Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis.

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring.We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks.Incidence of orofacial clefts.We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66-2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5-6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3-2.8) and CPO (OR 1.48, 95% CI 0.83-2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results.Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

[Effect of High-Volume Leukapheresis on Hematological Indexes of Patients with Hyperleukocytic Leukemia].

OBJECTIVE: To improve the collection efficiency of leukapheresis, explore relatively scientific and objective evaluation indicators for collection effect, and observe the effect of high-volume leukapheresis on blood cells and coagulation function. METHODS: A total of 158 times of high-volume leukapheresis were performed on 93 patients with hyperleukocytic leukemia by using continuous flow centrifugal blood component separator. 1/5-1/4 of total blood volume of the patients was taken as the target value of leukocyte suspension for single treatment. In addition, the total number of white blood cells (WBCs) subtracted, value of WBCs reduction, rate of WBCs reduction, decrease value of WBCs count, decrease rate of WBCs count, amount of hemoglobin (Hb) lost, value of Hb lost, decreased value of Hb, total number of platelet (PLT) lost, the value of PLT loss, and decrease value of PLT count were used to comprehensively evaluate the collection effect of leukapheresis and influence on Hb level and PLT count of the patients. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen (Fib) concentration were detected before and after treatment, and the effect of leukapheresis on coagulation function of the patients was observed. RESULTS: The volume of leukocyte suspension collected in a single treatment was 793.01±214.23 ml, the total number of WBCs subtracted was 353.25 (241.99-547.28)×109, the value of WBCs reduction was 86.98 (63.05-143.43)×109/L, the rate of WBCs reduction was 44.24 (28.37-70.48)%, decrease value of WBCs count was 65.73 (37.17-103.97)×109/L, decrease rate of WBCs count was (35.67±23.08)%, the amount of Hb lost was 17.36 (12.12-24.94) g, the value of Hb lost was 4.31 (3.01-6.12) g/L, decreased value of Hb was 4.80 (-1.25-9.33) g/L, total number of PLT lost was 222.79 (67.03-578.31)×109, the value of PLT loss was 54.45 (17.29-139.08)×109/L, and decrease value of PLT count was 26.00 (8.38-62.50)×109/L. Before and after a single treatment, the PT was 14.80 (13.20-16.98) s and 15.20 (13.08-16.90) s (z=-1.520, P>0.05), the aPTT was 35.20 (28.68-39.75) s and 35.40 (28.00-39.75) s (z=-2.058, P<0.05), the TT was 17.50 (16.30-18.80) s and 17.70 (16.70-19.10) s (z=-3.928, P<0.001), and the Fib concentration was 2.87±1.13 g/L and 2.64±1.03 g/L (t=7.151, P<0.001), respectively. CONCLUSION: High-volume leukapheresis can improve the efficiency of leukapheresis while maintaining the relative stability of the patients' circulating blood volume. The degree of influence on the patients' Hb level, PLT count, Fib concentration, and comprehensive coagulation indicators reflecting the patients' intrinsic and cxtrinsic coagulation activity is within the body's compensation range.

A pilot study of neoadjuvant combination of anti-PD-1 camrelizumab and VEGFR2 inhibitor apatinib for locally advanced resectable oral squamous cell carcinoma.

Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%-24.3%) and 95% (95% CI: 85.4%-100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC.

Mechanism of sensitivity to cisplatin, docetaxel, and 5-fluorouracil chemoagents and potential erbB2 alternatives in oral cancer with growth differentiation factor 15 overexpression.

The aim of this study was to: (a) explore the potential mechanism of cancer cell sensitivity to cisplatin, docetaxel, and 5-fluorouracil (TPF) in oral squamous cell carcinoma (OSCC) patients overexpressing growth differentiation factor 15 (GDF15); and (b) identify potential alternative agents for patients who might not benefit from inductive TPF chemotherapy. The results indicated that OSCC cells overexpressing GDF15 were sensitive to TPF through a caspase-9-dependent pathway both in vitro and in vivo. Immunoprecipitation combined with mass spectrometry revealed that the erbB2 protein was a potential GDF15-binding protein, which was verified by coimmunoprecipitation. Growth differentiation factor 15 overexpression promoted OSCC cell proliferation through erbB2 phosphorylation, as well as downstream AKT and Erk signaling pathways. When GDF15 expression was blocked, the phosphorylation of both the erbB2 and AKT/Erk pathways was downregulated. When OSCC cells with GDF15 overexpression were treated with the erbB2 phosphorylation inhibitor, CI-1033, cell proliferation and xenograft growth colony formation were significantly blocked (P < .05). Thus, GDF15-overexpressing OSCC tumors are sensitive to TPF chemoagents through caspase-9-dependent pathways. Growth differentiation factor 15 overexpression promotes OSCC proliferation through erbB2 phosphorylation. Thus, ErbB2 inhibitors could represent potential targeted drugs or an alternative therapy for OSCC patients with GDF15 overexpression.

Targeting ERK combined with apatinib may be a promising therapeutic strategy for treating oral squamous cell carcinoma.

Apatinib is an oral tyrosine kinase inhibitor that targets VEGFR2 signaling and shows potent antitumor effects in various cancers. In this study, we explored the efficacy of apatinib against oral squamous cell carcinoma (OSCC). The relationships between VEGFR2 protein expression and clinical variables were investigated in OSCC patients. OSCC tissues had higher VEGFR2 levels than paracancerous tissues. Compared to patients with low VEGFR2 expression, patients with high VEGFR2 expression had poorer overall survival (OS) and disease-free survival (DFS). Apatinib significantly induced G0/G1 phase arrest and apoptosis, inhibited cell growth and colony formation ability, and blocked autophagic flux by downregulating p-AKT and p-mTOR signaling via the VEGFR2/AKT/mTOR pathway in vitro. Moreover, the inhibition of ERK phosphorylation increased apatinib-induced apoptosis in vitro and in vivo. Apatinib synergized with SCH772984 to achieve a more significant suppression of tumor growth than individual treatment, suggesting the combination of apatinib and SCH772984 as a potent OSCC therapy.

A therapeutic approach with combination of interferon-gamma and autophagy inhibitor for oral squamous cell carcinoma.

Former clinical trials and experimental research have indicated that Interferon-gamma therapy does not achieve an ideal effect in solid tumors. Autophagy has been associated with tumor chemoresistance. The aim of this study was to explore the efficacy of Interferon-gamma and autophagy inhibitor in the combination treatment of oral squamous cell carcinoma. Interferon-gamma-induced apoptosis was evaluated by the expression of relative proteins (cleaved-PARP and caspase-3) and flow cytometry. Interferon-gamma induced autophagy was assessed by the expression of Beclin1, LC3B, and P62. The synergistic effect of interferon-gamma and autophagy inhibitor (chloroquine) was evaluated in vitro and in vivo. Interferon-gamma induced anti-proliferation, apoptosis, and autophagy in oral squamous cell carcinoma cells. Autophagy-related protein 5 was a key feature in Interferon-gamma-induced autophagy flux. Interferon-gamma and chloroquine had obvious synergistic effects on cellular growth inhibition and apoptosis promotion in oral squamous cell carcinoma cells and xenograft models. Our findings suggest that Interferon-gamma-induced autophagy plays a cellular protective role, and blocking autophagy flux can promote Interferon-gamma mediated oral squamous cell carcinoma cell apoptosis. The combination of Interferon-gamma and autophagy inhibitors represents a novel strategy for oral squamous cell carcinoma therapy.

Overcoming chemotherapy resistance using pH-sensitive hollow MnO2 nanoshells that target the hypoxic tumor microenvironment of metastasized oral squamous cell carcinoma.

BACKGROUND: Smart nanoscale drug delivery systems that target acidic tumor microenvironments (TME) could offer controlled release of drugs and modulate the hypoxic TME to enhance cancer therapy. The majority of previously reported MnO2 nanostructures are nanoparticles, nanosheets, or nanocomposites incorporated with other types of nanoparticles, which may not offer the most effective method for drug loading or for the controlled release of therapeutic payloads. Previous studies have designed MnO2 nanoshells that achieve tumor-specific and enhanced combination therapy for localized advanced cancer. However, the therapeutic effect of MnO2 nanoshells on metastatic cancer is still uncertain. RESULT: Here, intelligent "theranostic" platforms were synthesized based on hollow mesoporous MnO2 (H-MnO2) nanoshells that were loaded with chemotherapy agents docetaxel and cisplatin (TP) to form H-MnO2-PEG/TP nanoshells, which were designed to alleviate tumor hypoxia, attenuate angiogenesis, trigger the dissolution of Mn2+, and synergize the efficacy of first-class anticancer chemotherapy. The obtained H-MnO2-PEG/TP nanoshells decomposed in the acidic TME, releasing the loaded drugs (TP) and simultaneously attenuated tumor hypoxia and hypoxia-inducible factor-1α (HIF-1α) expression by inducing endogenous tumor hydrogen peroxide (H2O2) decomposition. In vitro experiments showed that compared with the control group, the proliferation, colony formation and migration ability of CAL27 and SCC7 cells were significantly reduced in H-MnO2-PEG/TP group, while cell apoptosis was enhanced, and the expression of hypoxia-inducible factor-1α(HIF-1α) was down-regulated. In vivo experiments showed that tumor to normal organ uptake ratio (T/N ratio) of mice in H-MnO2-PEG/TP group was significantly higher than that in TP group alone (without the nanoparticle), and tumor growth was partially delayed. In the H-MnO2-PEG/TP treatment group, HE staining showed that most of the tumor cells were severely damaged, and TUNEL assay showed cell apoptosis was up-regulated. He staining of renal and liver sections showed no obvious fibrosis, necrosis or hypertrophy, indicating good biosafety. Fluorescence staining showed that HIF-1α expression was decreased, suggesting that the accumulation of MnO2 in the tumor caused the decomposition of H2O2 into O2 and alleviated the hypoxia of the tumor. CONCLUSION: In conclusion, a remarkable in vivo and in vitro synergistic therapeutic effect is achieved through the combination of TP chemotherapy, which simultaneously triggered a series of antiangiogenic and oxidative antitumor reactions.

Anti-tumor effect of carrimycin on oral squamous cell carcinoma cells in vitro and in vivo.

PURPOSE: Carrimycin is a newly synthesized macrolide antibiotic with good antibacterial effect. Exploratory experiments found its function in regulating cell physiology, proliferation and immunity, suggesting its potential anti-tumor capacity. The aim of this study is to investigate the anti-tumor effect of carrimycin against human oral squamous cell carcinoma cells in vitro and in vivo. METHODS: Human oral squamous cell carcinoma cells (HN30/HN6/Cal27/HB96 cell lines) were treated with gradient concentration of carrimycin. Cell proliferation, colony formation and migration ability were analyzed. Cell cycle and apoptosis were assessed by flow cytometry. The effect of carrimycin on OSCC in vivo was investigated in tumor xenograft models. Immunohistochemistry, western blot assay and TUNEL assays of tissue samples from xenografts were performed. The key proteins in PI3K/AKT/mTOR pathway and MAPK pathway were examined by western blot. RESULTS: As the concentration of carrimycin increased, the proliferation, colony formation and migration ability of OSCC cells were inhibited. After treating with carrimycin, cell cycle was arrested in G0/G1 phase and cell apoptosis was promoted. The tumor growth of xenografts was significantly suppressed. Furthermore, the expression of p-PI3K, p-AKT, p-mTOR, p-S6K, p-4EBP1, p-ERK and p-p38 were down-regulated in vitro and in vivo. CONCLUSIONS: Carrimycin can inhibit the biological activities of OSCC cells in vitro and in vivo, and regulate the PI3K/AKT/mTOR and MAPK pathways.

High-risk lymph node ratio predicts worse prognosis in patients with locally advanced oral cancer.

BACKGROUND: To investigate the prognostic value of lymph node ratio (LNR), as well as the correlation with docetaxel, cisplatin, and 5-FU (TPF) induction chemotherapy, in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: Two-hundred and forty-five patients from a phase 3 trial involving TPF induction chemotherapy in stage III/IVA OSCC patients (NCT01542931) were enrolled in this study between 2008 and 2010. The clinical and pathological data were collected and analyzed. The cutoff value for LNR was calculated on the receiver operating characteristic (ROC) curve. Univariate and multivariate Cox regression models, and Kaplan-Meier method were used for survival analysis. RESULTS: According to the ROC curve, the cutoff value for LNR was 7.6%. With a median follow-up period of 80 months, the OSCC patients with high-risk LNR (> 7.6%), or positive extranodal extension (ENE) had significantly worse clinical outcomes than patients with low-risk LNR (≤7.6%) or negative ENE. Multivariate analysis on pathological covariates showed that only high-risk LNR was an independent negative predictive factor for survival (P < .05). The cutoff value of LNR of 7.6% was also verified with the similar results using an open TCGA database, high-risk LNR indicating worse overall survival (P < .001) and disease-free survival (P < .001). CONCLUSION: Oral squamous cell carcinoma patients with high-risk LNR have a worse clinical outcome than patients with low-risk LNR. High-risk LNR is an independent negative predictive factor for clinical outcome in patients with locally advanced OSCC.

Stathmin guides personalized therapy in oral squamous cell carcinoma.

The survival benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy in oral squamous cell carcinoma (OSCC) patients is not satisfactory. Previously, we identified that stathmin, a microtubule-destabilizing protein, is overexpressed in OSCC. Here, we further investigated its role as a biomarker that impacts on OSCC chemosensitivity. We analyzed the predictive value of stathmin on TPF induction chemotherapy and its impact on OSCC cell chemosensitivity. Then, we further investigated the therapeutic effects of the combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors in vitro and in vivo. We found that OSCC patients with low stathmin expression benefited from TPF induction chemotherapy, while OSCC patients with high stathmin expression could not benefit from TPF induction chemotherapy. Stathmin overexpression promoted cellular proliferation and decreased OSCC cell sensitivity to TPF treatment. In addition, inhibition of the PI3K-AKT-mTOR signaling pathway decreased stathmin expression and phosphorylation. The combination therapy of TPF chemotherapy and PI3K-AKT-mTOR inhibitors exhibited a potent antitumor effect both in vitro and in vivo. Therefore, stathmin can be used as a predictive biomarker for TPF induction chemotherapy and a combination therapy regimen based on stathmin expression might improve the survival of OSCC patients.

Normal BMI predicts the survival benefits of inductive docetaxel, cisplatin, and 5-fluorouracil in patients with locally advanced oral squamous cell carcinoma.

BACKGROUND & AIMS: This study aimed to evaluate the prognostic value of the body mass index (BMI), as well as the association with docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy in patients with locally advanced oral squamous cell carcinoma (OSCC). METHODS: This retrospective study enrolled 253 patients with locally advanced OSCC between 2008 and 2010 based on our previous prospective, randomized, phase 3 trial (NCT01542931). Univariate and multivariate Cox regression models, and the Kaplan-Meier method were used for survival analyses. RESULTS: Among the 253 patients, the BMI at the time of clinical diagnosis ranged from 13.16 to 34.66 kg/m2. Smoking status among patients showed a marked correlation with a higher BMI status at the time of clinical diagnosis (tobacco status: P < 0.001). The distribution of clinical nodal (cN) stage was significantly different, as patients with higher BMIs generally had earlier cN stages (P < 0.021) among the different BMI groups. The Kaplan-Meier analysis showed that the BMI was significantly correlated with overall survival (OS, P = 0.004), disease-free survival (DFS, P = 0.005), locoregional recurrence-free survival (LRFS, P = 0.003) and distant metastasis-free survival (DMFS, P = 0.007). When the BMI was included in the multivariate Cox regression model adjusted for potentially confounding clinical variables, the BMI was shown to be an independent predictive factor of OS (P = 0.015), DFS (P = 0.015), LRFS (P = 0.009), and DMFS (P = 0.023). The TPF group showed better 5-year clinical survival rates than the control group when analyzing patients with a normal BMI (OS: 64.2% vs. 55.9%; DFS: 54.7% vs. 46.4%; LRFS: 56.6% vs. 49.6%; DMFS: 64.2% vs. 56.0%), but no significant difference was observed. Subgroup survival analysis indicated that patients with a normal BMI and clinical stage IVA disease who accepted TPF induction chemotherapy had a significantly improved OS (HR: 0.425, 95% CI: 0.187-0.966, P = 0.035) and DMFS (HR: 0.425, 95% CI: 0.187-0.966, P = 0.034). CONCLUSION: The BMI at the time of clinical diagnosis was showed to be an independent predictive factor for patients with locally advanced OSCC. Compared with normoweight patients, underweight patients may have worse clinical outcomes, while overweight and obese patients have a better prognosis. A normal BMI in clinical stage IVA OSCC patients predicts significant OS and DMFS benefits of TPF induction chemotherapy.

[Effect of Highvolume Platelet Reduction Therapy on White Blood Cell Count and Hemoglobin Level in Patients with Thrombocytosis].

OBJECTIVE: To explore the effect of high volume platelet reduction therapy on the white blood cell (WBC) count and hemoglobin (Hb) level in patients with thrombocytosis. METHODS: Thirty-two plateletphoreses were performed for patients with thromocytosis by using ELP or MNC program of blood component isolator of COBE spectra continuous flow concentrifugation and the ACD-A preservation solution for blood as blood anticoagulant. In each treatment of patients, 2.5-3.0 tines total blood volume (TBV) were circulated, then the platelet suspension of 1/5-1/4 time TBV was prepared and collected. RESULTS: A single plateletpheresis took (212.53±41.54) minutes in which (8 812.63±2087.15) ml blood were treated, and (798.84±190.77) ml platelet suspension was collected. In the suspension, the platelet count was 4 486.50 (3 058.50-5 279.50)×109/L, containing 3 455.50 (2 288.68-4 226.71)×109. WBC count was 13.79 (10.21-20.72)×109/L, containing 11.90(7.81-14.40)×109. Hemoglobin concentration was (3.28±1.25) g/L，containing (2.62 ± 1.17) g. Before and after plateletpheresis, the patients' platelet count was 1 263.00 (1 052.50-1 807.50)×109/L and (778.83±247.25)×109/L（Z=4.94, P＜0.01), WBC count was 9.96(6.44-14.01)×109/L and 8.59(5.37, 13.12)×109/L (Z=13.31, P＜0.05), Hemoglobin concentration was (112.63 ± 24.56)g/L and (109.55 ± 24.46)g/L (t=1.68，P＞0.05). CONCLUSION: Using continuous flow centrifugation and blood component separating in plateletpheresis for the patients with thrombocytosis can obviously decrease the high ratio of platelets, and improve the effect of plateletpheresis. The high volume platelet reduction therapy can lead to decrease of WBC count to some alent, degree but WBC count still in the normal range, moreover not affect the hemoglobin level significantly.

Deciphering source contributions of trace metal contamination in urban soil, road dust, and foliar dust of Guangzhou, southern China.

Trace metal contamination prevails in various compartments of the urban environment. Understanding the roles of various anthropogenic sources in urban trace metal contamination is critical for pollution control and city development. In this study, the source contribution from various contamination sources to trace metal contamination (e.g., Cu, Pb, Zn, Co, Cr and Ni) in different environmental compartments in a typical megacity, Guangzhou, southern China, was investigated using the receptor model (Absolute Principal Component Scores-Multiple Linear Regression, APCS-MLR) coupled with the Kriging technique. Lead isotopic data and APCS-MLR analysis identified industrial and traffic emissions as the major sources of trace metals in surface soil, road dust, and foliar dust in Guangzhou. Lead isotopic compositions of road dust and foliar dust exhibited similar ranges, implying their similar sources and potential metal exchange between them. Re-suspended soil contributed to 0-38% and 25-58% of the trace metals in the road dust and foliar dust, respectively, indicating the transport of the different terrestrial dust. Spatial distribution patterns implied that Cu in the road dust was a good indicator of traffic contamination, particularly with traffic volume and vehicle speed. Lead and Zn in foliar dust indicated mainly industrial contamination, which decreased from the emission source (e.g., a power plant and steel factory) to the surrounding environment. The spatial influence of industry and traffic on the contamination status of road dust/foliar dust was successfully separated from that of other anthropogenic sources. This study demonstrated that anthropogenic inputs of trace metals in various environmental compartments (e.g., urban soil, road dust, and foliar dust) can be evaluated using a combined APCS-MLR receptor model and geostatistical analysis at a megacity scale. The coupled use of APCS-MLR analysis, geostatistics, and Pb isotopes successfully deciphered the spatial influence of the contamination sources in the urban environment matrix, providing some important information for further land remediation and health risk assessment.

Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis.

INTRODUCTION: Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression. MATERIALS AND METHODS: We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA. RESULTS: Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network. CONCLUSION: These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.

High pretreatment plasma D-dimer predicts poor survival of colorectal cancer: insight from a meta-analysis of observational studies.

D-dimer, one of the canonical markers of hypercoagulability, was reported to be a potential prognostic marker of colorectal cancer. However, an inconsistent conclusion existed in several published studies. Thus, we performed this meta-analysis to provide a comprehensive insight into the prognostic role for pretreatment D-dimer in colorectal cancer. Six databases (English: Pubmed, Embase and Web of Science; Chinese: CNKI, Wangfang and VIP) were utilized for the literature retrieval. Hazard ratio (HR) was pooled by Stata 12.0. A total of fifteen studies (2283 cases) corresponded to this meta-analysis and provided available data to evaluate the prognostic role of D-dimer for colorectal cancer. The pooled HR reached 2.167 (95%. CI (confidence interval): 1.672-2.809, P < 0.001) utilizing random effect model due to obvious heterogeneity among the included studies (I2: 73.3%; P < 0.001). To explore the heterogeneity among the studies, we conducted a sensitivity analysis and found a heterogeneous study. After removing it, the heterogeneity reduced substantially (I2: 0%; P = 0.549) and we obtained a more convincing result by fixed effect model (HR = 2.143, 95% CI = 1.922-2.390, P < 0.001, 14 studies with 2179 cases). In summary, high pretreatment plasma D-dimer predicts poor survival of colorectal cancer based on the current evidence. Further prospective researches are necessary to confirm the role of D-dimer in colorectal cancer.

Burden of disease measured by disability-adjusted life years and a disease forecasting time series model of scrub typhus in Laiwu, China.

BACKGROUND: Laiwu District is recognized as a hyper-endemic region for scrub typhus in Shandong Province, but the seriousness of this problem has been neglected in public health circles. METHODOLOGY/PRINCIPAL FINDINGS: A disability-adjusted life years (DALYs) approach was adopted to measure the burden of scrub typhus in Laiwu, China during the period 2006 to 2012. A multiple seasonal autoregressive integrated moving average model (SARIMA) was used to identify the most suitable forecasting model for scrub typhus in Laiwu. Results showed that the disease burden of scrub typhus is increasing yearly in Laiwu, and which is higher in females than males. For both females and males, DALY rates were highest for the 60-69 age group. Of all the SARIMA models tested, the SARIMA(2,1,0)(0,1,0)12 model was the best fit for scrub typhus cases in Laiwu. Human infections occurred mainly in autumn with peaks in October. CONCLUSIONS/SIGNIFICANCE: Females, especially those of 60 to 69 years of age, were at highest risk of developing scrub typhus in Laiwu, China. The SARIMA (2,1,0)(0,1,0)12 model was the best fit forecasting model for scrub typhus in Laiwu, China. These data are useful for developing public health education and intervention programs to reduce disease.