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Background: The Achilles tendon is the strongest tendon in the human body, although it is also prone to injury and rupture. Currently, the best treatment method for acute Achilles tendon rupture remains controversial. The aim of this study was to compare the efficacy of the Ma-Griffith method combined with a minimally invasive small incision (M-G/MISI) with the modified suture technique (MST).Methods: We conducted a retrospective review of the medical records of all patients who underwent treatment for acute Achilles tendon rupture between January 2012 and January 2020 at our hospital. Demographic characteristics, operative details, and postoperative complications were recorded, and data were statistically analyzed to compare the treatment efficacy of the two operative methods.Results: A total of 67 patients were enrolled in the study, 34 of whom underwent M-G/MISI treatment, and 33 of whom underwent MST treatment. The intraoperative blood loss in the M-G/MISI group (16.47 ± 13.23 ml) was significantly lower than that in the MST group (34.55 ± 13.01 ml), and the difference was statistically significant (P ˂0.001). The incision in the M-G/MISI group (3.79 ± 1.81 cm) was significantly shorter than that in the MST group (5.79 ± 1.00 cm), and the difference was statistically significant (P˂0.001). The Achilles tendon rupture score and the American Orthopedic Foot and Ankle Society (AOFAS) score were higher than those of the MST group at the sixth month after the operation (P˂0.001). Postoperatively, there was 1 case of traumatic Achilles tendon rupture in the M-G/MISI group and 1 case each of infection and deep vein thrombosis in the modified suture group.Conclusions: Compared with the MST group, the M-G/MISI group had better Achilles tendon and ankle function scores at 6 months postoperatively, and less bleeding and shorter incisions. M-G/MISI is less invasive than MST. [ABSTRACT FROM AUTHOR]

Crotonaldehyde (CRA)—one of the major environmental pollutants from tobacco smoke and industrial pollution—is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, β-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein–protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA. [ABSTRACT FROM AUTHOR]

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most frequent autoimmune paraneoplastic encephalitis, and is primarily associated with ovarian teratomas. Here, we report the first case of a patient diagnosed with chronic myelogenous leukemia (CML) during the recovery phase of anti-NMDAR encephalitis.Case Presentation: The patient was admitted with fever, headache, and seizures. Brain MRI revealed a cerebrospinal fluid (CSF)-containing arachnoid cyst in the left temporal lobe with no other abnormal signals. EEG showed diffuse background slowing in the delta-theta range. The patient tested positive for anti-NMDAR antibodies in both the serum and CSF. One year after the onset of encephalitis, the patient was referred to the Department of Hematology for extreme leukocytosis. Karyotype analysis showed the presence of Philadelphia chromosome t(9;22)(q34;q11). Quantitative reverse transcriptase PCR analysis further identified BCR/ABL1 fusion transcripts; thus, CML was diagnosed.Conclusions: To the best of our knowledge, this is the first case of anti-NMDAR encephalitis associated with CML. This report should alert clinicians to consider CML as a malignancy that is possibly associated with limbic encephalitis. [ABSTRACT FROM AUTHOR]

Background: Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge. Method: A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC–MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC–MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS). Results: Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3. Conclusion: Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) are involved in many fundamental biological processes, such as transcription regulation, protein degradation, and cell differentiation. Information on lncRNA in the melon fly, Zeugodacus cucurbitae (Coquillett) is currently limited. Results: We constructed 24 RNA-seq libraries from eight tissues (midgut, Malpighian tubules, fat body, ovary, and testis) of Z. cucurbitae adults. A total of 3124 lncRNA transcripts were identified. Among those, 1464 were lincRNAs, 1037 were intronic lncRNAs, 301 were anti-sense lncRNAs, and 322 were sense lncRNAs. The majority of lncRNAs contained two exons and one isoform. Differentially expressed lncRNAs were analyzed between tissues, and Malpighian tubules versus testis had the largest number. Some lncRNAs exhibited strong tissue specificity. Specifically expressed lncRNAs were identified and filtered in tissues of female and male Z. cucurbitae based on their expression levels. Four midgut-specific lncRNAs were validated by quantitative real-time polymerase chain reaction (RT-qPCR), and the data were consistent with RNA-seq data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of targets of midgut-specific lncRNAs indicated an enrichment of the metabolic process. Conclusions: This was the first systematic identification of lncRNA in the melon fly. Expressions of lncRNAs in multiple adult tissues were evaluated by quantitative transcriptomic analysis. These qualitative and quantitative analyses of lncRNAs, especially the tissue-specific lncRNAs in Z. cucurbitae, provide useful data for further functional studies. [ABSTRACT FROM AUTHOR]

Background: In the underdeveloped multi-ethnic regions of China,high tuberculosis (TB) burden and regional inequity in access to healthcare service increase the challenge of achieving the End TB goals. Among all the provinces,the highest TB burden is reported in Xinjiang,where ethnic minorities and older people have suffered most. However,current case-finding strategy is inadequate given the complex social determinants and suboptimal case detection rates. Thus,we developed an integrated TB control program to improve case detection and conducted a pilot in Xinjiang from 2014 to 2015. In this case study,we summarized the activities and key findings. We also shared the experiences and challenges of implementing interventions and provided recommendations to inform the TB control program in the future. Case presentation: The pilot interventions were implemented in one selected town in Yining based on local TB control programs. By applying tailor-made educational materials,outreach TB educational activities were conducted in diverse ways. In 22 Masjids,the trained imams promoted TB education to the Muslims,covering 20,440 persontimes in 88 delivered preaching sessions. In seven schools,1944 students were educated by the teachers and contributed to educating 6929 family members. In the village communities,13,073 residents participated in household education and screening. Among them,12,292 people aged under 65 years were investigated for suspicious pulmonary TB symptoms,where six TB patients were diagnosed out of 89 TB suspects; 781 older people were mobilized for screening directly by chest X-ray,where 10 patients were diagnosed out of 692 participants. Supportive healthcare system,multi-sectoral cooperation and multi-channel financing mechanism were the successful experiences of implementation. The interventions were proved to be more effective than the previous performance: the number of TB suspects consulting doctors and patients detected increased by 50% and 26%, respectively. The potential challenges,implications and recommendations should been taken into account for further program improvement. Conclusions: In underdeveloped multi-ethnic regions with high TB burden,improving case detection is necessary and the interventions can be feasible and effective within a supportive system. More intensive educational and training approaches,a high index of TB suspicion and prioritization of older people in screening are recommended. To sustain and scale up the program,the impacts,cost-effectiveness,feasibility and acceptability of interventions warrant further research and evaluation in each specific context. [ABSTRACT FROM AUTHOR]

Background: Cotton fiber, a natural fiber widely used in the textile industry, is differentiated from single cell of ovule epidermis. A large number of genes are believed to be involved in fiber formation, but so far only a few fiber genes have been isolated and functionally characterized in this developmental process. The Kinesin13 subfamily was found to play key roles during cell division and cell elongation, and was considered to be involved in the regulation of cotton fiber development. Results: The full length of coding sequence of GhKIS13A1 was cloned using cDNA from cotton fiber for functional characterization. Expression pattern analysis showed that GhKIS13A1 maintained a lower expression level during cotton fiber development. Biochemical assay showed that GhKIS13A1 has microtubule binding activity and basal ATPase activity that can be activated significantly by the presence of microtubules. Overexpression of GhKIS13A1 in Arabidopsis reduced leaf trichomes and the percentage of three-branch trichomes, and increased two-branch and shriveled trichomes compared to wild-type. Additionally, the expression of GhKIS13A1 in the Arabidopsis Kinesin-13a-1 mutant rescued the defective trichome branching pattern of the mutant, making its overall trichome branching pattern back to normal. Conclusions: Our results suggested that GhKIS13A1 is functionally compatible with AtKinesin-13A regarding their role in regulating the number and branching pattern of leaf trichomes. Given the developmental similarities between cotton fibers and Arabidopsis trichomes, it is speculated that GhKIS13A1 may also be involved in the regulation of cotton fiber development. [ABSTRACT FROM AUTHOR]

Background: This study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene and postoperative recurrence in patients with thyroid carcinoma (TC). Methods: A total of 312 patients diagnosed with TC were chosen for the study and categorized into recurrence (n = 75) and non-recurrence (n = 237) groups. The hTERT rs2736100 and rs2736098 polymorphisms were detected by performing polymerase chain reaction-restriction fragment length polymorphism. DNA methylation in the promoter region of hTERT gene was evaluated by pyrosequencing. A telephonic and/or outpatient follow-up was conducted for all patients. The correlations of DNA methylation and polymorphisms in the promoter region of hTERT with postoperative recurrence of TC patients underwent analysis. Results: The patient in the recurrence group showed evidently different pathological types and tumor stages in comparison to the non-recurrence group. The GG genotype of hTERT rs2736100 might increase the recurrence risk of TC patients. No correlations between hTERT rs2736098 polymorphisms and recurrence risk were observed. Compared to the TT + TG genotype frequency, the rs2736100 GG genotype frequency increased in patients without multicentricity, patients with extrathyroidal invasion, patients with lymph node metastasis, patients with undifferentiated carcinoma, and patients in the III + IV stage. The recurrence group showed significantly higher DNA methylation level compared to the non-recurrence group. The DNA methylation level was closely associated to tumor stage and lymph node metastasis of TC patients in the recurrence group. Conclusions: The DNA methylation and rs2736100 polymorphisms in the promoter region of hTERT gene might be in correlation to postoperative recurrence of TC patients. [ABSTRACT FROM AUTHOR]

With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included. Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets. TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and principals identified in this study will help to evaluate and improve current program, develop targeted strategy, as well as raise more discussions on the research priority settings and policy transitions. Given the scarceness of policy and evaluated interventions, as well as the unawareness of shifting TB epidemiology and strategy especially in developing countries, the increasing need of a ready TB program for the elderly warrants further research. [ABSTRACT FROM AUTHOR]

Background: The clonal spread of multiple drug-resistant Acinetobacter baumannii is an emerging problem in China. We analysed the molecular epidemiology of Acinetobacter baumanni isolates at three teaching hospitals and investigated the risk factors, clinical features, and outcomes of hospital-acquired pneumonia caused by extensive drug-resistant Acinetobacter baumannii (XDRAB) infection in Guangzhou, China.Methods: Fifty-two A. baumannii isolates were collected. Multilocus sequence typing (MLST) was used to assess the genetic relationships among the isolates. The bla OXA-51-like gene was amplified using polymerase chain reaction (PCR) and sequencing. The resistance phenotypes were determined using the disc diffusion method. A retrospective case-control study was performed to determine factors associated with XDRAB pneumonia.Results: Most of the 52 A. baumannii isolates (N = 37, 71.2%) were collected from intensive care units (ICUs). The respiratory system was the most common bodily site from which A. baumannii was recovered (N = 45, 86.5%). Disc diffusion classified the isolates into 17 multidrug-resistant (MDR) and 35 extensively drug-resistant (XDR) strains. MLST grouped the A. baumannii isolates into 5 existing sequence types (STs) and 7 new STs. ST195 and ST208 accounted for 69.2% (36/52) of the isolates. The clonal relationship analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. According to the sequence-based typing (SBT) of the bla OXA-51-like gene, 51 A. baumannii isolates carried OXA-66 and the rest carried OXA-199. There were no significant differences with respect to the resistance phenotype between the CC92 and non-CC92 strains (P = 0.767). The multivariate analysis showed that the APACHE II score, chronic obstructive pulmonary disease (COPD) and cardiac disease were independent risk factors for XDRAB pneumonia (P < 0.05). The mortality rate of XDRAB pneumonia was high (up to 42.8%), but pneumonia caused by XDRAB was not associated with in-hospital mortality (P = 0.582).Conclusions: ST195 may be the most common ST in Guangzhou, China, and may serve as a severe epidemic marker. SBT of bla OXA-51-like gene variants may not result in sufficient dissimilarities to type isolates in a small-scale, geographically restricted study of a single region. XDRAB pneumonia was strongly related to systemic illnesses and the APACHE II score but was not associated with in-hospital mortality. [ABSTRACT FROM AUTHOR]

As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuronspecific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anticancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis aimed to investigate the efficacy and safety of partial weight bearing (PWB) versus early full weight bearing (FWB) after uncemented total hip arthroplasty (THA). Methods: We conducted a search in PubMed, EMBASE, The Cochrane Library, and Web of Science for randomized controlled trials (RCTs) and non-RCTs comparing PWB and early FWB after uncemented THA. Two authors conducted the selection of studies, data extraction, and assessment of risk of bias independently. A pooled meta-analysis was performed using the RevMan 5.3 software. Results: Six RCTs and three non-RCTs met the inclusion criteria. The meta-analysis indicated that compared with PWB, the FWB group showed greater femoral subsidence at 3-month follow-up (MD = -0.12, 95% CI -0.22 to -0.01, P= 0. 03). There were no significant differences in the hip Harris score at 1-year and 2-year follow-up (MD = 1.54, 95% CI -0. 83 to 3.90, P= 0.20; MD = 0.08, 95% CI -1.19 to 1.34, P= 0.90, respectively), in femoral subsidence at 2-year follow-up and at two additional years of follow-up (MD = -0.03, 95% CI -0.31 to 0.25, P= 0.84; (MD = -0.02, 95% CI -0.37 to 0.33, P= 0.91, respectively). There were no significant differences in the incidences of bone ingrowth fixation, spot welds, and radiolucent lines. Conclusions: This meta-analysis shows that early FWB in patients with uncemented THA could be safe and could not increase the incidence of postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Antiangiogenic therapies are considered promising for the treatment of glioblastoma (GB). The non-collagenous C-terminal globular NC1 domain of type VIII collagen a1 chain, Vastatin, is an endogenous antiangiogenic polypeptide. Sustained enhanced expression of Vastatin was shown to inhibit tumour growth and metastasis in murine hepatocellular carcinoma models. In this study, we further explored the efficacy of Vastatin in the treatment of GB xenografts.Method: Treatment of Vastatin was carried out using a nanopolymer gene vector PEI600-CyD-Folate (H1). Antiangiogenic effect of Vastatin was tested in vitro by using co-culture system and conditioned medium. An orthotopic GB murine model was established to examine the in vivo therapeutic effect of Vastatin alone treatment and its combination with temozolomide.Results: Vastatin gene transfection mediated by H1 could target tumour cells specifically and suppress the proliferation of microvessel endothelial cells (MECs) through a paracrine inhibition manner. Enhancing Vastatin expression by intracerebral injection of H1-Vastatin significantly prolonged animal survival from 48 to 75 days in GB murine model, which was comparable to the effect of Endostatin, the most studied endogenous antiangiogenic polypeptide. The diminished presence of CD34 positive cells in the GB xenografts suggested that Vastatin induced significant antiangiogenesis. Moreover, a synergistic effect in extending survival was detected when H1-Vastatin was administered with temozolomide (TMZ) in GB chemoresistant murine models.Conclusion: Our results suggest, for the first time, that Vastatin is an antiangiogenic polypeptide with significant potential therapeutic benefit for GB. H1-Vastatin gene therapy may have important implications in re-sensitizing recurrent GB to standard chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Background: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown.Methods: We employed the rd10 mouse model (Pde6b rd10 mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration.Results: Inhibition of BET activity by intravitreal delivery of JQ1, a BET-specific inhibitor binding both Brom1 and Brom2, ameliorated photoreceptor degeneration and improved electroretinographic function. Rescue effects of JQ1 were related to the suppression of retinal microglial activation in vivo, as determined by decreased immunostaining of activation markers (IBA1, CD68, TSPO) and messenger RNA (mRNA) levels of inflammatory cytokines in microglia purified from rd10 retinas. JQ1 pre-treatment also suppressed microglial activation in vitro, decreasing microglial proliferation, migration, and mRNA expression of inflammatory cytokines (TNFα, MCP-1, IL-1β, IL-6, and RANTES). Expression of BET2, but not BET3 and BET4, was significantly elevated during photoreceptor degeneration at postnatal day (PN)24 in retinas of rd10 mice relative to age-matched wild-type controls. siRNA knockdown of BET2 but not BET4, and the inhibitor of Brom2 (RVX208) but not of Brom1 (Olinone), decreased microglial activation.Conclusions: These findings indicate that BET inhibition rescues photoreceptor degeneration likely via the suppression of microglial activation and implicates BET interference as a potential therapeutic strategy for the treatment of degenerative retinal diseases. [ABSTRACT FROM AUTHOR]

Background: The role of type I collagen, composed of collagen type I alpha 1 (COL1A1) and collagen type I alpha 2 (COL1A2), has been studied in several cancers. However, the expression of COL1A1 and COL1A2 in malignant, premalignant, and normal gastric tissues and their clinical significances in gastric cancer have not been elucidated. Methods: Real-time quantitative PCR was performed in 55 malignant, 27 premalignant, and 19 normal tissues to measure COL1A1 and COL1A2 messenger RNA (mRNA) expression, and the correlations between COL1A1 and COL1A2 expression and clinicopathological parameters and patients' survival rate were analyzed. Results: We found that COL1A1 mRNA expression was significantly upregulated in premalignant and malignant tissues than in normal tissues, whereas COL1A2 mRNA expression was significantly higher in malignant tissues than in premalignant and normal tissues. Moreover, COL1A1 expression was unrelated to clinicopathological parameters, while COL1A2 expression was positively related to tumor size and depth of invasion. Besides, higher COL1A1 and COL1A2 expression levels were related to lower overall survival. Conclusions: We find that COL1A1 might have its potential as a monitoring factor to screen early gastric cancer, and COL1A1 and COL1A2 might predict poor clinical outcomes in gastric cancer patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed at reseaching the immune effect of porcine circovirus type 2 (PCV2) DNA vaccine containing CpG motif on mice. Methods: A total of 40 6-week-old female BALB/c mice were randomly divided into four groups which were immunized by 18CpG-pVAX1-ORF2, pVAX1-ORF2, pVAX1 and PBS, respectively, and immunized again 2 weeks later. All mice were challenged with 0.2 mL PCV2 cells virulent strain SD (106.0 TCID50/mL) after 4 weeks. Average daily gain, blood antibody levels, microscopic changes and viremia were detected to estimate the effect of DNA vaccine. Results and Discussion: The results showed that compared to those of the control mice, groups immunized with pVAX1-ORF2 and 18CpG-pVAX1-ORF2 could induce PCV2-specific antibodies. The PCV2-specific antibodies level of 18 CpG-pVAX1-ORF2 groups was higher significantly than other groups and decreased slowly along with time. There was no distinct pathological damage and viremia occurring in mice that inoculated with CpG motif DNA vaccines. The results demonstrated that the DNA vaccine containing 18 CpG could build up resistibility immunity and reduce immune organ damage on mice. [ABSTRACT FROM AUTHOR]

Background: Xp11.2 translocation/transcription factor E3 (TFE3) rearrangement renal cell carcinoma (RCC) is a rare subtype of RCC with limited clinical and pathological data. Case presentation: Here we present an unusual high-grade Xp11.2 translocation RCC with a rhabdoid feature and SMARCB1 (INI1) inactivation in a 40-year-old man with end-stage kidney disease. The histological examination of the dissected left renal tumor showed an organoid architecture of the eosinophilic or clear neoplastic cells with necrosis and high mitotic activity. In some areas, non-adhesive tumor cells with eccentric nuclei were observed. Immunohistochemically (IHC), the tumor cells are positive for TFE3 and the renal tubular markers (PAX2 and PAX8), and completely negative for SMARCB1, an oncosuppressor protein. Break-apart florescence in situ hybridization and reverse transcription polymerase chain reaction confirmed TFE3 rearrangement on Xp11.2 and the presence of ASPSCR1-TFE3 fusion gene. DNA sequencing revealed a frameshift mutation in exon 4 of SMARCB1 gene. Conclusion: It is important to recognize this rare RCC with both TFE3 rearrangement and SMARCB1 inactivation, as the prognosis and therapeutic strategies, particularly targeted therapies for such tumors, might be different. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between tumor necrosis factor receptor-associated factor 6 (TRAF6) and the clinicopathological features in HCC as well as its biological function. Methods: Totally, 412 liver tissues were collected, including 171 hepatocellular carcinoma (HCC) and their corresponding non-tumor tissues, 37 cirrhosis and 33 normal liver tissues. The expression of TRAF6 was assessed by immunohistochemistry. Then, analysis of the correlations between TRAF6 expression and clinicopathological parameters in HCC was conducted. Furtherer, in vitro experiments on HepG2 and Hep3B cells were performed to validate the biological function of TRAF6 on HCC cells. TRAF6 siRNA was transfected into HepG2 and Hep3B cell lines and TRAF6 expression was evaluated with RT-qPCR and western blot. The assays of cell viability, proliferation, apoptosis and caspase- 3/7 activity were carried out to investigate the effects of TRAF6 on HCC cells with RNA interference. Cell viability was assessed with Cell Titer-Blue kit. Cell proliferation was tested with MTS kit. Cell apoptosis was checked through morphologic detection with fluorescence microscope, as well as caspase-3/7 activity was measured with fluorogenic substrate detection. Results: The positive expression rate of TRAF6 protein was 49.7% in HCC, significantly higher than that of normal liver (12.1%), cirrhosis (21.6%) and adjacent non-cancerous tissues (36.3%, all P < 0.05). Upregulated TRAF6 was detected in groups with metastasis (Z = -2.058, P = 0.04) and with low micro-vessel density (MVD) expression (Z = -2.813, P = 0.005). Spearman correlation analysis further showed that the expression of TRAF6 was positively correlated with distant metastasis (r = 0.158, P = 0.039) and negatively associated with MVD (r = -0.249, P = 0.004). Besides, knock-down of TRAF6 mRNA in HCC cell lines HepG2 and Hep3B both resulted in cell viability and proliferation inhibition, also cell apoptosis induction and caspase-3/7 activity activation. Conclusions: TRAF6 may contribute to metastasis and deterioration of the HCC via influencing cell growth and apoptosis. Thus, TRAF6 might become a predictive and therapeutic biomarker for HCC. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was performed to identify the benefits and disadvantages of the PEEK cage and titanium cage.Methods: We used "cervical or cervicle", "titanium", and "polyetheretherketone or PEEK" as keywords. Medline, Embase, Cochrane Central Register of Controlled Trials and other databases were searched to identify eligible studies that were published before October 2015. In addition, the Google search engine was used to manually search for relevant journals or conference proceedings. Randomized controlled trials and non-randomized controlled trials that compared the PEEK cage and titanium cage for anterior cervical surgery were included. The meta-analysis was performed with RevMan 5.1 software.Results: Two randomized and two non-randomized clinical trials were retrieved with a total of 184 segments from 107 patients in the PEEK cage group and 211 segments from 128 patients in the titanium cage group. The quality assessment scores ranged from 16 to 18 with high heterogeneity. There were no differences in functional status according to the Odom criteria, fusion rate, final local segmental angle and loss of correction between the two groups. Although more subsidence occurred in the titanium cage group, the effects of loss of the local segmental angle or the whole cervical Cobb angle on cervical function in the long-term are still not clear.Conclusion: The present meta-analysis indicated no significant difference in functional and radiographic performance between the PEEK and titanium cages, although more subsidence occurred in the titanium cage group. More high-quality studies are needed to confirm these results to offer more information for the choice in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Aldehyde-deformylating oxygenase (ADO) is an important enzyme involved in the biosynthetic pathway of fatty alk(a/e)nes in cyanobacteria. However, ADO exhibits quite low chain-length specificity with respect to the substrates ranging from C4 to C18 aldehydes, which is not suitable for producing fuels with different properties or different chain lengths. Results: Based on the crystal structures of cADOs (cyanobacterial ADO) with substrate analogs bound, some amino acids affecting the substrate specificity of cADO were identified, including the amino acids close to the aldehyde group and the hydrophobic tail of the substrate and those along the substrate channel. Using site-directed mutagenesis, selected amino acids were replaced with bulky ones introducing steric hindrance to the binding pocket via large functional groups. All mutants were overexpressed, purified and kinetically characterized. All mutants, except F87Y, displayed dramatically reduced activity towards C14,16,18 aldehydes. Notably, the substrate preferences of some mutants towards different chain-length substrates were enhanced: I24Y for n-heptanal, I27F for n-decanal and n-dodecanal, V28F for n-dodecanal, F87Y for n-decanal, C70F for n-hexanal, A118F for n-butanal, A121F for C4,6,7 aldehydes, V184F for n-dodecanal and n-decanal, M193Y for C6-10 aldehydes and L198F for C7-10 aldehydes. The impact of the engineered cADO mutants on the change of the hydrocarbon profile was demonstrated by co-expressing acyl- ACP thioesterase BTE, fadD and V184F in E. coli, showing that n-undecane was the main fatty alkane. Conclusions: Some amino acids, which can control the chain-length selectivity of substrates of cADO, were identified. The substrate specificities of cADO were successfully changed through structure-guided protein engineering, and some mutants displayed different chain-length preference. The in vivo experiments of V184F in genetically engineered E. coli proved the importance of engineered cADOs on the distribution of the fatty alkane profile. The results would be helpful for the production of fatty alk(a/e)nes in cyanobacteria with different properties. [ABSTRACT FROM AUTHOR]

Background: This study was aimed to explore the role of long noncoding RNA C17orf91 and its potential mechanisms in ovarian cancer development. Results: To assess its role in ovarian cancer, microarray datasets (GSE14407, GSE30587, and GSE17260) in Gene Expression Omnibus (GEO) were utilized to assess the expression and clinical significance of C17orf91 in ovarian cancer. Next, loss-of-function studies were performed to establish the role of C17orf91 and the underlying mechanisms in ovarian cancer development. It was found that elevated expression of C17orf91 was observed in omental metastases when compared with matched primary ovarian tumors(GSE30587, P = 0.016). Moreover, Log Rank analysis revealed that increased expression of C17orf91 was associated with shorter progression free survival(PFS)(HR = 1.90(1.19-3.03), P = 0.008). Overall survival(OS) also showed a similar trend, but did not reach statistical significance(HR = 1.75(0.97-3.13), P = 0.061). Loss-of-function studies further demonstrated that C17orf91 repression impaired migration, invasion and viability of ovarian cancer cells, and downregulated the pro-metastatic gene, MYC, at both mRNA and protein level. Conclusion: Collectively, our findings revealed that C17orf91 was a potential prognostic marker and functioned as an oncogene in ovarian cancer. It remains to be seen whether modulation of C17orf91 expression will cause phenotypic changes in vivo. [ABSTRACT FROM AUTHOR]

Background: Microbiota-oriented studies based on metagenomic or metatranscriptomic sequencing have revolutionised our understanding on microbial ecology and the roles of both clinical and environmental microbes. The analysis of massive metatranscriptomic data requires extensive computational resources, a collection of bioinformatics tools and expertise in programming. Results: We developed COMAN (Comprehensive Metatranscriptomics Analysis), a web-based tool dedicated to automatically and comprehensively analysing metatranscriptomic data. COMAN pipeline includes quality control of raw reads, removal of reads derived from non-coding RNA, followed by functional annotation, comparative statistical analysis, pathway enrichment analysis, co-expression network analysis and high-quality visualisation. The essential data generated by COMAN are also provided in tabular format for additional analysis and integration with other software. The web server has an easy-to-use interface and detailed instructions, and is freely available at http://sbb.hku.hk/COMAN/ Conclusions: COMAN is an integrated web server dedicated to comprehensive functional analysis of metatranscriptomic data, translating massive amount of reads to data tables and high-standard figures. It is expected to facilitate the researchers with less expertise in bioinformatics in answering microbiota-related biological questions and to increase the accessibility and interpretation of microbiota RNA-Seq data. [ABSTRACT FROM AUTHOR]

Background: Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox-tapeworm Echinococcus multilocularis. The disease is difficult to treat and an effective therapeutic drug is urgently needed. Reliable models are essential for drug development. In this study, we developed both in vitro and in vivo models of larval E. multilocularis. Results: The protoscoleces (PSC) of E. multilocularis from jirds were successfully cultured in a modified RPMI1640 based medium containing 25% (v/v) fetal bovine serum (FBS). After 100 days of culture, PSC developed to larval vesicles (small unilocular cysts) and the fast growing vesicles produced PSC in brood capsules. In addition, mice were intraperitoneally injected with 30 cultured small vesicles and 100% of the mice had resulting metacestode masses. Conclusions: Larval protoscoleces and vesicles of E. multilocularis grow healthily in vitro in the RPMI1640 based medium containing 25% FBS. Echinococcus multilocularis in vitro and in vivo models provide a valuable platform for investigating the biology of the parasite and screening effective therapeutic drugs against AE. [ABSTRACT FROM AUTHOR]

Background: Type B insulin resistance is a rare autoimmune disease characterized by the presence of autoantibodies against the insulin receptor. Helicobacter pylori (H pylori) infection may play a causative role in the autoimmune diseases. Case presentation: Here, we present a rare case of a 48-year old female patient, who had type B insulin resistance with systemic scleroderma and was successfully treated with multiple immune suppressants after eradication of Helicobacter pylori infection. Conclusion: The present case suggests H pylori infection-related pathological mechanism may contribute to type B insulin resistance syndrome and autoimmune disorders. Treatment toward H pylori may be helpful to relieve syndrome of type B insulin resistance for H pylori positive patients. [ABSTRACT FROM AUTHOR]

Background: Human embryos produced by in vitro fertilization (IVF) are usually cultured to day 6 after insemination, and good quality of embryos should develop to blastocyst stage at days 5 and 6. However, some embryos develop slowly, thus they may form blastocysts on day 7. Most IVF laboratories culture embryos to day 6 and then discard retarded embryos that do not develop to blastocyst stage. It has been reported that transfer of day 7 blastocysts can yield pregnancy although the rates were very low. In the present study, we evaluated the prevalence of aneuploidy in day 7 human blastocysts and also assessed embryo implantation after transfer of normal euploid blastocysts developed on day 7. Methods: Day 7 blastocysts were biopsied and screened for aneuploidy. Embryo implantation was assessed by transferring of euploid blastocysts. Results: A total of 1966 blastocysts from 367 IVF cycles were biopsied and screened for aneuploidy. It was found that 81.5 % of the patients had days 5 and 6 blastocysts and 18.5 % (68) patients had blastocysts developed on day 7, including 15.3 % had days 5-7 blastocysts and 3.3 % had only day 7 blastocysts. A total of 151 day 7 blastocysts, which accounted for 7.7 % of total blastocysts, were analyzed. It was found that 36.7 % of the blastocysts were euploid and 63.3 % had abnormal chromosomes, including aneuploidy and euploid with partial chromosome deletion. The aneuploidy rate was also maternal age dependent and was as high as 91.7 % in patients who were ⩾40 years old. During the study period, transfer of day 7 euploid blastocysts in 15 patients resulted in 2 healthy live births. Conclusion(s): Aneuploidy rates in day 7 human blastocysts produced by IVF are very high. However, good euploid blastocysts have potential to implant and transfer of day 7 euploid blastocysts can result in healthy live birth. It is suggested that day 7 blastocyst culture may be necessary in patients who need aneuploidy screening. [ABSTRACT FROM AUTHOR]

Background: Fertility-sparing surgery for patients with borderline ovarian tumors (BOTs) is still controversial. This study aimed to evaluate the oncological safety and fertility benefits in conservative surgery,as well as efficiency of surgical procedures and approaches. Results: In total 122 patients with BOTs, four types of fertility-sparing surgery were performed: unilateral adnexectomy (UA, n = 47), unilateral cystectomy (UC, n = 59), unilateral adnexectomy + contralateral cystectomy (UA + CC, n = 7) and bilateral cystectomy (BC, n = 9). Fifty-two (42.6 %) patients had undergone laparoscopy, while 70 (57.4 %) had undergone laparotomy. After a median follow-up of 58.0 months, eight patients (6.6 %) relapsed in average of 25.9 months. Only one patient progressed to invasive cancer. None died within our observational period. Univariate analysis showed that patients with elevated CA125, bilateral tumors, extra-ovary tumor or mucinous type tended to replase in shorter time (p < 0.05). Among all cases, 45 patients attempted to conceive and 34 (75.6 %) patients had successful pregnancy. The recurrence rates were successively increased (2.1 %, 6.8 %, 14.3 %, and 22.2 %), the recurrence interval were shortened (48.0, 25.3, 26.0 and 21.2 months) and the subsequent fertility rates were 76.9 %, 77.3 %, 66.7 % and 71.4 % in UA, UC, UA + CC, and BC groups, respectively. As for surgical approaches, three patients (5.8 %) relapsed in 26.3 months in the laparoscopy group and five (7.1 %) in 25.5 months in the laparotomy group. The subsequent fertility rate was higher in laparoscopy group (88.9 %) than in laparotomy group (66.7 %). In our study, 38 patients underwent staging surgery. Two patients (5.3 %) recurrent in average of 21.0 months, and the subsequent pregnancy rate of staging surgery group was 61.5 %. Twelve patients received adjuvant chemotherapy but they didn't get any benefit from it, both in term of recurrence (8.3 %, 26.0 months) and subsequent pregnancy rate (75.5 %). Conclusion: Fertility-sparing surgery is safe and beneficial for most young BOTs. UA through laparoscopy should be recommended as the first choice. To the patients with bilateral tumors, elevated CA125, extra-ovary tumor or mucinous type, conservative surgery should be carefully chosen and subsequent pregnancy should be attempted in short term. In addition, the benefit of comprehensive surgical staging is to be further investigated and adjuvant chemotherapy is not recommended. [ABSTRACT FROM AUTHOR]

Background: Dysregulation of microRNA-150 (miR-150) is commonly observed in solid tumor and has been reported to be involved in multiple important biological processes, such as cell proliferation, apoptosis, and metastasis. Elevated miR-150 level was also detected in cervical carcinoma, whereas its function in cancer progression has not been studied yet. Methods: The expression of miRNA-150 in cervical carcinoma was compared with normal cervical tissue and using qRT-PCR. The effects of miR-150 on cell cycle and apoptosis, as well as the expression of cycle- and apoptosis-related genes, were determined using flow cytometry, TUNEL assay, qRT-PCR, and Western blot, respectively. The direct target of miR-150 was confirmed using 3' untranslated region (UTR) luciferase reporter assay. Results: miR-150 promotes cervical cancer cell survival and growth, while the inhibition of miR-150 suppresses these actions. miR-150 also induced the cell cycle progression from G1/G0 to S phase, resulting in an enhancement of growth. Several cell cycle- and apoptosis-related genes, CyclinD1, p27, BIM, and FASL were modulated by miR-150. Moreover, miR-150 directly reduced the expression of FOXO4, which regulates the expression of CyclinD1, p27, BIM, and FASL, by targeting its 3' UTR. Conclusion: Taken together, our data demonstrated that elevated miR-150 targets FOXO4 expression and therefore regulates multiple genes expression, resulting in cervical cancer cell growth and survival. [ABSTRACT FROM AUTHOR]

Background: Pleistocene climatic oscillations and historical geological events may both influence current patterns of genetic variation, and the species in southern China that faced unique climatic and topographical events have complex evolutionary histories. However, the relative contributions of climatic oscillations and geographical events to the genetic variation of these species remain undetermined. To investigate patterns of genetic variation and to test the hypotheses about the factors that shaped the distribution of this genetic variation in species of southern China, mitochondrial genes (cytochrome b and NADH dehydrogenase subunit 2) and nine microsatellite loci of the Omei tree frog (Rhacophorus omeimontis) were amplified in this study. Results: The genetic diversity in the populations of R. omeimontis was high. The phylogenetic trees reconstructed from the mitochondrial DNA (mtDNA) haplotypes and the Bayesian genetic clustering analysis based on microsatellite data both revealed that all populations were divided into three lineages (SC, HG and YN). The two most recent splitting events among the lineages coincided with recent geological events (including the intense uplift of the Qinghai-Tibet Plateau, QTP and the subsequent movements of the Yun-Gui Plateau, YGP) and the Pleistocene glaciations. Significant expansion signals were not detected in mismatch analyses or neutrality tests. And the effective population size of each lineage was stable during the Pleistocene. Conclusions: Based on the results of this study, complex geological events (the recent dramatic uplift of the QTP and the subsequent movements of the YGP) and the Pleistocene glaciations were apparent drivers of the rapid divergence of the R. omeimontis lineages. Each diverged lineages survived in situ with limited gene exchanges, and the stable demographics of lineages indicate that the Pleistocene climatic oscillations were inconsequential for this species. The analysis of genetic variation in populations of R. omeimontis contributes to the understanding of the effects of changes in climate and of geographical events on the dynamic development of contemporary patterns of genetic variation in the species of southern China. [ABSTRACT FROM AUTHOR]

Objective: The prognostic value of anti-angiogenesis therapy in ovarian cancer patients is currently under debate. In this study, we assessed the effects of anti-angiogenesis therapy on the progression free survival (PFS) and overall survival (OS) of ovarian cancer patients. Materials and methods: PubMed was searched to identify relevant studies that evaluated the therapeutic value of anti-angiogenic agents in ovarian cancer (the final search was current to Dec. 13th 2014). Reviews of each study were conducted, and the data were extracted. The primary outcomes that were analysed were progression free survival (PFS) and overall survival (OS). The pooled hazard ratio (HR) and 95 % confidence intervals (CIs) were calculated using the random and fixed-effects models, and subgroup and sensitivity analyses were subsequently performed. Results: A total of 12 studies were included in the meta-analysis. The overall analysis revealed that the incorporation of anti-angiogenesis therapy was significantly associated with a longer PFS (HR, 0.66; 95 % CI, 0.58-0.75; P < 0.01) and a longer OS (HR, 0.89; 95 % CI, 0.82-0.97; P = 0.01) in the total population, and these findings were confirmed by one-way sensitivity analyses. Further subgroup analyses demonstrated that the administrations of each of the agents were associated with improved PFSs. The prognostic value of anti-angiogenesis therapy for the OS was significant in the trebananib subgroup (HR, 0.81; 95 % CI, 0.67-0.99; P = 0.04). The bevacizumab subgroup exhibited a similar trend that did not reach statistical significance (HR, 0.90; 95 % CI, 0.80-1.01; P = 0.08). Conclusions: The present meta-analysis indicated that anti-angiogenesis therapy in ovarian cancer patients was associated with a better clinical outcome. Further studies are warranted to identify the specific subgroup of patients who are most likely to benefit from anti-angiogenesis therapy. [ABSTRACT FROM AUTHOR]

Background: Current quantification methods for mass spectrometry (MS)-based proteomics either do not provide sufficient control of variability or are difficult to implement for routine clinical testing. Results: We present here an integrated quantification (InteQuan) method that better controls pre-analytical and analytical variability than the popular quantification method using stable isotope-labeled standard peptides (SISQuan). We quantified 16 lung cancer biomarker candidates in human plasma samples in three assessment studies, using immunoaffinity depletion coupled with multiple reaction monitoring (MRM) MS. InteQuan outperformed SISQuan in precision in all three studies and tolerated a two-fold difference in sample loading. The three studies lasted over six months and encountered major changes in experimental settings. Nevertheless, plasma proteins in low ng/ml to low μg/ml concentrations were measured with a median technical coefficient of variation (CV) of 11.9% using InteQuan. The corresponding median CV using SISQuan was 15.3% after linear fitting. Furthermore, InteQuan surpassed SISQuan in measuring biological difference among clinical samples and in distinguishing benign versus cancer plasma samples. Conclusions: We demonstrated that InteQuan is a simple yet robust quantification method for MS-based quantitative proteomics, especially for applications in biomarker research and in routine clinical testing. [ABSTRACT FROM AUTHOR]

Background: Current quantification methods for mass spectrometry (MS)-based proteomics either do not provide sufficient control of variability or are difficult to implement for routine clinical testing. Results: We present here an integrated quantification (InteQuan) method that better controls pre-analytical and analytical variability than the popular quantification method using stable isotope-labeled standard peptides (SISQuan). We quantified 16 lung cancer biomarker candidates in human plasma samples in three assessment studies, using immunoaffinity depletion coupled with multiple reaction monitoring (MRM) MS. InteQuan outperformed SISQuan in precision in all three studies and tolerated a two-fold difference in sample loading. The three studies lasted over six months and encountered major changes in experimental settings. Nevertheless, plasma proteins in low ng/ml to low μg/ml concentrations were measured with a median technical coefficient of variation (CV) of 11.9% using InteQuan. The corresponding median CV using SISQuan was 15.3% after linear fitting. Furthermore, InteQuan surpassed SISQuan in measuring biological difference among clinical samples and in distinguishing benign versus cancer plasma samples. Conclusions: We demonstrated that InteQuan is a simple yet robust quantification method for MS-based quantitative proteomics, especially for applications in biomarker research and in routine clinical testing. [ABSTRACT FROM AUTHOR]

Background: Current quantification methods for mass spectrometry (MS)-based proteomics either do not provide sufficient control of variability or are difficult to implement for routine clinical testing. Results: We present here an integrated quantification (InteQuan) method that better controls pre-analytical and analytical variability than the popular quantification method using stable isotope-labeled standard peptides (SISQuan). We quantified 16 lung cancer biomarker candidates in human plasma samples in three assessment studies, using immunoaffinity depletion coupled with multiple reaction monitoring (MRM) MS. InteQuan outperformed SISQuan in precision in all three studies and tolerated a two-fold difference in sample loading. The three studies lasted over six months and encountered major changes in experimental settings. Nevertheless, plasma proteins in low ng/ml to low μg/ml concentrations were measured with a median technical coefficient of variation (CV) of 11.9% using InteQuan. The corresponding median CV using SISQuan was 15.3% after linear fitting. Furthermore, InteQuan surpassed SISQuan in measuring biological difference among clinical samples and in distinguishing benign versus cancer plasma samples. Conclusions: We demonstrated that InteQuan is a simple yet robust quantification method for MS-based quantitative proteomics, especially for applications in biomarker research and in routine clinical testing. [ABSTRACT FROM AUTHOR]

Background: Many clinical trials had repeatedly shown that fast-track perioperative care and laparoscopic surgery are both preferred in the treatment of colorectal cancer. But few studies were designed to explore the diverse biochemical impacts of the two counterparts on human immunologic and nutritional status. Methods: Ninety-two cases of colorectal cancer patients meeting the inclusion criteria were randomized to four groups: laparoscopy with fast-track treatment (LAFT); open surgery with fast-track treatment (OSFT); laparoscopy with conventional treatment (LAC); open surgery with conventional treatment (OSC). Peripheral blood tests including nutritional factors (albumin, prealbumin, and transferrin), humoral immunologic factors (IgG, IgM, and IgA), and cellular immunologic factors (T and NK cells) were evaluated. Blood samples were collected preoperatively (baseline) and 12 and 96 h after surgery (indicated as POH12 and POH96, respectively). Results: Albumin, transferrin, prealbumin, and IgG levels were the highest in the LAFT group for both POH12 and POH96 time intervals. Repeated measures (two-way ANOVA) indicated that the difference of albumin, transferrin, and IgG level were attributed to surgery type (P < 0.05) and not perioperative treatment (P > 0.05). Only in the laparoscopy-included groups, the relative albumin and IgG levels of POH96 were obviously higher than that of POH12. Conclusion: Laparoscopic surgery accelerated postoperative nutrition and immune levels rising again while fast-track treatment retarded the drop of postoperative nutrition and immune levels. Laparoscopic surgery might play a more important role than fast-track treatment in the earlier postoperative recovery of nutritional and immunologic status. Combined laparoscopic surgery with fast-track treatment provided best postoperative recovery of nutrition and immune status. These results should be further compared with the clinical outcomes of our FTMDT trial (clinicaltrials.gov: NCT01080547). [ABSTRACT FROM AUTHOR]

Background Current quantification methods for mass spectrometry (MS)-based proteomics either do not provide sufficient control of variability or are difficult to implement for routine clinical testing. Results We present here an integrated quantification (InteQuan) method that better controls preanalytical and analytical variability than the popular quantification method using stable isotope-labeled standard peptides (SISQuan). We quantified 16 lung cancer biomarker candidates in human plasma samples in three assessment studies, using immunoaffinity depletion coupled with multiple reaction monitoring (MRM) MS. InteQuan outperformed SISQuan in precision in all three studies and tolerated a two-fold difference in sample loading. The three studies lasted over six months and encountered major changes in experimental settings. Nevertheless, plasma proteins in low ng/ml to low μg/ml concentrations were measured with a median technical coefficient of variation (CV) of 11.9% using InteQuan. The corresponding median CV using SISQuan was 15.3% after linear fitting. Furthermore, InteQuan surpassed SISQuan in measuring biological difference among clinical samples and in distinguishing benign versus cancer plasma samples. Conclusions We demonstrated that InteQuan is a simple yet robust quantification method for MS-based quantitative proteomics, especially for applications in biomarker research and in routine clinical testing. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is a near cosmopolitan zoonosis caused by the larval stage of the dog tapeworm Echinococcus granulosus. E. granulosus infection induces a polarized T-helper type 2 (Th2) systematic immune response in its intermediate hosts. However, it is not known whether the infection modulates lung inflammation by regulating local immune response. In this study, we examined the effects of E. granulosus infection on mouse ovalbumin (OVA)-induced asthma model. Methods: BALB/c mice were intraperitoneally transplanted with 50 small E. granulosus cysts cultured in vitro. At 3 months post-inoculation, the mice were sensitized and challenged with ovalbumin (OVA). For histopathological studies, hematoxylin eosin and periodic acid schiff staining was used to examine the inflammatory cells infiltration and goblet cells hyperplasia, respectively. Cytokine levels were measured by mouse cytometric bead array (CBA) Kit and quantitative RT-PCR and other molecular biological approaches. Airway hyperresponsiveness was assessed in response to increasing doses of methacholine. Serum immunoglobulins were determined by ELISA. Results: E. granulosus infection significantly increased Th2 and Treg cytokine levels in serum and lung tissues, but down-regulated the expression of IL-5 in the lungs and IL-17A in serum and lung tissues of asthmatic mice sensitized and challenged with OVA. Histological staining of lung tissues showed that E. granulosus infection significantly reduced the severity of OVA-induced airway inflammation including reduction of eosinophil cell infiltration and mucus production. The E. granulosus infection also reduced eosinophil accumulation induced by OVA in bronchoalveolar lavage fluid (BALF) and also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. Conclusions: E. granulosus infection remarkably reduces the severity of OVA-induced airway inflammation likely through enhancing IL-10 and down-regulation of IL-5 and IL-17A. [ABSTRACT FROM AUTHOR]

Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed. [ABSTRACT FROM AUTHOR]

Background Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide, and emphysema is a common component of COPD. Currently, it is very difficult to detect early stage emphysema using conventional radiographic imaging without contrast agents, because the change in X-ray attenuation is not detectable with absorption-based radiography. Compared with the absorption-based CT, phase contrast imaging has more advantages in soft tissue imaging, because of its high spatial resolution and contrast. Methods In this article, we used diffraction enhanced imaging (DEI) method to get the images of early stage emphysematous and healthy samples, then extract X-ray absorption, refraction, and ultra-small-angle X-ray scattering (USAXS) information from DEI images using multiple image radiography (MIR). We combined the absorption image with the USAXS image by a scatter plot. The critical threshold in the scatter plot was calibrated using the linear discriminant function in the pattern recognition. Results USAXS image was sensitive to the change of tissue micro-structure, it could show the lesions which were invisible in the absorption image. Combined with the absorption-based image, the USAXS information enabled better discrimination between healthy and emphysematous lung tissue in a mouse model. The false-color images demonstrated that our method was capable of classifying healthy and emphysematous tissues. Conclusion Here we present USAXS images of early stage emphysematous and healthy samples, where the dependence of the USAXS signal on micro-structures of biomedical samples leads to improved diagnosis of emphysema in lung radiographs. [ABSTRACT FROM AUTHOR]

Background The oral DPP-4 inhibitors are new incretin-based therapies for treatment of type 2 diabetes. To assess the efficacy and safety of three DPP-4 inhibitors (Saxagliptin, Sitagliptin and Vildagliptin) as add-on therapy to dual combination of traditional oral hypoglycemic agents in Chinese type 2 diabetes patients. Methods In this 24-week, randomized, open-label, parallel clinical trial, we enrolled inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ⩾7.5% to ⩽10%) patients with type 2 diabetes, who were treated by dual combination of metformin and another traditional oral hypoglycemic agent (glimepiride, acarbose or pioglitazone). 207 patients had been randomized to add-on 5 mg saxagliptin group or 100 mg sitagliptin once daily group, or 50 mg vildagliptin twice daily group for 24 weeks. HbA1c, fasting and postprandial blood glucose (FBG and P2hBG), body weight, body mass index (BMI), episodes of hypoglycemia and adverse events were evaluated. Result After 24 weeks, HbA1c, FBG, and P2hBG of each group were significantly decreased. (saxagliptin vs vildagliptin vs sitagliptin: HbA1c: -1.2% vs -1.3% vs -1.1%; FBG: -1.8 mmol/l vs -2.4 mmol/l vs -1.5 mmol/l; P2hBG: -3.4 mmol/l vs -3.7 mmol/l vs -3.2 mmol/l). The changes of HbA1c and P2hBG among the three groups had no significance. However, vildagliptin-added group showed the greatest reduction (p < 0.001), while, sitagliptin-added group showed the lowest reduction (p < 0.001) in terms of FPG changes. Proportions of patients achieving HbA1c < 7% at the end were similar in three groups (saxagliptin 59%, vildagliptin 65%, sitagliptin 59%). Mild hypoglycemia was commonly reported among the three groups (saxagliptin 6%, vildagliptin 2%, sitagliptin 3%). No significant between-group difference was shown in other AEs. Conclusion The three gliptins showed almost similar glycemic control and incidence of adverse events. However, for FBG control, saxagliptin demonstrated superiority to sitagliptin, while, inferiority to vildagliptin. [ABSTRACT FROM AUTHOR]

Background Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets -fruits, vegetables and herbs- are known as a source of molecules with pharmacological properties for treatment of several malignancies. Unquestionably, for developing specific intervention strategies to reduce cancer risk there is a need for a more extensive and holistic examination of the dietary components for exploring the mechanisms of action and understanding the nutrient-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway. Results We started from a unique vantage point by having a database of 158 plants that have been positively associated to colon cancer reduction and their molecular composition (∼3,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of ∼1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer that are targeted synergistically by phytochemicals and identify statistically significant and highly correlated protein networks that could be perturbed by dietary habits. Conclusion We propose here a framework for interrogating the critical targets in colon cancer process and identifying plant-based dietary interventions as important modifiers of this process using a systems chemical biology approach. Our methodology for better delineating the prevention of colon cancer by nutritional interventions relies heavily on the availability of information about the small molecule constituents of our diet and it can be expanded to any other disease class that previous evidence has linked to lifestyle. [ABSTRACT FROM AUTHOR]

Background Astrogliosis is a common phenomenon after spinal cord injury (SCI). Although this process exerts positive effects on axonal regeneration, excessive astrogliosis imparts negative effects on neuronal repair and recovery. Epidermal growth factor receptor (EGFR) pathway is critical to the regulation of reactive astrogliosis, and therefore is a potential target of therapeutics to better control the response. In this report, we aim to investigate whether blocking EGFR signaling using an EGFR tyrosine kinase specific inhibitor can attenuate reactive astrogliosis and promote functional recovery after a traumatic SCI. Method The astrocyte scratch injury model in vitro and the weight-drop SCI model in vivo were used as model systems. PD168393 was used to inhibit EGFR signaling activation. Astrocytic activation and phosphorylated EGFR (pEGFR) were observed after immunofluorescence staining and Western blot analysis. The rate of proliferation was determined by immunofluorescence detection of BrdU-incorporating cells located next to the wound. The levels of TNF-a, iNOS, COX-2 and IL-1ß in the culture medium under different conditions were assayed by ELISA. Western blot was performed to semi-quantify the expression of EGFR/pEGFR, glial fibrillary acid protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). Myelin was stained by Luxol Fast Blue Staining. Cresyl violet eosin staining was performed to analyze the lesion cavity volume and neuronal survival following injury. Finally, functional scoring and residual urine recording were performed to show the rats’ recovery. Results EGFR phosphorylation was found to parallel astrocyte activation, and EGFR inhibitor PD168393 potently inhibited scratch-induced reactive astrogliosis and proinflammatory cytokine/mediator secretion of reactive astrocytes in vitro. Moreover, local administration of PD168393 in the injured area suppressed CSPGs production and glial scar formation, and resulted in reduced demyelination and neuronal loss, which correlated with remarkable hindlimb motor function and bladder improvement in SCI rats. Conclusions The specific EGFR inhibitor PD168393 can ameliorate excessive reactive astrogliosis and facilitate a more favorable environment for axonal regeneration after SCI. As such, EGFR inhibitor may be a promising therapeutic intervention in CNS injury. [ABSTRACT FROM AUTHOR]

Background and aims Liraglutide treatment can improve glycemic control with a concomitant weight loss, but the underlying mechanism on weight loss is not completely understood. Cardiac natriuretic peptides (NPs) can resist body fat accumulation through increasing adipocytes lypolysis. In this study, we tested the hypothesis that liraglutide-induced weight loss was associated with increased plasma NPs concentrations. Methods Thirty-one outpatients with type 2 diabetes (T2D) treated with metformin and other oral antidiabetic drugs except for thiazolidinediones (TZDs) were subcutaneously administered with liraglutide for 12 weeks. Body composition, abdominal visceral adipose tissue areas (VAT) and subcutaneous adipose tissue areas (SAT) were assessed at pre- and post-treatment by dual-energy X-ray absorptiometry (DXA) scanning and abdominal computerized tomography (CT). Plasma atrial natriuretic peptides (ANP) and B-type ventricular natriuretic peptides (BNP) concentrations were tested by commercial ELISA Kit quantitatively. Results Following 12-week liraglutide treatment, body weight, waist circumference, total fat and lean mass, fat percentage, SAT and VAT areas were significantly reduced from baseline. Concurrently, plasma ANP and BNP levels were significantly increased following 12-week liraglutide treatment. There were significant correlations between the reductions in body compositions and the increases in both plasma ANP and BNP levels. Conclusions There were significant correlations between increases in both plasma ANP and BNP levels and changes in liraglutide-induced body composition. Our data implied that increases in plasma NPs may add a novel dimension to explain how liraglutide induces weight loss. [ABSTRACT FROM AUTHOR]

Background The clonal spread of Acinetobacter baumannii is a global problem, and carbapenems, such as imipenem, remain the first-choice agent against A. baumannii. Using synergy to enhance the antibiotic activity of carbapenems could be useful. Here, amlodipine (AML) was tested alone and with imipenem against A. baumannii isolates. Methods Forty-two isolates of A. baumannii were collected. Multilocus sequence typing (MLST) assessed the genetic relationship of the isolates. The resistance phenotypes were determined using disc diffusion. The minimum inhibitory concentrations (MICs) of the drugs were determined by broth microdilution. The combined effects of the drugs were determined by a checkerboard procedure. Metallo-β-lactamase (MBL) was determined using the MLB Etest. Results Forty-two A. baumannii isolates were collected from 42 patients who were mostly older than 65 years and had long inpatient stays (⩾7 days). A. baumannii was mostly recovered from the respiratory system (N = 35, 83.3%). Most patients (N = 27, 64.3%) received care in intensive care units (ICUs). Disc diffusion testing demonstrated that A. baumannii susceptibility to polymyxin B was 100%, while susceptibility to other antimicrobial agents was less than 30%, classifying the isolates into 10 MDR and 32 XDR strains. MLST grouped the A. baumannii isolates into 4 existing STs and 6 new STs. STn4 carried allele G1, with a T → C mutation at nt3 on the gpi111 locus. STn5 carried allele A1, possessing A → C mutations at nt156 and nt159 on the gltA1 locus. ST195 and ST208 accounted for 68.05% (29/42) of the isolates. Clonal relation analysis showed that ST195 and ST208 belonged to clonal complex (CC) 92. The inhibitory concentration of imipenem ranged from 0.5 to 32 μg/ml, and that of AML ranged from 40 to 320 μg/ml. In combination, the susceptibility rate of A. baumannii isolates increased from 16.7% to 54.8% (P = 0.001). In the checkerboard procedure, half of the isolates (N = 21, 50.0%) demonstrated synergy or partial synergy with the drug combination. The MBL Etest revealed that 1 A. baumannii strain (N = 1, 2.4%) produced MBL. Conclusions CC92 was the major clone spreading in our hospital. AML improved the activity of imipenem against A. baumannii isolates in vitro but did not inhibit MBL. [ABSTRACT FROM AUTHOR]

Background Human brucellosis incidence in China has been increasing dramatically since 1999. However, epidemiological features and potential factors underlying the re-emergence of the disease remain less understood. Methods Data on human and animal brucellosis cases at the county scale were collected for the year 2004 to 2010. Also collected were environmental and socioeconomic variables. Epidemiological features including spatial and temporal patterns of the disease were characterized, and the potential factors related to the spatial heterogeneity and the temporal trend of were analysed using Poisson regression analysis, Granger causality analysis, and autoregressive distributed lag (ADL) models, respectively. Results The epidemic showed a significantly higher spatial correlation with the number of sheep and goats than swine and cattle. The disease was most prevalent in grassland areas with elevation between 800-1,600 meters. The ADL models revealed that local epidemics were correlated with comparatively lower temperatures and less sunshine in winter and spring, with a 1-7 month lag before the epidemic peak in May. Conclusions Our findings indicate that human brucellosis tended to occur most commonly in grasslands at moderate elevation where sheep and goats were the predominant livestock, and in years with cooler winter and spring or less sunshine. [ABSTRACT FROM AUTHOR]

The advances in high throughput omics technologies have made it possible to characterize molecular interactions within and across various species. Alignments and comparison of molecular networks across species will help detect orthologs and conserved functional modules and provide insights on the evolutionary relationships of the compared species. However, such analyses are not trivial due to the complexity of network and high computational cost. Here we develop a mixture of global and local algorithm, BinAligner, for network alignments. Based on the hypotheses that the similarity between two vertices across networks would be context dependent and that the information from the edges and the structures of subnetworks can be more informative than vertices alone, two scoring schema, 1-neighborhood subnetwork and graphlet, were introduced to derive the scoring matrices between networks, besides the commonly used scoring scheme from vertices. Then the alignment problem is formulated as an assignment problem, which is solved by the combinatorial optimization algorithm, such as the Hungarian method. The proposed algorithm was applied and validated in aligning the protein-protein interaction network of Kaposi's sarcoma associated herpesvirus (KSHV) and that of varicella zoster virus (VZV). Interestingly, we identified several putative functional orthologous proteins with similar functions but very low sequence similarity between the two viruses. For example, KSHV open reading frame 56 (ORF56) and VZV ORF55 are helicase-primase subunits with sequence identity 14.6%, and KSHV ORF75 and VZV ORF44 are tegument proteins with sequence identity 15.3%. These functional pairs can not be identified if one restricts the alignment into orthologous protein pairs. In addition, BinAligner identified a conserved pathway between two viruses, which consists of 7 orthologous protein pairs and these proteins are connected by conserved links. This pathway might be crucial for virus packing and infection. [ABSTRACT FROM AUTHOR]

Background: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by both genetic and environmental factors. Recent Genome-Wide Association Studies (GWAS) have identified several loci affecting ALP levels; however, such studies in Chinese populations are limited. We performed a GWAS analyzing the association between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated the top SNPs in an additional 8,830 healthy Chinese Han individuals. The interactions between significant locus and environmental factors on serum ALP levels were further investigated. Results: The association between ABO locus and serum ALP levels was replicated (P = 2.50 × 10-21, 1.12 × 10-56 and 2.82 × 10-27 for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP rs651007 accounted for 2.15% of the total variance of serum ALP levels independently of the other 2 SNPs. When comparing our findings with previously published studies, ethnic differences were observed across populations. A significant interaction between ABO rs651007 and overweight and obesity was observed (FDR for interaction was 0.036); for individuals with GG genotype, those with normal weight and those who were overweight or obese have similar serum ALP concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels, but this effect was attenuated in overweight and obese individuals. Conclusions: Our findings indicate that ABO locus is a major determinant for serum ALP levels in Chinese Han population. Overweight and obesity modifies the effect of ABO locus on serum ALP concentrations. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Extragastrointestinal stromal tumors (eGISTs) of the mesoileum are extremely rare and are usually treated with surgery combined with imatinib therapy. Case presentation: We present the case of a 43-year-old man who developed a large eGIST in the mesoileum. Abdominal/pelvic computed tomography revealed a large heterogeneous mass with cystic and solid components that measured 20.0 × 12.0 × 8.0 cm. Three cycles of neoadjuvant chemotherapy with epirubicin, cyclophosphamide and hydroxycamptothecin; en bloc resection; and three more cycles of adjuvant chemotherapy with the same regimen and drugs resulted in five years of disease-free survival without any symptoms. Conclusions: Although imatinib treatment is usually chosen for eGISTs, resistance to imatinib remains a concern; these patients may receive neoadjuvant or adjuvant chemotherapy. In case of the former, further treatment, that is, surgery or adjuvant chemotherapy, depends on tumor response to the neoadjuvant chemotherapy. In addition, this treatment for eGIST is not only beneficial but also economical for patients compared with imatinib. A novel treatment approach that combined neoadjuvant chemotherapy, surgery and adjuvant chemotherapy resulted in long-term survival in our patient, thus showing promise as a potential therapy for eGISTs. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. Methods: Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability. Results: We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. Conclusions: Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods: Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results: The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion: The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. [ABSTRACT FROM AUTHOR]

Background: The purpose of this research is to compare the clinical results of different drainage methods in total knee arthroplasty (TKA). Methods: This retrospective comparative study included 55 patients who accepted primary unilateral TKA between October 2010 and November 2012. The patients were classified according to the drainage method used: 25 patients in the autotransfusion drainage group, 12 patients in the delayed drainage group, and 18 patients in the routine drainage group. Otherwise, the same operative procedures and postoperative care were applied to all patients. The variables recorded included total amount of postoperative drainage (including intraoperative blood loss); cases of allogenic blood transfusion; body temperatures on postoperative days 1, 3, and 7; and pre- and postoperative hemoglobin level. Some other elements such as postoperative swelling, range of motion, and wound healing were also compared. Results: Patients who underwent autotransfusion were found to have an amount of drainage (799.2 ± 196.7 mL) significantly greater than that in the routine drainage group (666.1 ± 155.0 mL), which in turn was significantly greater than that in the delayed drainage group (381.7 ± 129.2 mL). The postoperative hemoglobin level in the delayed drainage group (91.5 ± 7.9 g/L) was similar to that in the autotransfusion group (92.0 ± 9.6 g/L), while that in the routine drainage group (81.3 ± 9.9 g/L) was significantly lower. The patients in the autotransfusion group were observed to have higher body temperatures than those in the other two groups. In the routine drainage group, eight cases accepted allogenic blood transfusion, and the percentage (44.4%) was significantly higher than that in the other two groups. There were no significant between-group differences in swelling, healing qualities, and range of motion. Conclusions: Delayed postoperative drainage may reduce blood loss and the chance of allogenic blood transfusion compared with routine drainage and may also reduce the chance of postoperative fever and extra costs compared with autotransfusion. [ABSTRACT FROM AUTHOR]

Background: HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011. Methods: The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL. Results: The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively. Conclusions: This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL. [ABSTRACT FROM AUTHOR]