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Background: Puerarin, derived from a traditional Chinese herb Pueraria lobata (Willd.) Ohwi which was distributed globally and planted in most parts of China, has been extensively applied in patients with cardiovascular diseases in China. Yet a considerable proportion of the patients were accompanied with liver illnesses simultaneously because of all sorts of reasons., Hypothesis/purpose: It had been implied by some previous research that the absorption and the metabolism of puerarin were susceptible to liver issues due to changed P-gp and Ugt1a level, but pharmacokinetics of puerarin under such conditions were few concerned. Our study aimed to make sure whether and how much the behavior of puerarin in vivo was affected by hepatic diseases, and to explore the potential mechanisms., Methods: A CCl 4 induced rat model of hepatic fibrosis (HF) was prepared and verified. Single low/high doses of oral and intravenous administration of puerarin to HF and normal rats were performed. Pharmacokinetics of puerarin were determined by a validated HPLC method. The expression of P-gp, Ugt1a1, and Ugt1a7 in both liver and intestines were determined by quantitative RT-PCR and Western blot analysis respectively., Results: The systemic exposure of puerarin in HF rats of experimental groups were found decreased remarkably except for that of the high dose intravenous group. Moreover, the expression of P-gp, Ugt1a1, and Ugt1a7 in liver and intestines of HF rats were figured out increased., Conclusion: The results indicated that the HF originated overexpression of Ugt1a1, Ugt1a7, and P-gp level played important roles in pharmacokinetics of puerarin, suggested the clinical regimen of puerarin based on normal populations might be inappropriate for patients with chronic liver diseases. It was implied drugs whose absorption or elimination were related to P-gp, Ugt1a1, or Ugt1a7 might also be affected by hepatic illnesses., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Lignified stone cells substantially reduce fruit quality. Therefore, it is desirable to inhibit stone cell development using genetic technologies. However, the molecular mechanisms regulating lignification are poorly understood in fruit stone cells. In this study, we have shown that microRNA (miR) miR397a regulates fruit cell lignification by inhibiting laccase (LAC) genes that encode key lignin biosynthesis enzymes. Transient overexpression of PbrmiR397a, which is the miR397a of Chinese pear (Pyrus bretschneideri), and simultaneous silencing of three LAC genes reduced the lignin content and stone cell number in pear fruit. A single nucleotide polymorphism (SNP) identified in the promoter of the PbrmiR397a gene was found to associate with low levels of fruit lignin, after analysis of the genome sequences of sixty pear varieties. This SNP created a TCA element that responded to salicylic acid to induce gene expression as confirmed using a cell-based assay system. Furthermore, stable overexpression of PbrmiR397a in transgenic tobacco plants reduced the expression of target LAC genes and decreased the content of lignin but did not change the ratio of syringyl- and guaiacyl-lignin monomers. Consistent with reduction in lignin content, the transgenic plants showed fewer numbers of vessel elements and thinner secondary walls in the remaining elements compared to wild-type control plants. This study has advanced our understanding of the regulation of lignin biosynthesis and provided useful molecular genetic information for improving pear fruit quality., (© 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: To investigate the feasibility and safety of computed tomography-magnetic resonance imaging (CT-MRI) fusion-guided iodine-125 seed implantation for a single malignant brain tumor., Methods: From November 2015 to October 2016, 12 patients with a single malignant brain tumor were treated with permanent iodine-125 seeds implantation. CT-MRI fusion images were used to make the preoperative treatment plan, intraoperative dose optimization, postoperative verification, and tumor response follow-up. The dosimetry parameters of CT-MRI image fusion plans were compared between preprocedures and postprocedures, including plan target volume, V100 (the percentage of the target volume covered by the prescription dose [PD]), D90 (the dose that covers 90% of the target volume), and V200 (the percentage volume of the brain tumor receiving 200% of the PD). Adverse events were graded by the Common Terminology Criteria for Adverse Events. Clinical and radiological follow-ups were performed at a 3-month interval., Results: All the interstitial implantations were completed successfully under the guidance of CT-MRI image fusion. The dosimetry parameters of CT-MRI image fusion postplans did not differ significantly from those of preplans (P > 0.05). No higher than Grade 2 adverse events were observed during the follow-up. Tumor control was achieved in 10 of 12 patients (83.33%). The median overall survival time was 15.05 ± 3.35 months (95% confidence interval 12.99-17.26)., Conclusions: CT-MRI image fusion is feasible for the design, optimization, and verification of treatment planning. CT-MRI fusion-based brachytherapy may improve dosimetry of brain tumor while sparing the normal structures, potentially impacting disease control, treatment-related toxicity, and long-term survival., Competing Interests: None

Schizophrenia is a major psychiatric disorder with complex genetic, environmental, and psychological etiologies. Although DISC1 gene has been shown as a risk factor for schizophrenia in some reports, there is a lack of a consensus. We therefore performed separate meta-analyses aiming to assess the associations between DISC1 SNPs and schizophrenia risk. We found that SNP rs821597 is significantly associated with schizophrenia risk in terms of both allelic and genotypic distribution, while SNP rs821616 is associated with schizophrenia in terms of genotypic distribution, especially in cases above 40 years old., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the effect of different concentrations of rhPDGF-BB on bone marrow stromal stem cells(BMSCs) migration in diabetic rat, and related mechanisms of SDF-1 and its G-protein conjugated receptor regulation, provide a theoretical basis for the application of rhPDGF-BB to diabetic patients for bone regeneration therapy., Methods: Animal model with diabetes were induced by streptozotocin in rats. BMSCs of diabetic rats were cultured in vitro as the control group. Transwell chemokinesis model was adopted to detect the chemokinesis of BMSCs in vitro with rhPDGF-BB at concentrations of 0, 10, 50, and 100 ng/mL, and real-time PCR was used to detect the expression of BMSCs SDF-1, CXCR4 mRNA, determine the optimum concentration of the drug. The regulatory effects of rhPDGF-BB on SDF-1 and CXCR4 expression of BMSCs were confirmed in reverse with PI3K/Akt inhibitor. Statistical analysis of the data was performed using SPSS 17.0 software package., Results: In diabetic rats induced by streptozotocin, one week later, the rat tail vein blood glucose concentration higher than 16.7 mmol/L was selected as the successful model rats. Compared with BMSCs in diabetic rats, rhPDGF-BB promoted BMSCs migration in diabetic rats, 50 ng/mL rhPDGF-BB was the optimal concentration in diabetic rats, and PI3K/Akt inhibitors significantly inhibited the migration of BMSCs in diabetic rats., Conclusions: rhPDGF-BB promotes the migration of diabetic rat BMSCs and regulates its migration by regulating SDF-1/CXCR4 axis.

Background: This study was designed to assess the factor structure, internal consistency reliability, and preliminary psychometric properties of the Chinese version of the Future Disposition Inventory-24 (FDI-24) in a large sample of Chinese university students., Methods: We translated the English version of the Future Disposition Inventory-24 (FDI-24) into Chinese and examined its factor structure, estimates of internal consistency reliability, and psychometric properties in a representative sample of university students. In particular, students (N = 2,074) from two universities in Shandong Province in China were identified using the multi-stage stratified sampling method. In addition to the FDI-24, we collected preliminary data using self-report instruments that included the Beck Hopelessness Scale (BHS) and a general sociodemographic information questionnaire., Results: The results of the internal consistency reliability estimates were adequate regarding the scores on the three FDI-24 subscales: Cronbach's alpha = .89-.97, Omega total = .85-.96, Revelle's Omega total = .88-.96, the greatest lower bound (GLB) = .89-.96 and Coefficient H = .86-.94. Bivariate correlation analyses showed evidence for criterion and discriminant validity. The 3-factor oblique-Geomin-rotation solution accounted for 62.92% of the total variance in the exploratory factor analysis (EFA). The exploratory structural equation modeling (ESEM) result showed that the 3-factor model provided adequate fit statistics for the sample data: the robust comparative fit index (R-CFI) was .959, robust Tucker Lewis index (R-TLI) was .946 and robust root mean square error of approximation (R-RMSEA) was .090., Conclusion: The FDI-24 has a satisfactory factor structure, reliability estimates, and satisfactory evidence of concurrent validity estimates for students with different demographic and cultural backgrounds. The FDI-24 holds promise for use in future investigations with Chinese students.

During the regeneration of tissues and organs, growth factors (GFs) play a vital role by affecting cell behavior. However, because of the low half-life time and quick degradation of GFs, their stimulations on cells are relatively short and discontinuous. In this study, a releasing scaffold platform, consisting of polycaprolactone (PCL) nanofibers and vascular endothelial growth factor (VEGF)-encapsulated gelatin particles, was developed to extend the influence of GFs on mesenchymal stem cells (MSCs) and endothelial cells (ECs). The results showed that this kind of scaffold can direct the differentiation of MSCs to ECs and maintain the stability of the tubular structure, an indicator of the angiogenesis ability of ECs, for an extended period of time. Therefore, the results suggest the potential application of PCL/VEGF-encapsulated gelatin particles (PCL/VGPs) as a growth factor (GF)-releasing scaffold platform in vascular tissue engineering.

Objective: To understand the situations of departments of intensive care units (ICUs) of different level hospitals in Guizhou Province, and to provide directions and evidences for improving quality control in critical care medicine., Methods: A county-level hospital and a provincial-level hospital's comprehensive ICU in Guizhou Province were selected to record and analyze and compare the structural indicators, patient admission and transfer, disease distribution, ventilator associated pneumonia (VAP), intravascular catheter related blood stream infection (CRBSI) and catheter-associated urinary tract infection (CAUTI) of the two hospitals' comprehensive ICU in 2017., Results: The ICU of the People's Hospital of Suiyang County (county hospital) was found in 2012, and the ICU of the Affiliated Hospital of Guizhou Medical University (provincial hospital) was found in 1994. Until 2017, there were 10 and 46 beds, 6 (all of them hold bachelor's degree) and 18 physicians (6 of them hold PhD, 5 of them hold master's degree, 7 of them hold bachelor's degree), 17 (4 of them hold bachelor's degree, 13 of them hold college degree or graduated from secondary school) and 69 nurses (2 of them hold master's degree, 53 of them hold bachelor's degree, 14 of them hold college degree or graduated from secondary school) in the two ICUs respectively, there were significant differences in the education background of the physicians and nurses between the two ICUs (both P < 0.01). During 2017, 471 cases were admitted to the ICU of the county hospital while 1 633 cases were admitted to the ICU of the provincial hospital. Compared with the ICU of the provincial hospital, the ratio of the patients with acute physiology and chronic health evaluation II (APACHE II) ≥ 15 at admission was lower (74.8% vs. 85.1%, P < 0.01), the ratio of direct admission was higher (30.8% vs. 17.4%, P < 0.01), the ratio of the patients admitted to the ICU more than once was lower (0.8% vs. 5.0%, P < 0.01), the ratio of the patients whose the length of ICU stay less than 24 hours was higher (51.6% vs. 13.7%, P < 0.01), the ratio of the patients whose the length of ICU stay more than 28 days was lower (1.1% vs. 2.9%, P < 0.05), the ratio of the patients discharged against-advice (25.5% vs. 20.5%, P < 0.05) was higher, the ratio of the patients transferred to other hospitals was higher (5.1% vs. 0.3%, P < 0.05), and the ICU mortality was lower (4.0% vs. 13.9%, P < 0.01) in the ICU of the county hospital. The top three kinds of diseases treated in the ICU of the county hospital were brain injury (27.4%), trauma (19.1%) and toxication (6.8%); while in the ICU of the provincial hospital were brain injury (18.6%), sepsis (16.2%) and severe acute pancreatitis (4.8%). In addition, the incidences of VAP, CRBSI and CAUTI in the ICU of the county hospital were 10.0/1 000 ventilator days, 1.4/1 000 catheter days, 0.5/1 000 catheter days; while in the ICU of the provincial hospital were 5.8/1 000 ventilator days, 2.0/1 000 catheter days, 3.7/1 000 catheter days, respectively., Conclusions: There are short of physicians and nurses in the ICU of the provincial and county hospitals in Guizhou Province, and the educational level of the medical staff in the ICU of the county hospital is relatively low. Moreover, there were significant differences in the admissions and treatments and the outcomes of the critically ill patients between the two ICUs. The characteristics of the ICUs of county hospitals should be fully considered when the quality control of critical care medicine and continuing medical education are done.

This study investigated the effect of transcutaneous electrical nerve stimulation (TENS) for the treatment of patients with chronic pain after ankylosing spondylitis (AS).A total of 72 eligible patients with chronic pain following AS were included. All included patients received exercise and were assigned to a treatment group and a control group equally. In addition, patients in the treatment group also underwent TENS therapy. All patients were treated for a total of 6 weeks. The primary outcome of pain intensity was measured by visual analog scale (VAS). The secondary outcomes included degree of functional limitation, as assessed by Bath Ankylosing Spondylitis Functional Index (BASFI); and quality of life, as evaluated by Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire. All outcomes were assessed before and after 6 weeks treatment. Furthermore, adverse events were also recorded.After 6-week treatment, patients in the treatment group did not show more promising outcomes in pain reduction, as measured by VAS (P = .08); functional evaluation, as evaluated by BASFI (P = .19); as well as quality of life, as assessed by ASQoL (P = .18), compared with patients in the control group. No adverse events occurred in both groups.This study did not exert encouraging outcomes in patients with chronic pain following AS after 6-week treatment.

Phylogeny of hard ticks (Ixodidae) remains unresolved. Mitochondrial genomes (mitogenomes) are increasingly used to resolve phylogenetic controversies, but remain unavailable for the entire large Hyalomma genus. Hyalomma asiaticum is a parasitic tick distributed throughout the Asia. As a result of great morphological variability, two subspecies have been recognised historically; until a morphological data-based synonymization was proposed. However, this hypothesis was never tested using molecular data. Therefore, objectives of this study were to: 1. sequence the first Hyalomma mitogenome; 2. scrutinise the proposed synonymization using molecular data, i.e. complete mitogenomes of both subspecies: H. a. asiaticum and kozlovi; 3. conduct phylogenomic and comparative analyses of all available Ixodidae mitogenomes. Results corroborate the proposed synonymization: the two mitogenomes are almost identical (99.6%). Genomic features of both mitogenomes are standard for Metastriata; which includes the presence of two control regions and all three "Tick-Box" motifs. Gene order and strand distribution are perfectly conserved for the entire Metastriata group. Suspecting compositional biases, we conducted phylogenetic analyses (29 almost complete mitogenomes) using homogeneous and heterogeneous (CAT) models of substitution. The results were congruent, apart from the deep-level topology of prostriate ticks (Ixodes): the homogeneous model produced a monophyletic Ixodes, but the CAT model produced a paraphyletic Ixodes (and thereby Prostriata), divided into Australasian and non-Australasian clades. This topology implies that all metastriate ticks have evolved from the ancestor of the non-Australian branch of prostriate ticks. Metastriata was divided into three clades: 1. Amblyomminae and Rhipicephalinae (Rhipicephalus, Hyalomma, Dermacentor); 2. Haemaphysalinae and Bothriocrotoninae, plus Amblyomma sphenodonti; 3. Amblyomma elaphense, basal to all Metastriata. We conclude that mitogenomes have the potential to resolve the long-standing debate about the evolutionary history of ticks, but heterogeneous evolutionary models should be used to alleviate the effects of compositional heterogeneity on deep-level relationships.

Background: Tripterygium wilfordii Hook F (TwHF) alone or in combination with methotrexate (MTX) has been shown to be more effective than MTX monotherapy in controlling the manifestations in subjects with disease-modifying antirheumatic drug (DMARD)-naïve active rheumatoid arthritis (RA) over a 6-month period. The long-term impact of these therapies on disease activity and radiographic progression in RA has not been examined., Methods: Patients with DMARD-naïve RA enrolled in the "Comparison of Tripterygium wilfordii Hook F with methotrexate in the Treatment of Active Rheumatoid Arthritis" (TRIFRA) study were randomly allocated into three arms with TwHF or MTX or the two in combination. Clinical indexes and radiographic data at baseline and year 2 was collected and compared using an intent-to-treat (ITT) and a per-protocol (PP) analysis. Two radiologists blinded to the treatment scored the images independently., Results: Of 207 subjects 109 completed the 2-year follow up. The number of subjects withdrawing from the study and the number adhering to the initial regimens were similar among the three groups (p > = 0.05). In the ITT analysis, proportions of patients reaching American College of Rheumatology 50% (ACR50) response criteria were 46.4%, 58.0% and 50.7% in the MTX, TwHF and MTX + TwHF groups (TwHF vs MTX monotherapy, p = 0.004). Similar patterns were found in ACR20, ACR70, Clinical Disease Activity Index good responses, European League Against Rheumatism good response, remission rate and low disease activity rate at year 2. The results of the PP analysis agreed with those in the ITT analysis. The changes in total Sharp scores and joint erosion and joint space narrowing during the 2 years were associated with changes in disease activity measured by the 28-joint count Disease Activity Score and were comparable among the three groups (p > 0.05). Adverse events were similar in the three treatment groups., Conclusions: During the 2-year therapy period, TwHF monotherapy was not inferior to MTX monotherapy in controlling disease activity and retarding radiological progression in patients with active RA., Trial Registration: This is a follow-up study. Original trial registration: ClinicalTrials.gov , NCT01613079 . Registered on 4 June 2012.

Objective: To observe the clinical features of atrial fibrillation (AF) patients, and to explore the correlation between the routine detection index and the new-onset AF and to find out risk factors for new AF in critically ill patients., Methods: A prospective observational study was conducted. The patients with AF admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from March 2016 to June 2017 were enrolled. The patients were divided into new-onset AF group and past-existed AF group according to their past history of AF (including persistent AF, paroxysmal AF or permanent AF). In addition, patients in ICU without history of AF and new-onset AF were selected as the control group (no AF group). The general epidemiological characteristics of patients in three groups, and the blood biochemical, coagulation and other related indicators at the time of AF occurred (new-onset AF group) or 48 hours after ICU admission (AF group and no AF group) were analyzed; the difference of laboratory indexes between patients in new-onset AF group with AF within 48 hours before occurred and patients in no AF group within 48 hours after admission to ICU was compared. The relationship between each index and new-onset AF were analyzed. Pearson or Spearman rank correlation was used for analysis. Risk factors of new-onset AF were analyzed by Logistic regression analysis., Results: 1 673 patients were admitted to ICU, including 179 cases of AF (10.70%), and 106 males and 73 females, with an average age of (71.73±23.22) years. There was 75 new-onset AF (morbidity 4.48%), and had a 28-day mortality of 45.33% (34/75). There were differences in age, previous heart disease and heart failure (HF) among new-onset AF group (n = 75), past-existed AF group (n = 104) and no AF group (n = 75). Compared with other two groups, renal insufficiency rates, troponin, serum sodium, calcium and procalcitonin levels were higher, mechanical ventilation time and the length of ICU stay were significantly prolonged, ICU and hospitalization costs were higher in new-onset AF group. Compared with no AF group, new-onset AF patients with the higher percentage of septic shock, the accumulation of vascular contraction drugs within 24 hours after AF usage were higher, and used more anti-arrhythmic drugs, has higher brain natriuretic peptide (pro-BNP), serum creatinine, blood lactic acid levels, and lower albumin, oxygenation index, and serum potassium levels, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score and 28-day mortality were higher. Correlation analysis showed that age, APACHE II score, septic shock, HF, cardiovascular disease, renal insufficiency were positively correlated with new-onset AF (r values were 0.393, 0.270, 0.386, 0.251, 0.194, 0.170; P values were 0.000, 0.001, 0.000, 0.002, 0.017, 0.037, respectively). The age [odds ratio (OR) = 0.962, P = 0.046], basic oxygenation index (OR = 1.005, P = 0.028) and serum potassium levels (OR = 1.638, P = 0.022) were the risk factors for new-onset AF., Conclusions: Critical patients with a high incidence of AF, new-onset AF significantly prolong the length of ICU stay; age, APACHE II score, septic shock, cardiovascular disease, and renal insufficiency are related to new-onset AF; age, basic oxygenation index and serum potassium levels are risk factors for new-onset AF.

Objective: To observe the effect of hydrogen-rich water on the chondriosome damage and cytokines change in brain tissue of rats with traumatic brain injury (TBI)., Methods: Fifty-four health male Sprague-Dawley (SD) rats were divided into three groups by random number table: sham group, trauma group (TBI group), and trauma+hydrogen-rich water group (TBI+HW group), the rats in each group were subdivided into 1, 3 and 7 days subgroups according to the time points after trauma, with 6 rats in each subgroup. The TBI model was reproduced by using a modified Feency method for free fall impact, and the rats in sham group were not given brain impact after craniotomy. The rats in TBI+HW group were given intraperitoneal injection of hydrogen-rich water (5 mL/kg) after TBI model reproduction, and then once a day until being sacrificed; and the rats in sham group and TBI group were given the same amount of normal saline. The neurological severity scores (NSS) for neurologic deficits were calculated at corresponding time points, and then the rats were sacrificed to harvest brain tissue at 3 mm around lesion boundary. The cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme linked immunosorbent assay (ELISA); the protein expressions of Bax, Bcl-2 were determined by Western Blot; the RFU of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and mitochondrial membrane permeability (MPTP) were determined by fluorescence and enzyme sign method., Results: TBI and TBI+HW groups appeared obvious neurologic damage after injury in rats. NSS scores in TBI and TBI+HW groups showed a decreased tendency with time prolongation after TBI. NSS scores in TBI+HW group at 3 days and 7 days were significantly lower than those of TBI group (NSS score: 9.67±0.82 vs. 11.17±1.17, 6.83±0.75 vs. 8.50±1.04, both P < 0.05). Compared with sham group, the expressions of TNF-α, IL-1β, RFU of ROS in chondriosome, protein expression of Bax in brain tissue in TBI group and TBI+HW group were significantly increased, peaked at 1 day, then they gradually declined. Each time point of RFU of MMP, MPTP in chondriosome and protein expression of Bcl-2 were significantly decreased, and gradually increased after one-day valley value. Compared with TBI group, the expressions of TNF-α, IL-1β, RFU of ROS in chondriosome and protein expression of Bax in brain tissue were all declined at corresponding time points [TNF-α (ng/L): 54.14±1.11 vs. 81.49±2.76, IL-1β (ng/L): 74.53±1.75 vs. 119.44±3.56, ROS (RFU): 92.30±2.46 vs. 121.33±6.57, Bax: 0.89±0.01 vs. 1.10±0.01, all P < 0.01]; RFU of MMP, MPTP in chondriosome and the protein expression of Bcl-2 were all increased at corresponding time points [MMP (RFU): 99.28±3.97 vs. 74.72±3.00, MPTP (RFU): 188.82±4.44 vs. 160.01±2.04, Bcl-2: 0.52±0.02 vs. 0.30±0.02, all P < 0.01]., Conclusions: The high expressions of cytokines and chondriosome damage were involved in the early TBI. Early treatment with an intraperitoneally injection of hydrogen-rich water can reduce chondriosome damage and inflammation factor release, reduce the nerve cell apoptosis after TBI, and protect brain function.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China with high morbidity and mortality, and its mortality rate is only lower than that of gastric cancer. It poses a serious threat to patients' life, which needs to be given special concerns by clinicians and patients for active implementation of effective treatment methods. Generally, major operation is the mainstay of management. Radiotherapy has gained its popularity when diagnosed have no indications for surgical therapy. An effective radiotherapy plans promote the remission of hepatocellular carcinoma to improve patients condition, prognosis, and survival rate. Therefore, we conducted this study to know the research progress of radiotherapy for hepatocellular carcinoma.

Competing Interests: There are no conflicts of interest.

Objective: To approach the value of red cell distribution width (RDW) on the prognostic assessment of patients with abdominal sepsis., Methods: The clinical data of adult patients with abdominal sepsis admitted to intensive care unit (ICU) of Affiliated Hospital of Guizhou Medical University from January 2015 to September 2017 were retrospectively analyzed. The patients were divided into survival group and death group according to ICU prognosis. The levels of serum lactate (Lac), procalcitonin (PCT), RDW, and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours were recorded. Receiver operating characteristic (ROC) curve was plotted to analyze the prognostic value of Lac, PCT, RDW and APACHE II score., Results: 162 patients with abdominal sepsis were enrolled, 132 survived, and 30 died. Compared with survival group, the Lac, PCT, APACHE II score, and RDW in death group were significantly increased [Lac (mmol/L): 4.21±2.42 vs. 2.27±1.51, PCT (mg/L): 32.08±12.95 vs. 11.87±8.81, APACHE II score: 30.13±6.42 vs. 23.36±5.29, RDW: (16.64±1.38)% vs. (13.49±2.03)%, all P < 0.01]. ROC curve analysis showed that all indicators could be used to predict the prognosis of abdominal sepsis, with the maximum predictive value of RDW. The area under the ROC curve (AUC) was 0.888, it was greater than that of APACHE II score (AUC = 0.787), Lac (AUC = 0.767) and PCT (AUC = 0.696). When threshold value of RDW was 15.40%, the sensitivity was 83.3%, and the specificity was 85.6%., Conclusions: RDW can evaluate the prognosis of patients with abdominal sepsis, and its predictive value is greater than traditional evaluation parameters such as APACHE II score, Lac, and PCT.

Objective: All types of cerebral small vessel disease (SVD) markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds, and perivascular spaces were found to be associated with poststroke depressive symptoms (PDS). This study explored whether the combination of the four markers constituting an overall SVD burden was associated with PDS. Methods: A cohort of 563 patients with acute ischemic stroke were followed over a 15-month period after the index stroke. A score of ≥7 on the 15-item Geriatric Depression Scale was defined as clinically significant PDS. Scores of the four SVD markers ascertained on magnetic resonance imaging were summed up to represent total SVD burden. The association between SVD burden and PDS was assessed with generalized estimating equation models. Results: The study sample had a mean age of 67.0 ± 10.2 years and mild-moderate stroke [National Institutes of Health Stroke Scale score: 3, interquartile, 1-5]. PDS were found in 18.3%, 11.6%, and 12.3% of the sample at 3, 9, and 15 months after stroke, respectively. After adjusting for demographic characteristics, vascular risk factors, social support, stroke severity, physical and cognitive functions, and size and locations of stroke, the SVD burden was associated with an increased risk of PDS [odds ratio = 1.30; 95% confidence interval = 1.07-1.58; p = 0.010]. Other significant predictors of PDS were time of assessment, female sex, smoking, number of acute infarcts, functional independence, and social support. Conclusion: SVD burden was associated with PDS examined over a 15-month follow-up in patients with mild to moderate acute ischemic stroke.

To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.

Aims: This study explored the association between enlarged perivascular spaces (EPVS) and the health-related quality of life (HRQoL) in patients with acute ischemic stroke., Methods: This was an observational study of consecutively screened patients with acute ischemic stroke from March 2010 to March 2015. EPVS were rated in the basal ganglia and the centrum semiovale with a validated scale. The HRQoL was assessed 3 months after the stroke onset using the Stroke-Specific Quality of Life (SSQoL). Linear regression models were used to study the association between EPVS and HRQoL., Results: The study included 648 patients (mean age 65.8 years; 40.0% women) with mild to moderately severe stroke (median NIHSS score 2), of whom 640 (98.8%) exhibited signs of small vessel disease. The median EPVS scores in the basal ganglia and the centrum semiovale were 1 each. In linear regression analysis, EPVS in the basal ganglia were associated with a lower total SSQoL score (P = 0.02) and lower mobility (P = 0.01), mood (P = 0.03), and self-care (P < 0.01). EPVS in the centrum semiovale were associated only with a lower SSQoL work/productivity subscore (P = 0.002)., Conclusions: EPVS are associated with lower HRQoL in patients with mild to moderate acute ischemic stroke. Early identification and intervention of EPVS may improve HRQoL in stroke survivors., (© 2017 John Wiley & Sons Ltd.)

Objective : Cerebral small vessel disease (SVD) is associated with increased mortality, disability and cognitive decline, depression in stroke survivors. This study examined the association between SVD burden, defined by a combination of SVD markers, and health-related quality of life (HRQoL) in acute ischemic stroke. Methods : Patients admitted with acute ischemic stroke of any etiology were prospectively screened between January 2010 to December 2014 and enrolled in the study if they met study entry criteria. HRQoL was evaluated with the 12-item Stroke Specific Quality of Life (SSQoL) at 3 months after the onset of acute ischemic stroke. SVD was ascertained by the presence of any of the SVD markers including lacune, white matter hyperintensities (WMH), cerebral microbleeds (CMB) and enlarged perivascular spaces (EPVS) in the basal ganglia or their combinations on brain magnetic resonance imaging (MRI). The presence of each individual marker scored 1 point and was summed up to generate an ordinal "SVD score" (0-4) capturing total SVD burden. Linear regression was used to determine the associations between SVD burden and HRQoL. Results : Of the743 acute ischemic stroke patients that formed he study sample (mean age: 66.3 ± 10.6 years; 41.7% women), 49.3%, 22.5%, 16.0%, 9.2% and 3.1% had SVD scores of 0, 1, 2, 3 and 4, respectively. After adjusting for demographic, clinical and imaging variables, the SVD score was independently associated with lower overall score of SSQoL ( B = -1.39, SE = 0.56, p = 0.01), and its domains of mobility ( B = -0.41, SE = 0.10, p < 0.001) and vision ( B = -0.12, SE = 0.06, p = 0.03). Acute infract volume ( B = -1.44, SE = 0.54, p = 0.01), functional independence ( B = 5.69, SE = 0.34, p < 0.001) and anxious ( B = -1.13, SE = 0.23, p < 0.001) and depressive symptoms ( B = -3.41, SE = 0.22, p < 0.001) were also the significant predictors of the overall score of SSQoL. Conclusion : The brain's SVD burden predicts lower HRQoL, predominantly in domains of mobility and vision at 3 months after acute ischemic stroke. The evaluation of SVD burden could facilitate developing individual treatment strategies.

Background: Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods used for the diagnosis of small cell lung cancer during the same diagnostic bronchoscopic procedure. However, it is not clear which method provides better results., Patients and Methods: A retrospective analysis was performed of 140 patients who had undergone video bronchoscopy for diagnostic purposes. Bronchial brushings were obtained from all subjects. Biopsy specimens were also obtained from all subjects, except for 6 cases that could not be sampled; the TBNA method was used for some special lesions. The results were analyzed separately by histology and cytology., Results: The diagnostic yield of cytology was significantly greater than that of histology (P < .01) and that of conventional smear preparations in cytology was obviously greater than that of hematoxylin and eosin stains in histology (P < .01). The false-negative results were significantly lower with cytology than with histology (P < .01). Also, the cases of sampling site restriction with cytology were distinctly less than those with histology (P < .05). Stretch deformation of the tissue structure and cell morphology was the main reason for the false-negative results in the histologic diagnosis. The use of TBNA resolved all 4 cases of hilar adenopathy and 2 cases of lesions outside the bronchus. Multiple brushings of the tissue adjacent to cancer tissue and liquid-based preparations of cancerous necrotic tissue can significantly reduce the false-negative results from biopsy., Conclusions: The diagnostic yield of cytologic examination of brushings and TBNA for small cell lung cancer was superior to that of histologic examination of hematoxylin and eosin stains and immunohistochemistry., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rationale: Epithelioid trophoblastic tumor (ETT) is a distinctive but rare gestational trophoblastic neoplasia (GTN) composed of chorionic-type intermediate trophoblast cells. Approximately 50% ETT arose from the uterine cervix or lower uterine segment following a previous pregnancy with vaginal bleeding. With its unusual ability to simulate an invasive epithelioid neoplasm, ETT frequently poses a diagnostic challenge, especially involving the uterine cervix., Patient Concerns: We herein report the case of a 60-year-old female with persistent vaginal bleeding and middle-level elevation of serum human chorionic gonadotropin (hCG). Ultrasound revealed a 3.0 × 2.7 cm well-circumscribed, strongly echogenic lesion in the cervix, with a peripheral pattern of Doppler signals. The enhanced pattern by contrast-enhanced ultrasound displayed strong peripheral enhancement accompanied with globular appearance, then centripetal filling completely, and fading away rapidly., Diagnoses: The final pathological diagnosis was ETT accompanying mucinous adenocarcinoma., Interventions: Due to the pre-operative evaluation of a presumed IB2 cervix mucinous adenocarcinoma, the patient was treated with 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy., Outcomes: The patient is currently disease-free for the past 1 year., Lessons: This case report demonstrates that sonographic image of tumor shapes and blood flow could be helpful in differentiating ETT from another GTN and enable more accurate diagnosis before treatment.

Self-interactions Proteins (SIPs) is important for their biological activity owing to the inherent interaction amongst their secondary structures or domains. However, due to the limitations of experimental Self-interactions detection, one major challenge in the study of prediction SIPs is how to exploit computational approaches for SIPs detection based on evolutionary information contained protein sequence. In the work, we presented a novel computational approach named WELM-LAG, which combined the Weighed-Extreme Learning Machine (WELM) classifier with Local Average Group (LAG) to predict SIPs based on protein sequence. The major improvement of our method lies in presenting an effective feature extraction method used to represent candidate Self-interactions proteins by exploring the evolutionary information embedded in PSI-BLAST-constructed position specific scoring matrix (PSSM); and then employing a reliable and robust WELM classifier to carry out classification. In addition, the Principal Component Analysis (PCA) approach is used to reduce the impact of noise. The WELM-LAG method gave very high average accuracies of 92.94 and 96.74% on yeast and human datasets, respectively. Meanwhile, we compared it with the state-of-the-art support vector machine (SVM) classifier and other existing methods on human and yeast datasets, respectively. Comparative results indicated that our approach is very promising and may provide a cost-effective alternative for predicting SIPs. In addition, we developed a freely available web server called WELM-LAG-SIPs to predict SIPs. The web server is available at http://219.219.62.123:8888/WELMLAG/ .

Background: Recent empirical findings have suggested that imbalanced neural networks may underlie the pathophysiology of major depressive disorder (MDD). However, the contribution of the superior temporal gyrus (STG) and the caudate nucleus to its pathophysiology remains unclear., Methods: Functional magnetic resonance imaging (MRI) date were acquired from 40 patients with first-episode drug-naive MDD and 36 matched healthy controls during wakeful rest. We used whole-brain voxel-wise statistical maps to quantify within-group resting state functional connectivity (RSFC) and between-group differences of bilateral caudate and STG seeds., Results: Compared with healthy controls, first-episode MDD patients were found to have reduced connectivity between the ventral caudate and several brain regions including the superior frontal gyrus (SFG), the superior parietal lobule (SPL) and the middle temporal gyrus (MTG), as well as increased connectivity with the cuneus. We also found increased connectivity between the left STG and the precuneus, the angular gyrus and the cuneus. Moreover, we found that increased anhedonia severity was correlated with the magnitude of ventral caudate functional connectivity with the cuneus and the MTG in MDD patients., Limitations: Due to our small sample size, we did not correct the statistical threshold in the correlation analyses between clinical variables and connectivity abnormalities., Conclusions: The present study suggests that anhedonia is mainly associated with altered ventral caudate-cortical connectivity and highlights the importance of the ventral caudate in the neurobiology of MDD., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The association of the CYP2J2 G-50T polymorphism with coronary artery disease has been explored, but the results remain controversial. Thus, a meta-analysis was conducted to provide a comprehensive estimate of this association. We selected ten articles encompassing 12 independent case-control studies with 7063 cases and 10,453 controls for this meta-analysis. Overall, we found significant associations between the CYP2J2 G-50T polymorphism and coronary artery disease risk in three genetic models (allele model: odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.05-1.34; homozygote model: OR = 2.25, 95% CI = 1.27-4.01; recessive model: OR = 2.17, 95% CI = 1.22-3.86). In these three genetic models, a significant association was observed in Caucasians but not in Asians when the data were stratified by ethnicity. However, no significant associations were found between the CYP2J2 polymorphism G-50T and coronary artery disease risk in heterozygote model and dominant model. In conclusion, our meta-analysis suggested that the CYP2J2 G-50T polymorphism was associated with coronary artery disease risk in the allele, homozygote and recessive models in Caucasians., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

CRISPR/Cas9-mediated genome editing is a next-generation strategy for genetic modifications. Typically, sgRNA is constitutively expressed relying on RNA polymerase III promoters. Polymerase II promoters initiate transcription in a flexible manner, but sgRNAs generated by RNA polymerase II promoter lost their nuclease activity. To express sgRNAs in a tissue-specific fashion and endow CRISPR with more versatile function, a novel system was established in a polycistron, where miRNAs (or shRNAs) and sgRNAs alternately emerged and co-expressed under the control of a single polymerase II promoter. Effective expression and further processing of functional miRNAs and sgRNAs were achieved. The redundant nucleotides adjacent to sgRNA were degraded, and 5'- cap structure was responsible for the compromised nuclease capacity of sgRNA: Cas9 complex. Furthermore, this strategy fulfilled conducting multiplex genome editing, as well as executing neural- specific genome editing and enhancing the proportion of homologous recombination via inhibiting NHEJ pathway by shRNA. In summary, we designed a new construction for efficient expression of sgRNAs with miRNAs (shRNAs) by virtue of RNA polymerase II promoters, which will spur the development of safer, more controllable/regulable and powerful CRISPR/Cas9 system-mediated genome editing in a wide variety of further biomedical applications.

Anhedonia is associated with dysfunction of the neural circuitry of reward in patients with major depressive disorder (MDD). However, its neurobiological basis is not fully understood. The present study examined the association between anhedonia and white matter (WM) characteristics in patients with first-episode MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy controls (HC) to undergo diffusion weighted imaging. We examined specifically the correlation between WM characteristics and anhedonia measured with the Temporal Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial Statistics (TBSS), we found that MDD patients exhibited reduced fractional anisotropy (FA) in the left cingulum and the forceps minor. These patients also exhibited increased radial diffusivity (RD) in several major tracts including the bilateral anterior thalamic radiation, the corticospinal tract, the superior longitudinal fasciculus and the uncinate fasciculus in the left hemisphere. Correlational analysis showed that increased RD was significantly correlated with anticipatory anhedonia in the MDD group, while reduced mean FA was correlated with consummatory anhedonia in HC. These preliminary findings suggest that left-sided WM tracts abnormalities may contribute to the development of anhedonia in MDD patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objective: To assess the efficacy and safety of CT-guided iodine-125 seeds in the treatment of intracranial malignancies under control of target and dose. Methods: From November 2003 to May 2016, with the clinical data of 412 operations on 310 patients in 12 hospitals in the past 14 years, this study analyzed the method of CT guided iodine-125 particles brachytherapy in the treatment of intracranial malignant tumors and evaluated the efficacy and complications. Stratification analysis of intracranial malignant tumors was performed. Results: Overall survival (OS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 67, 41, 26, 23, 46 months respectively.And the progression free time (PFS) of patients with single brain metastases, low-grade glioma, high-grade gliomas, recurrence after surgery, recurrence after radiotherapy and others were 19, 42, 6, 9, 11, 12 months respectively.Various complications were observed with a relatively low incidence of 10.4%.Three cases deceased at an interval of 7-45 days after treatment. Conclusions: For patients with intracranial malignancies, iodine-125 seeds brachytherapy could achieve a satisfactory treatment efficacy with tolerated complications.Iodine-125 seeds brachytherapy may act as a first-line regimen.

Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia. Thus, the present study aimed to expand on previous investigations by examining causal effects of repeated ketamine exposure on white matter integrity in a non-human primate model. Ketamine or saline (control) was administered intravenously for 3 months to male adolescent cynomolgus monkeys ( n = 5/group). Diffusion tensor imaging (DTI) experiments were performed and tract-based spatial statistics (TBSS) was used for data analysis. Fractional anisotropy (FA) was quantified across the whole brain. Profoundly reduced FA on the right side of sagittal striatum, posterior thalamic radiation (PTR), retrolenticular limb of the internal capsule (RLIC) and superior longitudinal fasciculus (SLF), and on the left side of PTR, middle temporal gyrus and inferior frontal gyrus were observed in the ketamine group compared to controls. Diminished white matter integrity found in either fronto-thalamo-temporal or striato-thalamic connections with tracts including the SLF, PTR, and RLIC lends support to similar findings from DTI studies on schizophrenia in humans. This study suggests that chronic ketamine exposure is a useful pharmacological paradigm that might provide translational insights into the pathophysiology and treatment of schizophrenia.

IL-6 and IL-23 are both pleiotropic cytokines involved in the regulation of the immune response, inflammation, and hematopoeisis. They also could mediate effector cells and tolerance mediated by cells with regulatory function. Inflammatory bowel disease (IBD) is associated with a reduced ratio of Treg cells ato Th17 effector cells in peripheral blood and is characterised by a pro-inflammatory cytokine microenvironment which supports the continued generation of Th17 cells. It is well described in adults but little is known in a pediatric population. This study was aimed to investigate the role of IL-6, IL-23 and its association with Treg and Th17 subsets in pediatric IBD patients. Peripheral blood mononuclear cells from patients and controls were stimulated with PMA, ionomycin, and brefeldin A. The frequencies of CD4+Foxp3+ cells, and CD4+IL17a+ cells were analyzed by flow cytometry. The serum level of IL-6 and IL-23 was determined by Elisa kit. The mRNA expression of Foxp3, IL-17a, IL-6 and IL-23 was detected by real-time quantitative PCR. The ratio of Treg/Th17 decreased in pediatric IBD patients, and it strongly correlated with IL-6 and IL-23. The present study provides a quantitative analysis regarding the Th17/Treg cell balance in peripheral blood of children with IBD and its association with serum IL-6 and IL-23 level.

Chronic hepatitis B (CHB) is a major infectious disease which threatens people's health around the world. Health-related quality of life (HRQoL) has become an important index for evaluating the treatment and prognosis of patients with CHB. Many studies abroad have shown that the HRQoL of patients with CHB is influenced by various factors. Disease severity, clinical symptoms, and low self-efficacy are important influencing factors for patients' quality of life. Anti-viral therapy, proper physical therapy, or psychological intervention can significantly improve the HRQoL of community CHB patients, and HRQoL is even significantly improved in patients undergoing liver transplantation one year ago. These studies provide valid evidence for antiviral therapy for hepatitis B patients and liver transplantation techniques from the psychological level. At present, there still lacks studies on HRQoL of CHB patients in China. This article summarizes the measurement tools for HRQoL widely used in recent years in China and foreign countries, reviews the research advances in HRQoL in community patients with CHB, and discusses the perspectives for future studies.

To improve the phase-shifting accuracy, this paper presents a novel integrated framework for design, control and experimental validation of the piezoelectric actuated phase shifter with a trade-off between accuracy and cost. The piezoelectric actuators with built-in sensors are adopted to drive the double parallel four-bar linkage flexure hinge-based mechanisms. Three mechanisms form the tripod structure of the assembled phase shifter. Then, a semi-closed loop controller with inner feedback and outer feedforward loops via the external laser interferometer is developed for accurate positioning of the phase shifter. Finally, experiments related with travel range, step response, linearity and repeatability are carried out. The linearity error is 0.21% and the repeatability error of 10 μ m displacement is 3 nm. The results clearly demonstrate the good performance of the developed phase shifter and the feasibility of the proposed integrated framework.

Ginkgo bilob a extract (EGb 761) has been widely used clinically to reduce myocardial ischemia reperfusion injury (MIRI). Microvascular endothelial cells (MVECs) may be a proper cellular model in vitro for the effect and mechanism study against MIRI. However, the protective effect of EGb 761 on MVECs resisting hypoxia/reoxygenation (H/R) injury is little reported. In this study, H/R-injured MVECs were treated with EGb 761, and then the cell viability, apoptosis, ROS production, SOD activity, caspase-3 activity, and protein level of ATM, γ-H2AX, p53, and Bax were measured. ATM siRNA was transfected to study the changes of protein in the ATM pathway. EGb 761 presented protective effect on H/R-injured MVECs, with decreasing cell death, apoptosis, and ROS, and elevated SOD activity. Next, EGb 761 could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax in a dose-dependent manner. Moreover, ATM siRNA also could inhibit H/R-induced ATM, γ-H2AX, p53, and Bax. Overall, these findings verify that EGb 761 protects cardiac MVECs from H/R injury, and for the first time, illustrate the influence on the ATM pathway and apoptosis by EGb 761 via dampening ROS.

Objective: To observe the effect of hydrogen-rich water on the CD34 expression and angiogenesis in lesion boundary brain tissue of rats with traumatic brain injury (TBI)., Methods: A total of 54 adult male Sprague-Dawley (SD) rats were divided into three groups by random number table: namely sham-operated group (sham group), trauma group (TBI group), and trauma + hydrogen-rich water group (TBI+HW group), the rats in each group were subdivided into 1, 3 and 7 days subgroups according to the time points after trauma, with 6 rats in each subgroup. The TBI model was reproduced by using a modified Feency method for free fall impact, and the rats in sham group were not given brain impact after craniotomy. The rats in TBI+HW group were given intraperitoneal injection of hydrogen-rich water (5 mL/kg) after TBI model reproduction, and then once a day until being sacrificed, and the rats in sham group and TBI group were given the same amount of normal saline. The neurological severity scores (NSS) for neurologic deficits were calculated at corresponding time points, and then the rats were sacrificed for brain tissue at 3 mm around lesion boundary. After hematoxylin-eosin (HE) staining, the pathological changes in lesion boundary brain tissue were observed under light microscope. The expression of CD34 + cells was observed by immunohistochemical analysis, which markers were used to count the newborn blood capillary sprouts around the traumatic brain tissue. The protein expression of CD34 was determined by Western Blot., Results: NSS scores at all time points in sham group were 0. NSS scores in TBI and TBI+HW groups showed a decreased tendency with time prolongation after TBI, which showed more significant in TBI+HW group, NSS scores at 3 days and 7 days were significantly lower than those of TBI group (3 day: 8.67±0.52 vs. 11.56±1.94, 7 days: 7.33±0.52 vs. 8.17±0.98, both P < 0.05). Under light microscope, the brain tissue of rats in sham group was normal. After injury, pathological changes in lesion boundary brain tissue in TBI group were characterized by obvious hemorrhagic necrosis, severe brain edema, a large number of degeneration and necrosis of nerve cells and inflammatory cell infiltration, and the pathological changes were more obvious at 3 days. The edema area in TBI+HW group was slightly smaller than that of TBI group, and the surrounding edema was slightly reduced. It was shown by immunohistochemistry that only a very small number of neoformative capillaries were found in sham group. The number of neoformative capillaries in lesion boundary brain tissue was gradually increased with time prolongation in TBI group. The number of neoformative capillaries in TBI+HW group was more significantly, which was significantly higher than that of TBI group at 3 days and 7 days after injury (cells/HP: 10.59±1.88 vs. 8.61±1.22 at 3 days, 23.20±3.16 vs. 17.01±2.64 at 7 days, both P < 0.05). It was shown by Western Blot that the expression of CD34 protein at all time points in TBI group was significantly increased as compared with that of sham group. The expression of CD34 protein at 1 day and 3 days in TBI+HW group was slightly increased as compared with that of TBI group without significant difference, but it was significantly up-regulated at 7 days after injury, which was significantly higher than that of TBI group (gray value: 1.36±0.36 vs. 0.74±0.08, P < 0.05)., Conclusions: Hydrogen-rich water promote CD34 + cells home to the site of injured tissue in rats with TBI, is involved in angiogenesis, and improve clinical outcomes during brain functional recovery.

The biological properties of Piper sarmentosum render it a potential substitute for antibiotics in livestock feed. This study evaluated the effects of P. sarmentosum extract (PSE) on the growth performance, antioxidant capability and immune response of weaned piglets. Eighty 21-d-old weaned piglets were selected and randomly allocated to one of four dietary treatments with five replicates of four pigs each. The dietary treatments consisted of a basal diet supplemented with 0 (T0), 50 (T50), 100 (T100) or 200 (T200) mg/kg PSE. The feeding trial lasted 4 weeks. The results revealed that the T50 group had the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the feeding trial (p < 0.05). Additionally, the T50 group had higher (p < 0.05) serum glutathione peroxidase activity (GSH-Px) and lower (p < 0.05) serum malondialdehyde (MDA) levels than the T0 group at 4 weeks post-weaning (p < 0.05). Serum levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) decreased, while serum levels of interleukin-4 (IL-4), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) increased by PSE supplementation at 4 weeks post-weaning (p < 0.05). PSE supplementation upregulated the mRNA expression of IL-4, IL-10 and TGF-β and downregulated the mRNA expression of TNF-α, IL-1β and interleukin-6 (IL-6) in the ileal mucosal layer of piglets (p < 0.05). In summary, our study findings revealed that PSE supplementation improved the antioxidant capability, and reduced inflammation, which may be beneficial to weaned piglet health., (Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.)

Subclinical hypothyroidism is common in pregnant women and often related to adverse pregnancy outcomes, but its relationship with gestational diabetes remains controversial. In particular, the impact of thyroperoxidase antibodies status on the relationship between subclinical hypothyroidism and gestational diabetes is not clear. We investigated the association between combined thyroid stimulating hormone (TSH) level and thyroperoxidase antibodies status in early pregnancy (<20 weeks of gestation) and gestational diabetes mellitus. A total of 7084 pregnant women met the inclusion criteria, which included thyroperoxidase antibodies-positive subclinical hypothyroidism [TSH(H)TPOAb(+)] (n = 78), thyroperoxidase antibodies-negative subclinical hypothyroidism [TSH(H)TPOAb(-)] (n = 281), thyroperoxidase antibodies-positive euthyroidism [TSH(N)TPOAb(+)] (n = 648), and thyroperoxidase antibodies-negative euthyroidism [TSH(N)TPOAb(-)] (n = 6077). Of the 7084 cases included in our study, 1141 cases were diagnosed with gestational diabetes mellitus at 24-28 weeks of pregnancy. The prevalence of gestational diabetes mellitus in TSH(N)TPOAb(-), TSH(H)TPOAb(-), TSH(N)TPOAb(+), and TSH(H)TPOAb(+) was 14.65, 19.57, 24.85, and 46.15 %, respectively. Compared with TSH(N)TPOAb(-) women, the risk of gestational diabetes mellitus was increased in all other groups of women in early pregnancy. After dividing early pregnancy into first and second trimesters, we found that TSH(H)TPOAb(-) women in the first trimester do not show this increase. Our study suggests that subclinical hypothyroidism and thyroperoxidase antibodies-positive euthyroidism in early pregnancy are associated with an increased risk of gestational diabetes mellitus.

This meta-analysis aimed to estimate the association between folate level and schizophrenia in order to provide the evidence for the treatment of schizophrenia. Data were extracted from all the studies meeting our inclusion and exclusion criteria. The association between the folate level and schizophrenia was evaluated by the standardized mean difference (SMD) and 95% confidence interval (CI). The 20 published articles of our meta-analysis included 1463 (53.4%) cases and 1276 (46.6%) controls. The folate level was significantly lower in schizophrenia cases than in healthy controls. Subgroup analysis showed the folate level was lower in cases from Asia subgroup than in healthy controls. Sensitivity analysis showed that the current results were credible and reliable and the funnel plots indicated no publication bias in our meta-analysis. Our study indicates that schizophrenia patients may have lower folate levels. More epidemiological and laboratory studies are still needed to confirm whether it is necessary to supplement folate in schizophrenia patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Self-interacting proteins (SIPs) play an essential role in cellular functions and the evolution of protein interaction networks (PINs). Due to the limitations of experimental self-interaction proteins detection technology, it is a very important task to develop a robust and accurate computational approach for SIPs prediction. In this study, we propose a novel computational method for predicting SIPs from protein amino acids sequence. Firstly, a novel feature representation scheme based on Local Binary Pattern (LBP) is developed, in which the evolutionary information, in the form of multiple sequence alignments, is taken into account. Then, by employing the Relevance Vector Machine (RVM) classifier, the performance of our proposed method is evaluated on yeast and human datasets using a five-fold cross-validation test. The experimental results show that the proposed method can achieve high accuracies of 94.82% and 97.28% on yeast and human datasets, respectively. For further assessing the performance of our method, we compared it with the state-of-the-art Support Vector Machine (SVM) classifier, and other existing methods, on the same datasets. Comparison results demonstrate that the proposed method is very promising and could provide a cost-effective alternative for predicting SIPs. In addition, to facilitate extensive studies for future proteomics research, a web server is freely available for academic use at .

Objective: To explore the clinical manifestations and molecular features of 46, XX male syndrome. Method: The clinical and molecular data of five 46, XX male syndrome cases treated in the Department of Pediatrics of Shanghai Ruijin Hospital form August 2010 to August 2014 were retrospectively analyzed. Result: The five patients were all sociopsychologically males and came to hospital respectively for short stature, ambiguous genitalia or gynecomastia. They were all below the normal male's average height, and their karyotype was all 46, XX. One case in five was verified as sex determining region of Y chromosome (SRY gene) positive revealed no abnormality in their external genitalia. He had short stature since childhood, whose SRY gene fragments were shown by FISH transferred to the ends of X chromosome. Three cases in four were SRY gene negative with ambiguous genitalia of cryptorchidism and testicular dysplasia to different degrees. The copy number variations of SOX9 gene was found in one case, the loss of heterozygosity area in DHH gene of one case. Another SRY gene negative patient who had normal male external genitalia, came to the hospital due to puberty gynecomastia, that of SOX9 gene and its upstream gene both increased. Conclusion: The main clinical characteristics of 46, XX male syndrome are male phenotype, 46, XX karyotype, gonad of testis or ovotestis and no uterus. In addition, short stature, ambiguous genitalia or gynecomastia can be one reason for hospital visits. SRY gene translocation, SOX9 gene and its upstream gene copy number increase all can lead to 46, XX male syndrome. The cause of some may play an important role in 46, XX male syndrome, but has not yet been determined.

This study was designed to investigate the effect of Huangqin Tang (HQT) on TLR4/Myd88 pathway and the downstream cytokines in rats with ulcerative colitis (UC) to explore its underlying mechanisms of action. The model of UC rats with cell immunoreactivity was made using a compound method (trinitrobenzene sulfonic acid plus ethanol). Rats were randomly divided into the control group, the model group, the salazosulfapyridine (SASP) group, high, medium and low dose(20, 10, 5 g·kg-1) of HQT groups. After a three-day treatment, production of NO in serum was detected by Griess assay, the levels of interleukin (IL)-4, IL-10, IL-17 and prostaglandin E2（PGE2） in serum were detected by ELISA. After a five-day treatment, the positive protein expressions of COX-2 and iNOS in the colon tissue were determined by ICH method, the protein expressions of TLR4 and MyD88 in colon tissue were determined by Western blot. Compared with the control group, the levels of NO, IL-17, PGE2, the protein expressions of TLR4, MyD88 and the protein positive expressions of COX-2, iNOS were apparently higher in the model group. Compared with model group, the above indexes were significantly improved in the SASP and high-dose HQT groups (P < 0.05). These results show that HQT has a definite effect on UC in rats. Its mechanisms of action may be achieved by inhibiting the activity of TLR4/MyD88/NF-κB signal pathway and down-regulation of NO, IL-17 and PGE2 production.

We generated complete mitochondrial genome sequences data for 4 genera (Onchidium, Platevindex, Paraoncidium and Peronia) in Onchidiidae to construct a phylogenetic tree in conjunction with other 9 existing data among gastropods. The topology showed that the taxa clustered into two main groups of four species, one of which included Onchidium struma and the Platevindex mortoni, the other Paraoncidium reevesii and Peronia verruculata. The process in Pulmonata from sea to land in accordance with the evolution of respiratory organs from branchial gills to pulmonary cavity has been shown. This will also constitute a framework for phylogeny evolution analysis, systematic classfication of Onchidiidae and other euthyneurans (pulmonates and opisthobranchs).

The primary effect of the endoplasmic reticulum (ER) stress response or unfolded protein response (UPR) is to reduce the load of unfolded protein and promote survival. However, prolonged and severe ER stress leads to tissue injury and serious diseases. Thus, it is important to identify drugs that can attenuate ER stress for the treatment of diseases. Natural products continue to provide lead compounds for drug discovery and front‑line pharmacotherapy for people worldwide. Previous studies have indicated that selenoprotein S (SelS) is a sensitive and ideal maker of ER stress. In the present study, a firefly luciferase reporter driven by the SelS gene promoter was used to screen for natural compounds capable of attenuating ER stress. From this, paclitaxel (PTX) was identified to efficiently inhibit the promoter activity of the SelS gene, and further results revealed that PTX significantly inhibited the tunicamycin‑induced upregulation of SelS at the mRNA and protein levels in HepG2 and HEK293T cells. In addition, PTX was able to efficiently inhibit the expression of the ER stress marker, glucose‑regulated protein 78, in ER stress, indicating that PTX may reverse ER stress. Taken together, these results suggest that PTX is able to inhibit SelS expression during ER stress and attenuate ER stress.

The objective is to use orthogonal experiment to optimize the pretreatment on the determination of serum cholesterol and its markers by GC-MS. And then the method is evaluated in a methodological perspective. The methodis to Use L16(211) orthogonal experiment design to observe the influence of three key steps，althogether seven factors of pretreatment, which are saponification (KOH ethanol solution concentration, temperature and time), extraction (dose) and derivatization (temperature , time and dose). As for the results，the conditions of optimal pretreatment are as follows：the ethanol solution is 1 mol·L-1 KOH, the saponification temperature is 70 ℃;the saponification time is 60 min;the Solvent quantity is 2 mL;the derivatization temperature is 70 ℃;the derivatization time is 60 min，and the derivatization agent is 100 μL. Through the optimization by orthogonal design and methodological evaluation, the determination of serum cholesterol and its markers by GC-MS is excellent in terms of accuracy and precision, and methodological evaluation indexes are better than those reported in other papers.

Radiation therapy is a typical treatment for esophageal squamous cell carcinoma (ESCC), especially middle and upper segment esophagus, and inoperable patients. However, how to promote radiation sensitivity in radio-resistant cancer cells is a conundrum. Here, our study investigated the radiosensitizing effect of bortezomib, a specific and reversible dipeptide boronic acid analog, in ESCC cells. Human esophageal squamous carcinoma cell lines Eca109 and TE-13 were exposed to hypoxia and/or ionizing radiation (IR) with or without treatment of bortezomib. Cell proliferation assay was performed with CCK8. Cell apoptosis and cell cycle assay were performed with flow cytometry. The radiosensitization effect of was assessed by clonogenic survival and progression of tumor xenograft. The expression of HIF-1α, VEGF, and apoptosis proteins was evaluated by Western blot. Radiation-induced DNA double strand break and homologous recombination repair were assessed by immunofluorescence. Our results show that bortezomib efficiently radiosensitizes ESCC cells by decreasing the expression of HIF- 1α and VEGF, inducing apoptosis by activating caspase, and delaying DNA damage repair after radiation.

Background: The correlation between gestational hypertension-preeclampsia (GH-PE) and placenta previa (PP) is controversial. Specifically, it is unknown whether placenta previa has any effect on the various types of preeclampsia (PE), and the role PP with concurrent placenta accreta (PA) play in the occurrence of GH-PE are not well understood., Objective: The aim of this study was to identify the effects of PP on GH, mild and severe preeclampsia (MPE and SPE), and early- and late-onset preeclampsia (EPE and LPE). Another aim of the study was to determine if concurrent PA impacts the relationship between PP and GH-PE., Methods: A retrospective single-center study of 1,058 patients having singleton pregnancies with PP was performed, and 2,116 pregnant women were randomly included as controls. These cases were collected from a tertiary hospital and met the inclusion criteria for the study. Clinical information, including PP and the gestational age at the onset of GH-PE were collected. Binary and multiple logistic regression analyses were conducted after the confounding variables were controlled to assess the effects of PP on different types of GH-PE., Results: There were 155 patients with GH-PE in the two groups. The incidences of GH-PE in the PP group and the control group were 2.5% (26/1058) and 6.1% (129/2116), respectively (P = 0.000). Binary and multiple regression analyses were conducted after controlling for confounding variables. Compared to the control group, in the PP group, the risk of GH-PE was reduced significantly by 78% (AOR: 0.216; 95% CI: 0.135-0.345); the risks of GH and PE were reduced by 55% (AOR: 0.451; 95% CI: 0.233-0.873) and 86% (AOR: 0.141; 95% CI: 0.073-0.271), respectively; the risks of MPE and SPE were reduced by 73% (AOR: 0.269; 95% CI: 0.087-0828) and 88% (AOR: 0.123; 95% CI: 0.055-0.279), respectively; and the risks of EPE and LPE were reduced by 95% (AOR: 0.047; 95% CI: 0.012-0.190) and 67% (AOR: 0.330; 95% CI: 0.153-0.715), respectively. The incidence of concurrent PA in women with PP was 5.86%; PP with PA did not significantly further reduce the incidence of GH-PE compared with PP without PA (1.64% vs. 2.51%, P>0.05). Binary logistic regression analyses were conducted after controlling for confounding variables, compared with the non-PP + GH-PE group, and the AOR of FGR in the non-PP + non-GH-PE group was 0.206 (0.124-0.342). Compared with the PP + GH-PE group, the AOR of FGR in the PP + non-GH-PE group was 0.430 (0.123-1.500)., Conclusion: PP is not only associated with a significant reduction in the incidence of GH-PE, but also is associated with a reduction in incidence of various types of PE. Concurrent PA and PP do not show association with a reduction in incidence of GH-PE.

Objective: It has previously found that human oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) was overexpressed in breast cancer, and was positively correlated with lymph node metastasis of the patients. This study aimed to investigate the association between serum CIP2A and prognosis of breast cancer. Then, we investigated whether CIP2A could be as a therapeutic target in breast cancer treatment., Patients and Methods: Preoperative CIP2A levels of 240 patients with breast cancer and 480 cases of controls were measured by ELISA method. The association of CIP2A levels with clinicopathological outcomes was investigated by univariate and multivariate analyses. The effect of CIP2A on breast cancer MDA-MB-231 cells was evaluated by CIP2A siRNA-mediated depletion of the CIP2A protein followed by an analysis of cell proliferation, invasion, colony growth, and xenograft growth and metastasis., Results: The serum CIP2A levels in patients with breast cancer were (79.0 ± 74.2) ng/mL, which was significantly higher than that in those controls (25.6 ± 21.4) ng/mL for male and (24.8 ± 20.6) ng/mL for female control. Higher preoperative CIP2A levels were significantly associated with the American Joint Committee on Cancer (AJCC) stage, histological grade and lymph node metastasis. Patients with elevated CIP2A levels showed worse survival. In multivariate analysis, elevated preoperative CIP2A levels were independent prognostic factors. Patients with high CIP2A levels had significantly shorter overall survival (OS) and disease-free survival (DFS) times. Knockdown of CIP2A by stable CIP2A siRNA transfection inhibited MDA-MB-231 cell proliferation, invasion, colony growth in vitro, and xenograft growth and metastasis in vivo., Conclusions: Our results suggest that serum CIP2A is significantly higher in patients with breast cancer, which is a potential biomarker to make a distinction between breast cancer patients and healthy controls. Higher serum CIP2A levels positively associated with the aggressive phenotype of breast cancer, and forecasts poor prognosis for patients with breast cancer. Knockdown of CIP2A may be a novel target for prevention and treatment of breast cancer.

Human adenovirus 36 (HAdV-36), as the key pathogen, was supposed and discussed to be associated with obesity. We searched the references on the association between HAdV-36 infection and obesity with the different epidemiological methods, to explore the relationship with a larger sample size by meta-analysis and compare the differences of epidemiological methods and population subsets by the subgroup analyses.We conducted literature search on the association between HAdV-36 infections and obesity in English or Chinese published up to July 1, 2015. The primary outcome was the HAdV-36 infection rate in the obese and lean groups; the secondary outcomes were the BMI level and BMI z-score in the HAdV-36 positive and negative groups. The pooled odds ratio (OR) was calculated for the primary outcome; the standardized mean differences (SMDs) were calculated for the secondary and third outcomes. Prediction interval (PI) was graphically presented in the forest plot of the random effect meta-analyses. Metaregression analysis and subgroup analysis were performed.Finally 24 references with 10,191 study subjects were included in the meta-analysis. The obesity subjects were more likely to be infected with HAdV-36 compared to the lean controls (OR = 2.00; 95%CI: 1.46, 2.74; PI: 0.59, 6.76; P < 0.001) with a high heterogeneity (I = 80.1%; P < 0.001) estimated by the random effect model. Subgroup analysis demonstrated that the pooled OR of HAdV-36 infection for obesity were 1.77 (95%CI: 1.19, 2.63; PI: 0.44, 7.03; P = 0.005) and 2.26 (95%CI: 1.67, 3.07; PI: 1.45, 3.54; P < 0.001) in the adults and children, respectively. Compared to the HAdV-36 negative subjects, the SMD of BMI was 0.28 (95% CI: 0.08, 0.47; PI: -0.53, 1.08; P = 0.006) in the HAdV-36 positive subjects with a high heterogeneity (I = 86.5%; P < 0.001). The BMI z-score in the children with HAdV-36 infection was higher than those without HAdV-36 infection (SMD = 0.19; 95%CI: -0.31, 0.70; PI: -2.10, 2.49), which had no significantly statistical difference (P = 0.453).HAdV-36 infection increased the risk of obesity. HAdV-36 also increased the risk of weight gain in adults, which was not observed in children.