Evaluation of serum Epstein-Barr virus envelope glycoproteins antibodies and their association with systemic autoimmune diseases.

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.

Analysis Of The Association Between Sh2B1 chr16.28884655 And Type 2 Diabetes.

PURPOSE: To determine correlation between genetic susceptibility of type 2 diabetes mellitus (T2DM) and Src homology 2 B adapter protein 1 (SH2B1) gene polymorphism in a diabetic population.  Methods: A total of 111 T2DM patients (DM group) and 34 healthy controls (NC group) from Shanxi Provincial People's Hospital were included in this study. Exon 9 of the SH2B1 gene was detected using the Sanger sequencing method, and the relationship between SH2B1 gene polymorphism and diabetes was analyzed.  Results: Comparison of the data between the two groups showed that the values of TG, the updated HOMA of insulin resistance (HOMA2-IR), weight, body mass index, waist circumference, fasting blood glucose and fasting insulin levels of the DM group were higher than those of the NC group (P < 0.05). The HOMA2 insulin sensitivity (%S) of the DM group was lower than that of the NC group (P < 0.05). Sequencing analysis revealed that the following five single nucleotide polymorphisms in exon 9 of SH2B1 may be related to T2DM: rs181578610, rs550079240, chr16.28884655, chr16.28884659 and chr16.28884831. Among them, chr16.28884655 was found to be significantly related to diabetes; this site, located on the NM_015503 exon, was related to TG, LDL-C and waist circumference. CONCLUSION: The SH2B1 gene locus chr16.28884655 was found to be significantly related to genetic susceptibility to T2DM.

Pyopneumothorax from coinfection by Trichomonas tenax and Geotrichum capitatum in a child from China: a case report.

BACKGROUND: Trichomonas tenax may appear in the oral cavity of humans due to poor dentition or oral hygiene. Pyopneumothorax is a serious complication of lower respiratory tract infections that very rarely can be caused by a trichomonad species in predisposed individuals. We report a rare case of pleurisy due to T. tenax with coinfection by a fungus. CASE PRESENTATION: We describe a 16-year-old patient with cerebral palsy who presented with severe pyopneumothorax. T. tenax was identified by microscopic examination of the pleural effusion and next-generation sequencing. We also identified Geotrichum capitatum in the pleural effusion and bronchoalveolar lavage fluid cultures. Treatment with voriconazole and metronidazole successfully eliminated these pathogens and relieved the clinical symptoms. A literature review indicated this is the first reported case of pleurisy due to T. tenax with coinfection by a fungus. CONCLUSION: The rarity of pyopneumothorax caused by T. tenax coinfection with a fungus should not be overlooked in the clinic. These patients should be and treated in a timely manner.

Jatrophane Diterpenoids from Euphorbia peplus as Multidrug Resistance Modulators with Inhibitory Effects on the ATR-Chk-1 Pathway.

Twelve undescribed jatrophane diterpenoids, euphpepluones A-L (1-12), together with seven known analogues (13-19), were isolated from the whole plant of Euphorbia peplus, and their structures were elucidated by spectroscopic studies. The absolute configurations of 1 and 4 were assigned by X-ray crystallographic analysis. All isolates were investigated for their inhibitory effects against the ATR-Chk1 pathway using a Western blotting assay. As a result, 1, 2, 5, 8, 10, and 16 were found to suppress the camptothecin (CPT)-induced phosphorylation of Chk1, indicating that these compounds inhibit the activation of the ATR-Chk1 pathway. A preliminary structure-activity relationship (SAR) study of the isolates was conducted. When compound 10 and CPT were combined, apoptosis was induced in A549 cells with PARP cleavage, while there was no apoptotic effect by treatment with CPT or 10 alone. The data obtained indicate that 10 potentiates the chemotherapeutic sensitivity of A549 cells to CPT.

Comparative effectiveness of metformin monotherapy in extended release and immediate release formulations for the treatment of type 2 diabetes in treatment-naïve Chinese patients: Analysis of results from the CONSENT trial.

AIMS: Metformin treatment for type 2 diabetes mellitus (T2DM) can be limited by gastrointestinal (GI) adverse events (AEs), resulting in treatment discontinuation. We investigated whether once-daily metformin extended release (XR) is superior in terms of GI tolerability, with non-inferior efficacy, compared with thrice-daily metformin immediate release (IR) in treatment-naïve Chinese patients with T2DM. MATERIALS AND METHODS: This prospective, open-label, randomized, multicentre, phase IV interventional study enrolled Chinese T2DM patients to receive either metformin XR or metformin IR with a 2-week screening period, a 16-week treatment period and a 2-week follow-up period without treatment. Co-primary endpoints were a non-inferiority assessment of metformin XR vs metformin IR in glycated haemoglobin (HbA1c) least squares mean (LSM) change from baseline to week 16 and the superiority of GI tolerability for metformin XR vs metformin IR. RESULTS: Overall, 532 patients were randomized to metformin IR (n = 267) or metformin XR (n = 265). The HbA1c LSM change was -1.61% and -1.58% in each group, respectively (LSM difference, 0.03; 95% confidence interval [CI], -0.10, 0.17). Incidences of drug-related AEs were 26.5% (n = 66) in the metformin IR-only group and 32.2% (n = 85) in the metformin XR-only group, and GI AEs were 23.8% and 22.3% in each group, respectively (difference, -1.52; 95% CI, -8.60, 5.56). The treatment difference met the predefined non-inferiority upper CI margin of 0.4% in HbA1c. CONCLUSIONS: Metformin XR was non-inferior to metformin IR for the LSM change in HbA1c from baseline to week 16 and not superior to metformin IR for overall GI AE incidence during treatment of Chinese T2DM patients.

Impact of frailty on pneumonia outcomes in older patients: a systematic review and meta-analysis.

PURPOSE: The ideal method for identifying frailty remains unclear, but the condition is associated with poor prognoses in many illnesses. Despite the availability of studies, the prognostic implications of frailty on older patients with pneumonia remains unexplored. To determine the burden and effect of frailty on selected clinical outcomes among older patients with pneumonia. METHODS: We searched Medline, Google Scholar, and Science Direct databases for articles published in English following the PRISMA framework to guide our review. We included studies conducted on patients (> 60 years) with frailty and pneumonia, and reporting the effect of frailty on mortality, hospital stay, length readmission, and ICU admission. We performed a meta-analysis using STATA 14.2, calculating pooled odds ratios and 95% confidence intervals. RESULTS: We analysed data from 16 studies and calculated a pooled frailty prevalence of 49% (95% CI 37-60%) in older patients with pneumonia. Unadjusted analyses revealed an odds ratio (OR) of 2.50 (95% CI 1.88-3.32) for the intermediate risk group, and an OR of 3.51 (95% CI 3.05-4.05) for the high risk group regarding mortality. The high risk frailty group also exhibited significant elevations in the risk of readmissions and extended hospital stay lengths. Substantial heterogeneity was observed in both adjusted and unadjusted analyses. CONCLUSIONS: Our systematic review and meta-analysis results show that one in every two older individuals with pneumonia present frailty, a condition that significantly influences their rates of mortality and readmission, and their hospital stay length.

Human ß-defensin-3 and nuclear factor-kappa B p65 synergistically promote the cell proliferation and invasion of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a usual oral cancer. Therefore, it's essential to identify targets for its early diagnosis and therapy. This research aimed to explore the roles of human ß-defensin-3 (hBD-3) and nuclear factor-kappa B (NF-κB) p65 in the pathogenesis and progression of OSCC. The connection between NF-κB p65 and the carcinogenesis of oral cancer was analyzed by immunohistochemical staining. The relative expressions of hBD-3 and NF-κB p65 in OSCC cells were evaluated by qRT-PCR and Western blot. Afterward, hBD-3 was knocked down, and NF-κB p65 was overexpressed. The cell viability and invasion were tested via CCK-8 and Transwell experiment, and the expression of hBD-3, NF-κB p65, and its downstream molecules was evaluated by Western blot. The expression of NF-κB p65 was increased with the aggravation of the oral submucosal fibrosis. HBD-3 and NF-κB p65 were high-expressed in OSCC cells. The viability and invasion abilities of OSCC cells that knocked down hBD-3 were markedly decreased, while they were restored by the overexpression of NF-κB p65. The expressions of NF-κB p65 and c-myc were diminished while IκB and p21 were raised with the knockdown of hBD-3. After overexpression of NF-κB p65, the expression of hBD-3 and IκB did not change markedly, while c-myc was increased and p21 was decreased dramatically. HBD-3 and NF-κB p65 facilitate the proliferation and invasion of OSCC cells, and hBD-3 may promote this process by governing the expression of NF-κB p65 and its downstream c-myc and p21.

Immune microenvironment heterogeneity reveals distinct subtypes in neuroblastoma: insights into prognosis and therapeutic targets.

BACKGROUND: Neuroblastoma (NB) is a childhood cancer originating from immature nerve cells in the sympathetic nervous system. Current clinical and molecular subtyping methods for NB have limitations in providing accurate prognostic information and guiding treatment decisions. RESULTS: To overcome these challenges, we explored the microenvironment of NB based on the knowledge-based functional gene expression signatures (Fges), which revealed heterogeneous subtypes. Consensus clustering of Fges activity scores identified three subtypes (Cluster 1, Cluster 2, and Cluster 3) that demonstrated significant differences in prognosis compared to mainstream subtypes. We assessed the immune infiltration, immunogenicity, CD8T cytotoxicity, and tumor purity of these subtypes, uncovering their distinct biological functions. Cluster 1 and Cluster 2 exhibited higher immunoreactivity, while Cluster 3 displayed higher tumor purity and poor prognosis. Gene ontology annotation and pathway analysis identified immune activation in Cluster 1, epithelial-mesenchymal transition (EMT) in Cluster 2, and cell cycle processes in Cluster 3. Notably, the impact of EMT activity on prognosis may vary across NB subtypes. A classification model using XGBoost accurately predicted subtypes in independent NB cohorts, with significant prognostic differences. GPR125, CDK4, and GREB1 emerged as potential therapeutic targets in Cluster 3. CD4K inhibitors showed subtype-specific responses, suggesting tailored treatment strategies. Single-cell analysis highlighted unfavorable clinical features in Cluster 3, including high-risk classification and reduced cytotoxicity. Suppressed interactions between monocytes, macrophages, and regulatory T cells were observed, affecting immune regulation and patient prognosis. CONCLUSION: To summarize, we have identified a new independent prognostic factor in NB that underscores the significant correlation between tumor phenotype and immune contexture. These findings deepen our understanding of NB subtypes and immune cell interactions, paving the way for more effective treatment approaches.

Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1.

BACKGROUND: In recent years, studies have found that the occurrence and development of diabetic cardiomyopathy (DCM) is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1 (PARP-1) activity. PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress, the inflammatory response, apoptosis and myocardial fibrosis. AIM: To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats, further clarified the protective effect of liraglutide on the heart, and provided a new option for the treatment of DCM. METHODS: Forty healthy male SD rats aged 6 wk were randomly divided into two groups, a normal control group (n = 10) and a model group (n = 30), which were fed an ordinary diet and a high-sugar and high-fat diet, respectively. After successful modeling, the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group (further divided into a high-dose group and a low-dose group). The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention. Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles. Intact heart tissue was dissected, and its weight was used to calculate the heart weight index. Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry. RESULTS: The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group, and those in the intervention group were decreased compared with those in the model group, with a more obvious decrease observed in the high-dose group (P < 0.05). In the model group, myocardial fibers were disordered, and inflammatory cells and interstitial fibrosis were observed. The cardiomyopathy of rats in the intervention group was improved to different degrees, the myocardial fibers were arranged neatly, and the myocardial cells were clearly striated; the improvement was more obvious in the high-dose group. Compared with the normal control group, the expression of PARP-1 in myocardial tissue of the model group was increased, and the difference was statistically significant (P < 0.05). After liraglutide intervention, compared with the model group, the expression of PARP-1 in myocardial tissue was decreased, and the reduction was more obvious in the high-dose group (P < 0.05) but still higher than that in the normal control group. CONCLUSION: Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

Preparation of a nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material and a preliminary study of its effects on MC3T3-E1 cells.

A nanopearl powder/C-HA (chitosan-hyaluronic acid)/rhBMP-2 (recombinant human bone morphogenetic protein-2) composite artificial bone material was prepared, and its biological properties were evaluated. The nanopearl powder/C-HA/rhBMP-2 composite porous artificial bone material was prepared using the freeze-drying method after the nanopearl powder was prepared using mechanical ball milling. The particle was measured with a transmission electron microscope, its surface morphology and pore size were observed under a scanning electron microscope. The porosity of the artificial bone was determined using pycnometry, a compression performance test was conducted with a universal testing machine, and XRD (X-ray diffraction) patterns were recorded to examine the crystal form of the pearl powder in the composite artificial bone. Finally, the artificial bone was cocultured with mouse MC3T3-E1 cells to investigate its effects on cell proliferation and differentiation and the expression of osteogenesis-related genes. The pearl powder prepared in this experiment had a particle size in the nanometer range. This nanopearl powder, along with C-HA and rhBMP-2, was compounded into the nanopearl powder/C-HA/rhBMP-2 composite artificial bone, showing pore sizes of 188.53 ± 15.32 µm, a porosity of 86.43 ± 2.78% and a compressive strength of 0.342 ± 0.024 MPa. Notably, rhBMP-2 was released from the artificial bone in a sustained manner. Moreover, this artificial bone promoted the adhesion, proliferation, and differentiation of MC3T3-E1 cells and upregulated the expression of ColαI (collagen α1), OCN (osteocalcin), OPN (osteopontin) and Runx2 (runt-related gene 2). Conclusively, this nanopearl powder/C-HA/rhBMP-2 composite artificial bone material showed good performance and cytocompatibility, suggesting that it can be used for bone tissue engineering.

Safety and efficacy of SHR4640 combined with febuxostat for primary hyperuricemia: a multicenter, randomized, double-blind, phase II study.

BACKGROUND: To evaluate the safety, tolerability, and efficacy of SHR4640, a highly selective urate transporter-1 inhibitor, in combination with febuxostat, in patients with primary hyperuricemia. METHODS: In this randomized, double-blind, parallel-controlled phase II study, patients whose fasting serum uric acid (sUA) levels were ⩾ 480 µmol/L at screening with gout or sUA levels were ⩾ 420 µmol/L lasting for at least 3 months without gout, either with sUA levels ⩾ 540 µmol/L at screening or sUA levels ⩾ 480 µmol/L with comorbidities at screening, were enrolled. Patients were randomized (1:1:1) to receive SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg orally once daily. The primary end point was the incidence of treatment-emergent adverse events (TEAEs). RESULTS: A total of 93 patients were randomized and received treatment. TEAEs occurred in 55.9% of patients. The incidence of TEAEs was comparable among all the groups. Serious TEAEs occurred in one patient (1.1%), with no deaths observed. The proportion of patients who achieved the target sUA levels by week 4 was 79.3%, 96.6%, and 75.0% in the SHR4640 10 mg plus febuxostat 80 mg, SHR4640 10 mg plus febuxostat 40 mg, and SHR4640 5 mg plus febuxostat 20 mg groups, respectively. The mean percent reduction of sUA was 59.7%, 63.7%, and 41.8%, respectively. CONCLUSION: SHR4640 plus febuxostat exhibited a tolerable safety profile and substantial sUA lowering activity in patients with primary hyperuricemia. REGISTRATION: www.chinadrugtrials.org.cn; CTR 20192429.

[Experimental study of repairing rabbit femur defect with NPP/C-HA/ rhBMP-2].

PURPOSE: To investigate the osteogenic effect of nano-grade pearl powder(NPP)/chitosan-hyaluronic acid (C-HA)/recombinant human bone morphology protein-2 (rhBMP-2) artificial bone. METHODS: A bone defect model with a diameter of 7 mm and a height of 10 mm was made at the distal end of the femur. NPP/C-HA stent containing rhBMP-2 was prepared according to the shape of the defect. No material was implanted in the defect as blank group. NPP/C-HA was used as the control group, NPP/C-HA/rhBMP-2 was implanted into the experimental group. At 4 weeks, 8 weeks, and 12 weeks, the bone effects of each component were detected by cone-beam CT(CBCT), H-E and Masson staining. Serum ALP activity and OCN in tissues to determine the osteogenic differentiation and osteogenesis maturity were detected. SPSS 18.0 software package was used for statistical analysis. RESULTS: At 12 weeks, the defect was completely repaired in the experimental group. No immunological side effects such as inflammation and rejection were observed. At 8 and 12 weeks, CBCT showed that the experimental group had a higher CT value (Hounsfield units, HU) compared with the control group and the blank group(P<0.05). H-E and Masson staining showed that the experimental group had obvious new bone formation compared with the control group and the blank group at 8 weeks and 12 weeks, and ALP activity of the experimental group was significantly different from the control group and the blank group at 8 weeks. OCN immunohistochemical scoring of the experimental group was significantly different from the control group and the blank group(P<0.05). CONCLUSIONS: NPP/C-HA/rhBMP-2 has good tissue fusion, osteoinductivity, osteoconductivity and osteogenicity, which is expected to provide more effective treatment for bone repair.

Identification of a novel mutation site in maturity­onset diabetes of the young in a Chinese family by whole­exome sequencing.

The aim of the present study was to determine the mutant genes and mutation sites in a family with maturity­onset diabetes of the young (MODY), in order to provide evidence for the diagnosis and treatment of clinical MODY. Based on the clinical characteristics of MODY, one family was selected from the Department of Endocrinology of Shanxi Provincial People's Hospital (Shanxi, China). The family comprised seven individuals, four of which were healthy (without MODY), and the whole exome of the individual with MODY, her father and her mother were sequenced. A suspected case (patient's uncle) and a healthy individual (patient's aunt) were sequenced for verification. The Q30 ratio was >90% in the family of three and the sequencing quality was good. The alignment rate was >95%, while the repeat sequence was <10%, with a mean sequencing depth of >120x, which is sufficient to identify mutations. According to Mutation Taster and LRT, it was predicted that the p.leu73Pro mutation of the pancreatic and duodenal homeobox 1 (PDX1) gene was deleterious. The mutation was verified by next­generation sequencing as the pathogenic site in this family. In conclusion, a novel mutation site of MODY type 4 in the PDX1 gene was identified in a family with MODY, which may provide a basis for its clinical treatment. Whole­exome sequencing appears to be of assistance in accurately diagnosing MODY.

Aberrant DNA Methylation Involved in Obese Women with Systemic Insulin Resistance.

BACKGROUND: Epigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray. METHODS: The genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student's t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women. RESULTS: Relative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes. CONCLUSION: Based on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.

Renal-protective effect of thalidomide in streptozotocin-induced diabetic rats through anti-inflammatory pathway.

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats. METHODS: Male Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes. Diabetic rats were treated with thalidomide (200 mg/kg/d) for 8 weeks, and then blood and urine were collected for measurement of renal function-related parameters. Histopathology, immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analyses were performed to assess renal proinflammatory cytokines, fibrotic protein, and related signaling pathways. RESULTS: Diabetic rats exhibited obvious renal structural and functional abnormalities, as well as renal inflammation and fibrosis. Compared with diabetic control rats, those treated with thalidomide showed significantly improved histological alterations and biomarkers of renal function, as well as reduced expression of renal inflammatory cytokines, including NF-κB and MCP-1. Furthermore, renal fibrotic proteins, such as TGF-ß1, TßRII, TßRI, smad3, collagen IV, and fibronectin were also remarkably suppressed. Treatment with thalidomide markedly stimulated the phosphorylation of AMPKα. CONCLUSION: In this study, thalidomide suppressed the inflammatory and fibrotic processes in DN. These effects were partly mediated by the activation of AMPKα, and inhibition of the NF-κB/MCP-1 and TGF-ß1/Smad signaling pathways. These results suggest that thalidomide may have therapeutic potential in diabetic renal injury through the anti-inflammatory pathway.

[Relationship between expression of microRNA and inflammatory cytokines plasma level in pediatric patients with sepsis].

OBJECTIVE: Sepsis is the major cause of death in pediatric intensive care unit (PICU). The clinical manifestations of early sepsis is very similar to systemic inflammatory response syndrome (SIRS) caused by non-infectious reason. This study aimed to investigate the expression of miRNA and inflammatory cytokines in plasma in pediatric sepsis patients and its clinical significance. METHOD: Forty children with sepsis seen in Shenzhen children's hospital PICU from April 2012 to March 2013 were enrolled in this study, the median age was 0.75 (0.52, 1.90) years; 27 were males and 13 females, of whom 16 had severe sepsis. We selected 20 postsurgical patients with SIRS and 15 healthy children as a control group. The expression levels of plasma miR-21, miR-125b, miR-132, miR-146a, miR-155 and miR-223 were detected by real-time quantitative PCR (qRT-PCR). The predictive value of miRNA, PCT and CRP for sepsis were evaluated by Receiver operating characteristic curve (ROC). TNF-α and IL-10 levels in plasma detected by Cytometric Beads Array (CBA). Quantitative data of normal distribution was compared with ANOVA among the three groups and LSD-t test between two groups. To non-normal distribution of data, multiple comparisons among three groups were conducted by Kruskal-Wallis H test and differences between two groups were assessed by Mann-Whitney U test for post hoc analysis. RESULT: There were no significant differences between the age and gender of each group. Expression of miR-21, miR-125b, miR-132 and miR-155 in plasma had no significant difference in each group (all P > 0.05). MiR-146a and miR-223 levels in sepsis were upregulated compared with SIRS group and control group [(5.7 ± 3.5)×10(-5) vs. (2.4 ± 1.6)×10(-5) and (2.6 ± 1.2)×10(-5), (12.5 ± 7.7)×10(-4) vs. (8.3 ± 3.4)×10(-4) and (5.3 ± 2.2)×10(-4), all P < 0.01], expression levels of miR-223 in SIRS increased as compared to control group (P < 0.01). MiR-146a levels in severe sepsis were higher than those of the general sepsis [ (7.1 ± 3.3)×10(-5) vs. (4.6 ± 2.6)×10(-5), P < 0.01]. CRP and PCT levels are all higher in sepsis and SIRS groups than control group (all P < 0.01). The area under ROC curve (AUC) of miR-146a, miR-223, PCT and CRP to predict sepsis were 0.815 (95%CI: 0.708-0.922), 0.678(95%CI: 0.537-0.818), 0.706 (95%CI: 0.571-0.842) and 0.588 (95%CI: 0.427-0.748). Expression levels of IL-10 and IL-10/TNF-α in sepsis were upregulated compared with and SIRS group and the control group (all P < 0.01). There was a positive correlation between miR-146a, miR-223 and IL-10 and IL-10/TNF-α (r = 0.545, 0.305, 0.562, 0.373, all P < 0.01). CONCLUSION: The expression levels of miR-146a and miR-223 in plasma in pediatric patients with sepsis was significantly upregulated, and had a positive correlation with IL-10 and IL-10/TNF-α, which may be used as early diagnostic markers and can reflect the severity of condition to a certain degree.

[Clinical observation of non-invasive ultrasonic cardiac output monitor combined passive leg raising test in predicting the children volume responsiveness].

OBJECTIVE: To assess the ability of non-invasive ultrasonic cardiac output monitor (USCOM) combined with passive leg raising (PLR) test to predict volume responsiveness in septic shock children with spontaneous respiration. METHODS: Prospective and observational cohort study was performed in 40 septic shock children with spontaneous breathing admitted to pediatric intensive care unit (PICU) of Chongqing Medical University Shenzhen Children's Hospital from March 2011 to June 2013. The hemodynamic parameters including stroke volume (SV), cardiac output (CO) and systemic vascular resistance index (SVRI) were measured non-invasively by USCOM device before and after PLR and volume expansion (VE) test. And invasive mean arterial pressure (MAP) and central venous pressure (CVP) were monitored continuously. Based on the responsiveness of volume expansion [children were considered to be responders to volume expansion if SV increased (ΔSVVE)≥15%], all the children were divided into responders and non-responders. The roles of PLR in predicting volume responsiveness were evaluated by receiver operating characteristic curve (ROC curve). RESULTS: A total of 43 PLR and VE tests in 40 children were evaluated and resulting in 25 responders and 18 non-responders. There was no significant difference between two groups in the clinical data and hemodynamics indicators at incipient stage. After PLR and VE, the SV was increased compared with that at supine position in both responder group and non-responder group. The ΔSV after PLR (ΔSVPLR) and ΔSVVE in responder group were significantly higher than those in non-responder group [(14.95±3.44)% vs. (8.48±3.49)%, t=6.048, P=0.000; (18.28±2.84)% vs. (6.57±3.83)%, t=11.530, P=0.000]. Correlation analysis showed that there was the positive correlation between ΔSVPLR and ΔSVVE (r=0.649, P=0.000), but CVP increased (ΔCVPPLR) were unrelated with ΔSVVE (r=0.217, P=0.162). The area under the ROC curve (AUC) of ΔSVPLR and ΔCVPPLR for PLR predicting volume responsiveness and 95% confidence interval (95%CI) were 0.900±0.046 (95%CI 0.809-0.991, P=0.000) and 0.561±0.090 (95%CI 0.385-0.737, P=0.498). The ΔSVPLR≥12.25% was found to predict volume responsiveness with a sensitivity of 80.0% and specificity of 88.9%, the sensitivity and specificity of ΔCVPPLR≥15.48% were 76.0% and 38.9%, respectively. The capability of ΔSVPLR to predict volume responsiveness was better than ΔCVPPLR. CONCLUSIONS: ΔSVPLR measured by USCOM can predict the volume responsiveness in septic shock children patients with spontaneous respiration and it is reliable to guide fluid therapy.