Estimation of pathological subtypes in subsolid lung nodules using artificial intelligence.

Objective: This study aimed to investigate the value of artificial intelligence (AI) for distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with subsolid nodules (SSNs). Materials and methods: This retrospective study included 110 consecutive patients with 120 SSNs. The qualitative and quantitative imaging characteristics of SSNs were extracted automatically using an artificially intelligent assessment system. Then, radiologists had to verify these characteristics again. We split all cases into two groups: non-IA including 11 Atypical adenomatous hyperplasia (AAH) and 25 adenocarcinoma in situ (AIS) or IA including 7 minimally invasive adenocarcinoma (MIA) and 77 invasive adenocarcinoma (IAC). Variables that exhibited statistically significant differences between the non-IA and IA in the univariate analysis were included in the multivariate logistic regression analysis. Receiver operating characteristic (ROC) analyses were conducted to determine the cut-off values and their diagnostic performances. Results: Multivariate logistic regression analysis showed that the major diameter (odds ratio [OR] = 1.38; 95 % confidence interval [CI], 1.02-1.87; P = 0.036) and entropy of three-dimensional(3D) CT value (OR = 3.73, 95 % CI, 1.13-2.33, P = 0.031) were independent risk factors for adenocarcinomas. The cut-off values of the major diameter and the entropy of 3D CT value for the diagnosis of invasive adenocarcinoma were 15.5 mm and 5.17, respectively. To improve the classification performance, we fused the major diameter and the entropy of 3D CT value as a combined model, and the (AUC） of the model was 0.868 (sensitivity = 0.845, specificity = 0.806). Conclusion: The major diameter and entropy of 3D CT value can distinguish non-IA from IA. AI can improve performance in distinguishing pathological subtypes of invasive pulmonary adenocarcinomas in patients with SSNs.

Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway.

Objective: Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs. Methods: MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis. Results: The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels. Conclusion: Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Exploring temporal trends and influencing factors for thyroid cancer in Guangzhou, China: 2004-2018.

PURPOSE: Describe and analyze the trends of thyroid cancer incidence and mortality in Guangzhou, explore the potential influencing factors, and provide evidence for the government to formulate prevention and treatment measures. METHODS: Incident and death cases of thyroid cancer were retrieved from the Guangzhou cancer registry. The joinpoint regression models were used to estimate the incidence and mortality trends. Age-period-cohort models were used to estimate the age, period, and cohort effects on the time trends. Grey correlation analysis was performed to explore possible connections between thyroid cancer and social factors. RESULTS: A total of 15,955 new cases of thyroid cancer were registered in Guangzhou during 2004-2018, the age-standardized incidence rate (ASIR) of thyroid cancer increased from 4.29/105 in 2004 to 22.36/105 in 2018, with the average annual percentage change (AAPC) of 13.40%. The overall increase can be attributed to the increase in the incidence of papillary thyroid carcinoma (PTC), which was dominated by tumors <2 cm. The ASIR was higher in women (16.12/105) compared to men (5.46/105), and young and middle-aged individuals had higher incidence rates than older people. The number of thyroid cancer deaths registered between 2010 and 2018 was 356, and the age-standardized mortality rates (ASMRs) were stable (approximately 0.42/105). Men's ASMR (0.34/105) and women's (0.49/105) were similar, and those 60 and older had greater mortality. The period and cohort relative risks showed an overall increasing trend. Furthermore, there was a strong positive correlation between the ASIRs and social determinants. CONCLUSIONS: During the study period, the incidence rate of thyroid cancer among young and middle-aged people in Guangzhou showed a rapidly increasing trend, and the mortality was relatively stable. In the future, more effective preventive measures should be taken for this age group to reduce the burden of disease and avoid overdiagnosis.

The effect of anlotinib on the pharmacokinetic profile of oxycodone and the underlying mechanism.

PURPOSE: Cancer patients experience pain during medical treatment. Therefore, anticancer drugs and painkillers are often prescribed together. This study aims to determine the interaction between anlotinib and oxycodone and reveal the underlying mechanism. METHODS: UPLC-MS/MS, an efficient and sensitive method, was used for the simultaneous determination of oxycodone and oxycodone metabolites. Sprague-Dawley rats were given oxycodone with or without anlotinib. Then, UPLC-MS/MS was used to determine the blood concentration of oxycodone. To study the interaction mechanism, rat and human liver microsomes (HLMs) were used for determining enzyme kinetics. RESULTS: Long-term administration of oxycodone combined with anlotinib resulted in significantly increased pharmacokinetic parameters AUC(0-t), AUC(0-∞), and Cmax for oxycodone, indicating that anlotinib inhibited oxycodone. In vitro kinetic measurements indicated that anlotinib inhibited the metabolism of oxycodone through a mixed mechanism. Further studies indicated that in HLMs, anlotinib strongly inhibited the metabolism of oxycodone. CONCLUSION: This study showed that anlotinib inhibited the metabolism of oxycodone both in vitro and in vivo. It is recommended that the dose of oxycodone should be reconsidered when oxycodone is combined with anlotinib in clinical practice.

Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study.

Purpose: Colorectal cancer (CRC) is the third-most frequently diagnosed cancer globally. Studies have linked low serum albumin with increased risk of CRC, but the causal nature of the association remains unclear. In the present study, we explored the potential causal relationship using bidirectional Mendelian randomization (MR). Methods: Instrumental variants for albumin were obtained from a genome-wide association study (GWAS) on 102,223 Eastern Asian participants to investigate the effect of albumin on CRC. Summary statistics of CRC were obtained from a GWAS on 7,062 CRC cases and 195,745 controls of Eastern Asian ancestry. Bidirectional MR analysis was performed using inverse variance weighting (IVW) for primary analysis, supplemented with a maximum likelihood-based method, MR-PRESSO test, leave-one-out analysis, and MR-Egger regression. Stratification analyses were further performed. Results: We found that genetically predicted serum albumin per unit was associated with a lower risk of CRC (OR 0.75, 95% CI 0.59-0.95 with IVW). No evidence of pleiotropy was observed. Sex-stratified MR analysis showed that serum albumin was inversely associated with risk of CRC in men (OR 0.71, 95% CI 0.53-0.96), but not in women (OR 0.81, 95% CI 0.55-1.19) using IVW. Reverse MR analysis suggested a genetic predisposition toward CRC was not associated with serum albumin. Conclusion: Our study revealed a suggestive sex disparity in the effect of albumin, which deserves further exploration of the potential biological mechanism.

Melanin-gelatin nanoparticles with both EPR effect and renal clearance for PA/MRI dual-modal imaging of tumors.

As cancer nanotherapeutics, the ideal multifunctional nanoparticles not only have the processing ability to accumulate effectively in tumors, but also can be excreted rapidly from the body via renal clearance after effective treatment. Melanin is an endogenous biological material, and gelatin has natural biocompatibility and biodegradability. Such materials are more promising in the development of diagnostic and therapeutic nanoplatform for future clinical translation. In this study, we have developed a kind of size-shrinkable PA/MRI theranostic agent based on gelatin fabricated ultrasmall melanin nanoparticles (MNPs-GNP). The MNPs-GNP nanoparticles, with a size of about 100 nm, presented good dispersibility, broadband light absorbance, negligible cellular cytotoxicity, preferable tumor accumulation by EPR-based passive targeting. The dual-modal imaging results showed that the nanoparticles have excellent photoacoustic (PA) imaging and nuclear magnetic resonance (MRI) imaging after tumor-bearing mice were intravenously injected with MNPs-GNP. Additionally, gelatin is the substrate of matrix metalloproteinase-2 (MMP-2), following with the degradation of gelatin nanoparticles by MMP-2, the large-size MNPs-GNP turns to be small-size melanin, which could mainly be excreted via renal clearance avoiding potential toxicity to body tissues. These preliminary results indicated that MNPs-GNP can overcome the dilemma between EPR and renal clearance, which has clinical application potentiality as a PA/MRI dual-modal candidate agent for cancer theranostics.

Discovery of Novel 2,4-Dianilinopyrimidine Derivatives Containing 4-(Morpholinomethyl)phenyl and N-Substituted Benzamides as Potential FAK Inhibitors and Anticancer Agents.

Focal adhesion kinase (FAK) is responsible for the development and progression of various malignancies. With the aim to explore novel FAK inhibitors as anticancer agents, a series of 2,4-dianilinopyrimidine derivatives 8a-8i and 9a-9g containing 4-(morpholinomethyl)phenyl and N-substituted benzamides have been designed and synthesized. Among them, compound 8a displayed potent anti-FAK activity (IC50 = 0.047 ± 0.006 µM) and selective antiproliferative effects against H1975 (IC50 = 0.044 ± 0.011 µM) and A431 cells (IC50 = 0.119 ± 0.036 µM). Furthermore, compound 8a also induced apoptosis in a dose-dependent manner, arresting the cells in S/G2 phase and inhibiting the migration of H1975 cells, all of which were superior to those of TAE226. The docking analysis of compound 8a was performed to elucidate its possible binding modes with FAK. These results established 8a as our lead compound to be further investigated as a potential FAK inhibitor and anticancer agent.

MicroRNA-214-5p protects against myocardial ischemia reperfusion injury through targeting the FAS ligand.

INTRODUCTION: MicroRNAs (miRNAs) are considered as crucial modulators in myocardial ischemia and reperfusion (I/R) injury. The present study aimed to investigate the expression and biological functions of miR-214-5p via targeting Fas ligand (FASLG) in I/R injury. MATERIAL AND METHODS: Lactate dehydrogenase, casein kinase, malondialdehyde assay, reactive oxygen species (ROS) detection and cell apoptosis analysis measured cell damage and cell apoptosis in H9c2 cells under hypoxia/reperfusion (H/R) treatment. Bioinformatics and dual luciferase reporter assays demonstrated the molecular mechanism of miR-214-5p in cardiac cells. 2,3,5-Triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining and adenovirus injection were performed in I/R treated mice. RESULTS: The expression of miR-214-5p was decreased in H/R injured H9c2 cells compared with control cells (p < 0.001). Overexpression of miR-214-5p reduced cell damage and apoptosis in H9c2 cells under H/R treatment (p < 0.001). Further study revealed that FASLG was a target of miR-214-5p. Enhanced expression of FASLG attenuated the protective function of miR-214-5p in H9c2 cells subjected to H/R injury (P < 0.001). Moreover, the elevated expression of miR-214-5p by adenovirus injection protected cardiac cells from I/R injury in mice (n = 6/per group). CONCLUSIONS: We found that miR-214-5p exerted a protective role in I/R injured cardiac cells by direct targeting FASLG in vitro and in vivo.

Hybrids of Quinoline and Anilinopyrimidine: Novel EGFRT790M Inhibitors with Antiproliferative Activity against Non-Small Cell Lung Cancer Cell Lines.

BACKGROUND: The third-generation irreversible Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) inhibit the T790M mutation while sparing EGFRWT. However, the C797S point mutation confers resistance to existing irreversible EGFRT790M inhibitors. OBJECTIVE: Novel EGFRT790M inhibitors were designed through hybridization of quinoline and anilinopyrimidine, and biologically evaluated their antiproliferative activity against Non-Small Cell Lung Cancer (NSCLC) cell lines. METHODS: The target compounds 11a-h were synthesized and structurally characterized with 1H, 13C Nuclear Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). Their inhibitory effects on tumor cell proliferation and EGFR kinase were biologically evaluated. Additionally, molecular docking studies were also performed on the representative typical EGFRT790M inhibitor. RESULTS: Most of the evaluated compounds displayed moderate antiproliferative activity on H1975 cells with EGFRL858R/T790M. However, compound 11a (IC50 = 2.235 ± 0.565µM) showed stronger inhibition than gefitinib (IC50 = 8.830 ± 0.495µM) in concentration- and time-dependent manner. Moreover, compound 11a exhibited weaker inhibitory activities on cells with EGFRWT. Specifically, compound 11a strongly suppressed EGFRL858R/T790M (IC50 = 0.515 ± 0.011µM) relative to EGFRWT (IC50 = 0.913 ± 0.068µM). Furthermore, molecular docking studies demonstrated its strong binding contacts with the EGFRT790M enzyme through hydrogen bonds and other non-bonded interactions. CONCLUSION: Taken together, these results indicate that the hybrid of quinoline and anilinopyrimidine 11a, could be a potential inhibitor of EGFRT790M in NSCLC, which warrants further in-depth studies.

Resveratrol Inhibits the TGF-ß1-Induced Proliferation of Cardiac Fibroblasts and Collagen Secretion by Downregulating miR-17 in Rat.

Myocardial fibrosis (MF) can cause heart remodeling and it is an independent risk factor for malignant arrhythmias, sudden cardiac death, and other malignant cardiovascular events. It is often characterized by myocardial interstitial collagen deposition and hyperproliferation of cardiac fibroblasts (CFs). The transforming growth factor-ß1 (TGF-ß1) is the most influential profibrogenic factor. Resveratrol (RSV) is an active polyphenol substance that inhibits myocardial fibrosis. The mechanism of RSV-mediated inhibition of the proliferation of CFs at the microRNA level is not fully understood. We used TGF-ß1 to induce CFs proliferation to simulate the pathogenesis of myocardial fibrosis. Neonatal rat CFs were treated with TGF-ß1 in the presence or absence of resveratrol. Cell proliferation was measured using the CCK-8 and EdU assay. Collagen secretion was measured using hydroxyproline kit. Further, qPCR analysis was performed to determine microRNA levels after TGF-ß1 or resveratrol treatment. To identify the target gene for miR-17, miR-17 was overexpressed or silenced, and the mRNA and protein levels of Smad7 were assessed. The effects of miR-17 silencing or Smad7 overexpression on cell proliferation and collagen secretion were also examined. Resveratrol treatment significantly decreased the TGF-ß1-induced CF proliferation and collagen secretion. Resveratrol also decreased the levels of miR-17, miR-34a, and miR-181a in TGF-ß1-treated CFs. Overexpression of miR-17 decreased the Smad7 mRNA and protein levels while silencing miR-17 increased them. Additionally, silencing miR-17 or overexpressing Smad7 decreased the TGF-ß1-induced CFs proliferation and collagen secretion. In conclusion, resveratrol inhibits TGF-ß1-induced CFs proliferation and collagen secretion. This inhibitory effect of resveratrol is orchestrated by the downregulation of miR-17 and the regulation of Smad7.

Vincristine liposomes with smaller particle size have stronger diffusion ability in tumor and improve tumor accumulation of vincristine significantly.

The passive targeting is the premise of active targeting that could make nanocarrier detained in tumor tissue. The particle size is the most important factor that influences the diffusion and distribution of nanoparticle both in vivo and in vitro. In order to investigate the relationship between particle size and diffusion ability, two kinds of liposome loaded with Vincristine (VCR-Lip) were prepared. The diffusion behavior of VCR-Lip with different particle size and free VCR was compared through diffusion stability study. The diffusion ability from 12-well culture plate to Millipore transwell of each formulation reflected on HepG-2 cytotoxicity results. Different cell placement methods and drug adding positions were used to study the VCR-Lip diffusion behaviors, which influenced the apoptosis of HepG-2 cell. The different cell uptake of Nile red-Lip and free Nile red was compared when changed the adding way of fluorescent fluorescein. To study the penetration ability in HepG-2 tumor spheroids, we constructed 30 nm and 100 nm Cy5.5-Lip to compare with free Cy5.5. Then the anti-tumor effect, tissue distribution of free VCR injection, 30 nm and 100 nm VCR-Lip were further investigated on the HepG-2 tumor bearing nude mice. The results of these study showed that the diffusion ability of free drug and fluorescent fluorescein was remarkable stronger than which encapsulated in liposomes. Moreover, diffusion ability of smaller liposome was stronger than larger one. In this way, 30 nm liposome had not only faster and stronger tumor distribution than 100 nm liposome, but also higher tumor drug accumulation than free drug as well. Our study provided a new thinking to improve the targeting efficiency of nano drug delivery system, no matter passive or active targeting.

Dual Tumor-Targeting Nanocarrier System for siRNA Delivery Based on pRNA and Modified Chitosan.

Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size. To certify the delivering efficiency of this dual system, CNPPs, pRNA dimers alone, chitosan nanoparticles containing siRNA with folate conjugation and PEGylation (CNPS), and chitosan nanoparticles containing pRNA dimers alone (CN) were first prepared. Then, we observed that treatment with CNPPs resulted in increased cellular uptake, higher cell apoptosis, stronger cell cytotoxicity, and more efficacious gene silencing compared to the other three formulations. Higher accumulation of siRNA in the tumor site, stronger tumor inhibition, and longer circulating time were also observed with CNPPs compared to other formulations. In conclusion, this dual nanocarrier system showed high targeting and favorable therapeutic efficacy both in vitro and in vivo. Thereby, a new approach is provided in this study for specific and efficient delivery of siRNA, which lays a foundation for the development of pRNA hexamers, which can simultaneously carry six different substances.

Gene polymorphisms related to insulin resistance and gene-environment interaction in colorectal cancer risk.

BACKGROUND AND AIM: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC) and both IR and CRC physiologically overlap. As such, this study explored the relationship of IR-related gene polymorphisms and CRC risk. SUBJECTS AND METHODS: A total of 400 case-control pairs were profiled in terms of their lifestyle, dietary habits and blood sample. Classification and regression tree (CART) and generalized multi-factor dimensionality reduction (GMDR) were employed to test the gene-environment interactions in CRC risk. RESULTS: ADIPOQ rs2241766 TG + GG, ADIPOQ rs1501299 GT + TT and CAPN-10 rs3792267 GA + AA were significantly related to CRC risk. In CART, individuals with high red meat consumption, CAPN-10 rs3792267 GG, ADIPOQ rs1501299 GG and ADIPOQ rs2241766 TG + GG had an OR of 1.821 (95% CI = 1.124-2.951). The overall best GMDR model including the four factors had the maximal TBA (0.5943) and CVC (10/10) (p = 0.0010). Subjects with high red meat consumption and the three risk genotypes had a CRC risk 10.195-times (95% CI = 2.164-48.030) greater than those with low red meat and null risk genotypes. CONCLUSIONS: ADIPOQ rs2241766, ADIPOQ rs1501299 and CAPN-10 rs3792267 are significantly associated with CRC risk and the combination of the three polymorphisms and red meat affect CRC risk.

[Association between adiponectin rs2241766, rs1501299 polymorphisms and the risk of colorectal cancer].

OBJECTIVE: To explore the association between adiponectin rs2241766, rs1501299 polymorphisms and gene-environment interaction and the risk of colorectal cancer(CRC). METHODS: Four hundred CRC patients confirmed by histopathology and 400 healthy controls were recruited in this study. Cases and controls were matched on age and gender. A well-designed questionnaire was used to collect the information of demography, lifestyle and dietary habit on the 400 case-control pairs. Polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)was applied to detect the adiponectin rs2241766 and rs1501299 genotypes. RESULTS: Data from conditional logistic regression analysis showed that those carrying TG+GG genotype on rs2241766 having an increased risk compared to those that carrying TT genotype(OR = 1.354, 95%CI:1.004-1.827), and those that carrying GT+TT genotype on rs1501299 having an decreased risk when compared to those that carrying GG genotype(OR = 0.680, 95% CI:0.501-0.923), after adjusted by factors as CRC family history,BMI, sedentary time, red meat consumption, and tea-drinking habit. Data from generalized multifactor dimensionality reduction showed that the gene-environment interaction among rs2241766, rs1501299 and red meat consumption on the risk of CRC might be significant(P = 0.001). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (χ(2) = 8.458, P = 0.004). CONCLUSION: Both adiponectin rs2241766 and rs1501299 were associated with CRC risk and the two SNPs might have worked together with red meat consumption in affecting the CRC risk.

Calpain-10 SNP43 and SNP19 polymorphisms and colorectal cancer: a matched case-control study.

OBJECTIVE: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given that CRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored the association between CAPN10 and CRC risk. METHODS: Blood samples of 400 case-control pairs were genotyped, and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression (LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalized multifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to test gene-environment interactions for CRC risk. RESULTS: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Ins genotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/ Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDR and CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, and smoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testing balance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two risk genotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smoked meat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption, SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than those with low smoked and red meat consumption. CONCLUSIONS: Though the single loci of CAPN10 SNP43 and SNP19 are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meat consumption, and smoked meat consumption is associated with elevated risk.

Mitochondrial common deletion, a potential biomarker for cancer occurrence, is selected against in cancer background: a meta-analysis of 38 studies.

Mitochondrial dysfunction has been long proposed to play a major role in tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp deletion has been found in patients of various types of cancer. In order to comprehend the mtDNA 4,977 bp deletion status in various cancer types, we performed a meta-analysis composed of 33 publications, in which a total of 1613 cancer cases, 1516 adjacent normals and 638 healthy controls were included. When all studies were pooled, we found that cancerous tissue carried a lower mtDNA 4,977 bp deletion frequency than adjacent non-cancerous tissue (OR = 0.43, 95% CI = 0.20-0.92, P = 0.03 for heterogeneity test, I(2) = 91.5%) among various types of cancer. In the stratified analysis by cancer type the deletion frequency was even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR = 0.19, 95% CI = 0.06-0.61, P = 0.005 for heterogeneity test, I(2)= 82.7%). Interestingly, this observation became more significant in the stratified studies with larger sample sizes (OR = 0.70, 95% CI = 0.58-0.86, P = 0.0005 for heterogeneity test, I(2) = 95.1%). Furthermore, when compared with the normal tissue from the matched healthy controls, increased deletion frequencies were observed in both adjacent non-cancerous tissue (OR = 3.02, 95% CI = 2.13-4.28, P<0.00001 for heterogeneity test, I(2)= 53.7%), and cancerous tissue (OR = 1.36, 95% CI = 1.04-1.77, P = 0.02 for heterogeneity test, I(2)= 83.5%). This meta-analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous tissue and thus has the potential to be a biomarker for cancer occurrence in the tissue, but at the same time being selected against in various types of carcinoma tissues. Larger and better-designed studies are still warranted to confirm these findings.

Gene Polymorphisms of ADIPOQ +45T>G, UCP2 -866G>A, and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study.

As insulin resistance (IR) is an established risk factor for colorectal cancer (CRC), we explored the association between each of the IR-related gene polymorphisms of adiponectin (ADIPOQ) rs2241766, uncoupling protein 2 (UCP2) rs659366, and fatty acid-binding protein (FABP2) rs1799883 and CRC risk. Genotyping of blood samples and collection of lifestyle and dietary habits were performed for 400 case-control pairs. Unconditional logistic regression (ULR) was applied to assess the effects of the three single nucleotide polymorphisms (SNP), environmental factors. Both ULR and generalized multifactor dimensionality reduction (GMDR) were used to test the gene-gene and gene-environment interactions on CRC risk. Subjects carrying the ADIPOQ rs2241766 TG+GG genotype had a higher CRC risk than those carrying the TT genotype (OR = 1.429, 95% CI 1.069-1.909). The additive and multiplicative interactions between ADIPOQ rs2241766 and FABP2 rs1799883 on CRC were found by ULR (RERI = 0.764, 95%CI 0.218∼1.311, AP = 0.514, 95%CI 0.165∼0.864, S = -1.745, 95%CI is unachievable, and Pmulti = 0.017, respectively). Furthermore, the high order gene-gene interaction of the three SNPs were found by GMDR (P = 0.0107). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (Ptrend = 0.037). In GMDR, the gene-environment interaction among the three SNPs and red meat consumption on CRC risk was significant (P = 0.0107). Compared with subjects with low red meat consumption and null risk genotypes, those with high-red meat consumption and three risk genotypes had 3.439-fold CRC risk (95% CI 1.410-8.385). In conclusion, the results showed that the ADIPOQ rs2241766 TG+GG genotype increased CRC risk. Given the complexity of the carcinogen for CRC, ADIPOQ rs2241766, UCP2 rs659366, FABP2 rs1799883 and red meat consumption potentially worked together in affecting CRC risk.

catena-Poly[[[dipyridine-copper(II)]-µ-2,3,5,6-tetra-methyl-benzene-1,4-di-carboxyl-ato] monohydrate].

In the title complex, {[Cu(C(12)H(12)O(4))(C(5)H(5)N)(2)]·H(2)O}(n), the Cu(II) ion lies on an inversion center and is coordinated by two O atoms from two 2,3,5,6-tetra-methyl-benzene-1,4-dicarboxyl-ate (TBDC) ligands and two N atoms from two pyridine ligands in a slightly distorted square-planar environment. The TBDC ligands act as bridging ligands, forming chains along [110]. These chains are further linked into a two-dimensional network via inter-molecular O-H⋯O hydrogen bonds. The solvent water mol-ecule lies on a twofold rotation axis.

Changes of microvascular vasomotion and oxygen metabolism during cooling and rewarming period of cardiopulmonary bypass.

Microcirculation plays an important role in keeping a stable tissue metabolism during cardiopulmonary bypass (CPB). The relationship between microvascular vasomotion (MV) and total body's oxygen metabolism with temperature alteration during CPB remains unclear. Is there a relationship, or is the autoregulation a consequence of CO2, pressure and/or blood flow? The purpose of this study was to investigate the effect of temperature alteration on cutaneous MV and the total body's oxygen metabolism during CPB. Sixteen consecutive patients scheduled for elective cardiac valve replacement surgery were included in this study. The pump flow varied from 1.8-3.0 L/m(-2)min(-1) to maintain venous oxygen saturation above 65% and mean arterial blood pressure above 60 mmHg. At a nasopharyngeal temperature of 30 degrees C, oxygen consumption (VO2) and oxygen extraction (O2 ext) were measured during the cooling and rewarming periods. MV and skin microcircular flow (SMF) were monitored dynamically at the middle of two sides of the eyebrow with a laser Doppler flowmeter simultaneously VO2 and O2 ext at 30 degrees C were significantly lower during the cooling period (VO2, 49.9 +/- 17.7 mL/m(-2)/min(-1); O2 ext, 19.3 +/- 6.2%) than that during the rewarming period (VO2, 133.3 +/- 40.0 mL/m(-2)/min(-1); O2 ext, 35.2 +/- 9.2%) (p < .05). SMF was significantly depressed during CPB (p < .05). SMF during the cooling period (50.2% +/- 10.1%) was significantly less than that during the rewarming period (79.5% +/- 12.3%) (p < .05). MV was significantly less active during CPB than that before CPB (5.8 +/- 1.2 cyc/min) (p < .05), whereas there was no significant difference in MV between the cooling (3.7 +/- 1.8 cyc/min) and the rewarming period (4.1 +/- 1.5 cyc/min) and (p > .05). SMF and MV were depressed during hypothermic CPB, and there was some recovery during the rewarming period. Compared to baseline, SMF and MV were still significantly reduced during the warming period, indicating microvascular function was abnormal. Some measures should be taken for improvement of microvascular function during CPB.