRNA were used to change Notch1 expression. The expression of Notch1, autophagic and apoptotic markers were examined by Western blot and the apoptosis rate was detected by Flow cytometry analysis. RESULTS: Our results showed that activating autophagy reduced CSE-induced endothelial apoptosis, while blocking autophagy promoted cell apoptosis in HUVECs. RESV pretreatment attenuated the CSE-induced endothelial apoptosis and activated Notch1 signaling. RESV pretreatment also increased LC3b-II and Beclin1 production, decreased p62 and mTOR expression. 3-MA treatment inhibited autophagy and aggravated CSE induced apoptosis, while rapamycin promoted autophagy, led to a decrease in cell apoptosis. LV-N1ICD transfection upregulated autophagy and reduced apoptosis. However, this protective effect was abolished by 3-MA treatment. In cells treated with DAPT or Notch1 siRNA, autophagy was decreased, while apoptosis was increased. RESV partly rescued the DAPT or Notch1 siRNA induced apoptosis by activating Notch1 signaling. CONCLUSION: In HUVECs, RESV attenuates CSE induced endothelial apoptosis by inducing autophagy in a Notch1-dependent manner.

The clinical characteristics of East Asian patients with Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant disease that has been characterized by skin lesions, multiple pulmonary cysts, spontaneous pneumothorax, and renal tumors, but the patients in Asian countries may show fewer symptoms. We aimed to explore and summarize the clinical features of BHD patients in East Asia to facilitate early diagnosis and timely interventions. METHODS: We collected and analyzed the clinical data of patients diagnosed with BHD in our hospital by reviewing medical records. We performed a systematic literature search regarding the presenting clinical features in BHD patients from China, Japan, and Korea and then reviewed the publications that were identified. RESULTS: In our hospital, 10 patients were diagnosed with BHD from April 2015 to September 2019. After reviewing the literature, we recruited 38 articles, including 12, 20, and 6 reports from China, Japan, and Korea, respectively. A total of 166 patients were included in this study, and 100 of them (60.2%) were females. Multiple pulmonary cysts were present in 145 patients (87.3%), and 124 patients (74.7%) had a history of pneumothorax on at least one occasion. Skin biopsy confirmed fibrofolliculomas (FFs) alone in 22 patients (13.3%), trichodiscomas (TDs) alone in 3 patients (1.8%), and both FFs and TDs in 7 patients (4.2%). Renal carcinoma only occurred in 12 (7.2%) patients. The most frequent genetic mutations in East Asian patients were c.1285delC on exon 11 (18.4%), c.1285dupC on exon 11 (18.4%), and c.1347_1353dupCCACCCT on exon 12 (8.2%). CONCLUSIONS: Our findings suggested that pulmonary cysts are the most frequent radiological findings, and pneumothorax is the most common symptom in East Asian patients with BHD, and that skin lesions and kidney involvement are less frequent. To make an early diagnosis and minimize the severity of complications, careful observation, and timely genetic examination of the FLCN gene is essential.

Identification of a Novel Pathogenic Folliculin Variant in a Chinese Family With Birt-Hogg-Dubé Syndrome (Hornstein-Knickenberg Syndrome).

Birt-Hogg-Dubé syndrome (BHDS), which is also called Hornstein-Knickenberg syndrome (HKS), is a hereditary autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN, NM_144997). More pulmonary manifestations (pulmonary cysts and recurrent pneumothoraxes) but fewer skin fibrofolliculomas and renal malignancy are found in Asian BHDS patients compared with other BHDS patients. The atypical manifestation can easily lead to a missed or delayed diagnosis. Here, we report a Chinese family with BHDS that presented with primary spontaneous pneumothorax (PSP) and extensive pulmonary cysts in the absence of skin lesions or renal neoplasms. Next-generation sequencing (NGS) was used to sequence the FLCN gene, and Sanger sequencing was carried out on the samples to confirm the presence of these variants. Among the 13 family members, a novel frameshift variant of FLCN (c.912delT/p.E305KfsX18) was identified in seven individuals. This variant has not been reported before. Bioinformatics analysis showed that the novel variant might lead to a premature stop codon after 18 amino acid residues in exon 9, and this may affect the expression level of FLCN. The identification of this novel frameshift variant of FLCN not only further confirms the familial inheritance of BHDS in the proband but also expands the mutational spectrum of the FLCN gene in patients with BHDS.

Blood and Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumonia.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) has made a revolution in the mode of pathogen identification. We decided to explore the diagnostic value of blood and bronchoalveolar lavage fluid (BALF) as mNGS samples in pneumonia. METHODS: We retrospectively reviewed 467 mNGS results and assessed the diagnostic performance of paired blood and BALF mNGS in 39 patients with pneumonia. RESULTS: For bacteria and fungi, 16 patients had culture-confirmed pathogen diagnosis, while 13 patients were culture-negative. BALF mNGS was more sensitive than blood mNGS (81.3% vs. 25.0%, p=0.003), and the specificity in BALF and blood mNGS was not statistically significant different (76.9% vs. 84.6%, p=0.317). For 10 patients without culture test, treatments were changed in 2 patients. For viruses, Epstein-Barr virus was positive in blood mNGS in 9 patients. Human adenovirus was detected in both BALF and blood mNGS in 3 patients. CONCLUSION: Our study suggests that BALF mNGS is more sensitive than blood mNGS in detecting bacteria and fungi, but blood also has advantages to identify the pathogens of pneumonia, especially for some viruses.

The relationship between inflammation and neurocognitive dysfunction in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS), a state of sleep disorder, is characterized by repetitive apnea, chronic hypoxia, oxygen desaturation, and hypercapnia. Previous studies have revealed that intermittent hypoxia (IH) conditions in OSAS patients elicited neuron injury (especially in the hippocampus and cortex), leading to cognitive dysfunction, a significant and extraordinary complication of OSAS patients. The repeated courses of airway collapse and obstruction in OSAS patients resulted in apnea and arousal during sleep, leading to IH and excessive daytime sleepiness (EDS) and subsequently contributing to the development of inflammation. IH-mediated inflammation could further trigger various types of cognitive dysfunction. Many researchers have found that, besides continuous positive airway pressure (CPAP) treatment and surgery, anti-inflammatory substances might alleviate IH-induced neurocognitive dysfunction. Clarifying the role of inflammation in IH-mediated cognitive impairment is crucial for potentially valuable therapies and future research in the related domain. The objective of this article was to critically review the relationship between inflammation and cognitive deficits in OSAS.

Myeloid neoplasm with the abnormality of PDGFRB gene secondary interstitial pneumonia: A case report. / 伴PDGFRB重排髓系肿瘤继发性间质性肺炎1例.

We report a case of myeloid neoplasm with the abnormality of PDGFRB gene secondary interstitial pneumonia. A 66-year-old male complained dry cough and shortness of breath after regular activities. Two years ago, high-resolution computerized tomography (HRCT) showed interstitial lung diseases, and no clear etiology was found. At that time, the diagnosis was idiopathic pulmonary fibrosis. In the period of hospitalization, the interstitial lung disease was significantly advanced, and the peripheral blood eosinophil was significantly increased. ETV6-PDGFRB fusion genes was positive detected by FISH. Myeloid neoplasm with the abnormality of PDGFRB gene was diagnosed. The patient was treated with the tyrosine kinase inhibitor-imatinib mesylate which is the first choice for this disease currently.Myeloid neoplasm with the abnormality of PDGFRB gene is a rare hematologic tumor characterized by myeloid dysplasia, eosinophilia, and PDGFR gene rearrangement. Most of this tumor occurs in male, often with splenomegaly, and a few have damages in liver, skin, heart, and other organ tissues.

A case report. / æˆäººæœ—æ ¼æ±‰æ–¯ç»†èƒžç»„ç»‡ç»†èƒžå¢žç”Ÿç—‡ç´¯åŠè‚ºã€åž‚ä½“ã€ç”²çŠ¶è ºã€è‚ã€æ·‹å·´ç»“ã€çš®è‚¤1例.

Langerhans cell histiocytosis (LCH) is a rare and unexplained disease that can involve in any organ or system in the body and displays a variety of clinical manifestations. A 31-year-old man, who had a more than 10-year smoke history, initially presented dry cough, polydipsia and diuresis, with recurrent spontaneous pneumothorax. Pulmonary high-resolution computed tomography showed diffuse cystic and nodular lesions. Langerhans cell histiocytosis was confirmed by a transbronchial cryobiopsy. The disease is involved in the lung, pituitary, thyroid, liver, lymph node, and skin. Glucocorticoid or systemic chemotherapy is commonly used in the treatment for this disease. BRAF gene mutation inhibitor is a new direction for the treatment.