mTORC2 Activation Mediated by Mesenchymal Stem Cell-Secreted Hepatocyte Growth Factors for the Recovery of Lipopolysaccharide-Induced Vascular Endothelial Barrier.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.

Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study.

BACKGROUND: Genetic locus were identified associated with acute respiratory distress syndrome (ARDS). Our goal was to explore the associations between genetic variants and ARDS outcome, as well as subphenotypes. METHODS: This was a single-center, prospective observational trial enrolling adult ARDS patients. After baseline data were collected, blood samples were drawn to perform whole exome sequencing, single nucleotide polymorphism (SNP)/insertion-deletion to explore the quantitative and functional associations between genetic variants and ICU outcome, clinical subphenotypes. Then the lung injury burden (LIB), which was defined as the ratio of nonsynonymous SNP number per megabase of DNA, was used to evaluate its value in predicting ARDS outcome. RESULTS: A total of 105 ARDS patients were enrolled in the study, including 70 survivors and 35 nonsurvivors. Based on the analysis of a total of 65,542 nonsynonymous SNP, LIB in survivors was significantly higher than nonsurvivors [1,892 (1,848-1,942)/MB versus 1,864 (1,829-1,910)/MB, P=0.018], while GO analysis showed that 60 functions were correlated with ARDS outcome, KEGG enrichment analysis showed that SNP/InDels were enriched in 13 pathways. Several new SNPs were found potentially associated with ARDS outcome. Analysis of LIB was used to determine its outcome predicting ability, the area under the ROC curve of which was only 0.6103, and increase to 0.712 when combined with APACHE II score. CONCLUSIONS: Genetic variants are associated with ARDS outcome and subphenotypes; however, their prognostic value still need to be verified by larger trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT02644798. Registered 20 April 2015.

Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier.

Mesenchymal stem cells (MSCs) may improve the treatment of acute respiratory distress syndrome (ARDS). However, few studies have investigated the effects of mechanically stretched -MSCs (MS-MSCs) in in vitro models of ARDS. The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. We introduced a cocultured model of pulmonary microvascular endothelial cell (EC) and MSC medium obtained from MSCs with or without mechanical stretch. We found that Wright-Giemsa staining revealed that MSC morphology changed significantly and cell plasma shrank separately after mechanical stretch. Cell proliferation of the MS-MSC groups was much lower than the untreated MSC group; expression of cell surface markers did not change significantly. Compared to the medium from untreated MSCs, inflammatory factors elevated statistically in the medium from MS-MSCs. Moreover, the paracellular permeability of endothelial cells treated with LPS was restored with a medium from MS-MSCs, while LPS-induced EC apoptosis decreased. In addition, protective effects on the remodeling of intercellular junctions were observed when compared to LPS-treated endothelial cells. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS.

Treatment of Retroperitoneal Cavernous Lymphangioma: A Case Report.

A 32-year-old man who complained of recurrent nauseat and vomiting was admitted to our hospital. The contrast-enhanced computed tomography revealed a cystic mass located behind the duodenum which was suggestive of lymphangioma. Laparoscopic resection of the retroperitoneal mass was successfully performed. The postoperatively pathological examination confirmed the diagnosis of cavernous lymphangioma. Ultrasound and enhanced CT can be used for making a preoperative diagnosis. Once symptoms of the disease develop, complete surgical resection should be performed.

Diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis: a meta-analysis.

BACKGROUND: We aim to synthesize the up-to-date studies to investigate the diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis. RESULTS: A total of 19 studies with 2418 patients were finally enrolled in the meta-analysis. The pooled sensitivity was 0.82 (95% CI 0.73 to 0.89), specificity 0.81 (95% CI 0.75 to 0.86), positive likelihood ratio 4.3 (95% CI 3.02 to 6.12), negative likelihood ratio 0.22 (95% CI 0.24 to 0.35), diagnostic odds ratio 20 (95% CI 9 to 41) and AuROC 0.88 (95% CI 0.85 to 0.91). The meta-regression analysis revealed that the sample size, reference standard description, prevalence of sepsis in the trials and consecution of patient recruitment might be the source of heterogeneity. CONCLUSIONS: The serum sTREM-1 had a moderate ability in diagnosis in suspected sepsis based on the current studies. However, more large-scale studies were needed to further evaluate the diagnostic accuracy of sTREM-1.

Plasma Midkine Is Associated With 28-Day Mortality and Organ Function in Sepsis.

BACKGROUND: Midkine has been reported to play a crucial role in inflammatory, hypoxia, and tissue injury processes. We aimed to investigate plasma midkine in septic patients and its association with 28-day mortality and organ function. METHODS: Septic patients admitted to the Department of Critical Care Medicine, Zhongda Hospital, a tertiary hospital, from November 2017 to March 2018 were enrolled in the study. The baseline characteristics of the septic patients were recorded at admission. A peripheral blood sample was obtained at admission, and plasma midkine levels were evaluated with an immunoassay. All patients were followed up with for 28 days, with all-cause mortality being recorded. RESULTS: A total of 26 septic patients were enrolled, which included 18 survivors and 8 nonsurvivors at day 28. Plasma midkine levels were significantly elevated in the nonsurvivor group compared with the survivors (ng/L, 763.6 [404.7-1305], 268.5 [147.8-511.4]; P = .0387]. Plasma midkine levels were elevated in septic patients with moderate/severe acute respiratory distress syndrome (ARDS) compared with patients with non/mild ARDS (ng/L, 522.3 [336.6-960.1] vs 243.8 [110.3-478.9]; P = .0135) and in those with acute kidney injury compared with those without (ng/L, 489.8 [259.2-1058] vs 427.9 [129.6-510.3]; P = .0973). Changes in plasma midkine levels were also associated with extravascular lung water index (P = .063) and pulmonary vascular permeability index (P = .049). CONCLUSIONS: Plasma midkine was associated with 28-day mortality, as well as pulmonary and kidney injury, in septic patients.

Effect of high-flow nasal cannula oxygen therapy compared with conventional oxygen therapy in postoperative patients: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of high-flow nasal cannula oxygen therapy (HFNC) versus conventional oxygen therapy (COT) on the reintubation rate, rate of escalation of respiratory support and clinical outcomes in postextubation adult surgical patients. DESIGN: Systematic review and meta-analysis of published literature. DATA SOURCES: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Index and Wan fang databases were searched up to August 2018. ELIGIBILITY CRITERIA: Studies in postoperative adult surgical patients (≥18 years), receiving HFNC or COT applied immediately after extubation that reported reintubation, escalation of respiratory support, postoperative pulmonary complications (PPCs) and mortality were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: The following data were extracted from the included studies: first author's name, year of publication, study population, country of origin, study design, number of patients, patients' baseline characteristics and outcomes. Associations were evaluated using risk ratio (RR) and 95% CIs. RESULTS: This meta-analysis included 10 studies (1327 patients). HFNC significantly reduced the reintubation rate (RR 0.38, 95% CI 0.23 to 0.61, p<0.0001) and rate of escalation of respiratory support (RR 0.43, 95% CI 0.26 to 0.73, p=0.002) in postextubation surgical patients compared with COT. There were no differences in the incidence of PPCs (RR 0.87, 95% CI 0.70 to 1.08, p=0.21) or mortality (RR 0.45, 95% CI 0.16 to 1.29, p=0.14). CONCLUSION: HFNC is associated with a significantly lower reintubation rate and rate of escalation of respiratory support compared with COT in postextubation adult surgical patients, but there is no difference in the incidence of PPCs or mortality. More well-designed, large randomised controlled trials are needed to determine the subpopulation of patients who are most likely to benefit from HFNC therapy.

Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. METHODS: PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7-10-day, 28-30-day and 90-180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger's and Begger's test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). RESULTS: Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93-1.12), p = 0.65]. Subgroup analysis revealed no difference of 7-10-day mortality [RR(95%CI)) = 0.89(0.54-1.49), p = 0.66], 28-30-day mortality[RR(95%CI) = 1.00(0.89-1.12), p = 0.98] and 90-180-day mortality [RR(95%CI) = 1.11(0.94-1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(- 0.12-0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.

mTOR/STAT-3 pathway mediates mesenchymal stem cell-secreted hepatocyte growth factor protective effects against lipopolysaccharide-induced vascular endothelial barrier dysfunction and apoptosis.

Mesenchymal stem cells (MSCs) protect the endothelial barrier complex and survival, implicated in the pathogenesis of acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF). However, the mechanism of HGF in endothelial regulation remains unclear. Here, we introduced a coculture protocol of pulmonary microvascular endothelial cells (PMVECs) and overexpression of the HGF gene of MSCs (MSC-HGF). Immunofluorescence and endothelial permeability analysis revealed that MSC-HGF protected endothelial tight junction protein occludin expression and attenuated cellular permeability as well as endothelial apoptosis. To investigate the novel mechanism mammalian TOR (mTOR)/ signal transducer and activator of transcription 3 (STAT-3) signaling in HGF protective effects against endothelial barrier and apoptosis, we used recombinant mouse HGF in endothelial cells. In addition, we used mTOR inhibitor rapamycin to inhibit the mTOR pathway. Our study demonstrated that rapamycin decreased the protective effects of HGF on the endothelium by decreasing tight junction protein occludin expression and cell proliferation, and raising lipopolysaccharide (LPS)-induced endothelial permeability, endothelial cell injury factors ET-1 and vWF. Similarly, the protective effects of HGF on reducing endothelial barrier and apoptosis were weakened when PMVECs were treated with the STAT-3 inhibitor S3I-201. Moreover, mTOR/STAT-3 were activated by HGF demonstrated as raising mTOR (Ser2448) and STAT3 (Ser727) phosphorylation proteins, leading to endothelial barrier improvement and survival. Reversely, rapamycin or S3I-201 inhibited mTOR/STAT-3 activation. Taken together, our findings highlight that the activation of the mTOR/STAT-3 pathway provides novel mechanistic insights into MSC-secreted HGF protection against LPS-induced vascular endothelial permeability dysfunction and apoptosis, which contributes to decreasing microvascular loss and lung injury.

LincRNA-p21 promotes mesenchymal stem cell migration capacity and survival through hypoxic preconditioning.

BACKGROUND: Mesenchymal stem cells (MSCs) derived from bone marrow have potent stabilizing effects for the treatment of acute respiratory distress syndrome (ARDS). However, low efficiency and survival in MSC homing to injured lung tissue remains to be solved. Therefore, the aim of this study was to assess whether large intergenic noncoding RNA (LincRNA)-p21 promote MSC migration and survival capacity through hypoxic preconditioning in vitro. METHODS: MSCs were cultured and divided into the normoxia culture group (20% O2) and hypoxia culture group (1% O2). To determine roles and mechanisms, lentivirus vector-mediated LincRNA-p21 knockdown of MSCs and hypoxia-inducible factor (HIF-1α) inhibitor KC7F2 were introduced. Additionally, MSC migration was analyzed by scratch test and transwell migration assays. MSC proliferation was tested by cell counting kit-8 and trypan blue dye. Apoptosis was detected by Annexin V-PE/7-AAD stained flow cytometry. Moreover, LincRNA-p21 and HIF-1α mRNA was measured by reverse transcription-polymerase chain reaction, and HIF-1α and CXCR4/7 protein were assayed by western blot (WB) or enzyme-linked immunosorbent assay (ELISA). Apoptosis protein caspase-3 and cleaved-caspase-3 were investigated by WB analysis. Considering interactions between VHL and HIF-1α under LincRNA-p21 effect, co-immunoprecipitation was detected. RESULTS: Hypoxic preconditioning MSC promoted migration capacity and MSC survival than normoxia culture group. MSCs induced by hypoxic preconditioning evoked an increase in expression of LincRNA-p21, HIF-1α, and CXCR4/7(both were chemokine stromal-derived factor-1(SDF-1) receptors). Contrarily, blockade of LincRNA-p21 by shRNA and HIF-1α inhibitor KC7F2 abrogated upregulation of hypoxic preconditioning induced CXCR4/7 in MSCs, cell migration, and survival. Furthermore, co-immunoprecipitation assay revealed that hypoxic preconditioning isolated VHL and HIF-1α protein by increasing HIF-1α expression. CONCLUSIONS: Hypoxic preconditioning was identified as a promoting factor of MSC migration and survival capacity. LincRNA-p21 promotes MSC migration and survival capacity through HIF-1α/CXCR4 and CXCR7 pathway under hypoxic preconditioning in vitro.

Maternal allergic disease history affects childhood allergy development through impairment of neonatal regulatory T-cells.

BACKGROUND: Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood. METHODS: A total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study. Detailed questionnaires were administered yearly to determine the allergy status of the mothers and the newborns from birth to 3 years of age. Cord blood samples obtained at the time of birth were analysed for Treg counts, as well Treg activity, based on their response to Toll-like receptor (TLR) stimuli such as lipid A (LPA) and peptidoglycans (PPG). Surface markers, associated genes, suppressive capacity, and cytokine levels of Tregs were also measured. Possible correlations between Treg activity and maternal or neonate allergies were assessed. In addition, environmental microbial content and other known risk factors for allergies were measured. RESULTS: Cord blood mononuclear cells (CBMCs) from offspring with allergic mothers showed fewer CD4(+)CD25(+)FOXP3(+) T cells, lower expression levels of associated genes, and reduced cytokine production of interleukin (IL)-10 and interferon-γ (P < 0.05), especially via the PPG-TLR2 pathway. Suppression of effector T cells by Tregs from children of mothers with allergies was impaired, especially IL-13 production by Type 2 T helper (Th2) cells (P = 0.026). Children who developed allergies in the first 3 years of life had lower numbers of CD4(+)CD25(+)FOXP3(+) T cells and reduced FOXP3 expression and IL-10 production as newborns (P < 0.05). Maternal allergic background was identified as a risk factor for allergy development in the children (Odds ratio (OR) = 2.46, 95 % CI = 1.05-5.79); while declining Treg numbers, IL-10 production, and FOXP3 expression in neonates (PPG and LPA stimulated) were identified as independent risk factors for allergic diseases in offspring at 3 years of age after adjusting for maternal allergic history and environmental factors (P < 0.05). CONCLUSION: Maternal allergy correlated with impaired Tregs in neonates, and this could enhance the susceptibility of offspring to allergic diseases in early childhood due to an imbalance of Th1 and Th2 cells.

Asthma control and severe exacerbations in patients with moderate or severe asthma in Jilin Province, China: a multicenter cross-sectional survey.

BACKGROUND: No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China. METHODS: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire. RESULTS: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation. CONCLUSIONS: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China.

[Sodium nitrite enhanced the potentials of migration and invasion of human hepatocellular carcinoma SMMC-7721 cells through induction of mitophagy].

Nitrites play multiple characteristic functions in invasion and metastasis of hepatic cancer cells, but the exact mechanism is not yet known. Cancer cells can maintain the malignant characteristics via clearance of excess mitochondria by mitophagy. The purpose of this article was to determine the roles of nitrite, reactive oxygen species (ROS) and hypoxia inducing factor 1 alpha (HIF-1 α) in mitophagy of hepatic cancer cells. After exposure of human hepatocellular carcinoma SMMC-7721 cells to a serial concentrations of sodium nitrite for 24 h under normal oxygen, the maximal cell vitality was increased by 16 mg x (-1) sodium nitrite. In addition, the potentials of migration and invasion for SMMC-7721 cells were increased significantly at the same time. Furthermore, sodium nitrite exposure displayed an increase of stress fibers, lamellipodum and perinuclear mitochondrial distribution by cell staining with Actin-Tracker Green and Mito-Tracker Red, which was reversed by N-acetylcysteine (NAC, a reactive oxygen scavenger). DCFH-DA staining with fluorescent microscopy showed that the intracellular level of ROS concentration was increased by the sodium nitrite treatment. LC3 immunostaining and Western blot results showed that sodium nitrite enhanced cell autophagy flux. Under the transmission electron microscopy (TEM), more autolysosomes formed after sodium nitrite treatment and NAC could prevent autophagosome degradation. RT-PCR results indicated that the expression levels of COX I and COXIV mRNA were decreased significantly after sodium nitrite treatment. Meanwhile, laser scanning confocal microscopy showed that sodium nitrite significantly reduced mitochondrial mass detected by Mito-Tracker Green staining. The expression levels of HIF-1α, Beclin-1 and Bnip3 (mitophagy marker molecular) increased remarkably after sodium nitrite treatment, which were reversed by NAC. Our results demonstrated that sodium nitrite (16 mg x L(-1)) increased the potentials of invasion and migration of hepatic cancer SMMC-7721 cells through induction of ROS and HIF-1α mediated mitophagy.

Solvent-Induced Single Crystal-Single Crystal Transformation of an Interpenetrated Three-Dimensional Copper Triazole Catalytic Framework.

The 2-fold interpenetrated 3D framework 1 can be solvent-induced to noninterpenetrated framework 1' in a reversible single crystal-single crystal transformation fashion. In addition, 1' represents the first catalyst based on triazole to catalyze the aerobic homocoupling of various substituted arylboronic acids.

[Exposure of human hepatoma cells to nitrite and ammonia promotes invasive activity through activation of ROS/ODC pathway].

Recent studies have demonstrated that nitrite and ammonia levels are higher in the tumor environment, but their effects on cancer cells remains unclear. The present study was designed to determine the effects of nitrite and ammonia on tumor invasion and the role of reactive oxygen (ROS)/ornithine decarboxylase (ODC) pathway. SMMC-7721 cells were treated with sodium nitrite, ammonium chloride, sodium nitrite and ammonium chloride mixture for 24 h, the cell viability was analyzed using the MTT assay, cell invasion was analyzed with the transwell assay, the intracellular ROS levels were detected with a reactive oxygen species (ROS) test kits, the expression of intracellular ODC was examined with immunofluorescence and Western blot, the expression of matrix metallopeptidase-2 (MMP-2) and MMP-9 were analyzed by Western blot. Compared with the control group, SMMC-7721 cells exhibited an increase in cell viability, invasion ability, ROS levels and ODC protein after exposure to 150 µmol·L(-1) sodium nitrite and ammonium chloride mixture for 24 h. The invasive activity was reduced by ROS scavenger N-acetycysteine (NAC) in SMMC-7721 cells. The specific ODC inhibitor difluoromethylornithine (DFMO) increased ROS levels and weakened the ability of sodium nitrite and ammonium chloride mixture in the regulation of invasion of SMMC-7721 cells. These data demonstrated that sodium nitrite and ammonium chloride mixture promote invasion of SMMC-7721 cells by enhancing ROS/ODC pathway.

[Clinical analysis of hemolytic-uremic syndrome associated with Streptococcus pneumoniae serotype 3 infection in a child].

OBJECTIVE: To study the clinical characteristics of Streptococcus pneumonia-associated hemolytic uremic syndrome (SP-HUS) in children. METHOD: Clinical and laboratory data of a pediatric case of SP-HUS were retrospectively analyzed and the key points of diagnosis and therapy were reviewed. RESULT: An 18-month old girl was admitted with chief complaint of fever and cough for 5 days combined with mild labored breath. Breath sound was found weakened in right lung with lower lobe dullness on percussion. Laboratory tests revealed: WBC 3.7×10(9)/L, Hb 83 g/L, PLT 11×10(9)/L, C-reactive protein (CRP) > 180 mg/L. Morphological study of the RBCs showed marked anisocytosis and schistocytosis. Urinalysis showed 42.66 RBCs per high-power field, occult blood (+++), proteinura (++++). Streptococcus pneumoniae was isolated from blood, pleural fluid and sputum. Serotyping with simplified chessboard system was 3. The direct Coombs test was positive. Serum complement levels (C3 and C4) were depressed at 0.699 g/L, 0.064 g/L, respectively. Chest X-ray showed pleural effusion and infection of the right hemothorax. The computerized tomographic scan of the chest revealed pneumatoceles in the right lower lobe. The diagnosis on admission we considered was SP-HUS. Intravenous antibiotic therapy (vancomycin + cefoperazone/sulbactam) was administered. The renal replacement theraphy was administered to maintain electrolyte and fluid balances and adequate nutrition. Transfusions of washed red blood cells were administered to correct the anemia. One month after admission the patient was good with recovery. Liver and renal function recovered and the pneumonia was resolving, anemia and platelets were corrected. The direct Coombs test turned to be negative. Serum complement levels (C3 and C4) were normal. After 3-month follow-up, no clinical anomalies were detected. CONCLUSION: SP-HUS should be suspected when the following occurs in the context of pneumococcal infections: microangiopathic hemolytic anemia, thrombocytopenia, acute renal failure and a positive Coombs test result. Serotype 3 of SP was associated with HUS.