The immunosuppressive landscape in tumor microenvironment.

Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.

Association between the systemic immune inflammation index and periodontitis: a cross-sectional study.

BACKGROUND: Periodontitis is a chronic oral inflammatory disease that seriously affects people's quality of life. The purpose of our study was to investigate the correlation between the systemic immune inflammation index (SII) and periodontitis by utilizing a large national survey. This will establish a reference for the early identification and management of periodontitis. METHODS: This study comprised the adult US population who participated in a national periodontitis surveillance project during the six years from 2009 to 2014. Through the utilization of univariate and multivariate weighted logistic regression, we investigated the correlation between the systemic immune inflammation index and periodontitis. Additionally, we employed sensitivity analyses to evaluate the robustness of our findings. RESULTS: The study involved 10,366 participants with an average age of 51.00 years, of whom 49.45% were male (N = 5126) and 50.55% were female (N = 5240). The prevalence of periodontitis is estimated to be about 38.43% in the US adults aged 30 or older population. Our logistic regression models indicated a positive association between a SII higher than 978 × 109/L and periodontitis. The elder group (aged 50 or older) with SII higher than 978 × 109/L demonstrated a significant correlation with periodontitis in the fully adjusted model (Odds Ratio [OR] = 1.409, 95% Confidence Interval [CI] 1.037, 1.915, P = 0.022). However, there is no statistical difference among adults aged 30 to 50. The robustness of our findings was confirmed through sensitivity analyses. CONCLUSIONS: Our study highlights that SII is associated with periodontitis in a nationally representative sample of US adults. And the SII is significantly associated with a high risk of periodontitis in individuals aged 50 or older.

Cost-effectiveness analysis of continuing bevacizumab plus chemotherapy versus chemotherapy alone after first progression of metastatic colorectal cancer.

BACKGROUND: Continuation of bevacizumab plus second-line chemotherapy has significantly improved overall and progression-free survival in patients with metastatic colorectal cancer (mCRC). However, the cost-effectiveness of such high cost therapy is still uncertain in China; so this analysis was performed to evaluate the cost-effectiveness of these treatment options from the Chinese health care system perspective. METHODS: A cost-effectiveness analysis was conducted using data from the ML18147 trial (ClinicalTrials.gov identifier NCT00700102) by modeling a partitioned survival model. Main evaluation indicators were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) with a willingness to pay (WTP) threshold of $38,201 per QALY. One-way and probabilistic sensitivity analyses were conducted to assess the robustness and stability of the model. Subgroup and scenario analyses were also performed to make our study more relevant. RESULTS: Bevacizumab plus chemotherapy increased 0.12 QALYs and an incremental cost of $22,761.62 compared with chemotherapy, resulting in an ICER of $188,904.09 per QALY. The model was most sensitive to the utility of progression-free survival and the cost of bevacizumab. Compared with chemotherapy, bevacizumab plus chemotherapy had a 0% cost-effectiveness probability, and no cost-effectiveness in subgroups at the WTP threshold of $38,201 per QALY. The scenario analysis found that bevacizumab biosimilar gained an ICER of $126,397.38 per QALY when assuming the cost of drugs was calculated at the most affordable price. CONCLUSIONS: At the WTP threshold of $38,201 per QALY, continuation of bevacizumab plus chemotherapy is unlikely considered cost-effective for patients after first progression of mCRC.

Economic Evaluation of Neoadjuvant Versus Adjuvant Chemotherapy in Cancer Treatment: A Systematic Review and Meta-Analysis.

OBJECTIVES: In the absence of evidence on whether neoadjuvant (NAC) or adjuvant chemotherapy (AC) is more beneficial for various tumor treatments, economic evaluation (EE) can assist medical decision making. There is limited evidence on their cost-effectiveness and their prospective evaluation is less likely in the future. Therefore, a systematic review and meta-analysis about EE for NAC versus AC in solid tumor help compare these therapies from various perspectives. METHODS: Various databases were searched for studies published from inception to 2021. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and economic-specific guidelines. The data were pooled using a random effects model when possible. RESULTS: The retrieval identified 15 EE studies of NAC versus AC in 8 types of cancer. NAC is the dominant strategy for pancreatic, head and neck, rectal, prostate cancers and colorectal liver metastases. For ovarian cancer, NAC is cost-effective with a lower cost and higher or similar quality-adjusted life-year. There were no significant differences in cost and outcomes for lung cancer. For stage IV or high-risk patients with ovarian or prostate cancer, NAC was cost-effective but not for patients who were not high risk. CONCLUSIONS: The EEs results for NAC versus AC were inconsistent because of their different model structures, assumptions, cost inclusions, and a shortage of studies. There are multiple sources of heterogeneity across EEs evidence synthesis. More high-quality EE studies on NAC versus AC in initial cancer treatment are necessary.

Association between antihypertensive drugs and oral cancer: a drug target Mendelian randomization study.

Background: Recent reports have suggested that antihypertensive drugs may play an oncogenic role in common cancers, but it is still uncertain whether this could influence the risk of oral cancer. Through two-sample Mendelian randomization (MR), we sought to assess the causal effect of antihypertensive drugs on oral cancer outcomes. Methods: To proxy the exposure of antihypertensive drugs, we utilized two genetic instruments, including expression quantitative trait loci of drug target genes and genetic variants within or around drug target genes related to blood pressure from genome-wide association studies. Inverse-variance-weighted MR (IVW-MR) and summary-data-based MR (SMR) were employed to compute the instrument effect estimates. Results: It was observed through IVW-MR analysis that there is a positive relationship between KCNH2 (target of beta-adrenoceptor blockers)-mediated blood pressure and oral cancer (odds ratio [OR] = 1.197, 95% confidence interval [CI] = 1.028-1.394). Similarly, SMR analysis demonstrated that a higher expression of KCNH2 (target of beta-adrenoceptor blockers) was linked to a greater risk of oral cancer (OR = 2.223, 95% CI = 1.094-4.516). Both analyses yielded no consistent evidence of other associations. Conclusion: This two-sample MR study proposed a latent causal association between KCNH2 (target of beta-adrenoceptor blockers) inhibition and diminished risk of oral cancer.

Rucaparib inhibits lung adenocarcinoma cell proliferation and migration via the SHCBP1/CDK1 pathway.

Src homolog and collagen homolog binding protein 1 (SHCBP1) binds to the SH2 domain of SHC-transforming protein 1 (SHC1) and is involved in midbody organization and cytokinesis completion. SHCBP1 has been reported to be a cancer driver gene, promoting cancer progression. However, the functional role and underlying mechanism of SHCBP1 in regulating lung adenocarcinoma (LUAD) cell proliferation and migration are incompletely understood. Here, we discovered that SHCBP1 is overexpressed in LUAD tissues and is associated with a poor prognosis. SHCBP1 knockdown inhibited LUAD cell proliferation and migration by arresting the cell cycle and preventing epithelial-mesenchymal transition (EMT) via decreasing cyclin-dependent kinase 1 (CDK1) expression. Mechanistically, CDK1 overexpression reversed SHCBP1 knockdown-induced inhibition of proliferation and migration, confirming CDK1 as a key downstream target of SHCBP1. In addition, we proposed that rucaparib may be a small-molecule inhibitor of SHCBP1 and validated both in vitro and in vivo that rucaparib inhibits cell proliferation and migration via suppression of the SHCBP1/CDK1 pathway in LUAD. Our study elucidates a newly identified role of SHCBP1 in promoting cell proliferation and migration in LUAD, and suggests rucaparib as a potential inhibitor for LUAD treatment.

A celastrol-based nanodrug with reduced hepatotoxicity for primary and metastatic cancer treatment.

BACKGROUND: Cancer is the world's leading cause of death and a key hindrance to extending life expectancy. Celastrol, a bioactive compound derived from Tripterygium wilfordii, has been shown to have excellent antitumor activity, but its poor solubility and severe organ toxicity side effects have hampered its clinical application. METHODS: In this study, a self-assembled nanodrug (PLC-NP) was designed to deliver celastrol to tumor sites while efficiently reducing its side effects by conjugating celastrol with the bioactive material LMWH and P-selectin targeting peptide (PSN). Extensive in vitro and in vivo experiments were performed to investigate both therapeutic efficacy and adverse effects. Furthermore, the specific mechanism of the antitumor activity has also been explored. FINDING: The PLC-NP nanodrugs were spherical in shape, with a mean particle size of 115.83 ± 6.93 nm. PLC-NP was sufficiently stable during blood circulation, with a selective target to P-selectin-highly expressed tumor cells, followed by releasing the containing celastrol under acidic environment and high levels of esterase in tumor cells. Both in vitro and in vivo results confirmed that celastrol's antitumor and anti-metastatic abilities were not attenuated and were actually strengthened after being formed into nanodrugs. More importantly, the organ toxicities of the modified celastrol nanodrug were dramatically reduced. Mechanistic study indicated that the inactivation of PI3K/Akt/mTOR signaling pathway and ROS-mediated mitochondrial dysfunction play critical roles in celastrol-mediated autophagy and apoptosis. INTERPRETATION: Our findings could offer a potential strategy for the translation of toxic compounds into clinical therapeutic nanomedicine. FUNDING: See a detailed list of funding bodies in the Acknowledgements section at the end of the manuscript.

Identification of GINS1 as a therapeutic target in the cancer patients infected with COVID-19: a bioinformatics and system biology approach.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused a series of biological changes in cancer patients which have rendered the original treatment ineffective and increased the difficulty of clinical treatment. However, the clinical treatment for cancer patients infected with COVID-19 is currently unavailable. Since bioinformatics is an effective method to understand undiscovered biological functions, pharmacological targets, and therapeutic mechanisms. The aim of this study was to investigate the influence of COVID-19 infection in cancer patients and to search the potential treatments. METHODS: Firstly, we obtained the COVID-19-associated genes from seven databases and analyzed the cancer pathogenic genes from Gene Expression Omnibus (GEO) databases, respectively. The Cancer/COVID-19-associated genes were shown by Venn analyses. Moreover, we demonstrated the signaling pathways and biological functions of pathogenic genes in Cancer/COVID-19. RESULTS: We identified that Go-Ichi-Ni-San complex subunit 1 (GINS1) is the potential therapeutic target in Cancer/COVID-19 by GEPIA. The high expression of GINS1 was not only promoting the development of cancers but also affecting their prognosis. Furthermore, eight potential compounds of Cancer/COVID-19 were identified from CMap and molecular docking analysis. CONCLUSION: We revealed the GINS1 is a potential therapeutic target in cancer patients infected with COVID-19 for the first time, as COVID-19 will be a severe and prolonged pandemic. However, the findings have not been verified actually cancer patients infected with COVID-19, and further studies are needed to demonstrate the functions of GINS1 and the clinical treatment of the compounds.

Expandable carboxymethyl chitosan/cellulose nanofiber composite sponge for traumatic hemostasis.

Uncontrolled hemorrhage poses a severe life-threatening situation. However, traditional hemostats still have various limitations. It is urgent to develop a material with excellent biocompatibility and hemostatic ability. Evidence has shown that carboxymethyl chitosan (CMCS) has hemostatic properties and good compatibility. Herein, we develop an expandable hemostatic sponge by modifying CMCS with cellulose nanofibrils (CNFs) through the CO-NH cross-linking method. We verified its potential as a hemostatic agent both in vivo and in vitro. The results demonstrated that the prepared carboxymethyl chitosan/cellulose nanofiber composite (CNF-CMCS) sponges could absorb blood, quickly expand to exert pressure in the wound, and exhibit an excellent coagulation ability. The CNF-CMCS sponges significantly decreased the bleeding time and blood loss in several hemorrhage models and possessed a significant advantage in treating the deep penetrating injury hemorrhage. Therefore, the sponges provide a unique application prospect and potential as a penetrating trauma hemostatic agent.

Autophagy responsive intra-intercellular delivery nanoparticles for effective deep solid tumor penetration.

Deep tumor cells (cells in the center of solid tumors) play a crucial role in drug tolerance, metastasis, recurrence and microenvironment immune suppression. However, their deep location endows them with an untouched abdomen and makes them refractory to current treatments. Herein, we exploited the characteristic of higher autophagy in deep tumor cells than in superficial tumor cells and designed autophagy-responsive multifunctional nanoparticles (PGN) to enhance drug accumulation in deep tumor cells. PGNs were prepared by densely coating poly (lactic-co-glycolic acid) (PLGA) with cationic autophagy-responsive cell-penetrating peptide (GR9) and anionic 2,3-dimethylmaleic anhydride (DMA)-modified DSPE-PEG. The suitable nanoparticle size (122.4 nm) and charge-neutral surface (0.21 mV) of the NPs enabled long blood circulation. The hydrolysis of surface-anchored anionic DMA in the acidic microenvironment led to the exposure of the GR9 peptide and enhance tumor penetration. Once the PGN arrived in deep tumor cells with strong autophagy, GR9 was cut off by an autophagy shear enzyme, and the nanoparticles remained in the cells to undergo degradation. Furthermore, we prepared docetaxel (DTX) and chloroquine (CQ) loaded d-PGN. CQ inhibits autophagosome fusion with lysosomes, resulting in autophagosome accumulation, which further enhances the sensitivity of d-PGN to autophagy and their deep tumor retention. In vivo experiments showed that drug-loaded d-PGN achieved excellent antitumor efficacy with a peak inhibition rate of 82.1%. In conclusion, autophagy-responsive multifunctional nanoparticles provide a novel potential strategy for solid tumor treatment.

A comparison of qSOFA, SIRS and NEWS in predicting the accuracy of mortality in patients with suspected sepsis: A meta-analysis.

OBJECTIVE: To identify and compare prognostic accuracy of quick Sequential Organ Failure Assessment (qSOFA) score, Systemic Inflammatory Response Syndrome (SIRS) criteria, and National Early Warning Score (NEWS) to predict mortality in patients with suspected sepsis. METHODS: This meta-analysis followed accordance with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed, EMBASE, Web of Science, and the Cochrane Library databases from establishment of the database to November 29, 2021. The pooled sensitivity and specificity with 95% CIs were calculated using a bivariate random-effects model (BRM). Hierarchical summary receiver operating characteristic (HSROC) curves were generated to assess the overall prognostic accuracy. RESULTS: Data of 62338 patients from 26 studies were included in this meta-analysis. qSOFA had the highest specificity and the lowest sensitivity with a specificity of 0.82 (95% CI: 0.76-0.86) and a sensitivity of 0.46 (95% CI: 0.39-0.53). SIRS had the highest sensitivity and the lowest specificity with a sensitivity of 0.82 (95% CI: 0.78-0.85) and a specificity 0.24 (95% CI: 0.19-0.29). NEWS had both an intermediate sensitivity and specificity with a sensitivity of 0.73 (95% CI: 0.63-0.81) and a specificity 0.52 (95% CI: 0.39-0.65). qSOFA showed higher overall prognostic accuracy than SIRS and NEWS by comparing HSROC curves. CONCLUSIONS: Among qSOFA, SIRS and NEWS, qSOFA showed higher overall prognostic accuracy than SIRS and NEWS. However, no scoring system has both high sensitivity and specificity for predicting the accuracy of mortality in patients with suspected sepsis.

Nomograms for Predicting the Risk of SIRS and Urosepsis after Uroscopic Minimally Invasive Lithotripsy.

Objective: To analyze the potential risk factors that affect the development of urosepsis following uroscopic minimally invasive lithotripsy and to develop a nomogram that predicts the probability of postoperative urosepsis. Methods: We retrospectively analyzed the clinical data from patients that underwent percutaneous nephrolithotripsy (PCNL) or ureteroscopic lithotripsy (URL) between January 2018 and December 2019. The enrolled patients were grouped twice according to systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA). After univariate and multivariate logistic regression analyses, we identified the independent predictive factors affecting the development of postoperative SIRS and urosepsis, and built the nomograms. Results: From January 2018 to December 2019, 1959 patients underwent PCNL or URL, of whom 236 patients were accorded with the inclusion criteria. Of all 236 patients, 64 (27.12%) patients developed postoperative SIRS, and 17 (7.20%) patients developed postoperative urosepsis. Multivariate logistic regression analysis showed that positive preoperative urine culture (PUC+) (OR = 2.331, P = 0.044), procalcitonin (PCT) (OR = 1.093, P = 0.037), C-reactive protein (CRP) (OR = 1.017, P < 0.001), and neutrophil ratio (NEUT%) (OR = 1.091, P = 0.004) of postoperative were independent predictors of SIRS, and PCT (OR = 1.017, P = 0.003) and CRP (OR = 1.080, P < 0.001) were independent predictors of urosepsis. Additionally, the nomograms demonstrated good accuracy in predicting SIRS and urosepsis with a C-index of 0.884 (95% CI: 0.835-0.934) and 0.941 (95% CI: 0.885-0.996), respectively. Conclusions: The nomograms achieved the prediction of SIRS and urosepsis after uroscopic minimally invasive lithotripsy. Using this model, the risk of SIRS or urosepsis for an individual patient can be determined, which facilitates early diagnosis and rational treatment.

Noninvasively Evaluating the Grading of Glioma by Multiparametric Magnetic Resonance Imaging.

RATIONALE AND OBJECTIVE: To investigate the performance of multi-parametric magnetic resonance imaging (MRI) for glioma grading. MATERIALS AND METHODS: Seventy consecutive patients with histopathologically confirmed glioma were retrospectively evaluated by conventional MRI, dynamic susceptibility-weighted contrast-enhanced, multiple diffusion-weighted imaging signal models including mono-exponential, bi-exponential, stretched exponential, and diffusion kurtosis imaging. One-way analysis of variance and independent-samples t test were used to compare the MR parameter values between low and high grades as well as among all grades of glioma. Receiver operating characteristic analysis, Spearman's correlation analysis, and binary logistic regression analysis were used to assess their diagnostic performance. RESULTS: The diagnostic performance (the optimal thresholds, area under the receiver operating characteristic curve, sensitivity, and specificity) was achieved with normalized relative cerebral blood flow (rCBV) (2.240 ml/100 g, 0.844, 87.8%, and 75.9%, respectively), mean kurtosis (MK) (0.471, 0.873, 92.7%, and 79.3%), and water molecular diffusion heterogeneity index (α) (1.064, 0.847, 79.3% and 78.0%) for glioma grading. There were positive correlations between rCBV and MK and the tumor grades and negative correlations between α and the tumor grades (p < 0.01). The parameter of α yielded a diagnostic accuracy of 85.3%, the combination of MK and α yielded a diagnostic accuracy of 89.7%, while the combination of rCBV, MK, and α were more accurate (94.2%) in predicting tumor grade. CONCLUSION: The most accurate parameters were rCBV, MK, and α in dynamic susceptibility-weighted contrast, diffusion kurtosis imaging, and Multi-b diffusion-weighted imaging for glioma grading, respectively. Multiparametric MRI can increase the accuracy of glioma grading.

Protocol for a randomised, double-blind, placebo-controlled trial to explore the effect of tramadol in the prevention of postpartum depression (ETPPD).

INTRODUCTION: Postpartum depression is one of the most commonly experienced psychological disorders for women patients undergoing caesarean section, which accounts for about one-third of puerpera worldwide. Tramadol, a commonly used analgesic with an inhibitory effect on the reuptake of norepinephrine and serotonin, is an effective and well-tolerated agent for analgesia after caesarean section. Based on the role of changes in the postpartum levels of serotonin and norepinephrine in postpartum depression, we speculated that postoperative intravenous analgesia using tramadol may decrease the incidence of postpartum depression for caesarean patients. Therefore, this trial aimed to explore the effect of tramadol in the prevention of postpartum depression. METHODS AND ANALYSIS: A randomised double-blind placebo-controlled trial will be performed and 1230 singleton parturients will be randomised to receive patient-controlled intravenous analgesia with tramadol or hydromorphone, or patient-controlled epidural analgesia with ropivacaine. The primary outcome of this trial will be the incidence of postpartum depression at 4 weeks after the caesarean section, together with the collection of the relevant data during hospitalisation and at 3 months after the caesarean section. Subgroup data according to the preoperative depression score will be analysed. Demographic characteristics, postoperative analgesic effects and postoperative recovery score will also be summarised and presented. ETHICS AND DISSEMINATION: The current trial protocol was approved by the Institutional Ethics Committee of Xinqiao Hospital (ID: 2017-026), Third Military Medical University, Chongqing, China. The results of this trial will be disseminated at scientific meetings and in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03309163; Pre-results.

Diagnostic value of fibulin-3 for malignant pleural mesothelioma: A systematic review and meta-analysis.

BACKGROUND: Several studies have investigated the diagnostic value of fibulin-3 for malignant pleural mesothelioma (MPM), but the results were various. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic value of fibulin-3 for MPM. RESULTS: Eight studies were included in this work. The overall sensitivity of blood fibulin-3 were 0.87 (95% CI, 0.58 - 0.97) and 0.89 (95% CI, 0.77 - 0.95), respectively. The overall sensitivity and specificity of PF fibulin-3 for MPM were 0.73 (95% CI, 0.54 - 0.86) and 0.80 (95% CI, 0.60 - 0.91), respectively. The area under curve of blood and pleural effusion (PF) Fibulin-3 were 0.94 (95% CI, 0.91 - 0.96) 0.83 (95% CI, 0.79 - 0.86), respectively. METHODS: PubMed and EMBASE databases were searched up to July 29, 2016 to verify studies investigating the diagnostic value of fibulin-3 for MPM. The quality of eligible studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy tool (QUADAS-2). The overall sensitivity and specificity were pooled using a bivariate model. CONCLUSION: Fibuoin-3 is a useful diagnostic marker for MPM.

Effectiveness of problem-based learning in Chinese pharmacy education: a meta-analysis.

BACKGROUND: This review provides a critical overview of problem-based learning (PBL) practices in Chinese pharmacy education. PBL has yet to be widely applied in pharmaceutical education in China. The results of those studies that have been conducted are published in Chinese and thus may not be easily accessible to international researchers. Therefore, this meta-analysis was carried out to review the effectiveness of PBL. METHODS: Databases were searched for studies in accordance with the inclusion criteria. Two reviewers independently performed the study identification and data extraction. A meta-analysis was conducted using Revman 5.3 software. RESULTS: Sixteen randomized controlled trials were included. The meta-analysis revealed that PBL had a positive association with higher theoretical scores (SMD = 1.17, 95% CI [0.77, 11.57], P < 0.00001). The questionnaire results show that PBL methods are superior to conventional teaching methods in improving students' learning interest, independent analysis skills, scope of knowledge, self-study, team spirit, and oral expression. CONCLUSIONS: This meta-analysis indicates that PBL pedagogy is superior to traditional lecture-based teaching in Chinese pharmacy education. PBL methods could be an optional, supplementary method of pharmaceutical teaching in China. However, Chinese pharmacy colleges and universities should revise PBL curricula according to their own needs, which would maximize the effectiveness of PBL.

A novel mathematical model to predict prognosis of burnt patients based on logistic regression and support vector machine.

OBJECTIVE: To develop a mathematical model of predicting mortality based on the admission characteristics of 6220 burn cases. METHODS: Data on all the burn patients presenting to Institute of Burn Research, Southwest Hospital, Third Military Medical University from January of 1999 to December of 2008 were extracted from the departmental registry. The distributions of burn cases were scattered by principal component analysis. Univariate associations with mortality were identified and independent associations were derived from multivariate logistic regression analysis. Using variables independently and significantly associated with mortality, a mathematical model to predict mortality was developed using the support vector machine (SVM) model. The predicting ability of this model was evaluated and verified. RESULTS: The overall mortality in this study was 1.8%. Univariate associations with mortality were identified and independent associations were derived from multivariate logistic regression analysis. Variables at admission independently associated with mortality were gender, age, total burn area, full thickness burn area, inhalation injury, shock, period before admission and others. The sensitivity and specificity of logistic model were 99.75% and 85.84% respectively, with an area under the receiver operating curve of 0.989 (95% CI: 0.979-1.000; p<0.01). The model correctly classified 99.50% of cases. The subsequently developed support vector machine (SVM) model correctly classified nearly 100% of test cases, which could not only predict adult group but also pediatric group, with pretty high robustness (92%-100%). CONCLUSION: A mathematical model based on logistic regression and SVM could be used to predict the survival prognosis according to the admission characteristics.

Leukotriene inhibitors for bronchiolitis in infants and young children.

BACKGROUND: Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children. It is often caused by the respiratory syncytial virus (RSV). Management of bronchiolitis varies between clinicians, reflecting the lack of evidence for a specific treatment approach. The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis. Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis. However, the results from limited randomised controlled trials (RCTs) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children. OBJECTIVES: To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children. SEARCH METHODS: We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to April week 4, 2014), EMBASE (1974 to May 2014), CINAHL (1981 to May 2014), LILACS (1982 to May 2014), Web of Science (1985 to May 2014), WHO ICTRP and ClinicalTrials.gov (6 May 2014). SELECTION CRITERIA: RCTs comparing leukotriene inhibitors versus placebo or another intervention in infants and young children under two years of age diagnosed with bronchiolitis. Our primary outcomes were length of hospital stay and all-cause mortality. Secondary outcomes included clinical severity score, percentage of symptom-free days, percentage of children requiring ventilation, oxygen saturation, recurrent wheezing, respiratory rate and clinical adverse effects. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Collaboration methodological practices. Two authors independently assessed trial eligibility and extracted data, such as general information, participant characteristics, interventions and outcomes. We assessed risk of bias and graded the quality of the evidence. We used Review Manager software to pool results and chose random-effects models for meta-analysis. MAIN RESULTS: We included five studies with a total of 1296 participants under two years of age hospitalised with bronchiolitis. Two studies with low risk of bias compared 4 mg montelukast (a leukotriene inhibitor) daily use from admission until discharge with a matching placebo. Both selected length of hospital stay as a primary outcome and clinical severity score as a secondary outcome. However, the effects of leukotriene inhibitors on length of hospital stay and clinical severity score were uncertain due to considerable heterogeneity between the study results and wide confidence intervals around the estimated effects (hospital stay: mean difference (MD) -0.95 days, 95% confidence interval (CI) -3.08 to 1.19, P value = 0.38, low quality evidence; clinical severity score on day two: MD -0.57, 95% CI -2.37 to 1.23, P value = 0.53, low quality evidence; clinical severity score on day three: MD 0.17, 95% CI -1.93 to 2.28, P value = 0.87, low quality evidence). The other three studies compared montelukast for several weeks for preventing post-bronchiolitis symptoms with placebo. We assessed one study as low risk of bias, whereas we assessed the other two studies as having a high risk of attrition bias. Due to the significant clinical heterogeneity in severity of disease, duration of treatment, outcome measurements and timing of assessment, we did not pool the results. Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing. One study of 952 children reported two deaths in the leukotriene inhibitors group: neither was determined to be drug-related. No data were available on the percentage of children requiring ventilation, oxygen saturation and respiratory rate. Finally, three studies reported adverse events including diarrhoea, wheezing shortly after administration and rash. No differences were reported between the study groups. AUTHORS' CONCLUSIONS: The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis. The quality of the evidence was low due to inconsistency (unexplained high levels of statistical heterogeneity) and imprecision arising from small sample sizes and wide confidence intervals, which did not rule out a null effect or harm. Data on symptom-free days and incidence of recurrent wheezing were from single studies only. Further large studies are required. We identified one registered ongoing study, which may make a contribution in the updates of this review.

Effect of the urinary tryptin inhibitor ulinastatin on cardiopulmonary bypass-related inflammatory response and clinical outcomes: a meta-analysis of randomized controlled trials.

PURPOSE: Cardiopulmonary bypass (CPB) can cause systemic inflammatory responses and a series of subsequent complications that may harm patients. The aim of this study was to explore the effects of ulinastatin on inflammatory responses and clinical outcomes of CPB via a meta-analysis of published randomized controlled trials. METHODS: A literature search was conducted, both manually and by using the PubMed, EMBASE, Cochrane Library, and Web of Knowledge databases from inception to February 2013, to identify randomized controlled trials. The abstracted efficacy measures included changes in the plasma levels of cytokines (interleukin-6 [IL-6], IL-8, and tumor necrosis factor-α [TNF-α]) measured during the perioperative period and clinical indicators of efficacy, including the duration of mechanical ventilation and the length of intensive care unit stay. Ten ulinastatin-related randomized controlled trials related to cardiac surgeries involving CPB were selected. FINDINGS: In terms of cytokine concentrations, there were no significant differences between patients who received ulinastatin and those who received placebo before CPB. However, as the surgeries progressed, cytokine concentrations were all significantly lower in the ulinastatin group (P < 0.05 at 1 hour; P < 0.0001 at 6 hours), and the respective plasma concentrations returned to baseline values 24 hours after CPB. In terms of the clinical outcome indices, the length of intensive care unit stay was not significantly different, but the duration of mechanical ventilation (95% CI, -6.75 to -0.39; P = 0.03) was significantly shorter in the ulinastatin group. IMPLICATIONS: This meta-analysis found that changes in inflammatory cytokines occurred in a time-dependent manner and that the use of ulinastatin resulted in decreased duration of mechanical ventilation with CPB compared with placebo.