Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by airway inflammation. Airway inflammation dominated by eosinophils (EOS) has attracted increasing attention in the occurrence and development of COPD. EOS type COPD is a special population in a large number of COPD patients. In recent years, there have been many studies on EOS type COPD, involving type 2 immune response, COPD progression and the use of glucocorticoids. This article reviews the above relationships. It is helpful to further understand EOS type COPD and provide help for the clinical diagnosis and treatment of COPD.

BACKGROUND: There have been many significant advances in the diagnosis and treatment of non-small cell lung cancer (NSCLC). However, the mechanism underlying the progression of NSCLC is still not clear. Plant homodomain finger-like domain-containing protein 5A (PHF5A) plays an important role in processes of chromatin remodeling, morphological development of tissues and organs and maintenance of stem cell pluripotency. This study aims to investigate the role of PHF5A in the proliferation and migration of NSCLC. METHODS: A549 and PC-9 PHF5A overexpression cell lines were constructed. PHF5A expression was decreased in H292 and H1299 cells by using siRNA. Flow cytometry was used to detect the cell cycle. MTT assay and clone formation assay were used to examine the proliferative ability of NSCLC, while migration assay and wound healing assay were performed to evaluate the ability of migration. Western blot analysis was used to measure the expressions of PI3K, p-AKT and the associated downstream factors. RESULTS: Up-regulation of PHF5A in A549 and PC-9 cells increased the proliferation rate, while down-regulation of PHF5A in H292 and H1299 cells inhibited the proliferation rate at 24 h, 48 h and 72 h (P<0.05). The metastatic ability was elevated in the PHF5A-overexpresion groups, while reduced in the PHF5A-down-regulation group (P<0.05). In addition, reduced expression of PHF5A induced cell cycle arrest at G1/S phase (P<0.05). Furthermore, decreased expression of PHF5A reduced the expression levels of PI3K, phosphorylation of AKT, c-Myc (P<0.05) and elevated the expression of p21 (P<0.05). CONCLUSIONS These results demonstrated that PHF5A may play an important role in progression of NSCLC by regulating the PI3K/AKT signaling pathway.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Cell Line, Tumor ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Gene Expression Regulation, Neoplastic ; Trans-Activators/genetics* ; RNA-Binding Proteins/metabolism*

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

Objective:To investigate the value of sedation in colonoscopy.Methods:A retrospective cohort study of colonoscopy procedures was performed in our institution. Inclusion criteria: (1) colonoscopy procedures were performed by well-trained gastrointestinal surgeons our institution; (2) medical records were complete and colonoscopy was documented properly by notes, videos, photographs, and traceable pathological reports. Those with incomplete records or performed in other institution were excluded. According to above criteria, clinical data of 49 057 cases of clinic and hospitalization receiving diagnostic or therapeutic colonoscopyat Department of Gastric and Colorectal Surgery, Daping Hospital from July 2007 to February 2017 were collected. Among them, there were 24 638 (50.2%) males and 24 419 females, with mean age of (50.6±14.1) (4 to 98) years. Based on the application of sedation during colonoscopy, patients were divided into the sedation group (39 412 cases, 80.3%) and the non-sedation group (9 645 cases, 19.7%). Clinical characteristics of two groups were compared.Results:The sedation rate increased from 45.6% (369/810) to 94.8% (917/967) from 2007 to 2017. As compared to non-sedation group, a higher proportion of females [51.0% (20 095/39 412) vs. 44.8% (4 324/9 645), χ 2=117.422, P<0.001] and younger median age (50.0 years vs. 51.0 years, Z=-4.774, P<0.001) were found in the sedation group, whose differences were statistically significant. In all the 9645 cases in the non-sedation group, about 5.5% (534) of them terminated the examination because of unbearable discomfort, including 244 (4.6%) males and 290 (6.7%) females (χ 2=20.522, P<0.001). Among all the screening population who were ≥50 years old, there was no significant difference in the polyp detection rate (PDR) between the sedation group and the non-sedation group [26.7% (4 737/17 753) vs. 27.4% (1 093/3 984), χ 2=0.937, P=0.330]. The cecal intubation rate (CIR) in the sedation group was significantly higher than that in the non-sedation group [(85.2% (14 422/16 933) vs. 76.1% (2 803/3 682), χ 2=180.032, P<0.001]. Five cases in the sedation group developed iatrogenic colonic perforation (ICP), with none in the non-sedation group. Conclusions:The application of sedation in colonoscopy is increasingly popular. Sedation can significantly improve CIR in colonoscopy, while it has no positive influence on PDR. Meanwhile, sedation increases the medical expense and may result in higher ICP rate.

In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".

Objective To evaluate the correlation between cerebral blood flow perfusion and memory impairment in patients with severe stenosis of vertebral basilar artery (VBA).Methods 62 cases of patients with VBA stenosis diagnosed by digital subtraction angiography(DSA) in Beijing Tiantan Hospital from September 2016 to March 2017 were enrolled.Mental State Examination (MMSE),Clinical Memory Scale (CMS) test and CT perfusion(CTP) was performed.All patients were divided into memory normal group(n=24,including 1 excellent case,6 above normal cases,and 14 normal cases) and memory impairment group(n =38,including 18 below normal cases,12 periphery cases,8 impaired cases) according to CMS.The ratios of side-to-side period were compared between bilateral mesial temporal lobe and anterior circulation area.The relative time to peak (rTTP),relative mean transit time(rMTY),relative cerebral blood flow(rCBF) and relative cerebral blood volume (rCBV) were calculate.Results The incidence of CTP decompensation in the medial temporal lobe was higher than that in the patients with memory impairment(P＜0.05).The difference of rTTP and rMTT value between the two groups in the bilateral medial temporal lobes was statistically significant (rTFP:(1.131 ±0.037),(1.437±0.139),t=10.520,P＜ 0.05);rMTT:(1.081 ±0.059),(1.281 ±0.174),t=5.423,P＜0.05).Conclusion The patients with VBA severe stenosis are more likely to get memory impairment due to cerebral hypoperfusion.

The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein 1 (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMP1-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that regulated BBB formation, but also assigned a new function to DMP1-PG.
Animals ; Astrocytes ; cytology ; metabolism ; Blood-Brain Barrier ; cytology ; metabolism ; Cells, Cultured ; Extracellular Matrix Proteins ; genetics ; metabolism ; Female ; Glycosylation ; Male ; Mice ; Proteoglycans ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.
Aging ; genetics ; Animals ; Astrocytes ; cytology ; metabolism ; Brain ; cytology ; metabolism ; Cell Differentiation ; genetics ; Cell Division ; genetics ; Cell Proliferation ; genetics ; Gene Expression Regulation ; genetics ; Mice ; Neural Stem Cells ; metabolism ; Single-Cell Analysis ; Stem Cells ; cytology ; metabolism ; Transcriptome ; genetics