Clinical evaluation of targeted sedation nursing combined with comprehensive nursing in children with severe pneumonia.

The severity of severe pneumonia in children depends on the degree of local inflammation, spread of lung inflammation and systemic inflammatory response. Appropriate care can effectively reduce the mortality of children with severe pneumonia. This study was designed to explore the nursing effect of targeted sedation nursing and comprehensive nursing intervention in children with severe pneumonia. Eighty children with severe pneumonia who complained of the main complaint were selected, and they were evenly distributed to receive comprehensive care (control group) and targeted sedation care and comprehensive care (observation group). In each group, different degrees of sedation, pain scores, and changes in adverse reactions were evaluated. Before nursing, the sedation and pain scores of the 2 groups of children were not statistically significant; after nursing, the sedation and pain scores of the 2 groups of children improved with time, and the sedation effect of the observation group was significantly lower than that of the control. In the group, the pain score was lower than that of the control group, indicating improvement. The SAS and SDS of the observation group were lower than those of the control group, while the social support score was significantly higher than that of the control group. The difference was statistically significant (P < .05). The accidental extubation, delirium, respiratory depression, and laryngospasm of the 2 groups of children were significantly improved, and the observation group was significantly less than the control group. This difference was statistically significant (P < .05). Targeted sedation nursing and comprehensive nursing intervention can effectively reduce the incidence of adverse reactions in children with severe pneumonia, reduce the pain and discomfort of children with severe pneumonia, and significantly improve the degree of sedation, which has certain reference value for the care of children with severe pneumonia.

Anti-phosphatidylserine/prothrombin complex antibodies (aPS/PT) increase the risk for thrombosis based on lupus anticoagulant positivity.

BACKGROUND: Lupus anticoagulants (LA) increase the risk of thrombotic and obstetric events in patients with antiphospholipid syndrome than in those with other antiphospholipid antibodies. Anti-phosphatidylserine/prothrombin (aPS/PT) complex antibodies are thought to cause LA positivity. Therefore, we aimed to explore whether aPS/PT antibodies could prolong phospholipid (PL)-dependent clotting time and increase the risk of thrombosis or pregnancy complications based on LA positivity. METHODS: We recruited 222 patients with positive LA and estimated their aPS/PT, anticardiolipin (aCL), anti-ß2-glycoprotein I (aß2GPI), and anti-ß2GPI domain I (anti-D1) antibody (IgM and IgG) titers and PL-dependent clotting time. RESULTS: PT was longer in aPS/PT IgG-positive patients than in aPS/PT IgM-negative patients (P < 0.001), while there was no significant difference between aPS/PT IgM-positive and IgM-negative patients (P = 0.100). Both SCT-S and dRVVT-S were prolonged in aPS/PT (IgG and IgM)-positive patients compared to aPS/PT-negative patients (P < 0.001, P = 0.010, P < 0.001, P = 0.002, respectively). Similarly, the associations between aPS/PT IgG or IgM antibody titers and SCT-S or dRVVT-S were significant. SCT-C and dRVVT-C did not show any significant differences. The incidence of thrombosis in the aPS/PT IgG-positive group was much higher than that in the IgG-negative group (P = 0.012). Likewise, the incidence of thrombosis was higher in the anti-D1- and aPS/PT IgG-positive patients than in the negative controls (40 % vs 14.3 %, χ2 = 3.934, P = 0.047). Furthermore, the aPS/PT IgG-positive group showed the strongest association with thrombosis [OR 2.584, 95 % CI (1.213, 5.505)]. CONCLUSION: The aPS/PT antibodies prolonged PL-dependent clotting time, especially SCT-S and dRVVT-S. In addition, the presence of aPS/PT IgG antibodies increased the risk of thrombosis in LA positivity.

Evaluation of Urine NDRG1 as Noninvasive Biomarker for Bladder Cancer Diagnosis.

BACKGROUND: N-myc downstream regulated gene 1 (NDRG1) was involved in cell differentiation and was recently reported to exert various effects in tumorigenesis. The aim of this study was to assess its diagnostic value in urine as a useful marker for bladder cancer (BC). METHODS: In this study, we recruited 119 BC patients, 65 patients with non-cancerous bladder diseases, and 60 healthy volunteers as control. Their urine concentrations of NDRG1, nuclear matrix protein 22 (NMP22), and creatinine (Cr) were measured and relevant clinical information was retrieved from their medical history records. RESULTS: The expression of NDRG1/Cr and NMP22/Cr in urine were significantly higher in BC patients than those in non-cancerous bladder diseases (p = 0.009 and p = 0.023) and healthy controls (p = 0.005 and p = 0.002). The level of NDRG1/Cr was significantly associated with pathologic T stage (p < 0.001) and pathological grade (p < 0.001). The ROC of NDRG1/Cr to diagnose BC was 0.713 (95% CI, 0.630 - 0.797), with a sensitivity of 63.8% and a specificity of 73.4% at a cutoff of 76.3 ng/mg. NMP22/Cr was 0.705 (95% CI, 0.626 - 0.784), with a sensitivity of 64.2% and a specificity of 66.2% at a cutoff of 12.1 ng/mg. NDRG1/Cr in combination with NMP22/Cr shows a ROC of 0.719 (95% CI, 0.632 0.806) with a sensitivity of 64.9% and specificity of 75.9% Conclusions: Urine NDRG1 may be useful in a minimally invasive modality for determining bladder cancer. Predictive value of the two biomarkers was slightly higher than that of routine NMP22 parameter alone.

Effect of Food on the Pharmacokinetic and Pharmacodynamic Profiles of Hetrombopag in Healthy Volunteers.

PURPOSE: Hetrombopag, a novel, oral small molecule thrombopoietin receptor agonist, exhibits an obvious thrombocytopoietic effect with good safety. Hetrombopag is currently under clinical development for the treatment of chronic idiopathic thrombocytopenic purpura (ITP). The objectives of this study were to assess the effect of high-fat and high-calorie food on the pharmacokinetic and pharmacodynamic (PK/PD) profiles of hetrombopag in healthy volunteers. METHODS: An independent, single-dose, open-label, randomized-sequence, crossover trial was conducted. Healthy volunteers received hetrombopag 7.5-mg tablets in the fasted state or with a high-fat, high-calorie breakfast. The effects of the high-fat and high-calorie food on the PK/PD profiles of hetrombopag were evaluated by using a noncompartmental analysis and a semi-physiological model. FINDINGS: Twelve Chinese healthy volunteers were enrolled. Mean plasma AUC0-t and Cmax decreased by 98.7% and 95.0%, respectively, when hetrombopag was administered with high-fat and high-calorie food. The semi-physiological PK/PD model analysis showed that the absorption rate constant at the first absorption site was almost halved at the fed condition. The change in platelet counts in the fed condition was not sufficiently as sensitive as that in the fasted condition. IMPLICATIONS: High-fat and high-calorie food were associated with significantly reduced systemic exposure and platelet count sensitivity. Thus, hetrombopag should be taken in a fasted state to avoid the impact of food on bioavailability and platelet counts. ClinicalTrials.gov identifier: NCT02409394.

Transfer of MicroRNA-216a-5p From Exosomes Secreted by Human Urine-Derived Stem Cells Reduces Renal Ischemia/Reperfusion Injury.

Human urine-derived stem cells (USCs) protect rats against kidney ischemia/reperfusion (I/R) injury. Here we investigated the role of USCs exosomes (USCs-Exos) in protecting tubular endothelial cells and miRNA transfer in the kidney. Human USCs and USCs-Exos were isolated and verified by morphology and specific biomarkers. USC-Exos played a protective role in human proximal tubular epithelial cells (HK-2) exposed to hypoxia/reoxygenation (H/R). USCs-Exos were rich in miR-216a-5p, which targeted phosphatase and tensin homolog (PTEN) and regulated cell apoptosis through the Akt pathway. In HK-2 cells exposed to H/R, incubation with USC-Exos increased miR-216-5p, decreased PTEN levels, and stimulated Akt phosphorylation. Exposure of hypoxic HK-2 cells to USCs-Exos pretreated with anti-miR-216a-5p can prevent the increase of miR-216-5p and Akt phosphorylation levels, restore PTEN expression, and promote apoptosis. The dual-luciferase reported gene assay in HK-2 cells confirmed that miR-216a-5p targeted PTEN. In rats with I/R injury, intravenous infusion of USCs-Exos can effectively induce apoptosis suppression and functional protection, which is associated with decreased PTEN. Infusion of exosomes from anti-miR-216a-5p-transfected USCs weakened the protective effect in the I/R model. Therefore, USCs-Exos can reduce renal I/R injury by transferring miR-216a-5p targeting PTEN. Potentially, USCs-Exos rich in miR-216a-5p can serve as a promising therapeutic option for AKI.

Anti-domain 1 of beta2-glycoprotein I aids risk stratification in lupus anticoagulant-positive patients.

Lupus anticoagulant (LA) is considered a risk factor for thromboembolism (TE) and adverse pregnancy outcomes (APOs). However, quite a few patients diagnosed with LA positivity do not suffer these adverse events. Further testing of anticardiolipin (aCL), anti-beta2-glycoprotein I (anti-ß2GPI) or anti-domain 1 of ß2GPI (anti-D1) may help to assess the occurrence risk of TE and APOs. Therefore, we aimed to study how to stratify LA-positive patients. In our study, 167 LA-positive patients were consecutively enrolled from January 2015 to December 2016. Serum aCL and anti-ß2GPI (IgG, IgM and IgA) and anti-D1 IgG were simultaneously measured. Among these patients, 114 (68.3%) were followed for an average of 36.5 months for TE and APOs. The outcomes showed that 105 patients experienced TE and/or APOs, and 62 patients were LA carriers. Anti-D1 had good consistency with triple positivity (LA+, aCL+, anti-ß2GPI+) (kappa = 0.742). Elevated anti-D1 was related to increased risks for TE [odds ratio (OR) 29.87, 95% confidence interval (CI) 8.05-110.74] and APOs (OR 8.73, 95% CI 3.41-22.31). Area under curve showed that the diagnostic power of anti-D1 for TE and APOs was 0.856 (95% CI 0.743-0.970) and 0.682 (95% CI 0.599-0.765), respectively. Survival analysis revealed that patients with high anti-D1 titres had a high cumulative incidence of APOs (hazard ratio 4.66, 95% CI 1.46-14.87). In conclusion, anti-D1, based on good consistency with triple positivity in LA-positive patients, has a stronger association with TE and APOs and, to some degree, could predict pregnancy outcomes. Therefore, anti-D1 may aid risk stratification in LA-positive patients.

S100A16 regulated by Snail promotes the chemoresistance of nonmuscle invasive bladder cancer through the AKT/Bcl-2 pathway.

Objective: To fully investigate the effect of S100 proteins on the chemoresistance of nonmuscle invasive bladder cancer (NMIBC). Materials and methods: The mitomycin C-resistant bladder cancer cell line M-RT4 was established and liquid chromatography-tandem mass spectrometry was performed for proteomics analysis. RT-PCR and Western blot were then performed to confirm the findings. To investigate the mechanisms, S100A16 was knocked down by siRNA. Then, the sensitivity of M-RT4 to mitomycin C was analyzed by a cell counting kit-8 (CCK8) assay, and the molecular expression including epithelial-mesenchymal transition (EMT)-related and apoptosis-related markers were also examined by Western blot. Based on the cancer genome atlas (TCGA) data, the prognostic value of S100A16 was also investigated. Results: There were six S100 proteins with differential expression, among which S100A16 was confirmed to be the only upregulated protein in M-RT4 cells. The expression of S100A16 was regulated by the EMT-related transcription factor Snail. Knockdown of S100A16 suppressed the AKT/Bcl-2 pathway to promote apoptosis, greatly sensitizing M-RT4 cells to mitomycin C. The expression of S100A16 was negatively correlated with the overall survival of bladder cancer patients. Conclusion: S100A16 contributes to the chemoresistance of NMIBC by promoting the AKT/Bcl-2-mediated anti-apoptosis effect and could be a potential prognostic marker and therapeutic target for NMIBC patients.

Upregulation of NDRG1 predicts poor outcome and facilitates disease progression by influencing the EMT process in bladder cancer.

N-myc downstream regulated gene 1 (NDRG1) is an intracellular protein involved in cell differentiation and was recently reported to exert various effects in several cancers. However, its expression and role in bladder cancer remain unclear. Our study enrolled 100 bladder cancer patients to detect NDRG1 expression in tumour tissues by immunohistochemistry. Correlations between NDRG1 expression and clinical factors were analysed. An NDRG1 overexpression plasmid and NDRG1 siRNAs were transfected into bladder cancer cell lines. Cell biological behaviours were assessed by CCK-8, flow cytometry, wound healing and Transwell assays. Additionally, the influence of NDRG1 on epithelial-mesenchymal transition (EMT) was investigated by western blotting and real-time PCR. NDRG1 expression in urine from bladder cancer patients was examined by ELISA. NDRG1 protein levels were significantly increased in bladder cancer patients and correlated with tumour stage (p = 0.025), lymph node metastasis (p = 0.034) and overall survival (p = 0.016). Patients with high NDRG1 expression had poorer outcomes than those with low NDRG1 expression. NDRG1 overexpression was associated with increased cell proliferation, migration, and invasion and decreased apoptotic cell numbers; NDRG1 knockdown resulted in the inverse effects. Moreover, upregulated NDRG1 expression was associated with downregulated Cytokeratin 7 and Claudin-1 expression and upregulated N-cad, ß-catenin and slug expression. Downregulated NDRG1 expression was associated with the inverse effects. Urine protein levels could distinguish bladder cancer patients from healthy controls, with an area under the curve of 0.909. NDRG1 promoted EMT in bladder cancer and could be an effective diagnostic and prognostic biomarker in bladder cancer patients.

CXCL5 promotes mitomycin C resistance in non-muscle invasive bladder cancer by activating EMT and NF-κB pathway.

The emergence of chemoresistance greatly increases the recurrence risk for non-muscle invasive bladder cancer (NMIBC) patients, which is still a big concern of clinicians. Understanding the mechanisms of drug resistance is of great significance for preventing and reversing it. We showed here that CXC motif chemokine ligand 5 (CXCL5) was overexpressed in mitomycin C-resistant bladder cancer cell line M-RT4. Meanwhile, parental RT4 cell treated with recombinant human CXCL5 (rhCXCL5) reduced its sensitivity to mitomycin C. Conversely, knockdown CXCL5 sensitized M-RT4 cell. We further investigated the molecular mechanisms finding that epithelial mesenchymal transition (EMT) and NF-κB pathway were activated in M-RT4 cell, which could be attenuated by knockdown CXCL5. All these data indicated that CXCL5 may promote mitomycin resistance by activating EMT and NF-κB pathway. Thus, our study identifies CXCL5 as a novel chemoresistance-related marker in NMIBC, thereby providing new strategies to overcome chemoresistance for NMIBC patients.

Trimester-specific coagulation and anticoagulation reference intervals for healthy pregnancy.

BACKGROUND: Due to the normal physiological need of pregnancy and childbirth, the haemostatic system of pregnant women is different from that of healthy non-pregnant women. The aim of this study was to establish trimester-specific reference intervals of coagulation screening tests and thrombophilia markers in pregnancies without complications of females with Han ethnicity from North China. METHODS: In total 744 Han healthy pregnant women (first trimester 207 cases, second trimester 222 cases and third trimester 315 cases) and 121 healthy non-pregnant women were recruited in North China. Eight tests-activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fib), d-Dimer, antithrombin (AT), protein C (PC) and free protein S (fPS)-were processed on ACL TOP automated coagulation analyzer. The non-parametric 2.5th-97.5th percentiles reference intervals were calculated to establish trimester-specific reference intervals. RESULTS: The reference intervals for APTT, PT, TT, Fib, d-Dimer, AT, PC, and fPS at first trimester were 26.4-41.9s, 9.7-12.5s, 11.7-17.0s, 2.38-4.44g/L, 0.01-0.31µg/mL, 72-120%, 29-150%, 21-143%, respectively. At second trimester, the reference intervals were 24.4-35.8s, 8.5-13.2s, 10.0-16.0s, 2.40-5.97g/L, 0.05-0.73µg/mL, 68-125%, 20-138%, 24-155%, respectively. At third trimester, the reference intervals were 25.6-34.9s, 8.6-12.4s, 11.1-15.5s, 2.79-5.91g/L, 0.14-2.82µg/mL, 56-119%, 20-134%, 17-140%, respectively. From the first trimester to the third trimester, APTT, PT and TT presented shortened trends, Fib and d-Dimer presented increasing trends, AT, PC and fPS activity presented decreasing trends, respectively. CONCLUSIONS: The trimester-specific reference intervals of coagulation screening tests and thrombophilia markers in pregnancies without complications of females with Han ethnicity from North China are presented in this study, which may provide effective evidence for doctors to accurately diagnose and treat the disease during pregnancy.

Establishment of reference intervals for complete blood count parameters during normal pregnancy in Beijing.

OBJECTIVE: To observe the changes of complete blood count (CBC) parameters during pregnancy and establish appropriate reference intervals for healthy pregnant women. METHODS: Healthy pregnant women took the blood tests at all trimesters. All blood samples were processed on Sysmex XE-2100. The following CBC parameters were analyzed: red blood cell count (RBC), hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), white blood cell count (WBC), and leukocyte differential count. Reference intervals were established using the 2.5th and 97.5th percentile of the distribution. RESULTS: Complete blood count parameters showed dynamic changes during trimesters. RBC, Hb, Hct declined at trimester 1, reaching their lowest point at trimester 2, and began to rise again at trimester 3. WBC, neutrophil count (Neut), monocyte count (MONO), RDW, and PDW went up from trimester 1 to trimester 3. On the contrary, MCHC, lymphocyte count (LYMPH), PLT, and MPV gradually descended during pregnancy. There were statistical significances in all CBC parameters between pregnant women and normal women, regardless of the trimesters (P<.001). The median obtained were (normal vs pregnancy) as follows: RBC 4.50 vs 3.94×1012 /L, Hb 137 vs 120 g/L, WBC 5.71 vs 9.06×109 /L, LYMPH% 32.2 vs 18.0, Neut% 58.7 vs 75.0, and PLT 251 vs 202×109 /L. CONCLUSION: The changes of CBC parameters during pregnancy are described, and reference intervals for Beijing pregnant women are demonstrated in this study.

Pharmacokinetics and pharmacodynamics of dexmedetomidine.

Dexmedetomidine is an alpha-2 adrenoceptor agonist and has been used as a general anesthetic, sedative and analgesic for about 30 years. The aim of this paper is to review the pharmacokinetics and pharmacodynamics of dexmedetomidine, evaluate physiological factors that may affect the pharmacokinetics of dexmedetomidine, and summarize the pharmacodynamics of dexmedetomidine at different plasma levels. The pharmacokinetic parameters reported in previous studies according to noncompartmental analyses or population modeling results are compared. We concluded that the pharmacokinetic profile can be adequately described by a two-compartment model in population pharmacokinetic modeling. Body weight, height, albumin level, cardiac output, disease condition and other factors were considered to have significant influence on the clearance and/or distribution volume in different population pharmacokinetic models. The pharmacological effects of dexmedetomidine, such as sedation, heart rate reduction and biphasic change of blood pressure, vary at different plasma levels. These findings provide a reference for individualizing the dose of dexmedetomidine and achieving the desired pharmacological effects in clinical applications.

Complete loss of STAG2 expression is an indicator of good prognosis in patients with bladder cancer.

Stromal antigen 2 (STAG2) is an important member of cohesin, a conserved complex holding the sister chromatid together. Recent whole-genome sequencing studies have identified that genetic alterations of stag2 are common in bladder cancer (BC). The prognostic implications of STAG2 expression in BC remain unclear; we therefore analyzed its associations with the histopathological characteristics and clinical outcome in a Chinese population. We used immunohistochemistry assay to determine STAG2 protein expression in tumor tissues from 125 BC patients. STAG2 expression was analyzed according to clinicopathological features and patients' survival. Univariable and multivariable analyses were performed to identify predictors for recurrence-free survival (RFS) and cancer-specific survival (CSS). STAG2 expression was detected in 79.2 % of BC tissues, and 20.8 % of the tumor tissues had a complete loss of STAG2 protein expression. This STAG2-negative result was associated with a lower tumor histological grade with P = 0.009. The log-rank analysis revealed that the complete loss of STAG2 expression was associated with a lower risk of recurrence (P = 0.023) and a diminished risk of death (P = 0.034), especially in the subgroup of muscle-invasive BC (P = 0.043 for RFS and P = 0.087 for CSS). In multivariable Cox regression models, the loss of STAG2 expression remained a beneficial factor for RFS and CSS of BC patients. Univariate and multivariate analyses' results indicated that the complete loss of STAG2 expression was predictive for better RFS and CSS, suggesting its potential value as a prognostic biomarker.

Age and Gender Tailored Cutoff Value of hs-cTnT Contributes to Rapidly Diagnose Acute Myocardial Infarction in Chest Pain Patients.

BACKGROUND: Hs-cTnT concentrations are age and gender related, therefore establishment of age and gender optimized cutoff values for hs-cTnT might be essential. We aimed to define the age and gender specific hs-cTnT 99th percentile in reference population and assess its diagnostic and prognostic performance in patients with suspected AMI. METHODS: In this prospective study, 1725 healthy individuals (18 - 97 years old) and 812 patients (15 - 98 years old) with chest pain with suspected AMI presenting to the emergency department were enrolled. The measurement of biomarkers was performed at presentation and at 3 - 4 hours according to clinical requirement. We stratified the reference population by age and gender through applying strict exclusion criteria. Clinical follow-up was obtained after 2 years. RESULTS: The 99th percentile of hs-cTnT according to age and gender in adult Han population of Northern China is reported. The cutoff values of hs-cTnT in for subjects < 70 years, 70 - 79 years, and ≥ 80 years was 16 ng/L, 38 ng/L, and 57 ng/L, respectively. Among the 812 patients with chest pain, according to the age and gender tailored cutoff value, the specificity and positive predictive value of AMI diagnosis were increased from 53.9% to 72.2% and 48.6% to 60.8%, compared to 14 ng/L commonly recommended. Cumulative 2-year survival rate for patients with hs-cTnT levels above 14 ng/L was 93.3% compared to 99.5% in patients below that level (p < 0.001). The same was observed for the age and gender tailored cutoff value which was 92.5% compared to 98.5%, respectively (p < 0.001). CONCLUSIONS: Age and gender tailored cutoff value for hs-cTnT provides better diagnostic information, but yields no additional prognostic performance for risk prediction of death or major adverse cardiovascular events.

A multi-scale biomechanical model based on the physiological structure and lignocellulose components of wheat straw.

Biomechanical behavior is a fundamental property for the efficient utilization of wheat straw in such applications as fuel and renewable materials. Tensile experiments and lignocellulose analyses were performed on three types of wheat straw. A multi-scale finite element model composed of the microscopic model of the microfibril equivalent volume element and the macroscopic model of straw tissue was proposed based on the physiological structure and lignocellulose components of wheat straw. The tensile properties of wheat straw were simulated by ANSYS software. The predicted stress-strain data were compared with the observed data, and good correspondence was achieved for all three types of wheat straw. The validated multi-scale finite-element (FE) model was then used to investigate the effect of the lignocellulose components on the biomechanical properties of wheat straw. More than 80% of stress is carried by the cellulose fiber, whereas the strain is mainly carried by the amorphous cellulose.