Identification of priority pathogens for aetiological diagnosis in adults with community-acquired pneumonia in China: a multicentre prospective study.

BACKGROUND: Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well established based on the detection of both viral and bacterial agents. METHODS: A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated. RESULTS: Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP. CONCLUSIONS: The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.

RAC1B function is essential for breast cancer stem cell maintenance and chemoresistance of breast tumor cells.

Breast cancer stem cells (BCSC) are presumed to be responsible for treatment resistance, tumor recurrence and metastasis of breast tumors. However, development of BCSC-targeting therapies has been held back by their heterogeneity and the lack of BCSC-selective molecular targets. Here, we demonstrate that RAC1B, the only known alternatively spliced variant of the small GTPase RAC1, is expressed in a subset of BCSCs in vivo and its function is required for the maintenance of BCSCs and their chemoresistance to doxorubicin. In human breast cancer cell line MCF7, RAC1B is required for BCSC plasticity and chemoresistance to doxorubicin in vitro and for tumor-initiating abilities in vivo. Unlike Rac1, Rac1b function is dispensable for normal mammary gland development and mammary epithelial stem cell (MaSC) activity. In contrast, loss of Rac1b function in a mouse model of breast cancer hampers the BCSC activity and increases their chemosensitivity to doxorubicin treatment. Collectively, our data suggest that RAC1B is a clinically relevant molecular target for the development of BCSC-targeting therapies that may improve the effectiveness of doxorubicin-mediated chemotherapy.

Inhibiting ERK5 overcomes breast cancer resistance to anti-HER2 therapy by targeting the G1/S cell cycle transition.

Targeting the human epidermal growth factor receptor 2 (HER2) became a landmark in the treatment of HER2-driven breast cancer. Nonetheless, the clinical efficacy of anti-HER2 therapies can be short-lived and a significant proportion of patients ultimately develop metastatic disease and die. One striking consequence of oncogenic activation of HER2 in breast cancer cells is the constitutive activation of the extracellular-regulated protein kinase 5 (ERK5) through its hyperphosphorylation. In this study, we sought to decipher the significance of this unique molecular signature in promoting therapeutic resistance to anti-HER2 agents. We found that a small-molecule inhibitor of ERK5 suppressed the phosphorylation of the retinoblastoma protein (RB) in HER2 positive breast cancer cells. As a result, ERK5 inhibition enhanced the anti-proliferative activity of single-agent anti-HER2 therapy in resistant breast cancer cell lines by causing a G1 cell cycle arrest. Moreover, ERK5 knockdown restored the anti-tumor activity of the anti-HER2 agent lapatinib in human breast cancer xenografts. Taken together, these findings support the therapeutic potential of ERK5 inhibitors to improve the clinical benefit that patients receive from targeted HER2 therapies.

Comparative Transcriptome Analysis Unravels the Response Mechanisms of Fusarium oxysporum f.sp. cubense to a Biocontrol Agent, Pseudomonas aeruginosa Gxun-2.

Banana Fusarium wilt, which is caused by Fusarium oxysporum f.sp. cubense Tropical Race 4 (FOC TR4), is one of the most serious fungal diseases in the banana-producing regions in east Asia. Pseudomonas aeruginosa Gxun-2 could significantly inhibit the growth of FOC TR4. Strain Gxun-2 strongly inhibited the mycelial growth of FOC TR4 on dual culture plates and caused hyphal wrinkles, ruptures, and deformities on in vitro cultures. Banana seedlings under pot experiment treatment with Gxun-2 in a greenhouse resulted in an 84.21% reduction in the disease. Comparative transcriptome analysis was applied to reveal the response and resistance of FOC TR4 to Gxun-2 stress. The RNA-seq analysis of FOC TR4 during dual-culture with P. aeruginosa Gxun-2 revealed 3075 differentially expressed genes (DEGs) compared with the control. Among the genes, 1158 genes were up-regulated, and 1917 genes were down-regulated. Further analysis of gene function and the pathway of DEGs revealed that genes related to the cell membrane, cell wall formation, peroxidase, ABC transporter, and autophagy were up-regulated, while down-regulated DEGs were enriched in the sphingolipid metabolism and chitinase. These results indicated that FOC TR4 upregulates a large number of genes in order to maintain cell functions. The results of qRT-PCR conducted on a subset of 13 genes were consistent with the results of RNA-seq data. Thus, this study serves as a valuable resource regarding the mechanisms of fungal pathogen resistance to biocontrol agents.

Selection of the surgical approach for patients with cStage IA lung squamous cell carcinoma: A population-based propensity score matching analysis.

Background: This study aimed to conduct a comparative analysis of the survival rates after segmentectomy, wedge resection, or lobectomy in patients with cStage IA lung squamous cell carcinoma (SCC). Methods: We enrolled 4,316 patients who had cStage IA lung SCC from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards model was conducted to recognize the potential risk factors for overall survival (OS) and lung cancer-specific survival (LCSS). To eliminate potential biases of included patients, the propensity score matching (PSM) method was used. OS and LCSS rates were compared among three groups stratified according to tumor size. Results: Kaplan-Meier analyses revealed no statistical differences in the rates of OS and LCSS between wedge resection (WR) and segmentectomy (SG) groups for patients who had cStage IA cancers. In patients with tumors ≤ 1 cm, LCSS favored lobectomy (Lob) compared to segmentectomy (SG), but a similar survival rate was obtained for wedge resection (WR) and lobectomy (Lob). For patients with tumors sized 1.1 to 2 cm, lobectomy had improved OS and LCSS rates compared to the segmentectomy or wedge resection groups, with the exception of a similar OS rate for lobectomy and segmentectomy. For tumors sized 2.1 to 3 cm, lobectomy had a higher rate of OS or LCSS than wedge resection or segmentectomy, except that lobectomy conferred a similar LCSS rate compared to segmentectomy. Multivariable analyses showed that patients aged ≥75 and tumor sizes of >2 to ≤3 cm were potential risk factors for OS and LCSS, while lobectomy and first malignant primary indicator were considered protective factors. The Cox proportional analysis also confirmed that male patients aged ≥65 to <75 were independent prognostic factors that are indicative of a worse OS rate. Conclusions: The tumor size can influence the surgical procedure recommended for individuals with cStage IA lung SCC. For patients with tumors ≤1 cm, lobectomy is the recommended approach, and wedge resection or segmentectomy might be an alternative for those who cannot tolerate lobectomy if adequate surgical margin is achievable and enough nodes are sampled. For tumors >1 to ≤3 cm, lobectomy showed better survival outcomes than sublobar resection. Our findings require further validation by randomized controlled trial (RCT) or other evidence.

Mussel-inspired bioactive 3D-printable poly(styrene-butadiene-styrene) and the in vitro assessment of its potential as cranioplasty implants.

Challenges in cranial defect reconstruction after craniotomy arise from insufficient osteogenesis and biofilm infection, which requires novel biomaterials. Herein, we propose a mussel-inspired bioactive poly(styrene-butadiene-styrene) (SBS) as a promising cranioplasty material. The catechol-modified quaternized chitosan (QCSC) was employed in the bio-inert surface of 3D-printed SBS to provide the contact-killing ability against bacterial biofilms. The polydopamine-decorated zeolitic imidazolate framework-8 (pZIF-8) and polydopamine hybrid hydroxyapatite (pHA) were further modified on the surface to further enhance the antibacterial property and osteogenesis activity, effectively killing bacteria by no less than two orders of magnitude and significantly facilitating osteogenic gene expression and mineralization. Due to the lack of research using SBS as a cranioplasty material, we believe that the modified SBS materials developed in this study and the in vitro assessment may be beneficial for developing novel cranioplasty implants.

Metagenomic Approaches Reveal Strain Profiling and Genotyping of Klebsiella pneumoniae from Hospitalized Patients in China.

Klebsiella pneumoniae is a leading cause of highly drug-resistant infections in hospitals worldwide. Strain-level bacterial identification on the genetic determinants of multidrug resistance and high pathogenicity is critical for the surveillance and treatment of this clinically relevant pathogen. In this study, metagenomic next-generation sequencing was performed for specimens collected from August 2020 to May 2021 in Ruijin Hospital, Ningbo Women and Children's Hospital, and the Second Affiliated Hospital of Harbin Medical University. Genome biology of K. pneumoniae prevalent in China was characterized based on metagenomic data. Thirty K. pneumoniae strains derived from 14 sequence types were identified by multilocus sequence typing. The hypervirulent ST11 K. pneumoniae strains carrying the KL64 capsular locus were the most prevalent in the hospital population. The phylogenomic analyses revealed that the metagenome-reconstructed strains and public isolate genomes belonging to the same STs were closely related in the phylogenetic tree. Furthermore, the pangenome structure of the detected K. pneumoniae strains was analyzed, particularly focusing on the distribution of antimicrobial resistance genes and virulence genes across the strains. The genes encoding carbapenemases and extended-spectrum beta-lactamases were frequently detected in the strains of ST11 and ST15. The highest numbers of virulence genes were identified in the well-known hypervirulent strains affiliated to ST23 bearing the K1 capsule. In comparison to traditional cultivation and identification, strain-level metagenomics is advantageous to understand the mechanisms underlying resistance and virulence of K. pneumoniae directly from clinical specimens. Our findings should provide novel clues for future research into culture-independent metagenomic surveillance for bacterial pathogens. IMPORTANCE Routine culture and PCR-based molecular testing in the clinical microbiology laboratory are unable to recognize pathogens at the strain level and to detect strain-specific genetic determinants involved in virulence and resistance. To address this issue, we explored the strain-level profiling of K. pneumoniae prevalent in China based on metagenome-sequenced patient materials. Genome biology of the targeted bacterium can be well characterized through decoding sequence signatures and functional gene profiles at the single-strain resolution. The in-depth metagenomic analysis on strain profiling presented here shall provide a promising perspective for culture-free pathogen surveillance and molecular epidemiology of nosocomial infections.

CLEC12B suppresses lung cancer progression by inducing SHP-1 expression and inactivating the PI3K/AKT signaling pathway.

Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B, a C-type lectin-like receptor, is low-expressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo, CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B over-expression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumor-suppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway.

The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion.

There is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior.

Characterizing heterogeneity of non-small cell lung tumour microenvironment to identify signature prognostic genes.

Growing evidence has highlighted the immune response as an important feature of carcinogenesis and therapeutic efficacy in non-small cell lung cancer (NSCLC). This study focused on the characterization of immune infiltration profiling in patients with NSCLC and its correlation with survival outcome. All TCGA samples were divided into three heterogeneous clusters based on immune cell profiles: cluster 1 ('low infiltration' cluster), cluster 2 ('heterogeneous infiltration' cluster) and cluster 3 ('high infiltration' cluster). The immune cells were responsible for a significantly favourable prognosis for the 'high infiltration' community. Cluster 1 had the lowest cytotoxic activity, tumour-infiltrating lymphocytes and interferon-gamma (IFN-γ), as well as immune checkpoint molecules expressions. In addition, MHC-I and immune co-stimulator were also found to have lower cluster 1 expressions, indicating a possible immune escape mechanism. A total of 43 differentially expressed genes (DEGs) that overlapped among the groups were determined based on three clusters. Finally, based on a univariate Cox regression model, prognostic immune-related genes were identified and combined to construct a risk score model able to predict overall survival (OS) rates in the validation datasets.

Bartter syndrome with long-term follow-up: a case report.

Bartter syndrome is a rare inherited disease caused by CLCNKB mutation, which results in inactivation of the chloride channel Kb protein. Bartter syndrome is characterized by extreme hypokalemia, hypochloremia, metabolic alkalosis, hyperrenin-induced angiotensinemia, hyperaldosteronemia, and normal blood pressure. We herein report a case of Bartter syndrome that manifested as vomiting, hypokalemia, metabolic alkalosis, normal blood pressure, and significant hyperrenin-induced angiotensinemia. The patient, a 5-month-old girl, carried two known heterozygous pathogenic mutations: c.88C > T (p.Arg30*), which she had inherited from her father, and c.1313G > A (p.Arg438His), which she had inherited from her mother. Treatment with indomethacin, a nonsteroidal anti-inflammatory drug, led to rapid improvement of the hypokalemia, and treatment was continued for 14 years. The indomethacin also induced a sustainable reduction in the hypokalemia and metabolic alkalosis.

LncRNA LINC00520 Predicts Poor Prognosis and Promotes Progression of Lung Cancer by Inhibiting MiR-3175 Expression.

PURPOSE: The aim of this study was to study the roles and potential mechanism of LINC00520 in the progression of lung cancer. METHODS: The expression of LINC00520 and miR-3175 in lung cancer tissues and cells was detected by qRT-PCR. The relationship between LINC00520 level and disease stage was also calculated. Kaplan-Meier survival curve was drawn to observe the survival difference between high and low expression patients. Lipofectamine 2000 was used to transfect siLINC00520, miR-3175 inhibitor and their controls in lung cancer cells. CCK8 and colony formation assay were processed for cell proliferation. Transwell assay was undertaken for migration and invasion of lung cancer cells. MiRDB predicts the combination of LINC00520 and miR-3175. Luciferase and RNA pulldown assay were applied to verify the binding site. Correlation analysis of miR-3175 and LINC00520 expression in lung cancer tissues was shown. RESULTS: LINC00520 was highly expressed in lung cancer tissues and cells. Patients at III+IV stage were always with higher LINC00520 level than patients at I+II stage. Patients with high expression of lncRNA LINC00520 have short survival time (hazard ratio=1.7). Knockdown of LINC00520 inhibited proliferation, invasion and migration of lung cancer cells. LINC00520 targeted and negatively regulated miR-3175 (r=-0.528; P<0.001). MiR-3175 inhibitor rescued the effect of si-LINC00520 on lung cancer progression. CONCLUSION: LncRNA LINC00520 could predict poor prognosis and promote progression of lung cancer by inhibiting miR-3175 expression.

Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients.

The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.

MiR-148b suppressed non-small cell lung cancer progression via inhibiting ALCAM through the NF-κB signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. MiRNAs are recognized as important molecules in cancer biology. The aim of the study was to identify a novel biomarker miR-148b and its mechanism in the modulation of NSCLC progression. METHODS: The expressional level of miR-148b was analyzed by RT-PCR. The effect of miR-4317 on proliferation was evaluated through 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2Htetrazolium bromide (MTT) assay. The effect of miR-148b on the metastasis of NSCLC was detected through transwell assays. The verification of the target of miR-148b was assessed by TargetScan and dual-luciferase reporter assay. The related proteins in this study were analyzed by western blot. RESULTS: Our findings confirmed that miR-148b was decreased in NSCLC and NSCLC patients with lower expression exhibited poorer overall survival (OS). Increasing miR-148b significantly repressed proliferation, invasion and migration. More importantly, activated leukocyte cell adhesion molecule (ALCAM) was determined as the direct target of miR-148b, and reintroduction of ALCAM attenuated miR-148b effect on the progress of NSCLC. In addition, NF-κB signaling pathway was modulated by miR-148b/ALCAM axis. CONCLUSIONS: Our results indicated that miR-148b is able to suppress NSCLC growth and metastasis via targeting ALCAM through the NF-κB pathway. These findings provided new evidence that miR-148b serves as a potential biomarker and novel target for NSCLC treatment.

Dual targeting of survivin and X-linked inhibitor of apoptosis protein suppresses the growth and promotes the apoptosis of gastric cancer HGC-27 cells.

Gastric cancer can be a fatal tumor and therefore represents one of the primary challenges in modern oncology. Survivin and X-linked inhibitor of apoptosis protein (XIAP) are members of the IAP family, which exerts a strong inhibitory effect on cellular apoptosis. In previous studies, the expression levels of survivin and XIAP have been demonstrated to influence the prognosis of patients with gastric cancer; therefore, the present study investigated the effect of silencing survivin and XIAP on the biological activity of the gastric cancer HGC-27 cell line. It was demonstrated that the expression levels of survivin and XIAP were significantly increased in gastric cancer tissues, compared with the adjacent non-tumor tissues. Furthermore, it was observed that the expression levels of survivin and XIAP were similarly elevated in gastric cancer HGC-27 cells, compared with normal gastric epithelial GES-1cells. Furthermore, small interfering RNA-mediated surviving- or XIAP-knockdown, in addition to the dual knockdown of survivin and XIAP, inhibited the proliferation and promoted the apoptosis of HGC-27 cells. Simultaneous inhibition of XIAP and survivin expression was more effective, compared with inhibition of XIAP or survivin alone. These results indicated that the dual knockdown of survivin and XIAP may be an effective strategy for treating gastric cancer in the future.

K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O induces apoptosis in human lung cancer A549 cells.

Lung cancer is the leading cause of cancer-associated mortality worldwide. The present study investigated the effects of K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O (FNdPW), a chemically synthesized polyoxometalate that contains rare earth elements, on lung cancer growth, and explored the mechanism underlying its actions. The effects of FNdPW on the cell viability and apoptosis of human lung cancer A549 cells were measured using MTT assay, acridine orange/ethidium bromide staining and electron microscopy. The expression of apoptosis-related proteins, including B-cell lymphoma (Bcl)-2-associated death promoter (Bad), phosphorylated (p)-Bad, X-linked inhibitor of apoptosis (XIAP), apoptosis-inducing factor (AIF), Bcl-2-associated X protein (Bax) and Bcl-2, was determined by western blotting. Caspase-3 activity was measured using a caspase-3 activity kit. After 72 h of incubation, FNdPW reduced cell viability and induced apoptosis in A549 cells in a concentration- and time-dependent manner. FNdPW upregulated the pro-apoptotic Bad and Bax proteins, and downregulated the anti-apoptotic p-Bad, Bcl-2 and XIAP proteins. Furthermore, FNdPW also enhanced caspase-3 activity and increased the protein level of AIF in A549 cells, which was independent of the caspase-3 pathway. These events were associated with the regulation exerted by FNdPW on multiple targets involved in A549 cell proliferation. Therefore, FNdPW may be a novel drug for the treatment of lung cancer.

Identifying candidate agents for lung adenocarcinoma by walking the human interactome.

Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD) by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein-protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin). Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD.

[Analysis of molecular subtypes and microflora structure of Neisseria meningitidis strains isolated in Jiangxi province].

OBJECTIVE: To study the molecular subtypes and microflora structure of Neisseria meningitidis (Nm) strains isolated in Jiangxi province. METHODS: A total of 123 Nm strains separately isolated from patients, close contacts and health people in 1976-1987 and 2005-2008 were investigated by multilocus sequence typing (MLST) and PorA subtyping, to test the characteristics of gene Nm and sequence porA. Minimum spanning tree was constructed by using BioNumerics software based on data of MLST; and the microflora structure was then analyzed. RESULTS: The serogroups of 67 Nm strains isolated in 1976-1987 included group A (43 strains), group B (18 strains), group C (1 strains) and group W135 (5 strains); while the serogroups of 56 Nm strains isolated in 2005-2008 included group A (3 strains), group B (7 strains), group C (45 strains) and 1 ungrouped strain. The total 123 Nm strains could be divided into 40 MLST types; while the 46 strains in group A could be divided into 14 MLST types, 29 out of which belonged to ST-3 type, accounting for 63.0% (29/46) as the dominant type. All of the 29 strains were isolated between 1976 and 1987, while 14 strains were isolated from patients, 9 were from close contacts and 6 were from health people. The 46 strains in group C could be divided into 5 MLST types, 41 out of which belonged to ST-4821 type, accounting for 89.1% (41/46). All of the strains were isolated between 2005 and 2008, 6 strains were isolated from patients, 6 were from close contacts and 29 were from health people. The porA gene of the total 123 Nm strains were classified to 32 different types, including 24 different VR1 types and 22 different VR2 types. The dominant PorA type of the prevalent strain (ST-3 type, group A) between 1976 and 1987 was P1.7-1, 10, accounting for 39.1% (18/46) of the strains in group A; while the 18 strains were isolated from 11 patients, 4 close contacts and 3 health people. The dominant PorA type of the prevalent strain (ST-4821 type, group C) between 2005 and 2008 was P1.20, 9, accounting for 46.3% (19/41) of the ST-4821 strains in group C; while the 19 strains were isolated from 1 close contacts and 18 health people. P1.7-2, 14 dominated since 2006, including 22 strains, accounting for 53.7% (22/41) of the ST-4821 strains in group C, isolated from 6 patients, 5 close contacts and 11 health people. There were no dominant PorA type found in group B and all the 5 strains in group W135 belonged to ST-174 and the PorA type was P1.21, 16, isolating from 3 close contacts and 2 health people between 1979 and 1980. CONCLUSION: Nm isolated in Jiangxi province showed significant gene polymorphism, as well as predominant lineages existing. In different periods, the prevalent lineages varied a lot, as translating from serogroup A: ST-3:P1.7-1, 10 to serogroup C: ST-4821:P1.7-2, 14 nowadays.

Antiviral role of Toll-like receptors and cytokines against the new 2009 H1N1 virus infection.

People are generally susceptible to the 2009 new mutate of H1N1 influenza due to lack of appropriate immunity. Influenza H1N1 2009 infection triggers a massive inflammatory response that contributes to fever, lung impairment or other tissue damage, eventually leading to death. Infection with pathogenic influenza virus H1N1 induces severe pulmonary immune pathology. To date, more than 10,000 cases worldwide have died of the disease. It still has strong infectious ability although the mortality of influenza isn't currently high. Therefore, to explore the pathogenesis of H1N1 influenza can help with the disease prevention, diagnosis and provide a theoretical basis and the new ideas of treatment. Laboratory confirmed cases of pandemic influenza H1N1 2009 were enrolled to collect general information on pre-clinical, clinical and laboratory data for analysis. Blood samples were obtained from patients with H1N1, healthy volunteers and patients with bacterial pneumonia. Serum were separated and collected. RT-PCR and ELISA methods were applied to detect the different expression of TLRs and cytokines. The young, pregnant and postpartum women and infant are highly susceptible to influenza H1N1 2009 infection; degree of susceptibility is not associated with BMI. Biochemical changes can be seen in the patients with influenza H1N1 2009 infection: ALT, AST, CK, LDH increased in varying degrees. TLR2, TLR3, TLR9 expression increased in the patients with influenza H1N1 2009 infection; no obvious changes of TLR4, TLR7, TLR8 can be detected. In pregnant and postpartum women group, only TLR9 expression increased. The expression of IL-2, IL-6, IFN-γ, TNF-α in the patients with influenza H1N1 2009 infection was significantly increased; while IL-10 expression decreased and IL-4 expression did not change. H1N1 influenza-infected pregnant and postpartum women group, only IL-2 and TNF-α expression expression increased, other cytokines decreased or didn't change. TLR2, TLR3, TLR9 are the major members of TLR family in the recognition of the novel H1N1 virus to start the innate immune response and adaptive immune responses. TLR9 may be the key receptor among pattern recognized receptors to recognize and bind to H1N1 virus. Cellular immune responses induced by Th1 may participate in modulating the influenza H1N1 2009.