Diagnostic and Prognostic Values of KLF5 and RUNX1 in Acute Kidney Injury in Septic Patients.

Diagnostic and prognostic values of Kruppel-like factor 5 (KLF5) and Runt-related transcription factor 1 (RUNX1) were determined in sepsis-induced acute kidney injury (SI-AKI). The study included 120 septic patients and set two groups: SI-AKI group (n = 60) or non-AKI group (n = 60). Fasting venous blood was drawn, and KLF5 and RUNX1 levels were measured. The receiver operating characteristic curve was plotted for diagnostic evaluation of KLF5 and RUNX1 in SI-AKI. The correlation between KLF5 and RUNX1 and serum creatinine (Scr), cystatin C (Cys-C), and kidney injury molecule 1 (KIM-1) were assessed by Pearson method. Predictive values of KLF5 and RUNX1 in 28-day survival of SI-AKI patients were considered by Kaplan-Meier survival curves and multivariate Cox regression analysis. Serum KLF5 and RUNX1 in SI-AKI patients were upregulated. Serum KLF5 and RUNX1 were of high diagnostic value in distinguishing SI-AKI patients from non-AKI patients. KLF5 and RUNX1 were in a positive correlation with Scr, Cys-C, and KIM-1, respectively. The 28-day survival of SI-AKI patients with high serum KLF5 or RUNX1 expression was poor, and serum KLF5 and RUNX1 expression were independently correlated with SI-AKI patients' survival. KLF5 and RUNX1 have diagnostic and prognostic values in SI-AKI patients.

Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. METHODS: One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman's correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. RESULTS: Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. CONCLUSIONS: The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

Disseminated Human Parvovirus B19 Infection Induced Multiple Organ Dysfunction Syndrome in an Adult Patient With Alcoholic Hepatitis Complicated by Hemolytic Anemia: A Case Report and Literature Review.

Background: Human parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection. Case Presentation: A 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI). Conclusions: B19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.

A case of chlamydia psittaci caused severe pneumonia and meningitis diagnosed by metagenome next-generation sequencing and clinical analysis: a case report and literature review.

BACKGROUND: Psittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case. CASE PRESENTATION: This report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient's condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up. CONCLUSIONS: When clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

Disseminated Tuberculosis Associated Hemophagocytic Lymphohistiocytosis in a Pregnant Woman With Evans syndrome: A Case Report and Literature Review.

Background: Tuberculosis (TB) is a leading cause of morbidity and mortality in underdeveloped and developing countries. Disseminated TB may induce uncommon and potentially fatal secondary hemophagocytic lymphohistiocytosis (HLH). Timely treatment with anti-tuberculosis therapy (ATT) and downmodulation of the immune response is critical. However, corticosteroid treatment for TB-associated HLH remains controversial. Herein, we report a successful case of disseminated TB-associated HLH in a pregnant woman with Evans syndrome accompanied by a literature review. Case Presentation: A 26-year-old pregnant woman with Evans syndrome was transferred to the Third Affiliated Hospital of Sun Yat-Sen University because of severe pneumonia. She presented with cough, fever, and aggravated dyspnea. Nested polymerase chain reaction for Mycobacterium tuberculosis (M. tuberculosis) complex in sputum was positive. Sputum smear sample for acid-fast bacilli was also positive. Metagenome next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid identified 926 DNA sequence reads and 195 RNA sequence reads corresponding to M. tuberculosis complex, respectively. mNGS of blood identified 48 DNA sequence reads corresponding to M. tuberculosis. There was no sequence read corresponding to other potential pathogens. She was initially administered standard ATT together with a low dose of methylprednisolone (40 mg/day). However, her condition deteriorated rapidly with high fever, acute respiratory distress syndrome, pancytopenia, and hyperferritinemia. Bone marrow smears showed hemophagocytosis. And caseating tuberculous granulomas were found in the placenta. A diagnosis of disseminated TB-associated HLH was made. Along with the continuation of four drug ATT regimen, therapy with a higher dose of methylprednisolone (160 mg/day) combined with immunoglobulin and plasma exchange was managed. The patient's condition improved, and she was discharged on day 19. Her condition was good at follow-up with the continuation of the ATT. Conclusions: Clinicians encountering patients with suspected TB accompanied by unexplainable inflammation not responding to ATT should consider complications with HLH. Timely administration of ATT combined with corticosteroids may result in a favorable outcome.

Cytomegalovirus Infection in an Adult Patient With Neuromyelitis Optica and Acute Hemorrhagic Rectal Ulcer: Case Report and Literature Review.

Background: Previous infectious or inflammatory events may be involved in the pathogenesis of neuromyelitis optica (NMO), potentially by triggering an autoimmune response. Cytomegalovirus (CMV)-related NMO (CMV-NMO) is rarely reported. Acute hemorrhagic rectal ulcer (AHRU) is a rare disease with a largely unknown pathogenesis. Herein, we reported a co-NMO and AHRU case associated with CMV infection. In addition, we review previously reported cases of CMV-NMO and CMV-AHRU. Case presentation: A 40-year-old female diagnosed with aquaporin4 (AQP4)-IgG+ NMO and a poor response to high-dose intravenous methylprednisolone and immunoglobulin, followed by three rounds of plasma exchange was transferred to Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. She developed repeated acute lower gastrointestinal hemorrhage from the third day of admission. Abdominal computed tomography angiography (CTA) and interventional angiography did not detect any bleeding vessel. Bedside colonoscopy revealed a large ulcer-like lesion at 10 cm above the anus. Rectal biopsy pathology confirmed a CMV infection on day 23 post-admission, and cerebrospinal fluid (CSF) pathogen gene sequencing detected CMV gene copies on day 25 post-admission. After 2 weeks of treatment with ganciclovir and sodium phosphinate, the patient's lower gastrointestinal bleeding stopped, and her limb muscle strength and visual acuity gradually improved. After 4 weeks of antiviral therapy, colonoscopy showed that the intestinal wall of the original lesion was smooth. Hematoxylin and eosin (HE) staining and immunohistochemistry (IHC) of a biopsy specimen was negative for CMV, her right eye vision was normal, and limb muscle strength had recovered. Serum AQP4-IgG was negative, and lesions on brain magnetic resonance imaging (MRI) manifested shrinkage. Conclusions: The benefits of antiviral therapy remain unclear; however, clinicians should be aware of the possibility of CMV-related NMO, if NMO was refractory to high-dose intravenous methylprednisolone, immunoglobulin, and plasma exchange. Moreover, clinicians should consider the possibility of CMV-related AHRU when recurrent acute lower gastrointestinal bleeding occurs in a patient.

Aggravated MRSA pneumonia secondary to influenza A virus infection is derived from decreased expression of IL-1ß.

Secondary methicillin-resistant Staphylococcus aureus (MRSA) infection is a cause of severe pneumonia with high mortality during influenza A virus (IAV) pandemics. Alveolar macrophages (AMs) mount cellular defenses against IAV and MRSA infection, which occurs via the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. However, the activity and function of the NLRP3 inflammasome in MRSA pneumonia secondary to IAV infection remain unclear. To clarify this, we studied MRSA infection secondary to IAV both in vitro and in mouse model. The expression of the NLRP3 inflammasome was evaluated by quantitative reverse transcription polymerase chain reaction, immunofluorescence, Western blot, and enzyme-linked immunosorbent assay. The lung pathology and the rate of weight change were observed. We found that IAV infection for 1 week activated NLRP3 inflammasome. The enhanced expression of NLRP3, caspase-1, and cleaved caspase-1 was associated with MRSA infection secondary to IAV, but the expression of interleukin (IL)-1ß decreased in superinfection with MRSA both in vitro and in vivo. The aggravated inflammatory pathology in MRSA pneumonia secondary to IAV infection was associated with decreased expression of IL-1ß. And increased weight loss in MRSA pneumonia secondary to IAV infection was related to decreased concentration of IL-1ß in serum. It infers that superinfection with MRSA reduces expression of IL-1ß someway, and decreased expression of IL-1ß impairs the host immunity and leads to aggravated pneumonia. These results contributed to our understanding of the detailed activity of the NLRP3 inflammasome, IL-1ß, and their relationship with aggravation of MRSA pneumonia secondary to IAV infection. Immunotherapy targeting the IL-1ß signaling pathway could be possible therapeutic strategy for secondary MRSA pneumonia.

Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis.

Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis.

BACKGROUND: Human epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). METHODS: Serum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. RESULTS: Serum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8-90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3-64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1-42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574-0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What's more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = -0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). CONCLUSIONS: Elevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.

Metastatic infection caused by hypervirulent Klebsiella pneumonia and co-infection with Cryptococcus meningitis: A case report.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) used to affect mainly people with compromised immunity or weakened by other infections, but recent emergence of hypervirulent strains has increased infections even in healthy individuals. These infections include liver abscess, pneumonia, bacteremia, meningitis, necrotizing fasciitis, and endophthalmitis. Although metastatic infection by hypervirulent K. pneumoniae (hvKP) is increasingly recognized, co-infection with Cryptococcus neoformans (C. neoformans) meningitis in immunocompetent hosts is rare but fatal. So, it is necessary to determine the risk factors, complications, and comorbidity of this disease. CASE SUMMARY: This report describes a 58-year-old man with hvKP pulmonary abscess, bacteremia, and meningitis, accompanied by fatal Cryptococcus meningitis. This patient presented with fever for 1 wk and drowsiness for 3 d. Laboratory findings revealed pulmonary abscess and bacteremia of K. pneumoniae. He was given intravenous antibiotic therapy, and the infection was under control for about 1 wk. However, his condition deteriorated rapidly because of metastatic purulent meningitis. Although hvKP and C. neoformans were isolated and confirmed, the patient died of spontaneous respiratory and cardiac arrest caused by cerebral hernia. CONCLUSION: HvKP has emerged as a cause of metastatic infections in immunocompetent hosts. polymicrobial co-infections should be taken into consideration when metastatic infection is present.

A Case of Hemophagocytic Lymphohistiocytosis Secondary to Ralstonia Solanacearum Infection.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), as known as Hemophagocytic syndrome (HPS), is deemed to a severe clinical syndrome caused by excessive human being immune system activation. Bacteria of Ralstonia genus is a non-fermentative, gram-negative bacillus and also in the category of human opportunistic pathogenic bacteria. In this article, authors report a rare case of Hemophagocytic lymophohistiocytosis which probably was triggered by Ralstonia solanacearum (R. solanacearum) infection. METHODS: Hematologic investigation, biochemical examination, high throughput genetic test for infectious agents and bone marrow puncture. RESULTS: The patient achieved complete remission and no signs of relapse have as yet been found. CONCLUSIONS: The bacteria of Ralstonia genus merely infect humans, and there were no reports about the infection of R. solanacearum in humans and secondary HLH. The prognosis of the patient in this case was very good. This result, we think shows that the relationship between HLH and R. solanacearum infection should be taken into the diagnosis process. Recognition of this will promote the correct diagnosis in clinical work.

Therapeutic plasma exchange and continuous renal replacement therapy for severe hyperthyroidism and multi-organ failure: A case report.

BACKGROUND: Severe hyperthyroidism is a life-threatening exacerbation of thyrotoxicosis, characterized by high fever and multiorgan failure. The most common medical treatments are administration of antithyroid drugs and radioactive iodine, and thyroidectomy. In some patients, antithyroid therapy is limited due to serious adverse effects or failure to control disease progression. In some extreme cases, such as thyroid storm, conventional therapy alone does not yield effective and rapid improvement before the development of multiorgan failure. CASE SUMMARY: This report describes a Chinese patient with severe hyperthyroidism accompanied by multiorgan failure, who was transferred to the medical intensive care unit of our hospital. The patient presented with palpitations, vomiting, diarrhea, and shortness of breath for a week. Laboratory tests showed elevation of thyroid hormones. Hepatic failure occurred with high aminotransferase levels and jaundice. Given her abnormal liver function and medication history, we could not exclude diagnosis of propylthiouracil-induced hepatic failure. Moreover, she also suffered from heart failure. Therapeutic plasma exchange (commonly known as TPE) and continuous renal replacement therapy (commonly known as CRRT) were used as life-saving therapy, which resulted in notable improvement of clinical symptoms and laboratory tests. CONCLUSION: Combined TPE and CRRT are safe and effective for patients with hyperthyroidism and multiorgan failure.

Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial.

PURPOSE: Recent clinical data suggest that terlipressin, a vasopressin analogue, may be more beneficial in septic shock patients than catecholamines. However, terlipressin's effect on mortality is unknown. We set out to ascertain the efficacy and safety of continuous terlipressin infusion compared with norepinephrine (NE) in patients with septic shock. METHODS: In this multicentre, randomised, double-blinded trial, patients with septic shock recruited from 21 intensive care units in 11 provinces of China were randomised (1:1) to receive either terlipressin (20-160 µg/h with maximum infusion rate of 4 mg/day) or NE (4-30 µg/min) before open-label vasopressors. The primary endpoint was mortality 28 days after the start of infusion. Primary efficacy endpoint analysis and safety analysis were performed on the data from a modified intention-to-treat population. RESULTS: Between 1 January 2013 and 28 February 2016, 617 patients were randomised (312 to the terlipressin group, 305 to the NE group). The modified intention-to-treat population comprised 526 (85.3%) patients (260 in the terlipressin group and 266 in the NE group). There was no significant difference in 28-day mortality rate between the terlipressin group (40%) and the NE group (38%) (odds ratio 0.93 [95% CI 0.55-1.56]; p = 0.80). Change in SOFA score on day 7 was similar between the two groups: - 7 (IQR - 11 to 3) in the terlipressin group and - 6 (IQR - 10 to 5) in the NE group. There was no difference between the groups in the number of days alive and free of vasopressors. Overall, serious adverse events were more common in the terlipressin group than in the NE group (30% vs 12%; p < 0.001). CONCLUSIONS: In this multicentre, randomised, double-blinded trial, we observed no difference in mortality between terlipressin and NE infusion in patients with septic shock. Patients in the terlipressin group had a higher number of serious adverse events. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov: ID NCT01697410.

Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients.

BACKGROUND: Renal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. METHODS: A total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. RESULTS: Median serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6-300.2) compared with control subjects (34.3 pmol/l, IQR 30.4-42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. CONCLUSIONS: Serum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients.

Regulatory effects of miR-155 and miR-146a on repolarization and inflammatory cytokine secretion in human alveolar macrophages in vitro.

Macrophages play an important role in inflammatory responses; however, miRNA-mediated repolarization of macrophages is essential for fulfilling this function. To clarify a series of changes at the RNA level in alveolar macrophages under normal and inflammatory conditions, bronchial alveolar lavage liquid (BALF) was collected from healthy volunteers or patients with pneumonia. This approach, which differs from that used in previously, provides more accurate information about the states of macrophages in different lung microenvironments. In this study, the density plots of macrophage subtypes (M1 and M2) in the BALF of healthy volunteers differed from that of the patients with pneumonia. The M2 subtype dominated in healthy volunteers and was rapidly repolarized to M1 in response to miRNA-mediated gene regulation. Differential miRNA expression in the two macrophage subtypes revealed lower expression of miR-155 and MIR-146a in patients with pneumonia compared with healthy volunteers; this may be related to inflammation and the use of anti-inflammatory drugs. We also found increased TNF-α and IL-6 expression at the RNA level, while macrophage galactose-type C-type lectin 1 (MGL-1) expression decreased with downregulation of miR-155 and miR-146a expression. These results indicate that the gene regulation mediated by miR-155 and miR-146a contributes to human alveolar macrophage phenotype repolarization, thus leading to an early switch from pro-inflammatory to anti-inflammatory cytokine production.

Disseminated infection caused by Emmonsia pasteuriana in a renal transplant recipient.

Emmonsia pasteuriana is a thermally dimorphic fungus identified in very few human cases. Here, we report a case of a 43-year-old male renal transplant patient from China presenting with multiple painful skin eruptions on his head, nose and left thigh, later accompanied by respiratory failure. Histopathology of the biopsy collected from the left thigh upper ulcer and occipital nodule both demonstrated chronic inflammation with granuloma formation and yeast-like elements. Emmonsia pasteuriana was cultured from two biopsy specimens and their identity was confirmed by sequencing of the rDNA internal transcribed spacer. The patient in intensive care showed marked clinical improvement with antifungal treatment.

Protective effects of caffeoylxanthiazonoside isolated from fruits of Xanthium strumarium on sepsis mice.

CONTEXT: The fruit of Xanthium strumarium L. (Asteraceae) has been used for the treatment of various inflammatory diseases. OBJECTIVE: This study investigates the protective effect of caffeoylxanthiazonoside (CYXD) isolated from fruits of X. strumarium on sepsis mice in vitro and in vivo. MATERIALS AND METHODS: Cecal ligation and puncture (CLP) operation was used to establish the sepsis mice model, and sham mice were also performed. CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then the survival rate was measured in 96 h. Additionally, sepsis mice were induced by injection LPS (2 mg/kg); CYXD was administered by intraperitoneal injection (10, 20, and 40 mg/kg/d), then mice were sacrificed, and serum levels of TNF-α and IL-6 were determined by ELISA assay. Furthermore, the ability of CYXD to neutralize LPS was measured by using the LAL test, and expressions of TNF-α, IL-6 were determined by using real-time fluorogenic PCR. RESULTS: Results indicated that CYXD significantly elevated survival rates of sepsis mice induced by CLP (p < 0.05) with survival rates of 35%, 45%, and 65%. Furthermore, the LPS level was decreased obviously by CYXD (1, 2, and 4 mg/L) (p < 0.05). Additionally, CYXD (10, 20, and 40 mg/kg) can not only significantly decrease TNF-α and IL-6 levels induced by LPS in mice's serum (p < 0.05), but also inhibit mRNA expressions of TNF-α and IL-6 induced by LPS in RAW 264.7 cells at doses of 20, 40, and 80 µg/mL (p < 0.05). CONCLUSION: Our study demonstrated that CYXD has significant protective effects on sepsis mice.

STAT1 regulates MD-2 expression in monocytes of sepsis via miR-30a.

Sepsis is a major cause of morbidity and mortality in critically ill patients. MD-2 is a 25-kDa lipopolysaccharide (LPS)-binding protein that forms a heterodimer with TLR42, but its regulation in sepsis is not clear. This study aims to investigate the molecular mechanism of regulation of MD-2. Inflammation cytokines in monocytes were analyzed by real-time RT-PCR and ELISA, and it was found that IL-10 was elevated significantly in the monocytes with LPS treatment. And then, when the cells were treated with IL-10, STAT1 was activated in the monocytes using Western blotting. It was also found that STAT1 could enhance MD-2 expression on transcriptional and posttranscriptional levels. Finally, miR-30a was predicted to the molecule that may regulate STAT1 expression. It was verified that STAT1 was a new target gene of miR-30a. miR-30a could inhibit IL-10-induced cytokine release by targeting STAT1-MD-2 in monocytes. In conclusion, this study for the first time demonstrated that miR-30a inhibits MD-2 expression by targeting of STAT1 in human monocytes.

Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages.

Staphylococcus aureus (S. aureus) is the most common bacterium in sepsis and pneumonia involving gram-positive bacteria. Lipoteichoic acid (LTA) is a cell wall component of gram-positive bacteria. It is a potent inducer of inflammatory mediators in human dendritic cells, human pulmonary epithelial cells, and murine macrophages. However, the effect of LTA on human alveolar macrophages (AMs) which are the major effector cells in host defense against respiratory tract infections has hardly been studied. Statins have anti-inflammatory, immunomodulatory, antioxidative, anticoagulant, and antibacterial activities. These effects may be contributed to reduce the markers of systemic inflammation. Emerging retrospective studies have demonstrated that statin use decreased the mortality of pneumonia. However, the precise mechanisms responsible for these effects are unclear. The purpose of this study is to define the role of S. aureus LTA in human AMs and the effects of simvastatin (SV) on LTA-stimulated human AMs. The results showed that LTA induced tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), IL-8 mRNA expression, and suppressed IL-10 mRNA expression in human AMs. Simultaneously, LTA induced human AMs apoptosis. These effects were parallel with the up-regulation of the expression of NF-κB-P65 protein in the LTA-stimulated human AMs. The above effects of LTA on human AMs were inhibited significantly by SV. These data indicate that S. aureus LTA induces potent pro-inflammatory and pro-apoptotic effects on human AMs and statins exert anti-inflammatory effects by mediating inhibition of NF-κB activation and cytokine mRNA expression in human AMs. These results may explain, in part, the mechanisms responsible for favorable effects of statins on pneumonia.

Cost-Effectiveness of Linezolid versus Vancomycin among Patients with Methicillin-Resistant Staphylococcus aureus Confirmed Nosocomial Pneumonia in China.

OBJECTIVE: To estimate the cost-effectiveness of intravenous linezolid as a first-line agent against intravenous vancomycin in treating methicillin-resistant Staphylococcus aureus-confirmed nosocomial pneumonia in four Chinese cities. METHODS: A decision-analytic model of 4-week time horizon was used to conduct cost-effectiveness analyses from the payer's perspective. Clinical outcomes and resource use data were derived from a head-to-head trial, supplemented with local cost estimates based on hospital data via an expert panel. A series of scenario analyses were conducted to evaluate the impact of uncertainty around model inputs. All results were reported in 2012 Chinese Renminbi. RESULTS: The predicted probability of overall treatment success was 0.629 and 0.602 for linezolid and vancomycin, respectively. Total inpatient costs varied across the four cities, ranging from ¥58,835 to ¥86,894 for linezolid and ¥58,390 to ¥87,033 for vancomycin, respectively. Linezolid was demonstrated to be a dominant treatment strategy in Guangzhou. In Beijing, Nanjing, and Xi'an, incremental cost-effectiveness ratios in terms of additional successfully treated patient were ¥1,861, ¥163, and ¥16,509, respectively. Dominance by linezolid was observed in some scenario analyses with parameters such as treatment duration, inclusion of cost of managing adverse events, and drug acquisition costs being the main drivers of cost-effectiveness results. CONCLUSIONS: Despite linezolid's higher drug acquisition cost, its superior clinical efficacy renders it a likely cost-effective alternative for the treatment of methicillin-resistant Staphylococcus aureus-confirmed nosocomial pneumonia as compared with branded vancomycin from the payer perspectives of Beijing, Guangzhou, Nanjing, and Xi'an.