Heme oxygenase-1 directly binds STAT3 to control the generation of pathogenic Th17 cells during neutrophilic airway inflammation.

BACKGROUND: Specific JAK/STAT pathways play a critical role in the functional differentiation of distinct Th subsets. Previously, we showed that HO-1, a stress-inducible protein, inhibits Th17 cell differentiation and alleviates neutrophilic airway inflammation, but the responsible molecular basis remains unclear. METHODS: We employed Th17-skewing differentiation and NEA mouse models to study the role of HO-1 in regulating IL-6-STAT3-RORγt/SOCS3 signaling pathway to control Th17 cell-mediated neutrophilic airway inflammation. The levels of cytokines and expressions of relative signaling molecules were measured by ELISA, western blot, and qPCR, respectively. Frequency of CD4+ IL-17A+ , CD4+ IL-6R+ , and CD4+ IL-23R+ cells was analyzed by FCM. The interaction between HO-1 and signaling pathway-related proteins was determined by co-immunoprecipitation and western blot. RESULTS: Here, we show that hemin-induced HO-1 overexpression is required to mediate this process. Specifically, HO-1 decreased STAT3 phosphorylation but not IL-6R/IL-23R expression or JAK1/JAK2 activation in CD4+ T cells. The effect was accompanied by co-inhibition of SOCS3, a negative feedback factor of STAT3 activation. HO-1 bound to three domains on STAT3 (DNA-binding, linker, and transactivation domains) to directly regulate STAT3 activation. Conversely, either forced expression of a constitutively active STAT3 mutant or application of small-interfering RNA (siRNA) for HO-1 reversed these effects. CONCLUSIONS: Our data suggest that HO-1 exerts its inhibitory effect on Th17 cell differentiation by directly associating and blocking STAT3 phosphorylation. We speculate that hemin may be a potential therapeutic candidate for the treatment of other types of immune and pulmonary inflammatory-related diseases.

[High risk factors analysis of stillbirth].

Objective: To explore the high risk factors of stillbirth. Methods: 176 cases of stillbirth were collected in the Obstetrics and Gynecology Hospital of Fudan University from January 1(st), 2010 to December 31(st), 2016. All cases were analyzed retrospectively, including general profile, high risk factors of stillbirth in different years and pregnancy periods. Results: (1) The incidence of stillbirth was 0.178%(176/98 785). Stillbirth occured mostly at 28-28(+6) gestational weeks (10.8%,19/176), and the second peak was 29-29(+6) weeks(10.2%,18/176), while the third common period was 37-37(+6) weeks (9.1%,16/176). After 39 weeks, it maintained at a low level. (2) The top 5 high risk factors of stillbirth were infection (18.2%,32/176), unexplained (13.6%,24/176), hypertention disorders in pregnancy (13.1%, 23/176), umbilical cord torsion (12.5%, 22/176) and fetal malformations (10.2%, 18/176). (3) From 2010 to 2012, the top 3 high risk factors were unexplained, the umbilical cord torsion and infection, while hypertention in pregnancy, infection and fetal malformation became the top 3 high risk factors after 2013. (4) Early stillbirth (20-27(+6) weeks) accounted for 21.6%(38/176); and unexplained (47.4%, 18/38), fetal edema (13.2%, 5/38),infection (13.2%, 5/38), umbilical cord torsion (5.3%, 2/38) were the top 4 high risk factors. Late stillbirth (≥28 weeks) accounted for 78.4%(138/176), with infection (19.6%,27/138), hypertention in pregnancy (15.9%,22/138), umbilical cord torsion (14.5%,20/138) and fetal malformation(12.3%,17/138)being the top 4 high risk factors. Conclusions: More attention should be paid to maternal complications, especially infection and hypertension in pregnancy. Antenatal fetal monitoring, timely termination of pregnancy, standard management of stillbirth and looking for the causes may help reduce the incidence of stillbirth.

Association between XRCC1 polymorphisms and laryngeal cancer susceptibility in a Chinese sample population.

Laryngeal cancer is the major malignant tumor affecting the upper respiratory tract. Previous studies have reported on the association between XRCC1 genetic polymorphisms and risk of laryngeal cancer, but with conflicting results. In this study, we attempted to assess the association between XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms and risk of laryngeal cancer in a Chinese population. A total of 126 laryngeal cancer patients and 254 control subjects were recruited to this study from the Second Medical College of Jinan University between December 2013 and May 2015. The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphic sites were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Our results revealed a significant association between the AA genotype of XRCC1 Arg280His [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.29-4.87, P = 0.01] and an increased risk of laryngeal cancer susceptibility compared to the GG genotype. Moreover, the A allele showed a higher risk of laryngeal cancer susceptibility compared to the G allele (OR = 1.63, 95%CI = 1.19-2.50, P = 0.002). In conclusion, the results of our study suggest that the AA genotype and A allele of the XRCC1 Arg280His polymorphism are associated with an increased laryngeal cancer risk in a Chinese population.

[Predictive and prognostic value of monitoring lymphocyte subsets in peripheral blood before and after chemotherapy in patients with metastatic breast cancer].

OBJECTIVE: To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis. METHODS: The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy. The result was analyzed in combination with clinicopathological data. RESULTS: The proportion of regulatory T cells (Treg) after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034). The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survival (OS). The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg, which was 23.5 and 9.4 months respectively (P<0.05). CONCLUSION: The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

[Prenatal diagnosis of Thailand deletion of α-thalassemia 1 families].

OBJECTIVE: To conduct analysis and prenatal diagnosis on 11 couples carrying Thailand deletion (--(THΑI)) α-thalassemia 1, so as to provide information for clinical genetic counseling on α-thalassemia 1. METHODS: Altogether 11 Thailand deletion (--(THΑI)) α-thalassemia 1 families were collected from Fujian Maternal and Children Health Hospital from May 2009 to September 2015. Gap-polymerase chain reaction (gap-PCR) and reverse dot blot (RDB) technology were used to detect the thalassemia mutations in the couples and fetuses. RESULTS: In one family, Thailand deletion α-thalassemia 1 was detected in both the pregnant woman and her husband. In 10 families, Thailand deletion α-thalassemia 1 was detected in either the pregnant women or the husband, while the spouses had α-thalassemia heterozygote (1 combined with ß thalassemia heterozygote). Thailand deletion α-thalassemia 1 family members all had lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). In prenatal diagnosis of the 12 fetuses, 4 fetuses were found with hemoglobin(Hb) Bart's hydrops fetalis syndrome, 5 were with α-thalassemia heterozygote, and 3 were normal. CONCLUSIONS: For couples with positive hematological phenotype but normal results in routine genetic examination of α-thalassemia, attention should be paid especially for with a history of having babies of hydrops fetalis syndrome or hemoglobin H disease. It is necessary to consider the possibility of the rare Thailand deletion (--(THΑI)) α-thalassemia 1. Prenatal diagnosis for high-risk families plays an important role.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study.

BACKGROUND: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. METHODS: We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. RESULTS: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. CONCLUSION: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Environmental variability and the transmission of haemorrhagic fever with renal syndrome in Changsha, People's Republic of China.

The transmission of haemorrhagic fever with renal syndrome (HFRS) is influenced by climatic, reservoir and environmental variables. The epidemiology of the disease was studied over a 6-year period in Changsha. Variables relating to climate, environment, rodent host distribution and disease occurrence were collected monthly and analysed using a time-series adjusted Poisson regression model. It was found that the density of the rodent host and multivariate El Niño Southern Oscillation index had the greatest effect on the transmission of HFRS with lags of 2­6 months. However, a number of climatic and environmental factors played important roles in affecting the density and transmission potential of the rodent host population. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

Risk factors for oxaliplatin-induced peripheral neuropathy: a systematic review and meta-analysis.

OBJECTIVE: Oxaliplatin-induced neuropathy is a significant complication of cancer therapy. We aimed at investigating the risk factors of oxaliplatin-induced neuropathy (OIPN) and providing evidence to enhance its prevention. MATERIALS AND METHODS: PubMed, Medline, Web of Science, Embase, China Knowledge Resource Integrated Database, and the Wanfang Database were searched comprehensively for observational studies investigating the prevalence and risk factors of OIPN from inception to November 30, 2021. The Newcastle-Ottawa Scale was used by two independent reviewers to assess methodological quality. When applicable, we used meta-analysis to determine mean differences and odds ratios for continuous and nominal scaled data. RESULTS: We included 20 studies involving 10,900 participants for analysis. Factors associated with OIPN risk identified by meta-analysis were age, gender, diabetes, anemia, hypomagnesaemia, alcohol consumption, body mass index, body surface area, cumulative oxaliplatin dose and the number of chemotherapy cycles. Factors not associated with OIPN risk included smoking history and chemotherapy regimen. CONCLUSIONS: This meta-analysis identified multiple variables associated with OIPN. The recognition of modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.

[Proteomic analysis and verification of protein expression after upregulation of human CD99 in Hodgkin lymphoma cell line L428].

Objective: To investigate the proteins expression difference after upregulation of human CD99 in Hodgkin Lymphoma cell line, L428 cell, and verify the function of differential proteins. Methods: The differential proteins were detected by two-dimensional fluorescence difference gel electrophoresis and mass spectrometry analysis, cluster analysis was done by GOfact. Results: There were 38 proteins screened out, of which 21 proteins were positively associated with CD99, while 17 proteins were negative. Among the 38 proteins, 32 proteins participated in biological process, and 35 proteins were involved in the composition and construction. And 28 proteins participated in multifaceted biological activities including antioxidation, protein binding, catalytic activity, regulation of enzyme, signal transduction, molecular structure, regulation of translation and ion transport. Conclusions: The changes of the differential proteins, correlated with cytoskeleton, cell differentiation, signal pathway and regulating gene expression, are closely relevant to the translation between Hodgkin/Reed-Sternberg and B lymphocyte cell.

MiR-92b-5p inhibitor suppresses IL-18 mediated inflammatory amplification after spinal cord injury via IL-18BP up-regulation.

OBJECTIVE: The aim of this study was to investigate the effects of miR-92b-5p inhibitor and interleukin-18-binding protein (IL-18BP) on interleukin-18 (IL-18)-mediated inflammatory response after spinal cord injury (SCI). MATERIALS AND METHODS: In this work, microglia was isolated from the newborn C57/B6J mice spinal cord to in vitro culture. The expression of IL-18BP and IL-18 was measured by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) after transfection of miR-92b-5p into activated microglia. The expression of IL-18BP and IL-18 was determined following miR-92b-5p inhibitor treatment. In addition, the spinal cord injury model was established in mice. The expressions of miR-92b-5p, IL-18BP, and IL-18 were measured by qRT-PCR, and the expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α) and interleukin-1 ß (IL-1 ß) were determined by Western blot. After intrathecal injection of miR-92b-5p inhibitor, the mRNA expression of miR-92b-5p, IL-18BP, and IL-18 and the expression of iNOS, TNF-α, and IL-1 ß in the injured area of the spinal cord of mice were measured. Basso Mouse Scale (BMS) was used to determine the recovery of locomotor function after spinal cord injury and miR-92b-5p inhibition. RESULTS: After miR-92b-5p transfection, the expression of IL-18BP was significantly decreased compared with that of untransfected microglia cells, whereas the level of IL-18 mRNA was significantly increased. However, the level of IL-18BP elevated significantly and the level of IL-18 reduced markedly after treatment with corresponding inhibitors. In addition, compared with the sham operation group (Sham), the RNA level of miR-92b-5p in the SCI group was significantly higher than that in the Sham, but the expression of IL-18BP was evidently declined and the expression of IL-18 was significantly increased in the SCI group. Meanwhile, the expression of miR-92b-5p in miR-92b-5p inhibitor intrathecal injection mice was remarkably lower than that in SCI group, the expression level of IL-18BP was significantly increased, and the RNA expression of IL-18 was weakened accordingly. Moreover, the protein expression of iNOS, TNF-α, and IL-1 ß in miR-92b-5p inhibitor-treated mice was significantly lower than that in the SCI group. The locomotor evaluation of miR-92b-5p inhibitor group was dramatically higher than that of the SCI group. CONCLUSIONS: Suppressing the expression of miR-92b-5p after SCI can effectively intensify the level of IL-18BP, reduce the expanded inflammatory effect of IL-18, decline the release of iNOS, TNF-α, and IL-1 ß, thus alleviate the neuronal injury and improve the locomotor function after SCI.

Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma.

Constitutively activated nuclear factor-kappaB (NF-kappaB) has been associated with a variety of aggressive tumor types, including head and neck squamous cell carcinoma (HNSCC); however, the mechanism of its activation is not fully understood. Therefore, we investigated the molecular pathway that mediates constitutive activation of NF-kappaB in a series of HNSCC cell lines. We confirmed that NF-kappaB was constitutively active in all HNSCC cell lines (FaDu, LICR-LON-HN5 and SCC4) examined as indicated by DNA binding, immunocytochemical localization of p65, by NF-kappaB-dependent reporter gene expression and its inhibition by dominant-negative (DN)-inhibitory subunit of NF-kappaB (IkappaBalpha), the natural inhibitor of NF-kappaB. Constitutive NF-kappaB activation in HNSCC was found to be due to constitutive activation of IkappaBalpha kinase (IKK); and this correlated with constitutive expression of phosphorylated forms of IkappaBalpha and p65 proteins. All HNSCC showed the expression of p50, p52, p100 and receptor-interacting protein; all linked with NF-kappaB activation. The expression of constitutively active NF-kappaB in HNSCC is mediated through the tumor necrosis factor (TNF) signaling pathway, as NF-kappaB reporter activity was inhibited by DN-TNF receptor-associated death domain (TRADD), DN-TNF receptor-associated factor (TRAF)2, DN-receptor-interacting protein (RIP), DN-transforming growth factor-beta-activated kinase 1 (TAK1), DN-kappa-Ras, DN-AKT and DN-IKK but not by DN-TRAF5 or DN-TRAF6. Constitutive NF-kappaB activation was also associated with the autocrine expression of TNF, TNF receptors and receptor-activator of NF-kappaB and its ligand in HNSCC cells but not interleukin (IL)-1beta. All HNSCC cell lines expressed IL-6, a NF-kappaB-regulated gene product. Furthermore, treatment of HNSCC cells with anti-TNF antibody downregulated constitutively active NF-kappaB, and this was associated with inhibition of IL-6 expression and cell proliferation. Our results clearly demonstrate that constitutive activation of NF-kappaB is mediated through the TRADD-TRAF2-RIP-TAK1-IKK pathway, making TNF a novel target in the treatment of head and neck cancer.

[Application of the computer-based respiratory sound analysis system based on Mel-frequency cepstral coefficient and dynamic time warping in healthy children].

OBJECTIVE: We designed a computer-based respiratory sound analysis system to identify pediatric normal lung sound. To verify the validity of the computer-based respiratory sound analysis system. METHOD: First we downloaded the standard lung sounds from the network database (website: http: //www.easyauscultation.com/lung-sounds-reference-guide) and recorded 3 samples of abnormal loud sound (rhonchi, wheeze and crackles) from three patients of The Department of Pediatrics, the First Affiliated Hospital of Xiamen University. We regarded such lung sounds as"reference lung sounds". The"test lung sounds"were recorded from 29 children form Kindergarten of Xiamen University. we recorded lung sound by portable electronic stethoscope and valid lung sounds were selected by manual identification. We introduced Mel-frequency cepstral coefficient (MFCC) to extract lung sound features and dynamic time warping (DTW) for signal classification. RESULT: We had 39 standard lung sounds, recorded 58 test lung sounds. This computer-based respiratory sound analysis system was carried out in 58 lung sound recognition, correct identification of 52 times, error identification 6 times. Accuracy was 89.7%. CONCLUSION: Based on MFCC and DTW, our computer-based respiratory sound analysis system can effectively identify healthy lung sounds of children (accuracy can reach 89.7%), fully embodies the reliability of the lung sounds analysis system.

Methylprednisolone combined with low-dose indomethacin treating acute fibrinous and organizing pneumonia after a surgical resection of rectal adenocarcinoma: a case report and literature review.

OBJECTIVE: Acute Fibrinous and Organizing Pneumonia (AFOP) is a new pathologic pattern of acute lung injury characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" in a patchy distribution. CASE REPORT: A 65-years-old female after a surgical resection of rectal adenocarcinoma presented with typical manifestations of hospital-acquired pneumonia, but she didn't respond to the anti infective therapy. After an explicit diagnosis of AFOP via percutaneous needle lung biopsy, she got an impressive improvement with a long-term therapy of methylprednisolone and low-dose indomethacin. To date, a total of non-overlapped 45 individual AFOP cases and 4 single-center studies involving AFOP have been reported. The most common coexisting diseases are infections, connective tissue diseases and hematological diseases. Corticosteroids and immunosuppressants are the most common agents prescribed in AFOP. The prognosis of AFOP is unfavorable, associated with the pathologic characteristics and the clinical parameters. CONCLUSIONS: The immune system activated by infection may play an important role in the pathogenesis of AFOP. Low-dose indomethacin combined with methylprednisolone may be a new choice for AFOP treatment.

Hypereosinophilic obliterative bronchiolitis with an elevated level of serum CEA: a case report and a review of the literature.

A 44-year-old man presented with chronic, persistent cough and occasional wheezing. Airflow obstruction, blood eosinophilia and a remarkable elevated level of serum carcinoembryonic antigen (CEA) were found. Radiographic and pathological studies confirmed eosinophilic bronchiolitis. There was no evidence of neoplasms by extensive examinations. After a protracted oral steroid therapy, the blood eosinophil count, the serum CEA level and the lung lesions were all improved in parallel, whereas fixed airflow obstruction remained. This case was diagnosed as a new distinct syndrome, hypereosinophilic obliterative bronchiolits. Serum CEA and blood eosinophil cell count served as good markers of the disease condition for this syndrome.

Killing effect of TNF-related apoptosis inducing ligand regulated by tetracycline on gastric cancer cell line NCI-N87.

AIM: To clone the cDNA fragment of human TRAIL (TNF-related apoptosis inducing ligand) into a tetracycline-regulated gene expression system, the RevTet-On system, transduce expression vectors into a gastric carcinoma cell line-NCI-N87 and examine the effects of controlled expression of TRAIL in vitro on the gastric carcinoma cells. METHODS: The full-length cDNA of TRAIL was inserted into a vector under the control of the tetracycline-responsive element (TRE) to obtain the plasmid pRevTRE-TRAIL, which was transfected into a packaging cell line PT67. In addition, vector pRev-Tet On and pRevTRE were also transfected into PT67 separately. After hygromycin and G418 selection, the viral titer was determined. The medium containing retroviral vectors was collected and used to transduce a gastric carcinoma cell line NCI-N87. The resulting cell line NCI-N87-Tet On TRE-TRAIL and a control cell line, NCI-N87 Tet On-TRE, were established. TRAIL expression in the cell line was induced by incubating cells with doxycycline (Dox), which is a tetracycline analogue. The killing effect on gastric carcinoma cells was analyzed after induction. RESULTS: The recombinant plasmid pRev-TRE-TRAIL was constructed. After hygromycin or G418 selection, the producer cell lines PT67-TRE, PT67-TRE-TRAIL and PT67-Tet On were obtained,with titers of about 10(8)CFU.L(-1). By transducing NCI-N87 cells with retroviral vectors from these cell lines, stable cell lines NCI-N87-Tet-On TRE-TRAIL (NN3T) and control cell line NCI-N87-Tet-On-TRE (NN2T) were established. The growth curves of the selected cell lines were the same with the wild type NCI-N87. When Dox was added, cell death was obvious in the test groups (29%-77%), whereas no difference was observed in control and wild type cell lines. With the addition of a medium from the test group, human leukemia cell line Jurkat was activated till death (83%), indicating the secretion of active TRAIL proteins from the test cells to the medium. CONCLUSION: With the use of the RevTet-On system, a regulated expression system for TRAIL was constructed. Using this system, the selected killing effect of TRAIL on gastric carcinoma cell line NCI-N87 could be observed.

[In vitro cultivation of the exoerythrocytic stage of Plasmodium berghei].

This paper reports on an in vitro culture system for the exoerythrocytic (EE) stage of Plasmodium berghei (P.b.) using embryonic lung cells. The system was first developed by our laboratory in China. The embryonic lung cells were isolated by trypsin digestion of a human embryonic lung obtained from a therapeutic abortion case and was designated as cell line Elu 8801. Anopheles stephensi mosquitoes were infected by biting P.b. ANKA strain infected Kunming mice and after 18-21 days were dissected under aseptic conditions for preparation of a sporozoite suspension. This suspension was used to inoculate the monolayer cultures of Elu 8801. Regular examination found that following a cultivation for 48 hours, up to 100 multinuclear EE schizonts of P.b. could be observed on 1 x 1 cm cover slide. Seventy-two hours later mature merozoites were seen among part of the schizonts. An intraperitoneal inoculation of the supernatant culture medium to mice could induce malaria infection which could be transferred to other mice by blood inoculation. When the mice infected with the second generation were allowed to feed A. stephensi, sporozoites developed in the mosquitoes. The results demonstrate that the human embryonic lung cell line Elu 8801 established in our laboratory is susceptible to P.b. ANKA sporozoites and can support the developmental maturation of EE stages, producing potentially infectious merozoites.

[TNF-related apoptosis inducing ligand and its research progress on cancer treatment].

TRAIL (TNF-related apoptosis inducing ligand) belongs to the tumor necrosis factor (TNF) cytokine family, can induce apoptosis in a wide variety of tumor cell lines. This review introduces research progress on TRAIL from several aspects: the structure and function of TRAIL, the pathway of its inducing apoptosis, TRAIL and cancer treatment, and its foreground.

Beneficial effects of statins on outcomes in pneumonia: a systematic review and meta-analysis.

OBJECTIVES: There exist reports that statin treatment has beneficial effects for patients with pneumonia. The objective of this study was to evaluate whether the available published data support that statins as adjunctive therapy could reduce mortality associated with pneumonia and, thus, help to assess whether a randomized controlled study is warranted. MATERIALS AND METHODS: A meta-analysis of observational studies such as cohort studies and case-control studies identified in Pubmed, Scopus, EMBASE, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov. Eligible patients were adults with pneumonia. Studies that reported mortality of pneumonia grouped by statins usage were included. Data was analyzed and pooled using Revman 5.1. RESULTS: Fourteen studies with 269,739 participants were included in this study. Pooled analysis showed that statin treatment was associated with lower 30-day mortality, with an OR of 0.44 (95% CI, 0.29-0.67), and an adjusted OR of 0.59 (95% CI 0.48-0.73, NNT30d = 19). Statin therapy was also associated with lower long-term (> 30 days) mortality, with an OR of 0.49 (95% CI, 0.29-0.84) and an adjusted OR of 0.65 (95% CI, 0.51-0.82, NNTlong-term = 15). For pneumonia inpatients, the raw data demonstrated no significant benefit from statin therapy (OR = 0.86, 95% CI, 0.56-1.34). Adjusted data showed a marginal benefit (adjusted OR = 0.89, 95% CI, 0.81-0.97, NNTinpatient = 230). Subgroup analysis revealed that current statin users might have better outcomes than recent or past statins users. CONCLUSIONS: This meta-analysis supports that patients who happen to be receiving statin therapy have less mortality from pneumonia. However, it remains unclear whether initiation of statins at time of diagnosis is beneficial. There is only modest evidence to support the value of a well-designed randomized controlled clinical trial.