BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Humans ; Noninvasive Ventilation ; Cannula ; Airway Extubation ; Retrospective Studies ; Pulmonary Disease, Chronic Obstructive/therapy* ; Hypercapnia/therapy* ; Oxygen Inhalation Therapy ; Respiratory Insufficiency/therapy*

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) in elderly and patients with chronic respiratory diseases (COPD) had a poor prognosis. COPD is one of the most common chronic respiratory diseases. We explore the epidemiological characteristics of patients with severe COVID-19 with COPD patients in order to provide medical evidence for the prevention and treatment of severe COVID-19. METHODS: We retrospectively analyzed the clinical baseline characteristics, treatment strategies, disease progression and prognosis of 557 severe COVID-19 patients admitted to the West Court of Union Hospital of Huazhong University of Science and Technology from January 29, 2020 to April 8, 2020. RESULTS: A total of 465 patients with severe COVID-19 were enrolled in the study, including 248 (53.3%) males and 217 (46.7%) females. The median age of severe COVID-19 patients was 62.0 years, and 53 patients were complicated with COPD. Common symptoms at the onset included fever (78.5%), dry cough (67.1%), shortness of breath (47.3%) and fatigue (40.9%). Compared with non-COPD patients, patients with COPD had significantly lower levels of SpO2 in admission (90.0% vs 92.0%, P=0.014). In terms of laboratory examinations, patients with COPD had higher levels of C-reactive protein, interleukin-6, procalcitonin, total bilirubin, blood urea nitrogen, serum creatinine, lipoprotein (a), high-sensitivity troponin I, and D-dimer, while had lower levels of platelet counts, albumin and apolipoprotein AI. Severe COVID-19 patients with COPD had higher Sequential Organ Failure Assessment scores [3.0(2.0, 3.0) vs 2.0(2.0, 3.0), P=0.038] and CURB-65 score [1.0(1.0, 2.0) vs1.0(0.0, 1.0), P<0.001], and a higher proportion of progressing to critical illness (28.3% vs 10.0%, P<0.001) with more complications [e.g. septic shock (15.1% vs 6.1%, P=0.034)], had higher incidence rates of antibiotic therapies (90.6% vs 77.2%, P=0.025), non-invasive (11.3% vs 1.7%, P<0.001) and invasive mechanical ventilation (17.0% vs 8.3%, P=0.039), ICU admission (17.0% vs 7.5%, P=0.021) and death (15.1% vs 6.1%, P=0.016). Cox proportion hazard model was carried out, and the results showed that comorbid COPD was an independent risk factor for severe COVID-19 patients progressing to critical type, after adjusting for age and gender [adjusted hazard ratio (AHR)=2.38(1.30-4.37), P=0.005] and additionally adjusting for chronic kidney diseases, hypertension, coronary heart disease [AHR=2.63(1.45-4.77), P<0.001], or additionally adjusting for some statistically significant laboratory findings [AHR=2.10(1.13-3.89), P=0.018]. CONCLUSIONS Severe COVID-19 patients with COPD have higher levels of disease severity, proportion of progression to critical illness and mortality rate. Individualized treatment strategies should be adopted to improve the prognosis of severe COVID-19 patients.
Male ; Female ; Humans ; Aged ; Middle Aged ; COVID-19/complications* ; SARS-CoV-2 ; Retrospective Studies ; Critical Illness ; Pulmonary Disease, Chronic Obstructive/epidemiology*

To investigate the effect of Brucea javanica oil emulsion on proliferation, migration and autophagy of non-small cell lung cancer A549 cells.
 Methods: First, A549 cells were divided into a control group and a low, medium or high dose of Brucea javanica oil emulsion groups (0, 2.5, 5.0 or 10.0 mg/mL); then, the cells were divided into a 3-MA+Brucea javanica oil emulsion group and a Brucea javanica oil emulsion group in the presence or absence of 3-methyl adenine (3-MA). Cell counting kit-8 (CCK-8) and clone formation assay were used to detect cell proliferation, while the wound scratch and Transwell assay were used to measure cell migration. Cell immunofluorescence and Western blot were used to analyze autophagy.
 Results: Compared with the control group, the numbers of cell proliferation and colony-formation, the relative cell migration rate and numbers of trans-membrane cells were reduced in a dose-dependent manner in the Brucea javanica oil emulsion groups (all P<0.05). Meanwhile, compared with the control group, the aggregation of microtubule associated protein 1 light chain3 (LC3) green fluorescence and the LC3-II/LC3-I ratios were increased, while p62 level was decreased (all P<0.05) in the high dose group. Compared with the Brucea javanica oil emulsion group (5.0 mg/mL), the cell proliferation, numbers of cell clone formation, cell migration rate and numbers of Transwell transmembrane cells were increased in the 3-MA+Brucea javanica oil emulsion group (all P<0.05).
 Conclusion: Brucea javanica oil emulsion can promote the autophagy of non-small cell lung cancer A549 cells and inhibit the cell proliferation and migration.
A549 Cells ; Autophagy ; drug effects ; Brucea ; chemistry ; Carcinoma, Non-Small-Cell Lung ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Lung Neoplasms ; Plant Oils ; pharmacology

Nocardia is a genus of gram-positive,weakly acid-fast,filamentous aerobic actinomycetes,which mainly causes infection in immunocompromised persons. We reported a successfully treated fatal case of severe pneumonia caused by Nocardia farcinica in a hospital,then reviewed 25 domestic and abroad case reports about nocardiosis combined with severe pneumonia occurred since 2006,so as to improve health care workers'cognition on clinical manifestations,image features,pathogenic characteristics,and diagnostic and treatment schemes of se-vere pneumonia caused by Nocardia farcinica.

Objective To explore the effects of high background radiation on the expressions of miR-16, miR-106b, miR-449a, miR-34a and let-7g in peripheral blood plasma of the residents .Methods Totally 110 healthy female long-term local residents aged over 50 years were randomly selected from the high background radiation area and the control area , while their age, body mass index(BMI) and other indicators were surveyed .The relative expression levels of miRNAs in peripheral blood plasma of these women were quantitatively detected by real-time fluorescence quantitative PCR ( RT-PCR) .Then t-test was used to analyze the cumulative dose , age and BMI between the high background and control group .Mann-Whitney U-test was used for statistical analysis of miRNA expression levels between two groups , and the multiple regression analysis was used finally .Results Compared with the control group , the cumulative dose of individuals in the high background group was about four times higher (t=42.803, P<0.05), and the levels of miR-16 and miR-106b in plasma of high background group were down-regulated, while the level of miR-449a was up-regulated ( Z =4.180, 2.422, 2.794, P <0.05 ).After controlling of confounding factors such as age and BMI , the expression levels of miR-16 and miR-106b were negatively correlated with the cumulative dose of individuals (P<0.05).On the contrary, no significant correlation was observed between the levels of miR-449a, miR-34a, let-7g and the individual cumulative dose (P>0.05).Conclusions miR-16 and miR-106b may serve as biomarkers for the early stage of low dose radiation health effects .

OBJECTIVE: To explore the effect of chronic intermittent hypoxia (CIH) on liver injury and to examine the expression of liver CXC chemokine ligand-10 (CXCL10) in the rats, and to explore the effect of N-acetylcysteine (NAC).
 METHODS: A total of 21 male SD rats were randomly divided into a control group, a CIH group and a CIH+NAC group (n=7 in each group). The control group exposed to normal gaseous environment, the other 2 groups were exposed to CIH for 5 weeks (8 h/d); the control group and the CIH group were given daily saline lavage, the CIH+NAC group daily received NAC solution. After the end of 5 weeks, the rats were killed, and the MDA content and SOD activity in rat liver tissues were detected. The liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of CXCL10 in the liver tissues was detected by immunohistochemical method.
 RESULTS: Compared with the control group, the MDA levels in rat liver tissues were increased (P<0.05), and the SOD levels were decreased (P<0.05) in the CIH group and the CIH+NAC group. Compared with the CIH group, the SOD levels in the rat liver tissues were increased (P<0.05), and the MDA levels were decreased in the CIH+NAC group. Compared with the control group, the hepatic steatosis and inflammatory reactions were more severe in the CIH group and the CIH+NAC group (both P<0.01). Compared with the CIH group, the hepatic steatosis and inflammatory reactions were reduced in the CIH+NAC group (P<0.05). The liver damage in the CIH+NAC group was less than that in the CIH group (P<0.05). Compared with the control group, the CXCL10 expression in the CIH group and the CIH+NAC group was increased (both P<0.01). The CXCL10 expression in the CIH+NAC group was down-regulated compared with that in the CIH group (P<0.01).
 CONCLUSION CIH can lead to liver injury and induce CXCL10 expression in rat liver tissues. The NAC can alleviate rat liver oxidative stress and inflammation caused by CIH, and in turn to improve the liver injury in rats.
Acetylcysteine ; Animals ; Chemokine CXCL10 ; Fatty Liver ; Hypoxia ; Inflammation ; Male ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley

To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.
Abdominal Pain ; etiology ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Biopsy ; Cough ; epidemiology ; Death ; Deoxycholic Acid ; therapeutic use ; Diagnostic Errors ; Drug Combinations ; Fever ; etiology ; Hepatomegaly ; etiology ; Histoplasma ; Histoplasmosis ; complications ; diagnosis ; mortality ; therapy ; Humans ; Invasive Fungal Infections ; complications ; diagnosis ; therapy ; Itraconazole ; therapeutic use ; Lung ; microbiology ; surgery ; Lung Diseases, Fungal ; diagnosis ; surgery ; therapy ; Pneumonia ; complications ; mortality ; Recurrence ; Retrospective Studies ; Splenomegaly ; etiology ; Treatment Outcome ; Tuberculosis ; complications ; mortality

OBJECTIVE: To explore the effect of nerve growth factor (NGF) on the  differentiation of murine bone marrow-derived dendritic cells (DCs) in vitro.
 METHODS: The bone marrow cells of femur and tibia from healthy C57B -L/6 mice were isolated and divided into 4 groups: a phosphate buffered saline (PBS) group (PBS group), a NGF group, a granulocyte monocyte colony stimulating factor (GM-CSF) plus interleukin 4 (IL-4) group (GM-CSF+IL-4 group), and a GM-CSF plus IL-4 and NGF group (n=6 in each group). The positive rate of CD11c+ and the proportion of CD8a- were compared at the 7th day among the different groups by flow cytometry. The immature DCs were acquired by classic methods with GM-CSF and IL-4. The purified DCs were obtained by magnetic bead positive selection for CD11c+ cells. The immature DCs were divided into 4 groups: a PBS group, a NGF group, a LPS group, and a NGF+LPS group (n=6 in each group), which were incubated with PBS, NGF, LPS and NGF+LPS, respectively. Cytokine levels of IL-6, IL-10 and IL-12 were detected by ELISA after 24 hours..
 RESULTS: 1) the percentage of CD11c+ DCs in the NGF group were more than that in the PBS group, and lower than that in the the GM- CSF+IL-4 group (both P<0.05). There was no difference between the GM-CSF + IL-4 group and the NGF+GM-CSF+IL-4 group (P>0.05). CD8a- DCs were dominant in these four groups; 2) NGF could further up-regulate the LPS-induced cytokine secretion from DCs, such as IL-6, IL-10, and IL-12 (all P<0.05), but NGF alone had no such effect (all P<0.05).
 CONCLUSION NGF can promote the murine bone-marrow cells differentiation into CD11c+ DCs, with CD8a-subset; NGF could enhance LPS-induced cytokine secretion from DCs (IL-6, IL-10 and IL-12).
Animals ; Bone Marrow Cells ; cytology ; drug effects ; Cell Differentiation ; drug effects ; Cells, Cultured ; Dendritic Cells ; cytology ; drug effects ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Interleukin-10 ; analysis ; Interleukin-12 ; analysis ; Interleukin-4 ; pharmacology ; Interleukin-6 ; analysis ; Mice ; Mice, Inbred C57BL ; Nerve Growth Factor ; pharmacology