The management and outcome of cryptococcosis in patients with different immune statuses and treatment protocols: A multicenter real-world study in Jiangsu Province - China.

OBJECTIVE: The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients. METHODS: This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed. RESULTS: 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]. CONCLUSION: The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes.

Clinical Features, Treatment, and Outcome of Psittacosis Pneumonia: A Multicenter Study.

Background: We aimed to describe psittacosis pneumonia and risk factors for developing severe pneumonia in this multicenter clinical study. Methods: We collected the data of psittacosis pneumonia cases diagnosed with metagenomic next-generation sequencing (mNGS) assay from April 2018 to April 2022 in 15 tertiary hospitals in China. Results: A total of 122 patients were enrolled; 50.0% had a definite history of bird exposure. In 81.2% of cases, onset happened in autumn or winter. The common symptoms were fever (99.2%), cough (63.1%), fatigue (52.5%), shortness of breath (50.0%), chills (37.7%), central nervous system symptoms (36.9%), myalgia (29.5%), and gastrointestinal tract symptoms (15.6%). Laboratory tests showed that >70% of cases had elevated C-reactive protein, procalcitonin, erythrocyte sedimentation rate, D-dimer, lactate dehydrogenase, and aspartate aminotransferase, and >50% had hyponatremia and hypoproteinemia. The most common imaging finding was consolidation (71.3%), and 42.6% of cases met the criteria for severe pneumonia. Age >65 years and male sex were the risk factors for severe pneumonia. The effective proportion of patients treated with tetracyclines was higher than that of fluoroquinolones (66/69 [95.7%] vs 18/58 [31.0%]; P < .001), and the median defervescence time was shorter. After medication adjustment when the diagnosis was clarified, 119 of 122 (97.5%) patients were finally cured and the other 3 (2.5%) died. Conclusions: Psittacosis pneumonia has a high rate of severe disease. Proven diagnosis could be rapidly confirmed by mNGS. Tetracycline therapy had a rapid effect and a high cure rate.

Clinical features of psittacosis in 46 Chinese patients.

BACKGROUND: Psittacosis is a relatively uncommon cause of community-acquired pneumonia, often leading to diagnostic difficulty. METHODS: A retrospective study was conducted on the clinical features of psittacosis patients in China. Forty-six cases of Chlamydophila psittaci infection with atypical pneumonia of varying severity in the last two years were described retrospectively. RESULTS: Fever, relative bradycardia, and other systemic upsets were the main clinical presentation. The most common radiographic abnormality was segmental or lobar shadowing or consolidation. The total white cell counts were usually normal or slightly increased. The concentration of creatine kinase, C reactive protein, and lactic dehydrogenase increased, while albumin decreased remarkably. These cases exhibited good recovery after being treated with tetracycline or quinolone antibiotics. CONCLUSION: These features may help differentiate psittacosis from other traditional bacterial pneumonia. However, they do not provide a definitive diagnosis. Psittacosis diagnosis must perform the whole-genome sequencing for Chlamydophila psittaci in respiratory, blood, or sputum specimens. Increased awareness of psittacosis can shorten diagnostic delays and improve patient outcomes.

The Performance of Metagenomic Next-Generation Sequence in the Diagnosis of Suspected Opportunistic Infections in Patients with Acquired Immunodeficiency Syndrome.

Background: For acquired immunodeficiency syndrome (AIDS) patients with suspected opportunistic infections, the rapid and accurate identification of pathogens remains a challenge. Metagenomic next-generation sequencing (mNGS) has emerged as a pan-pathogen assay for infectious diseases diagnosis, but its guiding significance for diagnosis and antimicrobials treatment in AIDS patients with suspected opportunistic infections is still not well established. In this study, we compared the microbiological diagnostic value of mNGS with that of conventional microbiological tests (CMTs) in AIDS patients with suspected opportunistic infections. Methods: From January 2018 to February 2021, a retrospective study was performed at four tertiary teaching hospitals in China and data of 86 AIDS patients with suspected opportunistic infections were collected. The pathogen detection performance of mNGS and CMTs were compared. Results: Positive agreement between mNGS and clinical diagnosis was significantly higher than that of CMTs (65/86 (75.6%) vs 37/86 (43.0%)). In addition, mNGS identified more bacterial (25 vs 2), fungal (5 vs 3), viral (9 vs 2) organisms compared with CMTs. Mixed infection were detected in 34 patients by mNGS combined with CMTs. Viruses (94.1%, 32/34) and fungi (94.1%, 32/34) were commonly seen in the mixed infection cases. mNGS helped identify the pathogen or guide appropriate treatment in 49/86 (57%) patients. Meanwhile, CMTs also contributed in the decision of appropriate treatment in 28 patients. The successful de-escalation or discontinuation of treatment was supported in 37 patients with the help of mNGS. We observed a significant reduction in the number of patients being prescribed foscarnet (52.3% vs 23.26%, p < 0.001), moxifloxacin (34.9% vs 10.5%, p = 0.005), and levofloxacin (32.6% vs 14%, p = 0.001) before and after mNGS. Conclusion: For AIDS patients with suspected opportunistic infections, mNGS can provide early, noninvasive, and rapid microbiological diagnosis. mNGS may lead to a more precise antimicrobial treatment and reduced the unreasonable use of antimicrobials.

Screening rate and influential factors of lung cancer with low-dose computed tomography in Asian population: a systematic review and meta-analysis.

BACKGROUND: There are currently no studies synthesizing the screening rate and influential factors of low-dose computed tomography (LDCT)-screened lung cancer in Asian population. METHODS: A systematic review was conducted, using both English and Chinese language databases on March, 2019. The pooled screening rate and estimated odds ratios (ORs) of influential factors were analyzed using random effects models. Subgroup and meta-regression analyses were also employed to explore the heterogeneity. RESULTS: The pooled LDCT lung cancer screening rate was 1.12% (95% confidence interval (CI): 0.94%, 1.32%), and increased with age. Adenocarcinoma and stage I lung cancer had higher screening rates. Analysis of influential factors in the general population showed that female and elder age (≥50 years) were significantly influencing LDCT lung cancer screening rate (for female, OR = 1.32, 95% CI: 1.15-1.52; for adults ≥ 50 years, OR = 1.94, 95% CI: 1.52-2.49). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the sample size, risk population and source of population. CONCLUSIONS: Unlike European and American populations, female and adults > 50 years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BACKGROUND: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat. METHODS: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression). RESULTS: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015). CONCLUSIONS: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.

Wnt pathway-related three-mRNA clinical outcome signature in bladder urothelial carcinoma: computational biology and experimental analyses.

BACKGROUND: The Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied. METHODS: We obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator-Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan-Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. RESULTS: Thirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells. CONCLUSION: We found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer.

PURPOSE: To identify immune-related co-expressed genes that promote CD8+ T cell infiltration in bladder cancer, and to explore the interactions among relevant genes in the tumor microenvironment. METHOD: We obtained bladder cancer gene matrix and clinical information data from TCGA, GSE32894 and GSE48075. The "estimate" package was used to calculate tumor purity and immune score. The CIBERSORT algorithm was used to assess CD8+ T cell proportions. Weighted gene co-expression network analysis was used to identify the co-expression modules with CD8+ T cell proportions and bladder tumor purity. Subsequently, we performed correlation analysis among angiogenesis factors, angiogenesis inhibitors, immune inflammatory responses, and CD8+ T cell related genes in tumor microenvironment. RESULTS: A CD8+ T cell related co-expression network was identified. Eight co-expressed genes (PSMB8, PSMB9, PSMB10, PSME2, TAP1, IRF1, FBOX6, ETV7) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, and were enriched in the MHC class I tumor antigen presentation process. The proteins level encoded by these genes (PSMB10, PSMB9, PSMB8, TAP1, IRF1, and FBXO6) were lower in the high clinical grade patients, which suggested the clinical phenotype correlation both in mRNA and protein levels. These factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. PD-1 and PD-L1 positively correlated with these genes which suggested PD-1 expression level positively correlated with the biological process composed by these co-expression genes. In the high expression group of these genes, inflammation and immune response were more intense, and the tumor purity was lower, suggesting that these genes were immune protective factors that improved the prognosis in patients with bladder cancer. CONCLUSION: These co-expressed genes promote high levels of infiltration of CD8+ T cells in an immunoproteasome process involved in MHC class I molecules. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.

Three-gene risk model in papillary renal cell carcinoma: a robust likelihood-based survival analysis.

BACKGROUND: Papillary renal cell carcinoma (PRCC) accounts for 15% of all renal cell carcinomas. The molecular mechanisms of renal papillary cell carcinoma remain unclear, and treatments for advanced disease are limited. RESULT: We built the computing model as follows: Risk score = 1.806 * TPX2 - 0.355 * TXNRD2 - 0.805 * SLC6A20. The 3-year AUC of overall survival was 0.917 in the training set (147 PRCC samples) and 0.760 in the test set (142 PRCC samples). Based on the robust model, M2 macrophages showed positive correlation with risk score, while M1 macrophages were the opposite. PRCC patients with low risk score showed higher tumor mutation burden. TPX2 is a risk factor, and co-expression factors were enriched in cell proliferation and cancer-related pathways. Finally, the proliferation and invasion of PRCC cell line were decreased in the TPX2 reduced group, and the differential expression was identified. TPX2 is a potential risk biomarker which involved in cell proliferation in PRCC. CONCLUSION: We conducted a study to develop a three gene model for predicting prognosis in patients with papillary renal cell carcinoma. Our findings may provide candidate biomarkers for prognosis that have important implications for understanding the therapeutic targets of papillary renal cell carcinoma. METHOD: Gene expression matrix and clinical data were obtained from TCGA (The Cancer Genome Atlas), GSE26574, GSE2048, and GSE7023. Prognostic factors were identified using "survival" and "rbsurv" packages, and a risk score was constructed using Multivariate Cox regression analysis. The co-expression networks of the factors in model were constructed using the "WGCNA" package. The co-expression genes of factors were enriched and displayed the biological process. Based on this robust risk model, immune cells infiltration proportions and tumor mutation burdens were compared between risk groups. Subsequently, using the PRCC cell line, the role of TPX2 was determined by Cell proliferation assay, 5-Ethynyl-20-deoxyuridine assay and Transwell assay.

Advice on chemical weapons sample stability and storage provided by the Scientific Advisory Board of the Organisation for the Prohibition of Chemical Weapons to increase investigative capabilities worldwide.

The Scientific Advisory Board (SAB) of the Organisation for the Prohibition of Chemical Weapons (OPCW) has provided advice on the long-term storage and stability of samples collected in the context of chemical weapons investigations. The information they compiled and reviewed is beneficial to all laboratories that carry out analysis of samples related to chemical warfare agents and is described herein. The preparation of this report was undertaken on request from the OPCW Director-General. The main degradation products for chemicals on the Schedules in the Annex on Chemicals of the Chemical Weapons Convention are tabulated. The expertise of the 25 scientists comprising the SAB, a review of the scientific literature on environmental and biomedical sample analysis, and answers to a questionnaire from chemists of nine OPCW Designated Laboratories, were drawn upon to provide the advice. Ten recommendations to ensure the long-term storage and stability of samples collected in relation to the potential use of chemical weapons were provided and are repeated here for the consideration of all laboratories worldwide.

HOXC13 promotes proliferation of lung adenocarcinoma via modulation of CCND1 and CCNE1.

In this study, we confirmed that HOXC13 might be a potential oncogene in lung adenocarcinoma through an analysis of The Cancer Genome Atlas (TCGA) datasets. Further analysis revealed that the expression of HOXC13 was significantly higher in lung adenocarcinoma tissues than in adjacent normal tissues; importantly, its expression correlated with poor clinical characteristics and worse prognosis. In vitro experiments showed that HOXC13 expression generally increased in lung adenocarcinoma cell lines. Moreover, knockdown of HOXC13 inhibited lung adenocarcinoma cell proliferation, and induced G1-phase arrest via downregulation of CCND1 and CCNE1. Conversely, HOXC13 overexpression promoted lung adenocarcinoma cell proliferation, and decreased the percentage of cells in G1-phase via upregulation of CCND1 and CCNE1. We also found that miR-141 downregulated HOXC13, by directly targeting its 3'UTR, and inhibited proliferation of lung adenocarcinoma cells. Taken together, our results suggest that HOXC13, which is directly targeted by miR-141, is highly expressed in lung adenocarcinoma, and promotes proliferation of lung adenocarcinoma by modulating the expression of CCND1 and CCNE1.

Changes in four plasma adipokines before and after sleep in OSAS patients.

OBJECTIVES: This study aimed to investigate whether plasma levels of four adipokines (chemerin, macrophage migratory inhibitory factor [MIF], visceral adipose tissue-derived serine protease inhibitor [vaspin] and chemokine CXCL5) are associated with the presence of obstructive sleep apnea syndrome (OSAS) in patients. METHODS: A total of 58 male patients with OSAS and 16 healthy male subjects were enrolled in this study. RESULTS: Four plasma adipokines (chemerin, MIF, vaspin and chemokine CXCL5) were significantly higher (P < 0.05) in severe OSAS patients than in the control group after polysomnography. Plasma levels of these four adipokines were higher (P < 0.05) after sleep than before sleep. These levels were also associated with anthropometric measurements for BMI, neck circumference, body fat percentage, sleep parameters including the apnea/hypopnea index (AHI) and minimum SaO2 %. Multiple regression analyses showed that BMI, AHI and mean SaO2 % were major factors affecting the four plasma adipokine levels in OSAS patients. CONCLUSIONS: Plasma chemerin, MIF, vaspin and chemokine CXCL5 levels were severely elevated with OSAS, and were also connected with obesity.

Molecular and functional characterization of BAFF from the Yangtze alligator (Alligator sinensis, Alligatoridae).

B-cell activating factor (BAFF) from the TNF family is critical for B-cell survival and maturation. In this study, we identified a Yangtze alligator (Alligator sinensis, Alligatoridae) BAFF cDNA, designated as asBAFF, using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The open reading frame of this cDNA encodes a 287-amino acid protein containing a predicted transmembrane domain and a furin protease cleavage site, similar to mammalian and avian BAFF. The amino acid identity between biologically soluble asBAFF (assBAFF) and csBAFF, hsBAFF, and msBAFF is 94, 76, and 71%, respectively. Real-time quantitative PCR analysis showed that the asBAFF gene is strongly expressed in the spleen. Since BAFF is always expressed as inclusion bodies in bacteria, it is difficult to purify. To enhance the soluble expression of assBAFF in Escherichia coli, we fused the extracellular region of the asBAFF gene to a small ubiquitin-related modifier gene (SUMO). Purified assBAFF was able to promote the survival of splenic lymphocytes and co-stimulate the proliferation of mouse B cells with anti-mouse IgM. These findings suggest that asBAFF plays an important role in the survival and proliferation of Yangtze alligator B cells, and because it is evolutionarily highly conserved, functional cross-reactivity exists between mammalian and Yangtze alligator BAFF.

A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer.

PURPOSE: To assess the therapeutic value of biomarker-guided chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Eighty-five NSCLC patients at stage IIIb or IV were divided into two groups based on the feasibility of biomarker analysis. Group A included patients with biomarker data (n = 41); Group B were patients without biomarker results (n = 44). Tumor samples obtained by fiberoptic bronchoscopy and computerized tomography-guided needle biopsy were analyzed by immunohistochemistry for intratumoral level of excision repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and ß-tubulin III. Chemotherapy regimens in Group A were determined according to the status of molecular signatures, whereas a standard gemcitabine plus cisplatin regimen was used for Group B. Tumor response, patient survival, and adverse effects were monitored for both groups. RESULTS: The overall response rate, defined as complete response plus partial response, was 56.1% for Group A, significantly higher than that in Group B (31.8%; P = 0.024). The median progression-free survival (PFS) time was 5.2 months for Group A, significantly longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of Group A was 65.9%, significantly higher than that of Group B (40.9%; P = 0.021), whereas the median overall survival times were 13.5 versus 12.5 months for Groups A and B, respectively (P = 0.483). The adverse effects in the two groups were essentially the same. CONCLUSIONS: Biomarker-tailored chemotherapy based on ERCC1, RRM1, and ß-tubulin III expression showed significantly increased response rate, median PFS time, and 1-year survival rate in patients with NSCLC.

Different efficacy of EGFR tyrosine kinase inhibitors and prognosis in patients with subtypes of EGFR-mutated advanced non-small cell lung cancer: a meta-analysis.

BACKGROUND: Nearly 85 % of lung-cancer-specific epidermal growth factor receptor (EGFR) sensitive mutations comprise a substitution at position 858 (21L858R) and deletion mutants in exon 19 (19del). The aim of this study was to assess the role of EGFR mutation subtypes in predicting the efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs) and the prognosis of patients with advanced non-small cell lung cancer (NSCLC). METHOD: We systematically searched for eligible articles investigating the association between EGFR mutation subtypes and the efficacy of EGFR TKIs and the prognosis of patients with NSCLC. The summary risk ratio (RR) and mean difference (MD) were calculated using meta-analysis. In addition, we used variance analysis for the progression-free survival data (PFS) and used the rank sum test for the overall survival data. RESULTS: We identified 22 eligible trials involving 1,082 patients. The objective response rate of the 19del mutation group was significantly higher than the 21L858R mutation group (RR 1.23; 95 % CI 1.12-1.36; P < 0.0001). The PFS (MD 3.55; 95 % CI 0.90-6.20; P = 0.009; MD 2.57; 95 % CI 0.51-4.62; P = 0.01) and overall survival (OS) (MD 10.52; 95 % CI 5.10-15.93; P = 0.0001) of the 19del mutation group were significantly longer than the 21L858R mutation group; the same results were observed in the variance analysis and rank sum test. CONCLUSION: The 19del mutation may be a more efficient clinical marker for predicting the response of patients with NSCLC to EGFR TKIs. Furthermore, patients with the 19del mutation have both a longer PFS and OS. The 19del mutation is also the prognostic factor for patients with NSCLC.

[Changes of BDNF expression in hippocampus and serum of rats with artificial chronic obstructive pulmonary disease].

In clinical practice, we have found that cognitive impairment frequently occurs in chronic obstructive pulmonary disease (COPD) patients, but little is known about its pathophysiological mechanism. Given that brain-derived neurotrophic factor (BDNF) is affected by many factors such as smoking, infection, hypoperfusion and hypoxia, the present study was to explore the expression of BDNF in COPD rats. The rat COPD model was established by passive smoking and intratracheal instillation of lipopolysaccharide (LPS). Rats with the same age and gender ratios were divided into 4 groups: the control group (n = 6), the smoking group (n = 6), the LPS group (n = 6) and the smoking + LPS group (n = 6, COPD model). Level of BDNF in serum was measured by ELISA. And the expression of BDNF in the hippocampus was assessed using the immunohistochemistry and image analysis. The results showed that BDNF in the hippocampus and serum significantly increased in the smoking, LPS and smoking + LPS groups, compared to that in the control group. However, the expression of BDNF was less in the smoking + LPS group than that in the smoking or LPS group both in the hippocampus and serum. In conclusion, the expression of BDNF in the hippocampus and serum is highly increased in the COPD group. Smoking and intratracheal instillation of LPS induce the increase of BDNF level in the hippocampus and serum.