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PurposeTo develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions.MethodsA total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263).ResultsSix significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40).ConclusionsThe constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Abstract Background In insects, the chemosensory system is crucial in guiding their behaviors for survival. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. There is little known about the chemosensory genes in P. versicolora. Here, we conducted a transcriptome analysis of larvae heads in P. versicolora. Results In this study, 29 odorant binding proteins (OBPs), 6 chemosensory proteins (CSPs), 14 odorant receptors (ORs), 13 gustatory receptors (GRs), 8 ionotropic receptors (IRs) and 4 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. Compared to the previous antennae and foreleg transcriptome data in adults, 12 OBPs, 2 CSPs, 5 ORs, 4 IRs, and 7 GRs were newly identified in the larvae. Phylogenetic analyses were conducted and found a new candidate CO2 receptor (PverGR18) and a new sugar receptor (PverGR23) in the tree of GRs. Subsequently, the dynamic expression profiles of various genes were analyzed by quantitative real-time PCR. The results showed that PverOBP31, OBP34, OBP35, OBP38, and OBP40 were highly expressed in larvae, PverOBP33 and OBP37 were highly expressed in pupae, and PverCSP13 was highly expressed in eggs, respectively. Conclusions We identified a total of 74 putative chemosensory genes based on a transcriptome analysis of larvae heads in P. versicolora. This work provides new information for functional studies on the chemoreception mechanism in P. versicolora.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Objective To assess the ablative margin of microwave ablation (MWA) for stage I non-small cell lung cancer (NSCLC) using a three-dimensional (3D) reconstruction technique. Materials and methods We retrospectively analyzed 36 patients with stage I NSCLC lesions undergoing MWA and analyzed the relationship between minimal ablative margin and the local tumor progression (LTP) interval, the distant metastasis interval and disease-free survival (DFS). The minimal ablative margin was measured using the fusion of 3D computed tomography reconstruction technique. Results Univariate and multivariate analyses indicated that tumor size (hazard ratio [HR] = 1.91, P

Objective. To evaluate the association between neutrophil levels and all-cause mortality in geriatric hip fractures. Methods. Elderly patients with hip fractures were screened between January 2015 and September 2019. Demographic and clinical characteristics of the patients were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between neutrophil levels and mortality. Analyses were performed using Empower Stats and R software. Results. A total of 2,589 patients were included in this study. The mean follow-up period was 38.95 months. During the study period, 875 (33.80%) patients died due to various causes. Linear multivariate Cox regression models showed that neutrophil levels were associated with mortality after adjusting for confounding factors, when neutrophil concentration increased by 1∗109/L, the mortality risk increased by 3% (HR = 1.03, 95% CI: 1.00–1.06, and P=0210). Neutrophil concentration was used as a categorical variable; we only found statistically significant differences when neutrophil levels were high (HR = 1.27, 95% CI:1.05–1.52, and P=0.0122). In addition, the results are stable in P for trend and propensity score matching sensitivity analysis. Conclusions. Neutrophil levels are associated with mortality in geriatric hip fractures and could be considered a predictor of death risk in the long-term. This study is registered with the Chinese Clinical Trial Registry (ChiCTR) as number ChiCTR2200057323.

Objective To analysis the safety and outcome of intravenous thrombolysis with recombinant tissue plasminogen activator (rt⁃PA) in patients with acute mild ischemic stroke. Methods From November 2017 to October 2018, 252 patients with acute mild ischemic stroke who were admitted into our hospital within 4.50 h after onset (84 patients in intravenous thrombolysis group, 108 patients in aspirin and clopidogrel group, and 60 patients in aspirin or clopidogrel group). The general condition, the level of high⁃sensitivity C⁃reactive protein (hs⁃CRP) and erythrocyte sedimentation (ESR) were compared among 3 groups. The modified Rankin Scale (mRS) were evaluated on 7 d after admission or at earlier discharge, and 21 and 90 d. Symptomatic intracranial hemorrhage rates were compared among 3 groups. Results There were no significant difference in general clinical data, the initial level of hs⁃CRP and ESR between the intravenous thrombolytic group and the 2 non⁃thrombolysis groups. At 7 d after admission or earlier discharge, the descending range of hs⁃CRP and ESR in 3 groups were significant (P = 0.000, for all); there were significant differences among the 3 groups (P = 0.000, for all); pairwise comparison of 3 groups showed that the levels of hs⁃CRP and ESR in intravenous thrombolytic group at 7 d were significantly lower than aspirin and/or clopidogrel group (P = 0.000, 0.000; P = 0.000, 0.010). There was no significant difference in the rate of intracranial hemorrhage between thrombolytic group and other 2 groups at 24 h after treatment [1.19% (1/84) vs. 0 (0/168); χ 2discharge, the intravenous thrombolytic group had better prognosis than aspirin and/or dopidogrel group (P = 0.043, 0.012); At 21 and 90 d, the intravenous thrombolytic group had better prognosis than aspirin or clopidogrel group (P = 0.021, 0.037); but compared with aspirin and clopidogrel group, there was no significant difference (P = 0.070, 0.053). Conclusions Patients with mild ischemic stroke, especially that may induce disability should be treated with rt⁃PA intravenous thrombolysis timely. If it impossible by any causes, aspirin and clopidogrel should be given within 24 h after onset. DOI：10.3969/j.issn.1672⁃6731.2019.12.012

In probabilistic analysis, random variables with unknown distributions are often appeared when dealing with practical engineering problem. A Hermite normal transformation model has been proposed to conduct structural reliability assessment without the exclusion of random variables with unknown probability distributions. Recently, linear moments (L-moments) are widely used due to the advantages of stability and insensitivity. In this paper, the complete expressions of the inverse transformation of L-moments Hermite (L-Hermite) model have been proposed. The criteria are proposed to derive the complete inverse transformation of performance function and the complete expressions of the inverse transformation of L-Hermite model are formulated. Moreover, a first-order reliability method for structural reliability analysis based on the proposed inverse transformation of L-Hermite model is then developed using the first four L-moments of random variables. Through the numerical examples, the proposed method is found to be efficient for normal transformations since the results of the proposed L-Hermite are in close agreement with the results of Rosenblatt transformation. Additionally, the reliability index obtained by the proposed method using the first four L-moments of random variables provides a close result to the reliability index obtained by first-order reliability method with known probability density functions in structural reliability assessment.

Plagiodera versicolora (Coleoptera: Chrysomelidae) is a worldwide leaf-eating forest pest in salicaceous trees. The forelegs play important roles in the chemoreception of insects. In this study, we conducted a transcriptome analysis of adult forelegs in P. versicolora and identified a total of 53 candidate chemosensory genes encoding 4 chemosensory proteins (CSPs), 19 odorant binding proteins (OBPs), 10 odorant receptors (ORs), 10 gustatory receptors (GRs), 6 ionotropic receptors (IRs), and 4 sensory neuron membrane proteins (SNMPs). Compared with the previous antennae transcriptome data, 1 CSP, 4 OBPs, 1 OR, 3 IRs, and 4 GRs were newly identified in the forelegs. Subsequently, the tissue expression profiles of 10 P. versicolora chemosensory genes were performed by real-time quantitative PCR. The results showed that PverOBP25, PverOBP27, and PverCSP6 were highly expressed in the antennae of both sexes. PverCSP11 and PverIR9 are predominately expressed in the forelegs than in the antennae. In addition, the expression levels of PverGR15 in female antennae and forelegs were significantly higher than those in the male antennae, implying that it may be involved in some female-specific behaviors such as oviposition site seeking. This work would greatly further the understanding of the chemoreception mechanism in P. versicolora.

Tomato flower abscission is a critical agronomic problem directly affecting yield. It often occurs in greenhouses in winter, with the weak light or hazy weather leading to insufficient photosynthates. The importance of carbohydrate availability in flower retention has been illustrated, while relatively little is understood concerning the mechanism of carbohydrate regulation on flower abscission. In the present study, we analyzed the responding pattern of nonstructural carbohydrates (NSC, including total soluble sugars and starch) and the potential sugar signal pathway involved in abscission regulation in tomato flowers under shading condition, and their correlations with flower abscission rate and abscission-related hormones. The results showed that, when plants suffer from short-term photosynthesis deficiency, starch degradation in flower organs acts as a self-protection mechanism, providing a carbon source for flower growth and temporarily alleviating the impact on flower development. Trehalose 6-phosphate (T6P) and sucrose non-fermenting-like kinase (SnRK1) signaling seems to be involved in adapting the metabolism to sugar starvation stress through regulating starch remobilization and crosstalk with IAA, ABA, and ethylene in flowers. However, a continuous limitation of assimilating supply imposed starch depletion in flowers, which caused flower abscission.

Insects can sense surrounding chemical signals by their accurate chemosensory systems. This system plays a vital role in the life history of insects. Several gene families participate in chemosensory processes, including odorant receptors (ORs), ionotropic receptors (IRs), gustatory receptors (GRs), chemosensory proteins (CSPs), odorant binding proteins (OBPs), and sensory neuron membrane proteins (SNMPs). Plagiodera versicolora (Coleoptera: Chrysomelidae), is a leaf-eating forest pest found in salicaceous trees worldwide. In this study, a transcriptome analysis of male and female adult antennae in P. versicolora individuals was conducted, which identified a total of 98 candidate chemosensory genes including 40 ORs, 7 IRs, 13 GRs, 10 CSPs, 24 OBPs, and 4 SNMPs. Subsequently, the tissue expression profiles of 15 P. versicolora OBPs (PverOBPs) and 39 ORs (PverORs) were conducted by quantitative real-time PCR. The data showed that almost all PverOBPs and PverORs were highly expressed in the male and female antennae. In addition, several OBPs and ORs (PverOBP10, PverOBP12, PverOBP18, PverOR24, and PverOR35) had higher expression levels in female antennae than those in the male antennae, indicating that these genes may be taking part in some female-specific behaviors, such as find mates, oviposition site, etc. This study deeply promotes further understanding of the chemosensory system and functional studies of the chemoreception genes in P. versicolora.

Genome-wide association studies have been performed to identify genetic variants that are associated with susceptibility to colorectal cancer. Here, the authors expand on these studies and identify a variant that regulates the expression of ETV6 and find that over-expression of ETV6 blocks cell proliferation in vitro.

Background/Aims: FOXO3a is an essential tumor suppressor that regulates the mechanisms of tumorigenesis and leukemogenesis. FOXO3a polymorphisms have not been reported previously associated with an increased risk for childhood acute lymphoblastic leukemia (ALL). In this study, the rs4946936 polymorphism located in the 3'UTR of FOXO3a was selected to evaluate its relationship with a risk for ALL in Chinese children. Methods: Questionnaires, SNaPshot genotyping, real-time PCR, cell transfection and dual luciferase reporter assays were used in this study. Results: Parental alcohol consumption and whether the child's house had been painted had significantly different distributions among the cases and controls. In addition, the C to T mutation was significantly associated with the risk for ALL. We determined that FOXO3a expression levels in patients with the CT or TT genotype were significantly higher than those of patients with the CC genotype. The T allele significantly increased the expression levels in luciferase assays and affected the binding affinity of miR-223 to the FOXO3a 3'UTR. Conclusion: Rs4946936 in FOXO3a was highly associated with an increased risk of childhood ALL in a Chinese population.

In the past decades, a good deal of studies has provided the possibility of the circulating microRNAs (miRNAs) as noninvasive biomarkers for cancer diagnosis. The aim of our study was to detect the levels of circulating miRNAs in tissues and plasmas of gastric cancer (GC) patients and evaluate their diagnostic value.Tissue samples were collected from 85 GC patients. Plasma samples were collected from 285 GC patients and 285 matched controls. Differentially expressed miRNAs were filtered with by Agilent Human miRNA Microarray and TaqMan low density array (TLDA) with pooled samples, followed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation. Receiver operating characteristic (ROC) curves were structured to evaluate the diagnostic accuracy of the miRNAs. The plasma level of miR-26a in GC patients of different clinical stages was compared.Four miRNAs (miR-26a, miR-142-3p, miR-148a, and miR-195) revealed coincidentally decreased levels in tissue and plasma of the GC patients compared with controls, and ROC curves were constructed to demonstrate that miR-26a had a highest area under the ROC curve (AUC) of 0.882. Furthermore, miR-26a was stably detected in the plasma of GC patients with different clinical characteristics.Plasma miR-26a may provide a novel and stable marker of gastric cancer.

CyclinD proteins, the ultimate recipients of mitogenic and oncogenic signals, play a crucial role in cell-cycle regulation. CyclinD2, one of the cyclinD family, is overexpressed in T-acute lymphoblastic leukemia (ALL) and B-cell chronic lymphocytic leukemia and involved in the pathogenesis of leukemias. Recent reports indicated that CCND2 polymorphisms are associated with human cancer risk, thusly we hypothesized that CCND2 gene polymorphisms may contribute to childhood ALL susceptibility. We selected the polymorphism rs3217927 located in the 3'UTR region of CCND2 to assess its associations with childhood ALL risk in a case-control study. A significant difference was found in the genotype distributions of rs3217927 polymorphism between cases and controls (P = 0.019) and homozygous GG genotype may be an increased risk factor for childhood ALL (adjusted OR = 1.84, 95% CI = 1.14 -2.99). Furthermore, this increased risk was more pronounced with GG genotype among high-risk ALL (adjusted OR = 1.95, 95% CI = 1.04-3.67), low-risk ALL (adjusted OR = 2.09, 95% CI = 1.13-3.87), B-phenotype ALL patients (adjusted OR = 1.78, 95% CI = 1.08-2.95) and T-phenotype ALL patients (adjusted OR = 2.87, 95% CI = 1.16-7.13). Our results provide evidence that CCND2 polymorphism rs3217927 may be involved in the etiology of childhood ALL, and the GG genotype of rs3217927 may modulate the genetic susceptibility to childhood ALL in the Chinese population. Further functional studies and investigations in larger populations should be conducted to validate our findings.

BACKGROUND: A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population. METHODS: We examined the associations between rs7758229 and colorectal cancer risk among 1,147 cases and 1,203 controls matched by age and sex. Logistic regression model was used to assess the associations. RESULTS: No significant association was found between rs7758229 and colorectal cancer risk (OR = 0.95, 95%CI = 0.84-1.09, P = 0.463). Similar results were observed in the stratification of tumor location (OR = 0.94, 95%CI = 0.80-1.11, P = 0.481 for colon cancer, and OR = 0.96, 95%CI = 0.82-1.13, P = 0.621 for rectum cancer). CONCLUSIONS: Our findings did not support an association between rs7758229 in 6q26-q27 and the risk of colorectal cancer in a Chinese population.

PURPOSE:Recently, genetic polymorphism (rs3803662C>T) in TOX3 was reported to induce the risk of breast cancer. In this study, we hypothesized that rs3803662 could influence gastric cancer survival outcomes. METHODS:With multiplex SNaPshot method, we genotyped TOX3 rs3803662 in 880 gastric patients with surgical resection. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, Cox regression analysis models and the log-rank test. RESULTS:There was no association in the analyses of rs3803662 and survival of gastric cancer. However, the stratified analysis by histology showed that rs3803662 CT/TT genotype was associated with a significantly better survival for diffuse-type gastric cancer (log-rank p = 0.030, hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.46-0.96), than the CC genotype. In addition, this favorable effect was especially obvious among gastric cancer patients with tumor size >5 cm, T3 and T4 depth of invasion, lymph node metastasis, no drinking, no distant metastasis, no chemotherapy and gastric cardia cancer. CONCLUSIONS:TOX3 rs3803662 might play an important role in the prognostic outcome and treatment of gastric cancer, especially perhaps further help in explaining the reduced risk of death associated with diffuse-type gastric cancer.

PURPOSE: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate cell differentiation, proliferation, development, and apoptosis. The single nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR-27a. Here, we aimed to investigate whether SNP rs895819 was associated with the development of renal cell cancer (RCC) in a Chinese population. METHODS: In this case-control study, we recruited 594 RCC patients and 600 cancer-free controls with frequency matched by age and sex. We genotyped this polymorphism using the TaqMan assay and assessed the effect of this polymorphism on RCC survival. Logistic regression model was used to assess the genetic effects on the development of RCC and interactions between rs895819 polymorphism and risk factors. RESULTS: Compared with AA homozygote, individuals carrying AG/GG genotypes had a statistically significant reduced susceptibility to RCC (adjusted OR = 0.71, 95% CI = 0.56-0.90). Furthermore, AG/GG genotypes were associated with reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95% CI = 0.55-0.91), and similar effects were observed in well differentiated and poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55-0.93 for well differentiated, adjusted OR = 0.51, 95% CI = 0.28-0.93 for poorly differentiated). We also observed that rs895819 had multiplicative interactions with age and hypertension. However, the polymorphism did not influence the survival of RCC. CONCLUSION: Our results suggest that the pre-miR-27a rs895819 polymorphism can predict RCC risk in a Chinese population. Larger population-based prospective studies should be used to validate our findings.

BACKGROUND: Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 35 case-control studies was performed to address this issue. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with χ2-based Q-test. RESULTS: Overall, no significant associations between ADH1C Ile350Val polymorphism and cancer risk were observed in any genetic models (P>0.05). In the stratified analyses, there was a significantly increased cancer risk among African (Val/Val vs. Ile/Ile OR = 2.19, 95% CI = 1.29-3.73, P(heterogeneity) = 0.989; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.79, 95%CI = 1.18-2.71, P(heterogeneity) = 0.761; Val/Val vs. Ile/Val + Ile/Ile: OR = 1.92, 95% CI = 1.16-3.17, P(heterogeneity) = 0.981) and Asian (Ile/Val vs. Ile/Ile: OR = 1.58, 95% CI = 1.32-1.90, P(heterogeneity) = 0.375; Val/Val vs. Ile/Ile: OR = 3.84, 95% CI = 1.74-8.49, P(heterogeneity) = 0.160; Ile/Val + Val/Val vs. Ile/Ile: OR = 1.65, 95% CI = 1.38-1.96, P(heterogeneity) = 0.330; Val/Val vs. Ile/Val + Ile/Ile: OR = 3.54, 95% CI = 1.62-7.75, P(heterogeneity) = 0.154) studies. CONCLUSIONS: The results indicate that ADH1C Ile350Val polymorphism may contribute to cancer risk among Africans and Asians. Additional comprehensive system analyses are required to validate this association combined with other related polymorphisms.

The HOGG1 gene catalyzes the excision of modified bases and removal of DNA damage adducts. It may play an important role in the prevention of carcinogenesis. Ser³²⁶Cys polymorphism localizes in exon 7 of the hOGG1 gene. It takes the form of an amino acid substitution, from serine to cysteine, in codon 326. Several epidemiological association studies have been conducted on this polymorphism and its relationship with the risk of prostate cancer. However, results have been conflicting. To resolve this conflict, we conducted a meta-analysis on the association between this polymorphism and prostate cancer, taking into account race, country, sources of controls, and smoking status. A total of nine studies covering 2779 cases and 3484 controls were included in the current meta-analysis. Although no significant association was found between hOGG1 Ser³²⁶Cys polymorphism and prostate cancer susceptibility in the pooled analysis, individuals with Ser/Cys+Cys/Cys genotypes were found to have greater risk of prostate cancer if they were also smokers (OR = 2.66, 95% CI = 1.58-4.47) rather than non-smokers (OR = 2.18, 95% CI = 1.13-4.19), compared with those with Ser/Ser genotype. In conclusion, our meta-analysis demonstrates that hOGG1 Ser³²⁶Cys polymorphism is a risk factor for prostate cancer in smokers. Further studies are needed to confirm this relationship.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR=1.18, 95% CI=1.03-1.34, P