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The COVID-19 infection adversely affects the cardiovascular system. Transthoracic echocardiography has demonstrated diagnostic, prognostic and therapeutic utility. We report biventricular myocardial strain in COVID-19. Methods: Biventricular strain measurements were performed for 12 patients. Patients who were discharged were compared with those who needed intubation and/or died. Results: Seven patients were discharged and five died or needed intubation. Right ventricular strain parameters were decreased in patients with poor outcomes compared with those discharged. Left ventricular strain was decreased in both groups but was not statistically significant. Conclusion: Right ventricular strain was decreased in patients with poor outcomes and left ventricular strain was decreased regardless of outcome. Right ventricular strain measurements may be important for risk stratification and prognosis. Further studies are needed to confirm these findings.

This study aims to show our institute’s experience in the treatment of HH and its associated facial deformities in adults and growing adolescents and to investigate condylar remodeling and volumetric changes and long-term stability of orthognathic surgery in adults. The study included consecutive patients with clinical and radiological features of HH who underwent high condylectomy with or without simultaneous orthognathic surgery from 2013 to 2018. The clinical outcomes were assessed based on functional activities, TMJ pain, and recurrence. Postoperative 3D condylar remodeling and orthognathic stability were evaluated with the use of ITK-Snap and 3D Slicer. Thirteen patients (8 females and 5 males) with a mean age of 26.3 ± 5.79 years (range; 13–34 years) were included with facial asymmetry as the chief complaint. The patients were followed up for a minimum of 12 months and a maximum of 4 years (mean; 16.85 ± 10.04). There were no postoperative complications, and all patients achieved a satisfactory functional and aesthetic outcome using a one-stage surgical procedure. There was no incidence of recurrence or further asymmetries, with long-term stability at the selected points showing a mean difference of less than ±1 mm. The affected condylar volume was significantly reduced following high condylectomy, with mean changes between T1 and T2 of −144. 80 mm3 (p = .012). However, the contralateral condylar volume remained stable, with a mean change of 2.54 mm3 (p = .881). One-stage high condylectomy and orthognathic surgery is a viable measure for the treatment of HH and associated deformities in adults. High condylectomy in early adolescence could result in termination of the disease, and aesthetic improvement with further constant orthodontist-surgeon follow-up is required.

Aim. To investigate whether vitamin C performs well as a supplemental treatment for common cold.Method. After systematically searching through the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and Wanfang databases, 10 randomized controlled trials were selected for our meta-analysis with RevMan 5.3 software. Published in China, all 10 studies evaluated the effect of combined vitamin C and antiviral therapy for the treatment of common cold.Results. The total efficacy (RR=1.27, 95% CI (1.08, 1.48),P=0.003), the time for symptom amelioration (MD=−15.84, 95% CI (-17.02, -14.66),P<0.00001), and the time for healing (I, 95% CI (-14.98, -4.22),P=0.0005) were better with vitamin C supplementation than with antiviral therapy alone.Conclusions. Vitamin C could be used as a supplementary therapy along with antiviral regimens to relieve patients from the symptoms of common cold.

The GH (growth hormone)/IGFs (insulin-like growth factors) system has an important function in the regulation of growth. In this system, IGFBPs play a crucial regulatory role in IGF functions. As a member of the IGFBP family, IGFBP2 can bind to IGF and regulate IGF functions to regulate development and growth. In addition, IGFBP2 shows key regulatory functions in cell proliferation and metabolism. In this study, the igfbp2 gene was cloned from grass carp (Ctenopharyngodon idellus) liver. The ORF of grass carp igfbp2 is 834 bp long and encodes 277 amino acids. The tissue distribution results showed that igfbp2 is expressed in multiple tissues in grass carp and has a high expression level in the liver. In the OGTT, igfbp2 expression was significantly decreased in the liver and brain after 6 h of treatment with glucose. In vitro, igfbp2 expression in grass carp's primary hepatocytes was significantly suppressed by insulin after treatment for 6 and 12 h. Moreover, igfbp2 expression was markedly increased in a dose-dependent manner with glucagon incubation in grass carp's primary hepatocytes. To the best of our knowledge, this is the first report about Igfbp2 in grass carp. These results will provide a basis for the in-depth study of grass carp Igfbp2.

Introduction Early rehabilitation of mechanically ventilated patients is safe, feasible and beneficial to prevent ICU-AW and its consequences. However, there are no guidelines or evidence-based studies about the optimal protocol of early rehabilitation. There is traditional meta-analysis about the effect of simple protocol, such as active mobilization, neuromuscular electrical stimulation, in-bed cycling exercise, interactive video games and so on, but no studies to explore the effects of multiple protocols together. For the extensive clinical implementation, it is important to conduct a network meta-analysis to compare the effect of different protocols of early rehabilitation.Methods and analysis PubMed, Cochrane library, Web of Science, EMbase, grey literature and referent literature will be searched from inception to August 2019. Study selection, data extraction and quality assessment will be performed independently by two reviewers. The primary outcome is ICU acquired weakness (ICU-AW), secondary outcomes include the duration of mechanical ventilation and length of stay in ICU and hospital. Statistical analysis and graphical presentations will be conducted by R software (V.3.6.0). Cochrane Handbook for Systematic Reviews (V5.1.0) will be used to conduct the quality assessment. The rank possibility will be performed by the histogram. Statistical inconsistency assessment, sensitivity analysis and publication bias will be performed.Discussion This protocol is prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. The protocol gives an insight into the scope and parameters for the systematic review to be carried out.Registration number PROSPERO CRD42020141901

Background Tracheostomy and endotracheal intubation can result in subglottic tracheal stenosis, and predisposition to keloid scar formation can increase stenosis risk after tracheal injury. This study aims to compare the incidence and severity of subglottic tracheal stenosis in keloid and non‐keloid patients following iatrogenic tracheal injury, in particular tracheostomy. Methods From 2012 to 2017, 218 573 patients were intubated for surgery; 2276 patients received tracheostomy in People’s Hospital of Zhengzhou University, China. Among these patients, 133 patients, who developed tracheal stenosis after intubation and/or tracheostomy, were divided into keloid or non‐keloid groups; their Myer and Cotton grading of tracheal stenosis, time‐to‐onset of airway stenosis, and treatment outcome were assessed and compared. Results The percentages of high grade (Myer and Cotton grading III/IV) tracheal stenosis were higher among keloid patients than non‐keloid patients (intubation: 83.3% vs 25.7%; tracheostomy: 77.7% vs 33.3%). Time‐to‐onset of airway stenosis following intubation (tracheostomy) was 27 ± 5 (38 ± 13) and 41 ± 7 (82 ± 14) days for keloid and non‐keloid patients, respectively (P

ObjectivesTo identify echocardiographic signatures featuring left ventricular longitudinal strain (LS) associated with genetic risk for cardiac amyloidosis (CA) due to theTTRVal142Ile (V142I) variant in African American (AA) and Hispanic/Latinx (H/L) individuals.BackgroundHereditary transthyretin amyloidosis (hATTR) can cause CA in ∼60-70% of older V142I carriers, but amyloid deposition progresses over many years. Disease-modifying therapy for CA is now available and early initiation is a priority for improving outcomes. Genomic screening programs and familial cascade genetic testing uncover pre-symptomatic V142I carriers, yet no guidelines exist for early CA detection.MethodsExome sequencing data linked to electronic health records (EHRs) of BioMebiobank participants were queried for AA or H/LTTR- andTTR+ (V142I) subjects without hATTR diagnoses and with prior echocardiograms suitable for retrospective LS analysis. Systemic “red flag” features of ATTR were extracted from EHRs ofTTR+ subjects. Speckle tracking echocardiography was retrospectively applied to determine global (GLS) and segmental LS. Relative apical sparing (RAS) was calculated.Results57TTR+ and 46TTR-age- and ancestry-matched subjects were included. GLS declined with age in females but not males, and was abnormal (TTR+ and 7 (15.2%)TTR-subjects (p = 0.066). Apical sparing was observed in 13 (22.8%)TTR+ and 11 (23.9%)TTR-subjects (p = 1.0). After adjusting for relevant demographic and echocardiographic covariates, neither GLS nor RAS was associated withTTR+ V142I status. Red flag features were not associated with GLS or RAS inTTR+ subjects.ConclusionsNeither GLS nor RAS were significantly different betweenTTR+ andTTR-subjects. Since >50% ofTTR+ subjects were ≥ 60 years old, penetrance of CA by echocardiography among unselected V142I carriers may be lower than previously estimated. These findings indicate that surveillance for CA in individuals at increased genetic risk due to V142I should not rely solely on echocardiography, even with LS.

Since discovery, glucagon biology has remained enigmatic. Studies have shown that glucagon may have physiological effects beyond glucose regulation by binding to its receptor (Gcgr). The potential roles of glucagon and its receptor in the crosstalk between glucose metabolism and immune function of fish remain to be investigated. In the present study, we sequenced and characterized gcgra and gcgrb in grass carp. Phylogenetic analysis showed that they were highly homologous with their counterparts in fish. The gcgra and gcgrb mRNAs were ubiquitously expressed in all the tissues examined. The gcgra mRNA was highly expressed in the liver and gcgrb was mainly expressed in the liver and brain regions of grass carp. Furthermore, the results of oral glucose tolerance test (OGTT) showed that the expression levels of the two receptors were significantly increased at 12 h after treatment. In the hepatocytes, insulin inhibited gcgra and gcgrb mRNA expressions at 3−12 h and 6−12 h, respectively. While glucagon promoted their expressions at 3−12 h and 3 h, respectively. Intraperitoneal injection of lipopolysaccharide (LPS) increased hepatic gcgra mRNA level at 6 h post treatment, and up-regulated gcgrb mRNA abundance in the liver at 24 h. In response to polyinosinic polycytidylic acid [poly (I:C)] stimuli, however, gcgra and gcgrb mRNA levels were decreased. These results suggested that glucagon receptors were affected by bacterial-like and virus-like infection beyond their roles in the glucose metabolism of grass carp.

COVID-19 infection can affect the cardiovascular system. We sought to determine if left ventricular global longitudinal strain (LVGLS) is affected by COVID-19 and if this has prognostic implications. Materials & methods: Retrospective study, with LVGLS was measured in 58 COVID-19 patients. Patients discharged were compared with those who died. Results: The mean LV ejection fraction (LVEF) and LVGLS for the cohort was 52.1 and -12.9 ± 4.0%, respectively. Among 30 patients with preserved LVEF(>50%), LVGLS was -15.7 ± 2.8%, which is lower than the reference mean LVGLS for a normal, healthy population. There was no significant difference in LVGLS or LVEF when comparing patients who survived to discharge or died. Conclusion: LVGLS was reduced in COVID-19 patients, although not significantly lower in those who died compared with survivors., Lay abstract COVID-19 infection can affect the cardiovascular system including the heart muscle. Myocardial strain measures the function of the heart muscle at cell level and can pick up unusual heart function before routine measurements. Ejection fraction (how hard the heart muscle is squeezing) can be seen with our own eyes, but strain cannot and needs special techniques to see it. In this study we wanted to find out what was the strain on COVID-19 patients and if there was a relationship between strain and the outcome of the patients (if they were able to recover from COVID-19). The important finding of our study is that strain was low in all patients with COVID-19 infection regardless of routine measurements when compared with patients without the infection. However, in this study we found no correlation between the low strain and the result of the infection for the COVID-19 patients.

Background: The diagnostic guideline of Gaming Disorder was a new category proposed in the draft of ICD-11 by WHO’s Department of Mental Health and Substance Abuse (MSD) in 2018 and its reliability and clinical utility based on Chinese population has not been studied. The purpose of this field study is to clarify the reliability, clinical utility, and culture applicability of diagnostic guidelines of gaming disorder in ICD-11, and its comparability to the diagnostic guideline in DSM-5 in China. Methods: Participants included 21 pair clinical raters which constituted of seven psychiatrists and 200 gaming players aged from 15-18 years old with different risk level of Internet addiction based on the scores of Young’s Internet Addiction Test. Each participant received a semi-structured face-to-face interview by a paired clinical raters at the same time. Then clinical raters made the diagnoses and filled the clinical utility questionnaire independently within 30 minutes after the interview through an electronic platform according to the diagnostic guidelines for gaming disorder in both ICD-11 and DSM-5. In addition, two focus groups were conducted to inform the applicability, feasibility and preference of diagnostic guidelines for gaming disorder in ICD-11 in China. Outcomes: The diagnostic consistency coefficient (kappa value) between the paired clinical raters was 0∙545( p

Glucose transporter 2 (glut2) has been studied in mammals, aves, and several fish, while the comparative studies of glut2 in common carp are still lacking. In this study, glut2 was firstly isolated and characterized from the liver of common carp. The full-length cDNA of glut2 was 2351 bp with an open reading frame (ORF) of 1512 bp, encoding 503 amino acids. Alignment of glut2 amino acid sequences from different species revealed that common carp glut2 showed higher sequence identity with teleosts, and lower homology with mammals and amphibians. Tissue distribution demonstrated that glut2 mRNA level was mainly expressed in liver, foregut, and midgut. To investigate the actions of glut2 on glucose metabolism, the level of glut2 mRNA was detected after intraperitoneal injection of glucose, human insulin and glucagon (100 ng/g), respectively. Following glucose administration, glut2 gene expression was significantly upregulated at 3 h in the foregut. However, no change was found in hepatic glut2 mRNA level, indicating that glut2 may have a role in intestinal glucose uptake rather than in the liver. Following insulin treatment, the expression of glut2 was markedly downregulated at 3 h and 6 h in the liver, and at 3 h in the foregut, respectively. Furthermore, glut2 mRNA expression was unaffected by glucagon injection in the liver and foregut. These results suggested that the expression of glut2 regulated by pancreatic hormones was different. Taken together, our studies firstly revealed the structure of the glut2 gene and its potential functions in glucose metabolism of common carp.

This study aimed to evaluate whether ultrasound-guided techniques are superior compared to traditional palpation techniques in patients undergoing radial artery catheterization (RAC).Electronic databases of PubMed, Embase, and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs). The relative risks (RRs) or weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) were used to calculate the pooled effect estimates using the random effects model for categories and continuous data, respectively.A total of 19 RCTs comprising a total of 3220 individuals were selected for final analysis. The pooled RR suggested that ultrasound-guided techniques were associated with higher incidence of first attempt success than traditional palpation techniques (RR, 1.39; 95% CI, 1.21-1.59; P 0.001). Moreover, we noted that ultrasound-guided techniques were associated with fewer mean attempts to success (WMD, -0.80 s; 95% CI, -1.35 to -0.25; P = 0.004) and a shorter mean time to success (WMD, -41.18 s; 95% CI, -75.43 to -6.93; P = 0.018) than traditional palpation techniques. Furthermore, individuals using ultrasound-guided techniques had a reduced risk of hematoma (RR, 0.40; 95% CI, 0.22-0.72; P = 0.003).This study indicated that ultrasound-guided techniques were superior compared to traditional palpation techniques for RAC in terms of efficacy and complications.

This study aims to explore the potential benefits of antidepressant drugs related to metabolic enzyme and drug-targeted genes, identify the optimal treatment of major depression, and provide a reference for individualized medication selection. A prospective randomized single-blind investigation was conducted for 8 weeks. A pharmacogenomic-based interpretive report was provided to the treating physician in the guided group. Patients in this group were informed that their medication selection was directed by DNA testing. In the unguided group, treatment was provided based on the clinical experience of the physician without the guidance of pharmacogenomic testing. Pharmacogenomic-based interpretive report was not provided to these patients until treatment completion. The 17-item Hamilton depression scale (HAMD-17), Hamilton anxiety scale, and treatment emergent symptom scale were used to assess the clinical efficacy and side effects at baseline and after 2, 4, and 8 weeks of treatment. Among the 80 initially enrolled patients with depression, 71 participated in the full data analysis sets and were designated into guided (31) and unguided (40) groups, respectively. No significant difference (P > 0.05) in HAMD-17 total scores, response and remission rates was found between the guided and unguided groups at the end of the treatment. The incidence rate of adverse reaction was 55.56% in guided group and 57.89% in the unguided group. Our study suggested that pharmacogenomic testing might not considerably improve the clinical efficiency and safety for the guided group.

Objective: To summarize the nursing treatment of patients who underwent implantation of a blood flow diverter to treat complex intracranial aneurysms. Methods: Data from 22 patients with complex aneurysms, diagnosed at an interventional center for blood flow diverter implantation between February 2015 and February 2016, treated in the Henan Provincial People’s Hospital (Zhengzhou, China), were retrospectively analyzed. Nursing methods, including preoperative, intraoperative, and postoperative care, were analyzed. Results: All 22 patients underwent successful surgery, with no related complications or hospital mortality, and were cured in hospital. Conclusion: Interventional flow diverter therapy for patients with complex intracranial aneurysms is a new technology, and involves intensive care by nursing staff and appears to be a promising new treatment method. Keywords: Intracranial aneurysm, Flow diverter, Retrospective, Nursing

Background Xingnao Kaiqiao acupuncture involves needling of the Neiguan (PC6), Renzhong (DU26), and Sanyinjiao (SP6) acupoints. The technique has a significant clinical effect in many neurological diseases. In the present report, we have developed a protocol for a scientific trial to analyze whether Xingnao Kaiqiao can be used to treat gastrointestinal dysfunction after laparoscopic surgery. In this context, we intend to execute a double-blind, randomized controlled trial to assess the efficacy and safety of Xingnao Kaiqiao acupuncture via intradermal needling. Methods/design This will be a single-center, double-blind, randomized controlled clinical trial. It has been designed on the basis of the Consolidated Standards of Reporting Trials (CONSORT 2010) guidelines and the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA). The subjects will be recruited from among inpatients scheduled for laparoscopic surgery at the Department of Minimally Invasive Surgery, Tianjin Nankai Hospital, Tianjin, China. Using random numbers generated in SPSS 19.0, the recruited subjects will be allocated to either the “Xingnao Kaiqiao” group or the sham stimulation group. A specially appointed investigator will be in charge of the randomization. Xingnao Kaiqiao via intradermal needling (or sham needling) will be administered 6 h after laparoscopic surgery, and then every 12 h for a total of six sessions, each of which will last 3 min. The subjects will undergo their first evaluation shortly before the first treatment (6 h after laparoscopic surgery); evaluations will be repeated every 12 h until a total of seven evaluations have been completed. The primary outcome will be the time until the first postoperative flatus. The secondary outcomes will be: the time until the first postoperative defecation; levels of abdominal pain, abdominal distension, and nausea; blood ghrelin level; occurrence of vomiting; psychological status; and quality of life. Discussion This upcoming randomized clinical trial was designed as a standardized method to assess the efficacy and safety of Xingnao Kaiqiao acupuncture using intradermal needles on PC6, DU26, and SP6 in the treatment of gastrointestinal dysfunction after laparoscopic surgery. We aim to provide evidence and thus improve the clinical application of this technique. Trial registration Chinese Clinical Trial Registry, ChiCTR-IOR-17010763. Registered on 2 March 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2319-3) contains supplementary material, which is available to authorized users.

Background Primary dysmenorrhoea (PD), defined as painful menses in women with normal pelvic anatomy, is one of the most common gynaecological syndromes. Acupoint-stimulation could potentially be an effective intervention for PD. Our aim was to determine the effectiveness of acupoint-stimulation compared with Non-Steroidal Anti-Inflammatory Drugs (NASIDs) in the treatment of PD. Methods Six databases were searched to December 2014. Sixteen studies involving 1679 PD patients were included. We included randomized controlled trials that compared acupoint-stimulation with NASIDs for the treatment of PD. The main outcomes assessed were clinical effectiveness rate, symptom score, visual analogue score, variation in peripheral blood prostaglandin F2α (PGF2α) and side effects. All analyses were performed using Comprehensive Meta-Analysis statistical software. Results (1) The total efficacy was better than control group: odds ratio = 5.57; 95% confidence interval (95% CI) = 3.96, 7.83; P

Endometriosis has many hypothesized etiologies. Known risk factors include genetic predisposition, uterine outflow abnormalities, and iatrogenic causes. Of increasing concern is prenatal environmental exposures. However, the findings of studies investigating the relationships between prenatal environmental exposures and the development of endometriosis have not always been conclusive, and therefore, the relationships are debatable. This review presents a summary and analysis of the current studies that investigated the effects of prenatal environmental exposures on the development of endometriosis in female offspring. Prenatal exposureto estrogenic substances (such as ethinyl estradiol and diethylstilbestrol) and environmental toxins (such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, polychlorinated biphenyls, and bisphenol A) may increase the incidence of endometriosis in female offspring. However, exposure to cigarette smoke may protect againstthe development of endometriosis in female offspring mainly because of its antiestrogenic effects. Certain prenatal environmental exposures might result in the development of endometriosis in female offspring. In addition to known environmental exposures that predispose the development of endometriosis in adulthood, such as dioxin and radiation exposure (animal modeis), prenatal exposures are of increasing concern.

This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive disorder, and their influence on the prognostic quality of life. A total of 108 patients with epilepsy and depression were selected as research participants. Among them, 53 patients were treated by oxcarbazepine combined with escitalopram (group A) and 55 patients were treated by lamotrigine combined with escitalopram (group B). Following six-month treatment, efficacy, epilepsy frequency and duration, Hamilton Depression Rating (HAMD) and Montgomery-Asberg Depression Rating (MADRS) scores, adverse reactions, improvement of electroencephalogram (EEG) epileptic discharge, quality of life, 1-year drug retention rate and withdrawal reasons of the two groups were compared. There was no remarkable difference in the total efficacy rate between both groups. The number and duration of epileptic seizures, improvement of EEG epileptic discharge and quality of life in the two groups significantly improved after treatment, with no marked difference. HAMD and MADRS scores of patients from group B were significantly lower after treatment compared with those of patients from group A. The incidence rate of adverse reactions in group B was dramatically lower compared with group A, and the 1-year drug retention rate of group B was dramatically higher compared with that in group A. Both oxcarbazepine and lamotrigine combined with escitalopram exhibited good efficacy in patients with epilepsy and depressive disorder, and they may effectively improve the prognostic quality of life of patients. Lamotrigine combined with escitalopram presented with a better antidepressant effect and safety, with higher patient tolerance.

Objective. To comprehensively compare the effects of conventional therapy combined with intravenous vitamin C and conventional therapy on viral myocarditis in children through a meta-analysis. Methods. Relevant articles including clinical trials of normal treatment combined with intravenous vitamin C and conventional therapy for viral myocarditis in children that were published between January 2000 and February 2018 were selected from PubMed, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database, and WANFANG database. The quality of the included studies was assessed using the Cochrane systematic review method (version 5.1.0); data quality was evaluated by two independent researchers. The total effective rate; LDH, CK, and CK-MB levels; and other indicators were analyzed using Rev Man 5.3 software. Results. Eight studies were eligible for this meta-analysis, which included a total of 426 patients in the treatment group and 363 patients in the control group. The meta-analysis results of six studies showed that the total effective rate of intravenous vitamin C combined with conventional therapy was higher than that of conventional therapy alone [Z = 5.46, 95% confidence interval (CI): 1.21 (1.13 to 1.30), P < 0.00001]; that of five studies showed that LDH levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 3.70, 95% CI: −1.88 (−2.88 to −0.88), P = 0.0002]; that of three studies showed that CK levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 4.21, 95% CI: −0.55 (−0.81 to −0.30), P < 0.0001]; that of four studies showed that CK-MB levels were lower in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 13.64, 95% CI: −1.44 (−1.65 to −1.24), P < 0.00001]; that of two studies showed that CD3 levels were higher in children receiving intravenous vitamin C combined with conventional therapy than in those receiving conventional therapy alone [Z = 2.45, 95% CI: 0.41 (0.08–0.73), P = 0.01]; that of two studies showed no significant difference in changes in CD4 levels between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.28, 95% CI: −0.21 (−1.69 to 1.28), P = 0.78]; and that of two studies showed no significant difference in changes in CD4/CD8 between children receiving intravenous vitamin C combined with conventional therapy and those receiving conventional therapy alone [Z = 0.07, 95% CI: −0.03 (−0.73 to 0.67), P = 0.94]. Conclusion. The meta-analysis results showed that intravenous vitamin C combined with conventional therapy is better than the simple, conventional therapy for the treatment of viral myocarditis in children in terms of the total effective rate and LDH, CK, and CK-MB levels.

Adiponectin plays critical roles in energy metabolism and immunity of mammals by binding to its receptors (AdipoR1 and AdipoR2). However, they have not been fully understood in fish. The present study examined the distribution of adiponectin receptors (AdipoRs) mRNA in grass carp, and the changes of their expressions under glucose load, insulin or glucagon stimulation, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid [poly (I:C)] challenge. As for glucose load, fish were orally administrated with glucose (1.67 mg/g BW) for 1, 3, 6, 12 h. For insulin or glucagon stimulation, the primary hepatocytes of grass carp were incubated with 0, 10, 100, 1000 nM insulin or glucagon for 1, 3, 6, 12 h. In the immune challenge experiment, grass carp were intraperitoneally injected with LPS or poly (I:C) (5 μg/g BW) for 3, 6, 12, 24, 48 h. Finally, AdipoRs mRNA expression in all experiments was detected by Real-time quantitative PCR. The results showed that AdipoRs mRNA was widely expressed in various tissues of grass carp. The adipoR1a mRNA was highly expressed in the brain regions, and the highest level of adipoR2 mRNA was observed in the adipose tissue. Glucose load up-regulated adipoR1b and adipoR2 mRNA expressions in the liver at 6 h post administration and decreased adipoR1a expression in the muscle at 3 h. Insulin significantly enhanced adipoR1b and adipoR2 mRNA expressions in the hepatocytes at 1–12 h, and promoted adipoR1a mRNA expression at 1, 3 and 12 h, while glucagon had little effect on their expressions. LPS and poly (I:C) stimuli induced AdipoRs expression in the liver at 6 and 12 h, and their expressions in the muscle were decreased slightly or remained unchanged. In addition, LPS promoted AdipoRs expression in the kidney and spleen, whereas poly (I:C) only induced adipoR1a mRNA expression in the kidney, and increased adipoR2 mRNA level in the spleen. These results suggest that AdipoRs may act as one of the targets of insulin and immune response in grass carp, but whether they are direct target remains to be further studied.

Autoimmune hemolytic anemia (AIHA) is a rare disease in children, and its clinical severity varies. To better understand disease manifestation and treatment outcome, we analyzed 68 children diagnosed as AIHA for clinical characteristics, laboratory findings, and treatment outcomes. Data show that primary AIHA accounted for 39.7% of all patients, whereas secondary AIHA accounted for 60.3%. Among them, Evans syndrome (ES) accounted for 20 cases (29.4%). Average hemoglobin was lower in the 1-year or below age group than in the above 1-year age group, combined-antibody group than single-antibody group, and IgM-contained group than non-IgM-contained group (P

Ligustrazine is a principal ingredient of chuanxiong. Concerns regarding the evaluation of the effectiveness of ligustrazine in the treatment of UA have resulted in a meta-analysis combined with recent clinical evidence. Seven computer databases that included the China hospital knowledge database (CHKD), Wanfang Med Online, the Chinese medical journal database (CMJD), PubMed, Cochrane, Embase (Ovid), and Medline (Ovid) were systematically searched. We included randomized controlled trials and quasi-randomized controlled trials. Our systematic review identified 16 RCTs that met our eligibility criteria. Ligustrazine combined with conventional medicine was associated with an increased rate of marked improvement in symptoms and an increased rate of marked improvement of ECG compared with conventional Western medicine alone. Additionally, the use of ligustrazine was associated with significant trends in the reduction of the consumption of nitroglycerin and the level of fibrinogen when compared with conventional Western medicine alone. No firm results were found between the intervention and the control method groups in the reduction of the time of onset or the frequency of acute attack angina due to the high level of heterogeneity. In conclusion, our meta-analysis found that ligustrazine was associated with some benefits for people with unstable angina.

The left ventricle (LV) compensates for the increased afterload encountered in severe aortic stenosis (AS) through hypertrophy. However, a decreased left ventricular ejection fraction LVEF

Pathogenic gene variants in transthyretin ( TTR ) can cause heritable amyloidosis (hATTR) and confer a 60% risk of heart failure. Echocardiography with global longitudinal strain (GLS) discriminates fully manifest cardiac amyloid (CA) but its ability to detect preclinical CA is unknown. We

Generally, fish are thought to have a limited ability to utilize carbohydrate. Postprandial blood glucose is cleared sluggishly in fish, resulting in prolonged hyperglycemia. Facilitative glucose transporters (GLUTs) play an important role in glucose utilization. In the present study, the expression levels of glut2 in different tissues were detected in grass carp. Furthermore, the effects of oral glucose administration on glut2 mRNA expression in the liver, intestine and kidney were investigated, and we also evaluated the response of glut2 mRNA to insulin and glucagon in the primary hepatocytes of grass carp. The expression level of glut2 mRNA was highest in the liver, followed by the intestine and kidney, but lower in other tissues. The result of glucose tolerance test (GTT) showed that serum glucose reached the highest level at 3 h after GTT and recovered to the basic level at 6 h. The glut2 mRNA in the intestine was up-regulated at 1 h after GTT. However, the glut2 mRNA expression in the liver of grass carp was unchanged after GTT for 1, 3, 6 h, and even decreased at 12 h after GTT. In addition, the expression of glut2 mRNA in the primary hepatocytes was enhanced by insulin and glucagon at 3 h post treatment. These results suggested that glut2 expression in the liver of grass carp was sensitive to insulin and glucagon, but not blood glucose. The up-regulation of glut2 by these hormones might be involved in the bi-directional transportation of glucose in the liver.

Background HPV 18 is one of the most prevalent oncogenic types, only second to HPV 16, and included in the licensed vaccines on the market. In this study, we describe the production and characterization of a panel of monoclonal antibodies (mAb) to HPV18. Methods The immunocompetence of 1B1 and 4C2 mAbs for HPV L1 protein was evaluated by SDS-PAGE analysis, neutralization assays, affinity identification, and ELISA. The 1B1 and 4C2 genes were sequenced and analyzed. Finally, the detection kit with the two mAbs was assessed for linearity, repeatability and specificity. Results Both mAbs specifically recognized HPV18 L1 and virus-like particles (VLPs). These mAbs are conformation-neutralizing antibodies that have high affinity and type specificity. Based on these characteristics of these mAbs, we developed an ELISA kit for specifically detecting HPV 18 antigen. We showed that this kit displayed good linearity, repeatability and sensitivity for detecting HPV18 L1 pentamer and HPV18 VLP. Conclusions We characterized two monoclonal neutralizing antibodies for HPV L1 protein, and developed an ELISA kit for specifically detecting HPV 18 antigen. This newly developed kit can be used to monitor the potency of HPV vaccines throughout the entire production process as well as preliminary analysis of HPV18 infections.

BACKGROUND Vitamin D is a fat-soluble vitamin that is related to the health of the human body and is an indispensable nutrient for human beings. Some studies indicated that type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) may be associated with vitamin D deficiency, but the current understanding of this point of view remains controversial. This study aimed to evaluate the correlation between serum 25-hydroxyl vitamin D (25 [OH] D) concentration and DPN in patients with T2DM by a meta-analysis, and to provide a reference for doctors. METHODS Relevant studies were selected from the PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP databases, and Wanfang Data Knowledge Service Platform databases dating from 2000 to December 2017. A total of 75 articles related to serum 25 (OH) D and DPN were selected from 2000 to December 2017. Based on the inclusion and exclusion criteria of the literature, a quality assessment was conducted using the Newcastle-Ottawa scale, and a meta-analysis was performed by RevMan5.3 statistical software. RESULTS Thirteen studies that involved a total of 2814 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis results, heterogeneity test showed that, P

Aim. To investigate whether vitamin C is effective in the treatment of the common cold.Method. After systematically searching the National Library of Medicine (PubMed), Cochrane Library, Elsevier, China National Knowledge Infrastructure (CNKI), VIP databases, and WANFANG databases, 9 randomized placebo-controlled trials were included in our meta-analysis in RevMan 5.3 software, all of which were in English.Results. In the evaluation of vitamin C, administration of extra therapeutic doses at the onset of cold despite routine supplementation was found to help reduce its duration (mean difference (MD) = -0.56, 95% confidence interval (CI) [-1.03, -0.10], and P = 0.02), shorten the time of confinement indoors (MD = -0.41, 95% CI [-0.62, -0.19], and P = 0.0002), and relieve the symptoms associated with it, including chest pain (MD = -0.40, 95% CI [-0.77, -0.03], and P = 0.03), fever (MD = -0.45, 95% CI [-0.78, -0.11], and P = 0.009), and chills (MD = -0.36, 95% CI [-0.65, -0.07], and P = 0.01).Conclusions. Extra doses of vitamin C could benefit some patients who contract the common cold despite taking daily vitamin C supplements.

Objectives: This study was designed to observe the efficacy and safety of renal denervation from the inside and outside of renal arteries. Methods: Fourteen beagles were randomly divided into a control group (n = 4) and treatment group (n = 10). One renal artery in every beagle of the treatment group was randomly assigned to an intimal group (10 renal arteries) which underwent percutaneous renal denervation from the inside, and another renal artery was assigned to an adventitial group (10 renal arteries) which underwent renal denervation from the outside by laparotomy. Results: Compared with the intimal group, the renal norepinephrine (NE) concentration in the adventitial group had significantly decreased (p = 0.003) at 3 months postsurgery. Renal artery HE staining showed that the perineurium from the adventitial group appeared thickened. Western blotting showed that renal tissue tyrosine hydroxylase (TH) protein expression in the adventitial group was significantly lower than that in the intimal group (p < 0.01) at 3 months postsurgery. There was a renal artery stenosis and a renal atrophy in the intimal group after 1 month of follow-up. Conclusion: The inhibitory effect on renal sympathetic nerve activity was more effective in the adventitial group than the intimal group, and renal denervation in the former group was safe.

For children with precursor B (pre-B) acute lymphoblastic leukemia (ALL) with TCF3-PBX1 fusion gene, their prognosis has been a controversial topic. From January 2008 to December 2012 in our hospital, 450 patients were diagnosed as ALL. Clinical characteristics of 20 patients with TCF3-PBX1 fusion gene were analyzed retrospectively, which were classified to the intermediate-risk (IR) group according to Chinese Children Leukemia Group-2008 (CCLG-2008) risk-stratification criteria and protocol based on the backbone of BFM 95 trails. Eighty five cases without TCF3-PBX1 in the same IR group were regarded as the comparison group. There were no differences in age, gender, initial white blood cell (WBC) count, status of central nerves system (CNS) at diagnosis and complete remission (CR) rates of bone marrow (BM) between the two groups (P.05). The 5-year probability of event-free survival (EFS) rates were 84.4 ± 15.6% and 73.5 ± 15.6% in the TCF3-PBX1 group and the comparison group (P = .35), respectively. The 5-year probability of overall survival (OS) rates were 86.0 ± 17.6% and 81.8 ± 17.6% (P = .46), respectively. Relapse rates were 10.5% and 12.9% (P = 1.00), respectively. There were not cases with CNS relapse in the TCF3-PBX1 group. When intensive chemotherapy was used, the TCF3-PBX1 was associated with a favorable outcome in childhood pre-B ALL.

Background: Contrast-enhanced ultrasound (CEUS) is considered a novel method for diagnosing pancreatic cancer, but currently, there is no conclusive evidence of its accuracy. Using CEUS in discriminating between pancreatic carcinoma and other pancreatic lesions, we aimed to evaluate the diagnostic accuracy of CEUS in predicting pancreatic tumours. Methods: Relevant studies were selected from the PubMed, Cochrane Library, Elsevier, CNKI, VIP, and WANFANG databases dating from January 2006 to May 2017. The following terms were used as keywords: “pancreatic cancer” OR “pancreatic carcinoma,” “contrast-enhanced ultrasonography” OR “contrast-enhanced ultrasound” OR “CEUS,” and “diagnosis.” The selection criteria are as follows: pancreatic carcinomas diagnosed by CEUS while the main reference standard was surgical pathology or biopsy (if it involved a clinical diagnosis, particular criteria emphasized); SonoVue or Levovist was the contrast agent; true positive, false positive, false negative, and true negative rates were obtained or calculated to construct the 2 × 2 contingency table; English or Chinese articles; at least 20 patients were enrolled in each group. The Quality Assessment for Studies of Diagnostic Accuracy was employed to evaluate the quality of articles. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, summary receiver-operating characteristic curves, and the area under curve were evaluated to estimate the overall diagnostic efficiency. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals (CIs) were calculated with fixed-effect models. Results: Eight of 184 records were eligible for a meta-analysis after independent scrutinization by 2 reviewers. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratios were 0.86 (95% CI 0.81–0.90), 0.75 (95% CI 0.68–0.82), 3.56 (95% CI 2.64–4.78), 0.19 (95% CI 0.13–0.27), and 22.260 (95% CI 8.980–55.177), respectively. The area under the SROC curve was 0.9088. Conclusion: CEUS has a satisfying pooled sensitivity and specificity for discriminating pancreatic cancer from other pancreatic lesions.

Background Endometriosis is a multifactorial, oestrogen-dependent, inflammatory, gynaecological condition that can result in long-lasting visceral pelvic pain and infertility. Acupuncture could be an effective treatment for endometriosis and may relieve pain. Our aim in the present study was to determine the effectiveness of acupuncture as a treatment for endometriosis-related pain. Methods In December 2016, six databases were searched for randomised controlled trials that determined the effectiveness of acupuncture in the treatment of endometriosis-related pain. Ultimately, 10 studies involving 589 patients were included. The main outcomes assessed were variation in pain level, variation in peripheral blood CA-125 level, and clinical effective rate. All analyses were performed using comprehensive meta-analysis statistical software. Results Of the 10 studies included, only one pilot study used a placebo control and assessed blinding; the rest used various controls (medications and herbs), which were impossible to blind. The sample sizes were small in all studies, ranging from 8 to 36 patients per arm. The mean difference (MD) in pain reduction (pre- minus post-interventional pain level—measured on a 0–10-point scale) between the acupuncture and control groups was 1.36 (95% confidence intervals [CI] = 1.01–1.72, P

Objective Diabetes substantially increases the risk of cardiovascular disease (CAD) and is associated with an increased risk of CAD mortality. The purpose of this study was to investigate the differences in coronary artery plaque, coronary artery calcification (CAC) measured in outpatients with and without type 2 diabetes, and the occurrence rate of a major adverse cardiac event (MACE) throughout follow-up with the same patients. Methods Five hundred eighty-eight outpatients with suspected CAD comprising 208 diabetic and 380 non-diabetic patients were enrolled in this study. Coronary artery plaque and CAC scores were detected and measured by dual-source computed tomography. The major MACE during the follow-up period (4.0–20 months) was recorded and its relationship to type 2 diabetes and CAC was investigated. Results The diabetes group had higher CAC scores in the left anterior descending, left circumflex, and right coronary arteries and total CAC burden than the group without diabetes. The diabetes group had more diseased coronary segments and more obstructed vessels than the non-diabetes group. Logistic regression analysis demonstrated that diabetes is positively associated with mixed coronary plaque and non-calcified plaque. All patients in the diabetes group and all patients with higher CACs in both groups had a higher incidence rate of MACEs. Conclusion Patients with type 2 diabetes have a higher prevalence of obstructive CAD, higher CAC scores, and a higher incidence rate of MACEs than those without diabetes. Diabetes and higher CAC scores were the important predictors of the occurrence of MACEs throughout follow-up with patients.

Background Wilms’ tumor (WT) is one of the most common malignant neoplasms of the urinary tract in children. Anaplastic histology (unfavorable histology) accounts for about 10% of whole WTs, and it is the single most important histologic predictor of treatment response and survival in patients with WT; however, until now the molecular basis of this phenotype is not very clearly. Methods A real-time polymerase chain reaction (PCR) array was designed and tested. Next, the gene expression profile of pediatric anaplastic histology WT and normal adjacent tissues were analyzed. These expression data were anlyzed with Multi Experiment View (MEV) cluster software further. Datasets representing genes with altered expression profiles derived from cluster analyses were imported into the Ingenuity Pathway Analysis Tool (IPA). Results 88 real-time PCR primer pairs for quantitative gene expression analysis of key genes involved in pediatric anaplastic histology WT were designed and tested. The gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal controls; we identified 15 genes that are up-regulated and 16 genes that are down-regulated in the former. To investigate biological interactions of these differently regulated genes, datasets representing genes with altered expression profiles were imported into the IPA for further analysis, which revealed three significant networks: Cancer, Hematological Disease, and Gene Expression, which included 27 focus molecules and a significance score of 43. The IPA analysis also grouped the differentially expressed genes into biological mechanisms related to Cell Death and Survival 1.15E−12, Cellular Development 2.84E−11, Cellular Growth and Proliferation 2.84E-11, Gene Expression 4.43E−10, and DNA Replication, Recombination, and Repair 1.39E−07. The important upstream regulators of pediatric anaplastic histology WT were TP53 and TGFβ1 signaling (P = 1.15E−14 and 3.79E−13, respectively). Conclusions Our study demonstrates that the gene expression profile of pediatric anaplastic histology WT is significantly different from adjacent normal tissues with real-time PCR array. We identified some genes that are dysregulated in pediatric anaplastic histology WT for the first time, such as HDAC7, and IPA analysis showed the most important pathways for pediatric anaplastic histology WT are TP53 and TGFβ1 signaling. This work may provide new clues into the molecular mechanisms behind pediatric anaplastic histology WT. Electronic supplementary material The online version of this article (doi:10.1186/s12935-015-0197-x) contains supplementary material, which is available to authorized users.

ObjectiveTo evaluate the recanalization efficacy and safety of a novel stent retriever in a swine model of acute arterial occlusion.MethodsThe JRecan thrombectomy device, a stent retriever with a weaving stent design, was evaluated in 18 occluded cervicocerebral vessels of swine. The flow restoration effect immediately upon deployment, the reperfusion rate after retrieval, thromboembolic events, and complications were assessed. The histologic structure of the renal arteries after retriever passage was measured to further assess the safety of JRecan.ResultsImmediate flow restoration was achieved in 66.7% of occlusions (12/18). The reperfusion rate was 94.4% (two Thrombolysis in Cerebral Infarction (TICI) 2b and 15 TICI 3). Distal thromboembolic events did not occur. Microscopic examination of the arteries after retrieval showed mild degrees of endothelial loss in 96.6% (29/30), fibrin or platelet deposition in 53.3% (16/30), and disruption of the internal elastic lamina in 10% (3/30), without severe pathologic lesions.ConclusionsThe JRecan is highly effective at clot removal with a favorable safety profile and merits further development as a stent retriever for the treatment of acute ischemic stroke.

We have recently demonstrated that granulocyte colony-stimulating factor (G-CSF) stimulated the production of epithelial-cell-derived-neutrophil attractant-78 (ENA-78) by neutrophils and that ENA-78 might promote the accumulation of neutrophils that had migrated from the intravascular space into inflammatory tissues. In this study, we examined whether other chemokines could be secreted by neutrophils that had accumulated after migrating from the intravascular space into the inflammatory tissues. We demonstrated that adhesion to laminin contained in the basement membrane and Matrigel, which is an artificial basement membrane model, induced macrophage inflammatory protein-1 beta (MIP-1 beta) in neutrophils and that MIP-1 beta secreted by neutrophils induced the chemotaxis of dendritic cells. These findings suggest that neutrophils transmigrating through the basement membrane are stimulated to secrete MIP-1 beta by the basement membrane, inducing the transmigration of dendritic cells from the intravascular space into inflammatory tissues. We propose that neutrophils intervene between innate immune response and specific immune response by secreting MIP-1 beta during the transmigration through the basement membrane.

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2'-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.

Endometriosis is a complex disease that affects a large number of women worldwide and may cause pain and infertility. To systematically review published studies evaluating the relationship between menstrual cycle length and risk of endometriosis. We searched the Cochrane Library, PubMed, Web of Science, and EMBASE in databases in July 2014 using the keywords “case–control studies,” “epidemiologic determinants,” “risk factors,” “menstrual cycle,” “menstrual length,” “menstrual character,” and “endometriosis.” We included case–control studies published in English that investigated cases of surgically confirmed endometriosis and examined the relationship between endometriosis risk and menstrual cycle. Eleven articles that met the inclusion criteria included data of 3392 women with endometriosis and 5006 controls. Fixed-effects and random-effects models were used for the evaluation. For the association of risk of endometriosis and menstrual cycle length shorter than or equal to 27 days (SEQ27) or length longer than or equal to 29 days (LEQ29), the odds ratio was 1.22 (95% confidence interval [CI]: 1.05–1.43) and 0.68 (95% CI: 0.48–0.96), respectively. In conclusion, this meta-analysis suggests that menstrual cycle length SEQ27 increase the risk of endometriosis and cycle length LEQ29 decrease the risk.

Background and purpose The effect of very high WBC over 100 or 200*109/L at initial stage on the outcome of pediatric acute lymphoblastic leukemia (ALL) was much argued by different clinical trials. CCLG-2008 clinical trial has been carried out on pediatric ALL for 5 years in China and reports on the evaluation of very high WBC in pediatric ALL are still lacking. In this study, we assessed the clinical features, complications and outcome of ALL patients with hyperleukocytosis treated by CCLG-2008. Methods Between March 2009 and June 2013, 399 ALL patients were enrolled in this clinical trial in the Children's Hospital of Soochow University and were treated with the protocol on risk-based principle. 121 patients who had an initial WBC count above 50*109/L were further divided into four groups as 50-100*109/L, 100-200*109/L, 200-300*109/L, 300*109/L. The clinical features, complications, the rate of relapse, event free survival (EFS) and overall survival (OS) within the four groups were analyzed by using SPSS 18.0. Continuous variables were defined as median values if they were not normally distributed and Mann-Whitney test was used in these dates. Groups for categorical variables were analyzed by Chi-square or Fisher's exact tests. Relapses, EFS, and OS were estimated for various patient subgroups by using the Kaplan-Meier method, and the log-rank test was used to compare survival curves between groups. Cox regression analysis was performed to evaluate predictors of adverse events. P-values £¼0.05 were considered statistically significant. Results High WBC patients count for 30.33% for all patients (121/399), among which 38 cases (31.4%) with initial leukocyte counts of 100-200*109/L, 8 cases (6.61%) with a leukocyte count of 200-300*109/L, and 19 patients (15.70%) with a leukocyte count of 300*109/L. The data indicated that less than 1 year at diagnosis, T-cell immune phenotype, massive hepatomegaly, SIL-TAL1 fusion gene, serum levels of lactic dehydrogenase (LDH), and serum levels of α-Hydroxybutyrate (α-HBDH) were positively correlated to super-hyperleukocytosis, while fibrinogen(Fib) was negatively correlated to high WBC. Early complications occurred in 42 of 121 patients (34.7%). Of which, 17 patients had respiratory events,11 patients suffered a tumor lysis syndrome (TLS), 4 cases diagnosed as intracranial hemorrhage, 5 cases accompanied with disseminated intravascular coagulation (DIC) and 5 cases died at their early stage (ED). TLS, cerebral hemorrhage, DIC and ED occurred significantly more frequently in patients with extreme hyperleukocytosis. For 121 patients with high WBC counts, 101 patients completed the treatment with CCLG-2008 protocol, 20 cases gave up due to early complications, early death or economic status. The complete remission (CR) rate was 86.1% (87/101). No significant effect of a high WBC was found on MRD on day 33. 24 /87 (27.6%) patients relapsed with an initial WBC of 50-100*109/L in 3 cases, 100-200*109/L in 9 cases, and 300*109/L (50%) in 12 cases, respectively. No case with WBC of 200-300*109/L relapsed probably due to the smallest number of patient in this category. Bone marrow was the most common site of relapse involved either alone or in combination (20 cases, 83.8%). 13 patients (54.2%) relapsed at early or very early time after CR. The treatment related death (TRD) occurred in 18 /121patients (14.9%) with high WBC with a distribution as WBC 50-100*109/L in 4 cases, 100-200*109/L in 2 cases, 200-300*109/L in 4 cases, and 300*109/L in 8 cases. Patients with WBC ¡Ý 300*109/L had a significantly shorter EFS (P=.003), higher relapse (P=.019), higher ED (P=.001) and higher TRD (P=.036) (Figure 1 and 2). However, the WBC count seemed not to significantly influence the OS (Figure 2). Conclusion In conclusion, WBC300*109/L confers a poorer prognosis on pediatric ALL patients due to increasing adverse events such as higher relapse, higher ED and TRD which resulted in lower EFS. More efficient protocols need to reduce early complications, early relapse and improve their OS for these patients Figure 1 TRD was close related with super-high WBC (P=.036) Figure 1. TRD was close related with super-high WBC (P=.036) Figure 2 5 years EFS and OS of ALL patients with high WBC Figure 2. 5 years EFS and OS of ALL patients with high WBC Disclosures No relevant conflicts of interest to declare.

Objective: MLL gene rearrangement in pediatric acute lymphoblastic leukemia (ALL) was regarded as high risk factor because of the poorer outcome of overall survival(OS). Some reports further proved that patients with MLL/AF4 had the worse outcome than MLL rearranged with other partners. CCLG-ALL2008 protocol has been carried out in China for more than 5 years. However, there was no reports to evaluate its efficiency on pediatric ALL patients with MLL rearrangement. In this study, we analyzed the data of ALL patients to compare the outcome of patients with MLL rearrangement positive and negative treated by CCLG-2008 protocol. Methods During the period from 2009 to 2013, 379 patients were enrolled in this protocol, of which 19 cases were MLL rearrangement positive and treated with CCLG-ALL2008 protocol for high-risk (HR) group. The treatment efficiency was evaluated on the time points of day 7, day15, day 33 and 12th week after treatment, respectively. OS and treatment-related mortality (TRD) was calculated within high risk groups of MLL positive and negative. Results Patients with MLL rearrangement positive accounted for 5.01% of all patients. The characteristics and response to the treatment were illustrated in Table 1. Cases younger than 2 years old, with initial white blood cell (WBC) 50*109/L , or MRD more than 10-2 on day 33 had a lower OS (P0.05). Compared with the male, female patients had a better 5 year EFS (100% versus 50%±17%, P Conclusion Factors including female, older than 2 years of age, sensitivity to prednisone, are good prognostic index in predicting the outcome of 5 years of OS and EFS in childhood ALL with MLL gene rearrangement. Table 1 Clinical and laboratory characteristics of ALL patients with MLL positive Table 1. Clinical and laboratory characteristics of ALL patients with MLL positive Figure 1 Gender exerts influence on 5 years EFS in MLL rearrangement group Figure 1. Gender exerts influence on 5 years EFS in MLL rearrangement group Figure 2 Figure 2. Age influenced 5 years EFS in MLL rearrangement group Disclosures No relevant conflicts of interest to declare.

Background and purpose CCLG-2008 protocol has been carried out for more than 5 years in most parts of China. This retrospective cohort study analyzed the clinical features and the role of prognosis index on the outcomes of patients with childhood acute lymphoblastic leukemia (ALL) treated by CCLG-2008 protocol in the Children's Hospital of Soochow University, Suzhou, China. Procedure From 2009 to 2013, 379 evaluable patients were enrolled in this protocol. ALL diagnosis was made by MICM and early prognosis index including age, gender, white blood cell (WBC), immunotype, molecular findings, karyotype and prednisone response were evaluated as predictors of adverse events by using SPSS 16.0. P-values Results The overall relapse treated with CCLG-2008 protocol was 17.4%, with 16.9% and 23.3% in B-ALL and T-ALL. Bone marrow, central nervous system and testis relapse counts for 95.4%, 3% and 1.52% respectively. Comparing with B-ALL (n=349), T-ALL (n=30) was associated with a high WBC (>100*109/L, P120 months, P=0.018), more adverse karyotype distribution, a poor prednisone response (P100*109/L) or increased age (>120 months) showed higher disease-relapse risk than other groups (P=0.003, 100*109/L. Patients with WBC < 50*109/L displayed the best survival while those with WBC higher than 100*109/L had the worst survival (Figure 1). The results of molecular alterations detected by multiple RT-PCR suggested that the MLL gene related and BCR-ABL positive patients exhibited the worst trend for EFS and OS (Figure 2a). Those with favorable karyotypes exhibited prolonged EFS and OS (Figure 2b). 44 cases who were not responsive well to prednisone displayed a shorter EFS and OS (Figure 3). Cox regression analysis indicated that WBC count, age, karyotype and prednisone response are independent factors as prognosis index for pediatric B-ALL treated by CCLG-2008 protocol . Conclusions Patients with T-ALL subtype often had higher risk factors, such as high WBC counts, increased age, adverse genes and karyotypes. It is more prone to resistance to prednisone and disease relapse, and has a poor survival outcome. WBC count, age, karyotype and prednisone response are independent factors in predicting prognosis at initial stage of B-ALL. Patients with either very high WBC ¡Ý100*109/L or older than 120 months have short survival and need more intensive therapy or novel drug combination regimen to improve their EFS and OS. Figure 1 EFS and OS of patients with different number of WBC. Patients with WBC >100*109/L have the shortest survival. Figure 1. EFS and OS of patients with different number of WBC. Patients with WBC >100*109/L have the shortest survival. Figure 2 a EFS and OS of B-ALL patients with fusion gene positive or negative. Figure 2. a EFS and OS of B-ALL patients with fusion gene positive or negative. Figure 2b EFS and OS of B-ALL patients with different risk of karyotype. Figure 3 EFS and OS of patients with different response to prednisone. Figure 3. EFS and OS of patients with different response to prednisone. Disclosures No relevant conflicts of interest to declare.

We have previously reported that transforming growth factor beta (TGF-beta) produced by rat hepatoma cell line KDH-8 cells suppressed the interleukin-2 (IL-2) production of T cells and the tumoricidal activity of macrophages in KDH-8 tumor-bearing rats and that the inhibition of TGF-beta production by low-dose bleomycin restored these activities significantly. In this study, we established three transfectant clones with stable expression of soluble TGF-beta receptor type II (sTRII), namely KT1, KT2 and KT3, and one with an empty vector used as control vector (KV), and then investigated the effects of sTRII on the tumorigenicity of KDH-8 cells and immune responses in syngeneic Wistar King Aptekman/Hok (WKAH) rats. We found that sTRII expressed in sTRII transfectants could abolish growth inhibition of Mv1Lu cells by TGF-beta1 produced by the cells themselves, and that tumor growth of KT2 and KT3 clones in vivo was suppressed significantly compared with that of parent, KV and KT1 clones. Furthermore, we demonstrated that IL-2 production of splenocytes and IL12p40 mRNA expression in tumor tissues were restored in rats inoculated with KT2 and KT3 clones, whereas such restoration was not observed in rats inoculated with parent, KV and KT1 clones. Combined with a low expression of sTRII in KT1 tumor tissues, these results suggest that sTRII may to some extent be able to abolish the tumor-promoting activity of TGF-beta, and imply that sTRII might have a therapeutic effect on TGF-beta-producing tumors.