Obstructive Sleep Apnea Plasma-Derived Exosomes Mediate Cognitive Impairment Through Hippocampal Neuronal Cell Pyroptosis.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with impaired cognitive function. Exosomes are secreted by most cells and play a role in OSA-associated cognitive impairment (CI). The aim of this study was to investigate whether OSA plasma-derived exosomes cause CI through hippocampal neuronal cell pyroptosis, and to identify exosomal miRNAs in OSA plasma-derived. MATERIALS AND METHODS: Plasma-derived exosomes were isolated from patients with severe OSA and healthy comparisons. Daytime sleepiness and cognitive function were assessed using the Epworth Sleepiness Scale (ESS) and the Beijing version of the Montreal Cognitive Assessment Scale (MoCA). Exosomes were coincubated with mouse hippocampal neurons (HT22) cells to evaluate the effect of exosomes on pyroptosis and inflammation of HT22 cells. Meanwhile, exosomes were injected into C57BL/6 male mice via caudal vein, and then morris water maze was used to evaluate the spatial learning and memory ability of the mice, so as to observe the effects of exosomes on the cognitive function of the mice. Western blot and qRT-PCR were used to detect the expressions of Gasdermin D (GSDMD) and Caspase-1 to evaluate the pyroptosis level. The expression of IL-1ß, IL-6, IL-18 and TNF-α was detected by qRT-PCR to assess the level of inflammation. Correlations of GSDMD and Caspase-1 expression with clinical parameters were evaluated using Spearman's rank correlation analysis. In addition, plasma exosome miRNAs profile was identified, followed by Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. RESULTS: Compared to healthy comparisons, body mass index (BMI), apnea-hypopnea index (AHI), oxygen desaturation index (ODI), and ESS scores were increased in patients with severe OSA, while lowest oxygen saturation during sleep (LSaO2), mean oxygen saturation during sleep (MSaO2) and MoCA scores were decreased. Compared to the PBS group (NC) and the healthy comparison plasma-derived exosomes (NC-EXOS), the levels of GSDMD and Caspase-1 and IL-1ß, IL-6, IL-18 and TNF-α were increased significantly in the severe OSA plasma-derived exosomes (OSA-EXOS) coincubated with HT22 cells. Compared to the NC and NC-EXOS groups, the learning and memory ability of mice injected with OSA-EXOS was decreased, and the expression of GSDMD and Caspase-1 in hippocampus were significantly increased, along with the levels of IL-1ß, IL-6, IL-18 and TNF-α. Spearman correlation analysis found that clinical AHI in HCs and severe OSA patients was positively correlated with GSDMD and Caspase-1 in HT22 cells from NC-EXOS and OSA-EXOS groups, while negatively correlated with clinical MoCA. At the same time, clinical MoCA in HCs and severe OSA patients was negatively correlated with GSDMD and Caspase-1 in HT22 cells from NC-EXOS and OSA-EXOS groups. A unique exosomal miRNAs profile was identified in OSA-EXOS group compared to the NC-EXOS group, in which 28 miRNAs were regulated and several KEGG and GO pathways were identified. CONCLUSIONS: The results of this study show a hypothesis that plasma-derived exosomes from severe OSA patients promote pyroptosis and increased expression of inflammatory factors in vivo and in vitro, and lead to impaired cognitive function in mice, suggesting that OSA-EXOS can mediate CI through pyroptosis of hippocampal neurons. In addition, exosome cargo from OSA-EXOS showed a unique miRNAs profile compared to NC-EXOS, suggesting that plasma exosome associated miRNAs may reflect the differential profile of OSA related diseases, such as CI.

Effect of continuous positive airway pressure treatment on Th17/Treg imbalance in patients with obstructive sleep apnea and a preliminary study on its mechanism.

BACKGROUND: Obstructive sleep apnea (OSA) can be considered a chronic inflammatory disease that impacts all bodily systems, including the immune system. This study aims to assess the Th17/Treg pattern in patients with OSA and the effect of continuous positive airway pressure (CPAP) treatment. METHODS: OSA patients and healthy controls were recruited. OSA patients recommended for CPAP treatment were followed up for three months. Flow cytometry was employed to determine the proportion of Th17 and Treg cells. Real-time quantitative polymerase chain reaction (PCR) and western blotting were utilized to detect the mRNA and protein levels of receptor-related orphan receptor γt (RORγt) and forkhead/winged helix transcription factor (Foxp3), respectively, in peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum levels of interleukin-17 (IL-17), IL-6, transforming growth factor-ß1 (TGF-ß1), and hypoxia-induced factor-1α (HIF-1α). RESULTS: A total of 56 OSA patients and 40 healthy controls were recruited. The proportion of Th17 cells, Th17/Treg ratio, mRNA and protein levels of RORγt, and serum IL-17, IL-6, and HIF-1α levels were higher in OSA patients. Conversely, the proportion of Treg cells, mRNA and protein levels of Foxp3, and serum TGF-ß1 levels were decreased in OSA patients. The proportion of Th17 and Treg cells in OSA can be predicted by the apnea hypopnea index (AHI), IL-6, TGF-ß1 and, HIF-1α. 30 moderate-to-severe OSA patients were adherent to three-month CPAP treatment, with improved Th17/Treg imbalance, IL-17, IL-6, TGF-ß1, and HIF-1α levels compared to pre-treatment values. CONCLUSION: There was a Th17/Treg imbalance in OSA patients. The prediction of Th17 and Treg cell proportions in OSA can be facilitated by AHI, as well as serum IL-6, TGF-ß1, and HIF-1α levels. Furthermore, CPAP treatment can potentially improve the Th17/Treg imbalance and reduce proinflammatory cytokines in OSA patients.

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 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.

Residents' cognition and attitude towards obstructive sleep apnea hypopnea syndrome. / ä½é™¢åŒ»å¸ˆå¯¹é˜»å¡žæ€§ç¡çœ å‘¼å¸æš‚åœä½Žé€šæ°”ç»¼åˆå¾çš„è®¤çŸ¥åŠæ€åº¦.

OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) may cause damage to many organs of the body and is a potentially fatal disease, which has a serious impact on health and quality of life for patients. Residents play an important role in the screening of OSAHS. This study aims to evaluate the cognition and attitude level of residents towards OSAHS, and to provide evidence for the intervention and diagnosis of the disease. METHODS: A cross-sectional survey of residents at a teaching hospital was conducted from December 1, 2021 to December 1, 2022. A questionnaire was used to assess residents' knowledge, attitudes, and confidence in dealing with OSAHS patients. RESULTS: Of the 200 residents who responded to the questionnaire, 183(91.5%) completed it. The average score on the knowledge scale of Obstructive Sleep Apnea Knowledge and Attitudes Questionnaire (OSAKA) for all residents in this study was 13.12±2.46. The knowledge score of internal medicine residents was higher than that of non-internal medicine residents (13.46±2.22 vs 12.33±2.83, P<0.05), and the mean knowledge score of residents with respiratory rotation experience was higher than that of residents without respiratory rotation experience (13.46±2.35 vs 12.69±2.56, P<0.05). The average score of the attitude/confidence scale on the OSAKA questionnaire for all residents in this study was 3.64±0.62. Of the 183 residents, 60.7% of residents considered OSAHS to be extremely important as a clinical disorder, 72.7% of residents were confident in the identification of OSAHS patients, but only 50.3% were confident in the management of OSAHS patients, and only 42.6% were confident in the management of patients treated with continuous positive pressure ventilation. There was a weak positive correlation among levels of knowledge, attitude, and confidence. CONCLUSIONS: Most residents are aware of the clinical importance of OSAHS, but their knowledge and confidence for OSAHS diagnosis and management are still insufficient, and they need to be trained to manage OSAHS patients.

Clinical characteristics of 32 cases of diffuse panbronchiolitis. / 32例弥漫性泛细支气管炎的临床特征.

OBJECTIVES: Diffuse panbronchiolitis (DPB) is a chronic airway inflammation with low specificity and its diagnosis is often missed or delayed. This study aims to summarize the clinical characteristics and treatment of DPB in order to improve the understanding and diagnosis of the disease. METHODS: The clinical data of 32 DPB patients were collected, analyzed and summarized from March 1, 2013 to March 1, 2022 in the Second Xiangya Hospital of Central South University. The basic information, clinical manifestations, laboratory tests, pulmonary function, imaging tests, treatment, and regression of patients were analyzed. RESULTS: A total of 32 patients were enrolled in the final analysis, with a male-to-female ratio at 1.67. The median age at symptom onset was 26.5 (11.0-69.0) years, and the median age of diagnosis was 47.5 (16.0-77.0) years. All patients presented with chronic cough and copious sputum production. A total of 26 patients had post activity shortness of breath and 14 patients had a positive result (blood cold agglutination test titer≥1꞉64). Pulmonary function examination was performed in 31 patients, 18 patients showed mixed pulmonary ventilation dysfunction, 12 patients showed obstructive pulmonary ventilation, and 1 patient had normal pulmonary ventilation function. A total of 31 patients had a bilateral, diffuse, small nodule pattern on chest CT. All patients were treated with macrolides. A total of 31 patients showed improvement, and 20 patients showed improvement in partial pressure of oxygen and blood oxygen saturation compared with before at discharge. A total of 12 patients were re-examined by chest CT after completing macrolides treatment, 6 cases showed less diffuse nodules, 5 cases showed no significant changes, and 1 case showed more diffuse nodules, which indicated the disease progression. Seven patients received pulmonary function tests after completing macrolides treatment, forced expiratory volume in one second (FEV1) and FEV1/forced vital capacitywere improved, but forced expiratory flow at 25% of vital capacity did not change significantly. CONCLUSIONS: The clinical manifestations of DPB are nonspecific. Early diagnosis and treatment are very important for the prognosis of 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.

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 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.

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.

Pulmonary hypertension complicating mediastinal fibrosis secondary to tuberculosis: A case report and literature review. / ç»“æ ¸åŽçºµéš”çº¤ç»´åŒ–è‡´è‚ºåŠ¨è„‰é«˜åŽ‹1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

The clinical data for a patient with pulmonary hypertension complicating mediastinal fibrosis secondary to tuberculosis admitted to the Second Xiangya Hospital, Central South University has been retrospectively analyzed, and the relevant literature has been reviewed. A 55-year-old Han Chinese woman initially presented with increasing shortness of breath on exertion for 7 months was admitted to our hospital in August 2013. Admission examination revealed an increased erythrocyte sedimentation rate, positive in T-SPOT TB test, multiform lesions in both lungs, the enlarged lymph nodes with calcification in mediastinum and bilateral hilar, the narrowed bilateral main bronchial lumen, and the thickened bilateral pleural, as well as adhesion band in the left pleural cavity under the thoracoscope. These results indicated that mycobacterium tuberculosis infection may be present. After 4 months of anti-tuberculosis treatment, there is no improvement in symptom of the patient. In 2016, the patient was admitted to our hospital again because of shortness of breath after exercise. The computed tomography pulmonary angiography revealed ill-defined soft tissue density lesions with calcification on bilateral hilar and mediastinum, encasing the major mediastinal vascular structures. The lesions compressed and wrapped the pulmonary artery and vein branches, resulting in their lumens narrowed severely. Moreover, the main pulmonary artery trunk was widened and the right ventricular was enlarged significantly. The patient was finally diagnosed as mediastinal fibrosis with the potential pathogenic mechanisms being tuberculosis, secondary pulmonary hypertension. Mediastinal fibrosis is an uncommon, benign and progressive condition characterized by an invasive proliferation of the fibrous tissue within the mediastinum, which can lead to pulmonary hypertension. Due to lack of specific clinical manifestations, diagnosis is difficult in the early stage. Physicians should pay attention to mediastinal fibrosis when accepting patients with unexplained pulmonary hypertension. Contrast-enhanced CT should be performed as early as possible to avoid mis-diagnosis or missed diagnosis.

Effect of continuous positive air pressure on cognitive impairment associated with obstructive sleep apnea. / æŒç»­æ°”é“æ­£åŽ‹é€šæ°”å¯¹é˜»å¡žæ€§ç¡çœ å‘¼å¸æš‚åœæ‚£è€ è®¤çŸ¥åŠŸèƒ½çš„å½±å“.

Obstructive sleep apnea (OSA) is a kind of sleep-related breathing disorder, involving multiple organs and systems, which can lead to cognitive impairment. At present, the pathophysiological mechanism of cognitive impairment related to OSA is not clear. It is still unknown whether continuous positive airway pressure (CPAP) has therapeutic effect on cognitive impairment in patients with OSA. These patients repeatedly experience intermittent hypoxia and have sleep fragmentation, which results in abnormal brain structure and function, characterizing by extensive cognitive impairment. Appropriate CPAP can correct the abnormal pathophysiological process of OSA patients, restore brain structure and function to a certain extent, and improve cognitive function. Domestic OSA patients have poor acceptance and compliance to CPAP, while the therapeutic effect of CPAP depends on the timing of treatment and compliance, so many patients do not get effective treatment. Systematically expounding the influence of CPAP on the cognitive function of patients with OSA can help clinicians and patients improve their understanding of CPAP treatment and establish a correct concept of early and standardized treatment.

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.

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.

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.

Attenuation of intermittent hypoxia-induced apoptosis and fibrosis in pulmonary tissues via suppression of ER stress activation.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis and endothelial apoptosis in pulmonary tissues. Chronic intermittent hypoxia (IH) is considered to be the primary player in OSA, but the mechanisms underlying its effect on pulmonary tissues are unknown. Endoplasmic reticulum (ER) stress induced by IH treatment plays an important role in accelerating the process of fibrosis and induction of apoptosis. METHODS: Mice were placed in IH chambers for 4 weeks with an oscillating oxygen (O2) concentration between 5 and 21%, cycling every 90s for 8 h daily. Mice were randomly divided into four groups: control group (normal oxygen), tauroursodeoxycholic acid (TUDCA) group (normal oxygen intraperitoneally injected with TUDCA), IH group and IH + TUDCA group. After 4 weeks, the proteins in three branch signaling pathways of ER stress, including protein kinase RNA (PKR)-like/Pancreatic ER kinase (PERK), activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1), were evaluated. The cleaved caspase-3, caspase-12 and TUNNEL staining was assessed. Furthermore, the expression of transforming growth factor-ß1 (TGF-ß1) and thrombospondin-1(TSP-1), two extracellular matrix proteins that play critical role in fibrosis, were examined. Finally, Masson's trichrome staining was performed to detect the expression of collagen. RESULTS: After 4 weeks of IH treatment, the expressions of two ER stress markers, glucose regulated protein-78 (Grp78) and transcription factor C/EBP homologous protein (CHOP) were increased which was prevented by administration of the ER stress attenuator, TUDCA. The expressions of PERK, but not those of ATF-6 and IRE-1, were increased. The effects of IH were accompanied by an increased number of apoptotic cells and increased expressions of cleaved caspase-3 and caspase-12 in pulmonary tissues. In addition, histological examination suggested the presence of fibrosis after chronic IH treatment, indicated by increased expression of collagen, which was associated with the up-regulation of TGF-ß1 and TSP-1 that are known to promote fibrosis. Similarly, TUDCA could reduce the extent of fibrotic area and the expression levels of these proteins. CONCLUSIONS: It reveals the roles of ER stress, especially the PERK pathway, in IH induced apoptosis and fibrosis in pulmonary tissues that might underlie the pulmonary complications observed in OSA.

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.

Clinical analysis for 12 patients with thoracic Castleman's disease. / 累及胸部的Castlemanç— 12例临床分析.

OBJECTIVES: To explore the clinical characteristics and differential diagnosis for patients with thoracic Castleman's disease, thus to improve doctor's cognition and therapeutic level for the disease. METHODS: The clinical data of 12 patients with thoracic Castleman's disease were analyzed retrospectively, including clinical features, laboratory examination, imaging finding, pathological examination, treatment outcome, and prognosis. RESULTS: All 12 patients were diagnosed by mass or lymph code biopsy. Seven patients with unicentric Castleman's disease were asymptomatic or oligosymptomatic. Of them, the lung imaging features were mostly solitary and well-defined pulmonary hilar soft tissue mass and infrequently invasive mass. Pathologically, 7 patients were all hyaline vascular type. Six patients underwent surgery of complete mass resection, and 1 received chemotherapy because the nidus could not be resected completely. The prognosis of 7 patients was good. The clinical manifestations of 5 patients with multicentric Castleman's disease were diverse with negative prognosis. Their radiological features mainly showed multiple mediastinal/hilum lymph node enlargement, multiple serous cavity effusion, and hepatosplenomegaly, along with multifocal lymphadenopathy. Pathological features of 3 patients' mass were hyaline vascular type, 1 was plasma cell type, and 1 was mixed type. Three patients received comprehensive treatment on the basis of chemotherapy and another 2 patients did not receive any therapy. CONCLUSIONS: Unicentric Castleman's disease involving the chest is mainly manifested as mediastinal or hilar soft tissue mass with single clinical manifestation, while multicentric Castleman's disease involving the chest is mainly manifested as diffuse mediastinal/hilar lymph node enlargement, multifocal lymphadenopathy and multiple clinical manifestation. For patients with mediastinal/hilum mass or with multifocal lymphadenopathy, Castleman's disease should be considered the differential diagnosis. And early mass or lymph code biopsy is of great significance for diagnosis and treatment of Castleman's disease.

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.

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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.