Transforming Growth Factor ß Signaling Promotes HIV-1 Infection in Activated and Resting Memory CD4+ T Cells.

Understanding the facilitator of HIV-1 infection and subsequent latency establishment may aid the discovery of potential therapeutic targets. Here, we report the elevation of plasma transforming growth factor ß (TGF-ß) during acute HIV-1 infection among men who have sex with men (MSM). Using a serum-free in vitro system, we further delineated the role of TGF-ß signaling in mediating HIV-1 infection of activated and resting memory CD4+ T cells. TGF-ß could upregulate both the frequency and expression of the HIV-1 coreceptor CCR5, thereby augmenting CCR5-tropic viral infection of resting and activated memory CD4+ T cells via Smad3 activation. The production of live HIV-1JR-FL upon infection and reactivation was increased in TGF-ß-treated resting memory CD4+ T cells without increasing CD4 expression or inducing T cell activation. The expression of CCR7, a central memory T cell marker that serves as a chemokine receptor to facilitate T cell trafficking into lymphoid organs, was also elevated on TGF-ß-treated resting and activated memory CD4+ T cells. Moreover, the expression of CXCR3, a chemokine receptor recently reported to facilitate CCR5-tropic HIV-1 infection, was increased on resting and activated memory CD4+ T cells upon TGF-ß treatment. These findings were coherent with the observation that ex vivo CCR5 and CXCR3 expression on total resting and resting memory CD4+ T cells in combination antiretroviral therapy (cART)-naive and cART-treated patients were higher than in healthy individuals. Overall, the study demonstrated that TGF-ß upregulation induced by acute HIV-1 infection might promote latency reservoir establishment by increasing infected resting memory CD4+ T cells and lymphoid organ homing of infected central memory CD4+ T cells. Therefore, TGF-ß blockade may serve as a potential supplementary regimen for HIV-1 functional cure by reducing viral latency. IMPORTANCE Incomplete eradication of HIV-1 latency reservoirs remains the major hurdle in achieving a complete HIV/AIDS cure. Dissecting the facilitator of latency reservoir establishment may aid the discovery of druggable targets for HIV-1 cure. This study showed that the T cell immunomodulatory cytokine TGF-ß was upregulated during the acute phase of infection. Using an in vitro serum-free system, we specifically delineated that TGF-ß promoted HIV-1 infection of both resting and activated memory CD4+ T cells via the induction of host CCR5 coreceptor. Moreover, TGF-ß-upregulated CCR7 or CXCR3 might promote HIV-1 latent infection by facilitating lymphoid homing or IP-10-mediated viral entry and DNA integration, respectively. Infected resting and central memory CD4+ T cells are important latency reservoirs. Increased infection of these cells mediated by TGF-ß will promote latency reservoir establishment during early infection. This study, therefore, highlighted the potential use of TGF-ß blockade as a supplementary regimen with cART in acute patients to reduce viral latency.

Racial Disparities in MiT Family Translocation Renal Cell Carcinoma.

Racial disparities have been documented in the biology and outcome of certain renal cell carcinomas (RCCs) among Black patients. However, little is known about racial differences in MiT family translocation RCC (TRCC). To investigate this issue, we performed a case-control study using data from The Cancer Genome Atlas (TCGA) and the Chinese OrigiMed2020 cohort. A total of 676 patients with RCC (14 Asian, 113 Black, and 525 White) were identified in TCGA, and TRCC was defined as RCC with TFE3/TFEB translocation or TFEB amplification, leading to 21 patients with TRCC (2 Asian, 8 Black, 10 White, and 1 unknown). Asian (2 of 14 [14.3%] vs 10 of 525 [1.9%]; P = .036) and Black (8 of 113 [7.1%] vs 1.9%; P = .007) patients with RCC showed significantly higher prevalence of TRCC compared with White patients with RCC. The overall mortality rate of TRCC was slightly higher in Asian and Black patients compared with White patients (HR: 6.05, P = .069). OrigiMed2020 Chinese patients with RCC had a significantly higher proportion of TRCC with TFE3 fusions than TCGA White patients with RCC (13 of 250 [5.2%] vs 7 of 525 [1.3%]; P = .003). Black patients with TRCC were more likely to exhibit the proliferative subtype than White patients (6 of 8 [75%] vs 2 of 9 [22.2%]; P = .057) for those who had RNA-seq profiles. We present evidence of higher prevalence of TRCC in Asian and Black patients with RCC compared with White patients and show that these tumors in Asian and Black patients have distinct transcriptional signatures and are associated with poor outcomes.

Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV-infected patients on antiretroviral therapy.

T follicular helper (Tfh) cells and their interactions with B cells within the germinal center play extensive roles in human immunodeficiency virus (HIV) pathology. However, their association with immune reconstitution during antiretroviral therapy (ART) is still unclear. The aim of this study was to determine the impact of Tfh and memory B cell function on T helper cell recovery in patients with acute or chronic HIV infection. A total of 100 HIV-infected individuals were enrolled in our study, classified into acute and chronic HIV infection groups (60 and 40, respectively), and subsequently classified into immunological responder (IR) and immunological nonresponder (INR) subgroups according to immune recovery outcomes after 96 weeks of ART. Liquid chromatography-mass spectrometry was used to quantify the temporal regulation patterns of B and CD4+ T-cell profiles among patients, and flow cytometry was used to investigate certain subsets of B and T cells. Here we showed that the prevalence of Tfh cells in the T helper cell population correlated negatively with CD4+ T-cell recovery. The proportion of CXCR3-  Tfh cells in patients with acute or chronic infection was associated with CD4+ T-cell count recovery, and the proportion of CD21+ memory B cells at baseline was significantly higher in those with improved immune recovery outcomes. Universal proteomic dysregulation of B and CD4+ T cells at baseline was detected in patients with acute infected and poor CD4+ T-cell recovery. Proteomics analysis revealed distinct temporal regulation profiles of both T helper cells and B cells between IRs and INRs among patients with acute infection. Our results suggest that the functions of memory B cells in INRs are dysregulated at the early stage of ART, possibly through disruption of Tfh cell function. The frequency and function of Tfh cells and their subsets are potential predictors of poor immune recovery.

Natural Sunlight Photocatalytic Synthesis of Benzoxazole-Bridged Covalent Organic Framework for Photocatalysis.

Although natural sunlight-mediated photocatalysis is a clean, efficient, and green approach to access organic products, its application in the synthesis of covalent organic frameworks (COFs), however, is still unprecedented. Herein, we first report the sunlight photocatalytic synthesis of COF under ambient conditions. Furthermore, this "window ledge" reaction generated benzoxazole-linked COF is stable and can be applied as a reusable photocatalyst to highly promote visible-light-driven aerobic oxidation of sulfides to sulfoxides. These results not only enrich the COF synthetic methodology but also open a new route to access COFs in a green and sustainable way.

CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia.

The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).

MOVICS: an R package for multi-omics integration and visualization in cancer subtyping.

SUMMARY: Stratification of cancer patients into distinct molecular subgroups based on multi-omics data is an important issue in the context of precision medicine. Here, we present MOVICS, an R package for multi-omics integration and visualization in cancer subtyping. MOVICS provides a unified interface for 10 state-of-the-art multi-omics integrative clustering algorithms, and incorporates the most commonly used downstream analyses in cancer subtyping researches, including characterization and comparison of identified subtypes from multiple perspectives, and verification of subtypes in external cohort using two model-free approaches for multiclass prediction. MOVICS also creates feature rich customizable visualizations with minimal effort. By analysing two published breast cancer cohort, we signifies that MOVICS can serve a wide range of users and assist cancer therapy by moving away from the 'one-size-fits-all' approach to patient care. AVAILABILITY AND IMPLEMENTATION: MOVICS package and online tutorial are freely available at https://github.com/xlucpu/MOVICS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Multiomics data reveals the influences of myasthenia gravis on thymoma and its precision treatment.

Thymoma is a rare characterized by a unique association with autoimmune diseases, especially myasthenia gravis (MG). However, little is known about the molecular characteristics of MG-associated thymoma individuals. We aim to examine the influences of MG on thymoma by analyzing multiomics data. A total of 105 samples with thymoma was analyzed from TCGA and these samples were divided into subgroups with MG (MGT) or without MG (MGF) according to clinical information. We then characterized the differential gene expression, pathway activity, somatic mutation frequency, and likelihood of responding to chemotherapies and immunotherapies of the two identified subgroups. MGT subgroup was characterized by elevated inflammatory responses and metabolically related pathways, whereas the MGF subgroup was predicted to be more sensitive to chemotherapy and presented with mesenchymal characteristics. More copy number amplifications and deletions were observed in MGT, whereas GTF2I mutations occur at significantly higher frequencies in MGF. Two molecular subtypes were further identified within MGF samples by unsupervised clustering where one subtype was enriched in TGF-ß and WNT pathways with higher sensitivity to relevant targeted drugs but hardly respond to immunotherapy. For another subtype, a higher recurrence rate of thymoma and more likelihood of responding to immunotherapy were observed. Our findings presented a comprehensive molecular characterization of thymoma patients given the status of MG, and provided potential strategies to help individualized management and treatment.

Neo-adjuvant radiation therapy provides a survival advantage in T3-T4 nodal positive gastric and gastroesophageal junction adenocarcinoma: a SEER database analysis.

BACKGROUND: Due to negative results in clinical trials of postoperative chemoradiation for gastric cancer, at present, there is a tendency to move chemoradiation therapy forward in gastric and gastroesophageal junction (GEJ) adenocarcinoma. Several randomized controlled trials (RCTs) are currently recruiting subjects to investigate the effect of neo-adjuvant radiotherapy (NRT) in gastric and GEJ cancer. Large retrospective studies may be beneficial in clarifying the potential benefit of NRT, providing implications for RCTs. METHODS: We retrieved the clinicopathological and treatment data of gastric and GEJ adenocarcinoma patients who underwent surgical resection and chemotherapy between 2004 and 2015 from Surveillance, Epidemiology, and End Results (SEER) database. We compared survival between NRT and non-NRT patients among four clinical subgroups (T1-2N-, T1-2N+, T3-4N-, and T3-4N+). RESULTS: Overall, 5272 patients were identified, among which 1984 patients received NRT. After adjusting confounding variables, significantly improved survival between patients with and without NRT was only observed in T3-4N+ subgroup [hazard ratio (HR) 0.79, 95% confidence interval (CI): 0.66-0.95; P = 0.01]. Besides, Kaplan-Meier plots showed significant cause-specific survival advantage of NRT in intestinal type (P <  0.001), but not in diffuse type (P = 0.11) for T3-4N+ patients. In the multivariate competing risk model, NRT still showed survival advantage only in T3-4 N+ patients (subdistribution HR: 0.77; 95% CI: 0.64-0.93; P = 0.006), but not in other subgroups. CONCLUSIONS: NRT might benefit resectable gastric and GEJ cancer patients of T3-4 stages with positive lymph nodes, particularly for intestinal-type. Nevertheless, these results should be interpreted with caution, and more data from ongoing RCTs are warranted.

Cigarette smoking and all-cause mortality in rural Chinese male adults: 15-year follow-up of the Anqing cohort study.

BACKGROUND: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. METHODS: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. RESULTS: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). CONCLUSIONS: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

Characterization of the prognostic values and response to immunotherapy/chemotherapy of Krüppel-like factors in prostate cancer.

At present, the overall genetic and epigenetic effects of Krüppel-like factors (KLFs) on prostate cancer (PCa) remain unclear. Therefore, we systematically investigated the molecular differences in KLFs of transcription expression, promoter methylation and genetic alteration. Univariate and multivariate Cox proportional hazard regression was used to analyse the effect on RFS and establish the prognostic signature in the TCGA cohort, MSKCC and GSE116918 cohorts employed to validate the signature. Biological pathway enrichment and the potential response to immunotherapy and chemotherapy were inferred. The transcription levels of most KLFs are associated with the clinical outcome of PCa. Gleason score (P = .009), pathology T stage (P = .006), KLF3 (P = .034), KLF5 (P = .002) and KLF7 (P = .035) were independent prognostic factors. A prognostic signature was established in the TCGA cohort (P < .001) and validated in the MSKCC (P < .001) and GSE116918 cohorts (P = .006). Demethylation of KLF5 by 5-azacytidine led to increased protein levels, whereas knockdown of KLF5 promoted cell proliferation. Patients in KLF-F were more likely to respond to immunotherapy (P < .001) and bicalutamide (P < .001). In summary, we found that the KLFs and clinical feature-based signatures may improve prognosis prediction in PCa and further promote patient stratification and disease management.

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications.

BACKGROUND: Immunotherapy could trigger durable response in advanced gastric cancer, but it only benefits a minority of patients. We aimed to propose a robust molecular classification of gastric cancer microenvironment to identify ideal candidates for tailoring effective immunotherapy. METHODS: A training cohort of 375 gastric cancer samples with RNA sequencing data was analysed. We virtually microdissected tumour, stromal, and immune cell gene expression patterns employing a non-negative matrix factorization algorithm. These expression patterns were annotated using immune- and stromal-related gene signatures. Validation of immunogenomic classification was performed across six microarray datasets of 1406 samples. RESULTS: We found approximately half of gastric cancer samples to have higher immune cell infiltrates, PD-L1 expression, markers of cytolytic activity, and fewer copy number aberrations (all P < 0.05). We termed this group of tumours the Immune Class, which incorporated two components, namely Immune Activation and Immunosuppressive Subtype, according to immunosuppressive or activated microenvironment. Immune Activation Subtype was associated with improved survival in multivariate survival analysis and shared similar genomic characteristics with responders of anti-PD-1 therapy. Immunosuppressive Subtype featured high immune infiltration, stromal enrichment, and transforming growth factor (TGF)-ß signalling pathway activation and correlated with non-responsiveness signature of checkpoint blockade therapy, which might be suitable for anti-PD-L1 and anti-TGF-ß combined therapy. CONCLUSIONS: We proposed and independently validated three reproducible immune molecular subtypes of gastric cancer, which may provide implications for patient selection of immunotherapy.

Continuously available ratio of SpO2/FiO2 serves as a noninvasive prognostic marker for intensive care patients with COVID-19.

RATIONALE: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been described as potential predictor of poor outcome for COVID-19, without considering its time-varying behavior though. METHODS: Prognostic value of SpO2/FiO2 was evaluated by jointly modeling the longitudinal responses of SpO2/FiO2 and time-to-event data retrieved from 280 severe and critically ill (intensive care) patients with COVID-19. RESULTS: A sharply decrease of SpO2/FiO2 from the first to second measurement for non-survivors was observed, and a strong association between square root SpO2/FiO2 and mortality risk was demonstrated, with a unit decrease in the marker corresponding to 1.82-fold increase in mortality risk (95% CI: 1.56-2.13). CONCLUSIONS: The current study suggested that SpO2/FiO2 could serve as a non-invasive prognostic marker to facilitate early adjustment for treatment, thus improving overall survival.

Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis.

BACKGROUND: Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated. METHODS: We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan-Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching. RESULTS: Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35-1.81, P < 0.001) and cancer-specific mortality (adjusted HR: 1.33, 95% CI: 1.05-1.68, P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19-1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10-2.05, P = 0.01) in 1:1 propensity score-matched analysis. CONCLUSION: Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.

Genomic characterization of cervical cancer based on human papillomavirus status.

OBJECTIVE: It is uncommon for cervical cancer patients to be diagnosed without a human papillomavirus (HPV) infection. As prophylactic vaccines against high-risk HPV types are an ineffective preventive measure for these patients it is essential to identify differential biomarkers that may be associated with detection, prognosis and novel targeted therapies. The objective of this study was to compare the two entities, HPV+ and HPV- cervical cancers, based on TCGA public data. METHODS: We collected and analyzed clinical information of 299 cervical cancer patients as the first step, then identified differential expressed genes and conducted downstream analyses to characterize this tumor based on HPV status, including functional annotation, pathway mapping, survival analysis and comparative somatic mutation landscapes. We further inferred the likelihood of responding to traditional treatment including radiotherapy and chemotherapy. RESULTS: It was found that HPV- tumors were likely to occur at an older age and were often adenocarcinomas or adenosquamous carcinomas, and there was no significant overall survival difference between HPV+ vs. HPV- tumors. Gene expression profiles of HPV+ and HPV- tumors differed especially in ANKRD7, SERPINB3, EMX2, MEI1, RNF212, RP11-13 K12.5, RP11-325F22.2 and ZFR2 which were significantly relevant to cervical cancer prognosis. TP53, ARID5B, ARID1A, CTNNB1 and PTEN were significantly differentially mutated between HPV+ and HPV- tumors. Results of radiotherapy analyses demonstrated that CDO1, PCDHB2 and MYOD1 were different between the two subsets. In addition, RP11-299 L17.3, SLC14A2, FGF18 and OASL represented different drug-sensitivity to cisplatin between both. CONCLUSIONS: These potential biomarkers may offer insights to further personalize therapeutic decision-making to improve survival in HPV- cervical cancer patients.

Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation.

Highly active antiretroviral therapy can reduce the human immunodeficiency virus (HIV) viral load in the plasma to undetectable levels. However, because of the presence of latent HIV reservoirs, it is difficult to completely eradicate HIV in infected patients. Our objective was to assess the potency of chidamide, a novel histone deacetylase inhibitor recently approved for cancer treatment by the China Food and Drug Administration, to reactivate latent HIV-1 via histone acetylation. Viral reactivities of chidamide were accessed in 2 latent HIV pseudotype virus cell reporter systems (J-Lat Tat-green fluorescent protein clone A72 and TZM-bl), a latently infected full-length HIV virus cell system (U1/HIV), and resting CD4+ T cells from 9 HIV-infected patients under highly active antiretroviral therapy with undetectable viral load. Chidamide was able to increase HIV expression in each cell line, as evidenced by green fluorescent protein, luciferase activity, and p24, as well as to reactivate latent HIV-1 in primary CD4+ T cells of HIV-infected patients. Histone acetylation adjacent to the HIV promoter in A72 cells was determined by chromatin immunoprecipitation. Chidamide was able to increase histone H3 and H4 acetylation at the HIV promoter. In brief, chidamide induced the reactivation of latent HIV in pseudotype virus reporter cells, latently infected cells, and primary CD4+ T cells, making this compound an attractive option for future clinical trials.

Dynamic Characteristics of Sequential Acute Exacerbations and Risk Windows in AECOPD Rats Induced by Cigarette-Smoke and Exposure to Klebsiella pneumoniae.

The risk-window (RW) of chronic obstructive pulmonary disease (COPD) is a period after an acute exacerbation (AE) but before the following stable phase, in which exacerbations are easy to relapse. We established a sequential COPD-AE-RW rat model by cigarette-smoke and bacterial exposures in the first 8 weeks, and was challenged with Klebsiella pneumonia to mimic an AE on Day 1 of week 9, and found that body temperature, white blood cell, neutrophils, serum amyloid A (SAA) and C-reactive protein (CRP) increased in AECOPD rats 24 h after challenge, and declined in 3-6 d, while lung function declined in 48 h, and recovered in 7-16 d. When sacrificed, pulmonary forced expiratory volume (FEV)100 and FEV300 decreased, while elevated bronchoalveolar lavage fluid (BALF) neutrophils and marked airway inflammation, remodeling and emphysema were observed. Sequential COPD-AE-RW rat model was established successfully and AE phase lasts for approximately 5-7 d, followed by a 10-d around risk-window.

Dusuqing granules (DSQ) suppress inflammation in Klebsiella pneumonia rat via NF-κB/MAPK signaling.

BACKGROUND: Dusuqing granules (DSQ) have been used in the treatment of bacterial pneumonia clinically, with remarkable benefits. This study was initiated to explore the effects of DSQ on pulmonary inflammation by regulating nuclear factor (NF)-κB/mitogen-activated protein kinase (MAPK) signaling in bacterial pneumonia rats. METHODS: Rat model was duplicated with Klebsiella pneumonia by a one-time intratracheal injection. Rats were randomized into control, model, DSQ and levofloxacin (LVX) groups. After administrated with appropriate medicines for 7 days, lung tissues were harvested and prepared for pathological analysis, and interleukin (IL)-1, IL-6, monocyte chemotactic protein (MCP)-1and macrophage inflammatory protein (MIP)-2 detections. NF-κB mRNA was measured by real-time qPCR, and the phosphorylation and total proteins of P38MAPK, JNK46/54, ERK42/44 were determined by Western blotting. RESULTS: Marked pathological impairments were observed in model rats, whereas were improved in DSQ group. The cytokines levels, NF-κB mRNA expression and the phosphorylation of P38MAPK, JNK46/54 and ERK42/44 proteins were significantly higher in model group, and were significantly depressed in DSQ group. CONCLUSION: The protective effects of DSQ on Klebsiella pneumonia might be attributed to its inactivative effects of NF-κB/ MAPK pathway.