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Objective To demonstrate the clinical characteristics and prognosis of invasive pulmonary aspergillosis (IPA) in respiratory intensive care unit (ICU), for early diagnosis and treatment. Methods The clinical features, treatment and outcome of 17 patients diagnosed as IPA in RICU from May 2015 to April 2018 were analyzed retrospectively. Results The basic diseases of 17 patients were mostly chronic respiratory diseases (14 cases, while 11 cases were chronic obstructive pulmonary disease). One case was proven by IPA criteria, 13 cases were probable and 3 cases were possible. All patients were treated with broad-spectrum antibiotics during hospitalization, and 6 patients were treated with glucocorticoids (oral/intravenous) within 3 weeks of admission and during hospitalization. The main clinical symptoms included cough sputum, dyspnea and fever, among which 4 cases had hemoptysis. Infiltrates were seen in 8 cases, multiple nodules with cavitary lesions in 4 cases, multiple small nodules along the bronchi in 2 cases, and left upper lobe consolidation in the proven case. Sixteen patients were treated with voriconazole alone or in combination with caspofungin. Fourteen patients were tested for voriconazole serum concentration, while 4 were in normal range, 10 were elevated (2 cases were significantly elevated, ＞10 μg/L). Serum concentration of bilirubin did not increase significantly in all paitents after treatment. Serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 4 cases with elevated serum concentration of voriconazole and 2 cases with normal serum concentration of voriconazole. Patients with elevated voriconazole concentration did not show significant difference in prognosis compared with those with normal concentration. Eight cases were improved and discharged and 9 gave up and died due to the worsening of the disease. Eight patients received mechanical ventilation (6 cases were invasive and 2 cases were non-invasive), 7 of them eventually gave up treatment and died. Conclusions The clinical features of chronic respiratory diseases with IPA are atypical, however, the patient is critically ill with high mortality. Elevated serum concentration of voriconazole might be more common in severe patients. For those who have a history of systemic application of glucocorticoids, clinical symptoms with hemoptysis, short of breath, radiology with infiltrates, nodular and/or with cavity, and with no response to antibiotics, clinicians should actively seeking evidence of IPA, for early diagnosis, standardized treatment, and improve the prognosis of patients with chronic respiratory diseases complicated with IPA.
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OBJECTIVE: To explore the relationship of formaldehyde exposure, genome-wide DNA methylation, and prevalence of childhood acute lymphocytic leukemia( cALL).METHODS: A case-control study was conducted.Fifty-nine newly diagnosed cALL patients were selected as case group,and 54 orthopedic patients were included in control group.Enzyme-linked immunosorbent assay was used to measure the level of formaldehyde-human serum albumin( FA-HSA) and immunofluorescence method was used to examine the genome-wide DNA methylation level in whole blood.RESULTS: The level of FA-HAS in the blood of the case group was higher than that in the control group( median: 59.61 vs 35.06 fg/L,P < 0.01).Genomic-wide DNA methylation level in the case group was lower than that in the controls[( 2.86 ± 0.31) vs( 3.00 ± 0.28),P < 0.05].Formaldehyde exposure level was not associated with genomic-wide DNA methylation( Spearman correlation coefficient =-0.18,P > 0.05).High FA-HAS level and hypomethylation of genomic-wide DNA were risk factors for cALL onset( P < 0.05).CONCLUSION: Patients with high level of formaldehyde exposure and hypomethylation of genomic-wide DNA have a high risk of cALL.
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Objective To investigate the characteristics of distribution and expression profiles of plasma miRNA in childhood acute lymphocytic leukemia (cALL) patients;the association between cALL incidence risk and plasma miRNA levels;the feasibility of plasma miRNA serving as cALL diagnostic biomarker.Methods A total of 111 pairs of newly diagnosed cALL patients and patients with fractures were collected from Shenzhen Children's Hospital,China,between January 2015 and November 2016.Age and sex of the cases and controls were 1 ∶ 1 matched and LNATM miRNA microarray was performed using 4 pairs of cALL and controls selected from the sample population.The expression level of miRNA was validated by real time quantitative PCR.Conditional logistic regression analysis was applied to evaluate the association between miRNA expression levels and the incidence risk of cALL.The receiver operating characteristic curve (ROC) and reclassification analysis were conducted to assess the feasibility of miRNAs serving as biomarkers for cALL.Results A total of 204 differentially expressed miRNA were screened out and let-7f-5p,miR-5100,miR-25-3p and miR-3654 were selected for validation identified according to the inclusion criteria.The expression levels of let-7f-5p,miR-5100 and miR-25-3p in the cALL patients were significantly lower than those of the controls (P＜0.01).After adjusting for confounding factors,3 miRNAs remained significantly associated with the risk of cALL (OR and 95％CI were 0.84 (0.76-0.92),0.81 (0.73-0.90)and 0.81 (0.74-0.89),respectively.Results from both the ROC analysis and reclassification analysis showed that introduction of one or more miRNA to traditional risk factors improved the area under the curve (P＜0.05) and provided additional values to diagnosis (P＜0.01).Conclusion The expression levels of let-7f-5p,miR-5100 and miR-25-3p were significantly associated with the incidence rate of cALL,and these miRNAs might serve as promising biomarkers for cALL.
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Immune checkpoint inhibitors have become an important alternative for advanced non-small cell lung cancer (NSCLC) patients to surgery, chemotherapy, radiotherapy and targeted therapy. Monoclonal antibodies directed against immune checkpoint have shown better results in the application of first- or second-line treatment of NSCLC and for both squamous and non-squamous cell carcinoma patients, especially for those with positive PD-L1 tumor cells. Some comments will be made in present paper about the efficacy, biomarker, combined therapy and the resistant mechanism of immune checkpoint inhibitors.
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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become the preferred treatment option for advanced non-small-cell lung cancer (NSCLC) patients with activating mutations in epidermal growth factor receptor (EGFR) according to major practice guidelines. Gefitinib, elortinib and icotinib formed the cornerstone of first-line EGFR-TKIs in the clinical practice in our country. Now, with the continuously emerging of new types of EGFR-TKIs and ever-increasing publication of clinical trial results on afatinib, AZD9291 and other TKIs, we have more first-line choices for patients with EGFR mutations. Meanwhile, the development of gene detection technology is facilitating investigators to get insights on the molecular biological behavior of NSCLC and to elucidate the mechanism of drug resistance. This review will focus on precision first-line therapy for advanced NSCLC patients harboring EGFR mutation.
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Objective To investigate the characteristics of distribution and expression profiles of plasma miRNA in childhood acute lymphocytic leukemia (cALL) patients;the association between cALL incidence risk and plasma miRNA levels;the feasibility of plasma miRNA serving as cALL diagnostic biomarker.Methods A total of 111 pairs of newly diagnosed cALL patients and patients with fractures were collected from Shenzhen Children's Hospital,China,between January 2015 and November 2016.Age and sex of the cases and controls were 1 ∶ 1 matched and LNATM miRNA microarray was performed using 4 pairs of cALL and controls selected from the sample population.The expression level of miRNA was validated by real time quantitative PCR.Conditional logistic regression analysis was applied to evaluate the association between miRNA expression levels and the incidence risk of cALL.The receiver operating characteristic curve (ROC) and reclassification analysis were conducted to assess the feasibility of miRNAs serving as biomarkers for cALL.Results A total of 204 differentially expressed miRNA were screened out and let-7f-5p,miR-5100,miR-25-3p and miR-3654 were selected for validation identified according to the inclusion criteria.The expression levels of let-7f-5p,miR-5100 and miR-25-3p in the cALL patients were significantly lower than those of the controls (P＜0.01).After adjusting for confounding factors,3 miRNAs remained significantly associated with the risk of cALL (OR and 95％CI were 0.84 (0.76-0.92),0.81 (0.73-0.90)and 0.81 (0.74-0.89),respectively.Results from both the ROC analysis and reclassification analysis showed that introduction of one or more miRNA to traditional risk factors improved the area under the curve (P＜0.05) and provided additional values to diagnosis (P＜0.01).Conclusion The expression levels of let-7f-5p,miR-5100 and miR-25-3p were significantly associated with the incidence rate of cALL,and these miRNAs might serve as promising biomarkers for cALL.