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Expression of transmembrane protein 106A (TMEM106A) has been reported to be dysregulated in several types of cancers. However, the role of TMEM106A in hepatocellular carcinoma (HCC) is still unknown. In the present study, we demonstrate that TMEM106A is markedly downregulated in HCC compared with normal liver tissue. In particular, tumor-specific DNA methylation of TMEM106A is frequently observed in tumor tissues from HCC patients. Immunohistochemistry and pyrosequencing reveal a significant relationship between TMEM106A methylation and downregulation of protein expression. Receiver operating characteristic (ROC) curve analysis reveals that methylation of TMEM106A in tumor samples is different from that in non-malignant adjacent tissues of HCC patients. Moreover, HCC patients with TMEM106A hypermethylation have a poor clinical prognosis. 5-Aza-2'-deoxycytidin treatment of hypermethylated TMEM106A in highly metastatic HCC cells increases the expression of TMEM106A. Functional assays reveal that overexpression of TMEM106A significantly suppresses the malignant behavior of HCC cells

The complement cascade plays a "complementing" role in human immunity. However, the potential roles of complement system in impacting molecular and clinical features of hepatocellular carcinoma (HCC) remain unclear. In this study, eleven public datasets are analyzed to compare the complement status between normal and cancerous samples based on 18 classical complement-associated genes. The complement scores are constructed to quantify complement signatures of individual tumors. HCC patients in the The Cancer Genome Atlas (TCGA) cohort are focused to perform systematical analyses between complement status and immune infiltration, miRNA expression, DNA methylation, clinicopathological features, and drug response. The results show that the complement scores in normal tissues are dramatically higher than those of tumor tissues. Tumor samples in the TCGA cohort are classified into complement score-low and score-high groups. Pathway analysis reveals that tumor-promoting pathways are typically inhibited in complement score-high group. This study also shows that tumor-killing immune cells, such as CD8

Osteosarcoma is the most common primary malignancy in the musculoskeletal system. It is reported that copy number variation- (CNV-) derived lncRNAs contribute to the progression of osteosarcoma. However, whether CNV-derived lncRNAs affect the prognosis of osteosarcoma remains unclear. Here, we obtained osteosarcoma-related CNV data and gene expression profiles from The Cancer Genome Atlas (TCGA) database. CNV landscape analysis indicated that copy number amplification of lncRNAs was more frequent than deletion in osteosarcoma samples. Thirty-four CNV-lncRNAs with DNA-CNV frequencies greater than 30% and their corresponding 294 mRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analyses revealed that these mRNAs were mainly enriched in olfaction, olfactory receptor activity, and olfactory transduction processes. Furthermore, we predicted that a total of 23 genes were cis-regulated by 16 CNV-lncRNAs, while 30 transcription factors (TFs) were trans-regulated by 5 CNV-lncRNAs. Through t -tests, univariate Cox regression analysis, and the least absolute shrinkage and selection operator (LASSO), we constructed a CNV-related risk model including 3 lncRNAs (AC129492.1, PSMB1, and AC037459.4). The Kaplan-Meier (K-M) curves indicated that patients with high-risk scores showed poor prognoses. The areas under the receiver operating characteristic (ROC) curves (AUC) for predicting 3-, 5-, and 7-year overall survival (OS) were greater than 0.7, showing a satisfactory predictive efficiency. Gene set enrichment analysis (GSEA) revealed that the prognostic signature was intimately linked to skeletal system development, immune regulation, and inflammatory response. Collectively, our study developed a novel 3-CNV-lncRNA prognostic signature that would provide theoretical guidance for the clinical prognostic management of osteosarcoma.

Monocarboxylate transporter (MCT) 4 is a high-affinity lactate transporter that is primarily involved in the maintenance of intracellular pH homeostasis and highly expressed in different tumors. However, the role of MCT4 in modulating immune responses against HCC remains unknown.In this study, we demonstrated that MCT4 was overexpressed in HCC, which was associated with poor prognosis in patients. Genetic or pharmacological inhibition of MCT4 using VB124 (a highly potent MCT4 inhibitor) suppressed HCC tumor growth in immunocompetent mice model by enhancing CD8Our results revealed that lactate exportation by MCT4 has a tumor-intrinsic function in generating an immunosuppressive HCC environment and demonstrated the proof of the concept of targeting MCT4 in tailoring HCC immunotherapeutic approaches.

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer.Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty.Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters.Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

BACKGROUND In the CELESTIAL trial for patients with advanced hepatocellular carcinoma (HCC), cabozantinib showed improved survival compared with placebo but comes at a price. We aimed to investigate the cost-effectiveness of cabozantinib for sorafenib-resistant HCC from the payer's perspective of the USA, UK and China. METHODS We developed Markov models to simulate the patients pre-treated with first-line sorafenib following the CELESTIAL trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated for the treatment with cabozantinib or best supportive care. The list price for drugs was acquired from the Red Book, the British National Formulary, West China hospital and reported literature. Adverse events, utilities weights, and transition likelihood between states were sourced from the published randomized phase III trial. A willing-to-pay threshold was set $150 000/QALY in the USA, $70 671/QALY (£50 000/QALY) in the UK and $26 481/QALY (3x GDP per capita) in China. Deterministic and probabilistic sensitivity analyses were developed to test the models' uncertainty. RESULTS In the base case, treatment with cabozantinib increased effectiveness by 0.13 QALYs, resulting in an ICER vs best supportive care of $833 497/QALY in the USA, $304 177/QALY in the UK and $156 437/QALY in China. The models were most sensitive to assumptions about transitions to progression with both cabozantinib and best supportive care, the utility associated with being progression free. These results were robust across a range of scenarios and sensitivity analyses, including deterministic and probabilistic analyses. CONCLUSIONS Cabozantinib at its current cost would not be a cost-effective treatment option for patients with sorafenib-resistant HCC from the payer's perspective in the USA, UK or China. Substantial discounts are necessary to meet conventional cost-effectiveness thresholds.

Acupuncture reportedly relieves chronic knee pain and improves physical function in patients diagnosed with osteoarthritis, but the duration of these effects is controversial. The aim of this study was to evaluate the temporal effects of acupuncture on chronic knee pain due to knee osteoarthritis by means of a meta-analysis.The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for studies published through March 2015. Ten randomized controlled trials of acupuncture compared with sham acupuncture, usual care, or no intervention for chronic knee pain in patients with clinically diagnosed or radiographically confirmed knee osteoarthritis were included. All of the studies were available in English. Weighted mean differences (WMDs), 95% confidence intervals (CIs), publication bias, and heterogeneity were calculated.The acupuncture groups showed superior pain improvement (p0.001; WMD = -1.24 [95% CI, -1.92 to -0.56]; I(2)50%) and physical function (p0.001; WMD = 4.61 [95% CI, 2.24 to 6.97]; I(2)50%) in the short term (up to 13 weeks). The acupuncture groups showed superior physical function (p = 0.016; WMD = 2.73 [95% CI, 0.51 to 4.94]; I(2)50%) but not superior pain improvement (p = 0.199; WMD = -0.55 [95% CI, -1.39 to 0.29]; I(2)50%) in the long term (up to 26 weeks). Subgroup analysis revealed that the acupuncture groups tended to have better outcomes compared with the controls. Significant publication bias was not detected (p0.05), but the heterogeneity of the studies was substantial.This meta-analysis demonstrates that acupuncture can improve short and long-term physical function, but it appears to provide only short-term pain relief in patients with chronic knee pain due to osteoarthritis.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Background Nedaplatin-based concurrent chemoradiotherapy became an alternative doublet treatment strategy to cisplatin-based concurrent chemoradiotherapy in patients with locoregional, advanced nasopharyngeal carcinoma. Materials and methods Using a Markov model, we simulated patients with nasopharyngeal carcinoma from disease-free to death. Input data for the model were collected from published literature and the standard fee database of West China Hospital. The outcome was expressed in quality-adjusted-years (QALYs), net monetary benefit at the threshold of $25,841, three times the Gross Domestic Product of China in 2017. The costs and benefits were discounted at 3% annually and a half-cycle correction was considered. The input parameters were varied in one-way sensitivity analysis to confirm the robustness of the model. All of the primary analyses used second-order probabilistic sensitivity analysis to capture the impact of parameter uncertainty based on 10,000 Monte-Carlo simulations. Results The mean QALYs of treatment in stage II-IVB nasopharyngeal carcinoma were comparable: 2.90 QALYs for nedaplatin and 3.12 QALYs for cisplatin. Nedaplatin cost $34,505 compared with $27,167 for cisplatin, generating an incremental net monetary benefit of nedaplatin versus cisplatin of $-13,357 at the ceiling ratio of $25,841. The results of nedaplatin remained cost-ineffective over the majority of the sensitivity analyses. The cost-effectiveness curve showed that the probability of strategies being cost-effective were 0% for nedaplatin and 100% for cisplatin in stage II-IVB nasopharyngeal carcinoma at any willingness-to-pay threshold. Conclusions Nedaplatin is a dominated, cost-ineffective alternative to concurrent chemoradiotherapy in stage II-IVB nasopharyngeal carcinoma compared with cisplatin from the perspective of Chinese society.

The objective is to explore the clinical curative effects of methylprednisolone combined with MTX and DXM intrathecal injection in treating neuropsychiatric systemic lupus erythematosus (NPSLE) and its effects on autoantibody level and anti-N-methyl-D-aspartate receptor subtype NR2a/2b antibody (anti-NR2 antibody) level. Thirty six admitted NPSLE patients were treated by methylprednisolone combined with MTX and DXM intrathecal injection. Thirty six SLE patients without neuropsychiatric symptoms were selected as non-NPSLE group. Clinical indexes including SLE activity index, erythrocyte sedimentation rate (ESR), cerebrospinal fluid pressure (CSFP), cerebrospinal fluid protein were observed before and after treatment. Autoantibodies including anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA antibody), anti-extractable nuclear antigen antibody (ENA-Ab) were detected before and after treatment. Enzyme linked immunosorbent assay was used to detect NR2 antibody level before and after treatment in two groups. Upon treatment of methylprednisolone combined with MTX and DXM intrathecal injection, SLE activity index, ESR, CSFP, cerebrospinal fluid protein of 36 NPSLE patients were significantly decreased. Before treatment, positive rates of ANA, anti-dsDNA antibody, and anti-ENA antibody in both NPSLE group and non-NPSLE group had no significant difference. However, positive rate of anti-NR2 antibody in NPSLE group was significantly higher than that of non-NPSLE group. After treatment, positive rates of autoantibodies and anti-NR2 antibody in both NPSLE and non-NPSLE group were significantly decreased. Anti-NR2 antibody can be a screening index of NPSLE, and methylprednisolone combined with MTX and DXM intrathecal injection has significant curative effects and can effectively decrease autoantibody level and anti-NR2 antibody level.

Meta-regression to explore possible confounding effects on risk of rebleeding, surgery, and mortality. (DOCX 45 kb)

Contribution plot and study limitation graph. (DOCX 258 kb)

Ranking table. (DOCX 83 kb)

Cochrane risk of bias tool results. (DOCX 284 kb)

Comparison-adjusted funnel plot for the dual therapies network. (DOCX 240 kb)

Assessment of inconsistency between direct and indirect evidence. (DOCX 66 kb)

Search strategy. (DOCX 37 kb)

Cyclin B2 (CCNB2), a member of cyclin family proteins, serves a key role in progression of G2/M transition. The clinical value of CCNB2 in non-small cell lung cancer is still unknown. The aim of our study is to identify the role of CCNB2 in NSCLC patients. The status of CCNB2 in NSCLC tissues and normal lung tissues was observed in Gene Expression Omnibus (GEO: GSE19804). CCNB2 mRNA and protein expressions were detected in NSCLC and normal lung tissues by using Real-time PCR and immunohistochemistry. The association of CCNB protein expression with clinical characteristics of 186 NSCLC patients was analyzed by immunohistochemistry. Based on microarray data (GEO: GSE19804), we observed that CCNB2 was significantly overexpressed in NSCLC tissues compared with paired adjacent normal lung tissue. Furthermore, we verified mRNA and protein levels of CCNB2 expression were both increased in NSCLC tissues. We found high levels of CCNB2 protein were positively associated with the status of differentiated degree, tumor size, lymph node metastasis, distant metastasis, and clinical stage. Meanwhile, CCNB2 protein overexpression was an independent unfavorable prognostic factor for the overall survival of patients with NSCLC. In conclusion, overexpression of CCNB2 protein is associated with clinical progression and poor prognosis in NSCLC.

With the development of optical fiber communication technology, optical spectrum analyzer (OSA) suitable for field use is urgently required. The laboratory-based OSA can be available only in a laboratory environment and unsuited to field use. By eliminating unwanted functions and fine design, the portable OSA can meet the requirement for field test and provide low cost and high performance. In this paper, a kind of high speed and portable OSA suitable for plastic fiber field test is designed, whose wavelength measurement accuracy is better than 0.1nm and spectrum energy measurement sensitivity is -30dBm.