Reduction of cardiovascular complications during delivery hospitalization in patients undergoing bariatric procedures.

BACKGROUND: The global surge in obesity presents a significant health challenge, leading to increased adoption of bariatric surgery as an intervention. However, the correlation between bariatric surgery and cardiovascular outcomes during subsequent pregnancies remains unclear. The aim of our study was to determine the prevalence of cardiovascular complications during delivery hospitalizations in patients with bariatric procedure. METHODS: We performed a retrospective analysis utilizing the National Inpatient Sample database to examine data from delivery admissions of pregnant women with obesity and a history of bariatric surgery. These admissions were identified using International Classification of Diseases (ICD) codes from 2009 to 2019. In comparing pregnant individuals who had undergone bariatric surgery with those with obesity but had no such surgical history, we assessed the prevalence of cardiovascular complications. RESULTS: Our study included 3,027,987 pregnancies in individuals with obesity and an additional 117,350 pregnancies following bariatric surgery. Compared to patients without bariatric surgery, post-surgery patients were older (32.84 years vs 29.02 years), primarily White (59.0%), and mostly treated in large urban hospitals. Cardiovascular outcomes showcased reduced odds of congestive heart failure [Adjusted odds ratios (AOR) 0.11, 95% confidence intervals (CI) 0.01-0.74], gestational hypertensive complications (AOR 0.55, 95% CI 0.53-0.59), and cardiac arrhythmia (AOR 0.76, 95% CI 0.64-0.89) in the post-surgery group, with no significant difference in peripartum cardiomyopathy rates (AOR 0.72, 95% CI 0.29-1.76) and no instances of stroke or acute MI. Perinatally, the surgery cohort had higher odds of preterm birth (AOR 1.30, 95% CI 1.24-1.38) and fetal growth restriction (AOR 2.47, 95% CI 2.32-2.63) but fewer incidents of being large for gestational-age (AOR 0.35, 95% CI 0.32-0.38). As bariatric surgery became increasingly recognized as a significant factor in certain complications, its prevalence among the study population increased from 2009 to 2019. CONCLUSION: In summary, our research indicates that bariatric surgery is associated with a decreased risk of cardiovascular complications during delivery. This study highlights how insights from bariatric surgery outcomes could shape clinical guidelines for managing obesity in pregnant women.

Production of azimuthally polarized beam with helical phase by use of the axicons and annular glass cylinder.

In this paper, we proposed a method for producing the azimuthally polarized vector beam experimentally. The experimental setup includes two of the same axicons and one annular glass cylinder. The top angles of the two axicons were placed facing each other and the annular cylinder was set among the two axicons. One circular polarized beam was passed through the first axicon, the annular cylinder, and the second axicon in turn. When the beam incident on the inner surface of the annular cylindrical satisfied the Brewster angle, we obtained the azimuthally polarized beam for the reflected light from the annular cylindrical that only contains the $s$s-polarization component. We have derived that the azimuthally polarized vector beam has the helical phase factor with the helical phase factor of ${\exp}( - {\rm i}\varphi )$exp(-iφ) for the left circularly polarized beam incident and ${\exp}({\rm i}\varphi )$exp(iφ) for the right circularly polarized beam incident.

Genome-wide identification of cancer-specific alternative splicing in circRNA.

Circular RNA (circRNA) is a group of RNA families generated by RNA circularization, which was discovered ubiquitously across different cancers. However, the internal structure of circRNA is difficult to determine due to alternative splicing that occurs in its exons and introns. Furthermore, cancer-specific alternative splicing of circRNA is less likely to be identified. Here, we proposed a de novo algorithm, CircSplice, that could identify internal alternative splicing in circRNA and compare differential circRNA splicing events between different conditions ( http://gb.whu.edu.cn/CircSplice or https://github.com/GeneFeng/CircSplice ). By applying CircSplice in clear cell renal cell carcinoma and bladder cancer, we detected 4498 and 2977 circRNA alternative splicing (circ-AS) events in the two datasets respectively and confirmed the expression of circ-AS events by RT-PCR. We further inspected the distributions and patterns of circ-AS in cancer and adjacent normal tissues. To further understand the potential functions of cancer-specific circ-AS, we classified those events into tumor suppressors and oncogenes and performed pathway enrichment analysis. This study is the first comprehensive view of cancer-specific circRNA alternative splicing, which could contribute significantly to regulation and functional research of circRNAs in cancers.

Generation of propagation-invariant vector beams with square array by use of 2D binary phase mask and pentagonal prism.

In this paper, we realize the generation of propagation-invariant vector beams with square array by use of a 2D binary phase mask and pentagonal prism in a typical Mach-Zehnder optical system. The binary phase mask set in the optical system is perpendicular to the optical axis, and its periodic orientation is 45° relative to the horizontal and vertical directions. One polarizer was used to produce the linearly polarized beam with the angle of 45° relative to the horizontal and vertical directions. One mirror in the Mach-Zehnder optical system was replaced by a pentagonal prism, as the light will be reflected twice inside the pentagonal prism. The intensity distribution of the two branches with the mirror and pentagonal prism have mirror symmetry, and the output optical field of the two branches has an orthogonal polarization state. By adjusting the position of the phase plate accordingly, the total optical field of the two branches can form a vector beam with a square array. The experimental results coincide with the simulation results very well and demonstrate the feasibility of this method.

Nanopore back titration analysis of dipicolinic acid.

Here, we report a novel label-free nanopore back titration method for the detection of dipicolinic acid, a marker molecule for bacterial spores. By competitive binding of the target analyte and a large ligand probe to metal ions, dipicolinic acid could be sensitively and selectively detected. This nanopore back titration approach should find useful applications in the detection of other species of medical, biological, or environmental importance if their direct detection is difficult to achieve.

Nanopore stochastic detection: diversity, sensitivity, and beyond.

Nanopore sensors have emerged as a label-free and amplification-free technique for measuring single molecules. First proposed in the mid-1990s, nanopore detection takes advantage of the ionic current modulations produced by the passage of target analytes through a single nanopore at a fixed applied potential. Over the last 15 years, these nanoscale pores have been used to sequence DNA, to study covalent and non-covalent bonding interactions, to investigate biomolecular folding and unfolding, and for other applications. A major issue in the application of nanopore sensors is the rapid transport of target analyte molecules through the nanopore. Current recording techniques do not always accurately detect these rapid events. Therefore, researchers have looked for methods that slow molecular and ionic transport. Thus far, several strategies can improve the resolution and sensitivity of nanopore sensors including variation of the experimental conditions, use of a host compound, and modification of the analyte molecule and the nanopore sensor. In this Account, we highlight our recent research efforts that have focused on applications of nanopore sensors including the differentiation of chiral molecules, the study of enzyme kinetics, and the determination of sample purity and composition. Then we summarize our efforts to regulate molecular transport. We show that the introduction of various surface functional groups such as hydrophobic, aromatic, positively charged, and negatively charged residues in the nanopore interior, an increase in the ionic strength of the electrolyte solution, and the use of ionic liquid solutions as the electrolyte instead of inorganic salts may improve the resolution and sensitivity of nanopore stochastic sensors. Our experiments also demonstrate that the introduction of multiple functional groups into a single nanopore and the development of a pattern-recognition nanopore sensor array could further enhance sensor resolution. Although we have demonstrated the feasibility of nanopore sensors for various applications, challenges remain before nanopore sensing is deployed for routine use in applications such as medical diagnosis, homeland security, pharmaceutical screening, and environmental monitoring.

Generation of arbitrary vector beams with cascaded liquid crystal spatial light modulators.

A flexible approach is presented to generate vector beams with arbitrary polarization and complex amplitude by means of two cascaded transmissive liquid crystal spatial light modulators (LCSLMs). The configuration of the cascaded LCSLM system and its modulation characteristic are introduced. Theoretical analysis and experimental demonstration prove that the system in combination with a double-pass computer-generated hologram and a black-and-white pattern can generate vector beams with arbitrary polarization and complex amplitude by respectively controlling the complex amplitudes of two orthogonal polarization components of the beams. Using this system, we successfully generate radially polarized vector beams with helical phase distributions and vector Bessel beams with inhomogeneous amplitude distributions in experiments.

Decoding the biology and clinical implication of neutrophils in intracranial aneurysm.

OBJECTIVE: Abundant neutrophils have been identified in both ruptured and unruptured intracranial aneurysm (IA) domes, with their function and clinical implication being poorly characterized. MATERIALS AND METHODS: We employed single-cell RNA sequencing (scRNA-Seq) datasets of both human and murine model, and external bulk mRNA sequencing datasets to thoroughly explore the features and functional heterogeneous of neutrophils infiltrating the IA dome. RESULTS: We found that both unruptured and ruptured IA dome contain a substantial population of neutrophils, characterized by FCGR3B, G0S2, CSF3R, and CXCR2. These cells exhibited heterogeneity in terms of function and differentiation. Despite similar transcriptional activation, neutrophils in IA dome expressed a repertoire of gene programs that mimicked transcriptomic alterations observed from bone marrow to peripheral blood, showing self-similarity. In addition, the recruitment of neutrophils in unruptured IA was primarily mediated by monocytes/macrophages, and once ruptured, both neutrophils, and a specific subset of inflammatory smooth muscle cells (SMCs) were involved in the process. The receiver operator characteristic curve (ROC) analysis indicated that distinct neutrophil subclusters were associated with IA formation and rupture, respectively. By reviewing current studies, we found that neutrophils play a detrimental role to IA wall integrity through secreting specific ligands, ferroptosis driven by ALOX5AP and PTGS2, and the formation of neutrophil extracellular traps (NETs) mediated by PADI4. INTERPRETATION: This study delineated the biology and potential clinical implications of neutrophils in IA dome and provided a reliable basis for future researches.

Red and processed meat intake and risk of esophageal adenocarcinoma: a meta-analysis of observational studies.

AIMS: Inconsistent results relating dietary red and processed meat intake and risk of esophageal adenocarcinoma (EAC) have been reported. This article summarizes and quantifies the current evidence in a meta-analysis of observational studies. METHODS: Electronic search of MEDLINE and EMBASE databases was performed to identify peer-reviewed manuscripts up to 31 May 2012. Random-effects models were used to pool study results. RESULTS: Ten manuscripts from 3 cohort studies and 7 case-control studies were identified. The summary relative risks (SRRs) of EAC for highest versus lowest intake categories were 1.31 (95 % confidence intervals [CIs]: 1.05-1.64) for red meat consumption, and 1.41 (95 % CIs 1.09-1.83) for processed meat consumption. Subgroup analyses indicated that these positive relations were seen in case-control studies, but not in cohort studies. Based on dose-response analysis, similar results were found; the SRRs were 1.45(95 % CIs 1.09-1.93) per 100 g/day of red meat intake and 1.37 (95 % CIs 1.03-1.81) per 50 g/day of processed meat intake. CONCLUSIONS: The results of this meta-analysis indicate that consumption of red and processed meat may be associated with increased risk of esophageal adenocarcinoma. More studies, particularly prospective studies, are needed.

Radial Hilbert transform with the spatially variable half-wave plate.

We analyzed the point spread function (PSF) of the typical 4f optical image processing system by use of a spatially variable half-wave plate as the spatial filter and found that the PSF is an elementary vector beam. Theoretical analysis and real experiments show that the optical system can be used for a radially symmetric Hilbert transform that permits two-dimensional edge enhancement as the spiral phase plate. This kind of radial Hilbert transform is useful for image processing because it can enhance the edges of an input image selectively by exerting a polarization analyzer before the output plane. The optical system also can be used for generation of vector beams with arbitrary array and shape in real time conveniently.

Maternal and perinatal outcomes of pregnant patients with colorectal cancer: a population-based study.

PURPOSE: This study aimed to investigate the maternal and perinatal outcomes of pregnant patients with CRC using a large population-based database. METHODS: A retrospective cohort study was conducted using the Nationwide Inpatient Sample (NIS) from 2009 to 2019. Pregnant patients with and without CRC were compared for demographic characteristics, comorbidities, maternal and perinatal outcomes, and hospital burden. RESULTS: The study included 306 pregnancies with CRC and 40,887,353 pregnancies without CRC. Pregnant patients with CRC were older and more likely to be White. A significant association was observed between CRC and a history of inflammatory bowel disease or a family history of gastrointestinal cancer. Pregnant patients with CRC had higher odds of maternal death (AOR 260.99, 95% CI 33.36-2041.64), cardiac arrhythmia (AOR 13.73, 95% CI 4.21-44.76), acute kidney injury (AOR 32.6, 95% CI 5.29-200.77), severe sepsis (AOR 163.98, 95% CI 22.05-1219.65), and respiratory failure (AOR 31.67, 95% CI 4.11-243.98). Furthermore, the CRC group experienced higher odds of cesarean section (AOR 1.78, 95% CI 1.05-3.03), preterm birth (AOR 4.16, 95% CI 2.05-8.47), and intrauterine death (AOR 13.18, 95% CI 3.33-52.16). Distinct differences in maternal and perinatal outcomes were observed based on the location of CRC. Pregnant patients with CRC faced higher hospital charges and had longer hospital stays during delivery hospitalization compared to those without CRC. CONCLUSION: Pregnant patients with CRC are at increased risk for adverse maternal and perinatal outcomes, emphasizing the importance of early detection, timely intervention, and comprehensive management during pregnancy.

Classification models for Tobacco Mosaic Virus and Potato Virus Y using hyperspectral and machine learning techniques.

Tobacco Mosaic Virus (TMV) and Potato Virus Y (PVY) pose significant threats to crop production. Non-destructive and accurate surveillance is crucial to effective disease control. In this study, we propose the adoption of hyperspectral and machine learning technologies to discern the type and severity of tobacco leaves affected by PVY and TMV infection. Initially, we applied three preprocessing methods - Multivariate Scattering Correction (MSC), Standard Normal Variate (SNV), and Savitzky-Golay smoothing filter (SavGol) - to corrected the leaf full-length spectral sheet data (350-2500nm). Subsequently, we employed two classifiers, support vector machine (SVM) and random forest (RF), to establish supervised classification models, including binary classification models (healthy/diseased leaves or PVY/TMV infected leaves) and six-class classification models (healthy and various severity levels of diseased leaves). Based on the core evaluation index, our models achieved accuracies in the range of 91-100% in the binary classification. In general, SVM demonstrated superior performance compared to RF in distinguishing leaves infected with PVY and TMV. Different combinations of preprocessing methods and classifiers have distinct capabilities in the six-class classification. Notably, SavGol united with SVM gave an excellent performance in the identification of different PVY severity levels with 98.1% average precision, and also achieved a high recognition rate (96.2%) in the different TMV severity level classifications. The results further highlighted that the effective wavelengths captured by SVM, 700nm and 1800nm, would be valuable for estimating disease severity levels. Our study underscores the efficacy of integrating hyperspectral technology and machine learning, showcasing their potential for accurate and non-destructive monitoring of plant viral diseases.

Preoperative Cyfra21-1 and SCC-Ag serum titers predict survival in patients with stage II esophageal squamous cell carcinoma.

BACKGROUND: The purpose of this study is to evaluate the predictive significance of preoperative serum level of cytokeratin 19 fragments (Cyfra21-1) and squamous cell carcinoma antigen (SCC-Ag) after complete resection in patients with stage II esophageal squamous cell carcinoma (ESCC). METHODS: Between 1995 and 2006, a total of 379 patients in stage II ESCC who underwent complete resection were consecutively recruited. Statistical analyses were applied to test the associations between preoperative serum titers of Cyfra21-1 and SCC-Ag, clinicopathological factors and prognoses. RESULTS: Preoperative high and normal serum level of Cyfra21-1 and SCC-Ag were found in 47.8%, 52.2% and 72.8%, 27.2%, respectively. The 1-, 3-, 5-year overall survival rate for the entire cohort of patients was 95%, 78%, and 56%, respectively. Median overall survival (OS) was 45.3 months longer in patients with low preoperative serum level of Cyfra21-1 (91.9 months) than those with high preoperative serum level of Cyfra21-1 (46.6 months) (P < 0.001). Median OS among patients with SCC-Ag-low level was also longer than those with SCC-Ag-high level (89.7 vs. 63.7 months, P < 0.001), especially for those with stage IIB (P < 0.001). After multivariate analysis, along with pTNM stage, preoperative serum level of Cyfra21-1 and SCC-Ag were independently and significantly predictive factors (P < 0.001, P < 0.001). Furthermore, the five-year survival rate in double-low subset, either-low subset and double-high subset was 100%, 83% and 27%, respectively (P < 0.001). CONCLUSIONS: The preoperative serum level of Cyfra21-1 and SCC-Ag are independently significant predictors which negatively affected the survivals of patients with stage II ESCC.

Measuring the topological charge of optical vortices with an axicon.

We analyzed the spatial spectrum of the diffraction intensity pattern of an ideal Bessel beam and found an implicit rule that the number of the bright rings in the spatial spectrum is equal to the topological charge of the Bessel beam. The radius of the bright and dark rings has some relation with the topological charge and can be determined accurately. It provides us with a new way for measuring the topological charge of an optical vortex through its diffraction intensity pattern after an axicon. The results of simulation coincide with the theory.

Association Between eNOS, MMP-9, BAG-6 Gene Polymorphisms and Risk of Hypertensive Disorders of Pregnancy in the Northern Chinese Population.

The objective of this study was to investigate the role of endothelial nitric oxide synthase (eNOS), matrix metalloproteinases (MMP)-9, and Bcl2-associated oncogene 6 (BAG-6) gene polymorphisms, as well as the combined role of single nucleotide polymorphisms (SNPs) in hypertensive disorders of pregnancy (HDP) patients. This case-control study consisted of women with 326 HDP and 312 healthy pregnant controls. Multiplex PCR combined with next-generation sequencing method was used for determination of gene polymorphisms. Nine SNPs were analyzed, and we classified these case samples in depth by preeclampsia (PE) non-PE or blood pressure stages. We undertook allele and genotype haplotype association studies in all the cases and in the subgroups, as well as adjust age by binary logistic regression. Furthermore, the distribution of the haplotypes formed by the nine SNPs mentioned between the HDP patients and healthy pregnant controls were analyzed. There were no statistically significant differences in the nine SNPs of eNOS, MMP-9, and BAG-6 gene allele and genotype frequencies between HDP or subtypes and controls. However, for haplotype analyses, we found that the frequencies of AGACGCCGA (p = 3.67e-005), AGACGCGCA (p = 0.03127), and GAACACCGA (p = 0.02449) were significantly lower in the cases than in the controls. However, the haplotype of GGACGCCGA (p = 0.000686) was higher in the cases than in the controls. Our results suggested protective effect of the haplotypes AGACGCCGA, AGACGCGCA, and GAACACCGA against the development of HDP, and the haplotype GGACGCCGA was the risk factor of HDP.

Effects of transarterial chemoembolization on the immunological function of patients with hepatocellular carcinoma.

The present study aimed to investigate the effects of transarterial chemoembolization (TACE) on the immune function of patients with hepatocellular carcinoma (HCC). A total of 114 patients with HCC were selected and their peripheral blood was collected before and 1 month after TACE treatment. Flow cytometry and reverse transcription-quantitative PCR were performed to analyze the changes in immune function in patients before and after treatment. Kaplan-Meier curves were plotted for survival analysis. The programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD1) expression before TACE treatment were significantly higher in patients with poor TACE response compared with those patients with well response. Higher PD-L1 mRNA expression in the peripheral blood mononuclear cells after TACE predicted a superior prognosis. After TACE treatment, the proportion of CD4+/CD8+ cells were decreased while the expression levels of programmed cell death protein 1 (PD1) were significantly increased. To conclude, TACE could reduce the proportion of CD4+/CD8+ cells and improve the mRNA expression levels of PD1 in patients with HCC. The expression levels of PD1 and PD-L1 were closely related to the therapeutic effect of TACE and the prognosis of patients with HCC. TACE combined with immunotherapy may have potential clinical value for patients with HCC.

Reconstructing unknown wavefronts by use of diffraction-intensity pattern subtraction.

We propose an easy method for unknown wavefront reconstruction by a typical Fourier transform system based on an amplitude-only spatial light modulator (SLM). The Fourier transform of the diffraction intensity pattern on the backfocal plane is the autocorrelation of the wavefront-transmitted SLM. Two intensity patterns were recorded when we set the transmittance of one corner pixel on the SLM as 0 and 1, separately, under the condition that the transmittances of the other pixels equal 1. The complex amplitude of the wavefront-transmitted SLM can be extracted from the Fourier transform of the diffraction intensity pattern subtraction without complicated calculations. The simulation results certifying our theories are also given. Our method provides us with an easy way for detecting the wavefront with high speed and high quality in real time without the reference wave.

[Rule of acupoint combination in acupuncture treatment of hiccup: a study based on complex network analysis].

OBJECTIVE: To explore the rule of acupoint combination in acupuncture treatment of hiccups. METHODS: Original research articles on acupuncture treatment of hiccup were collected from databases of CNKI, Wanfang, VIP, and Pubmed by using key words of "hiccup", "acupuncture" "diaphragmatic spasm" "body acupuncture" "filiform needle" and "electroacupuncture". According to our inclusive and exclusive criteria, the collected data were extracted to establish an acupuncture prescription database for hiccup. Then, the regularities of acupoint combinations for hiccup were analyzed by using Gephi complex network analysis software. RESULTS: ;A total of 606 articles containing 634 acupoint prescriptions for acupuncture treatment of hiccups were brought into analysis. There were 133 single-acupoint prescriptions (20.98%), which was significantly lower than the multi-acupoint prescription (501, accounting for 79.02%). There were mainly acupoints in multi-acupoint prescriptions, and distal-proximal acupoint combination method were often used as the basis of acupoint selection (326, accounting for 65.07%). A total of 163 acupoints were involved, with a total frequency of 2 969. Among them, Neiguan(PC6) was used most frequently (400 times, accounting for 13.47%), followed by Zusanli (ST36), Zhongwan (CV12), Danzhong (CV17), and Taichong (LR3). The acupoints of the Conceptional Vessel(666 times, accounting for 22.43%), and Stomach Meridian, Pericardium Meridian and Liver Meridian were chiefly used. There were 67 specific acupoints, the frequency of use was 2 555 times(accounting for 86.05% of the total frequency), among which the frequency of the five Shu-points was the highest (875 times, accounting for 29.47% of the total frequency), and followed by eight confluence points. CONCLUSION: ;The core acupoints are PC6, ST36, CV12, etc. and the distal-proximal acupoint combination method found in this study are often used as the basis of acupoint selection and acupoint prescription for acupuncture treatment of hiccup.

CVm6A: A Visualization and Exploration Database for m6As in Cell Lines.

N6-methyladenosine (m6A) has been identified in various biological processes and plays important regulatory functions in diverse cells. However, there is still no visualization database for exploring global m6A patterns across cell lines. Here we collected all available MeRIP-Seq and m6A-CLIP-Seq datasets from public databases and identified 340,950 and 179,201 m6A peaks dependent on 23 human and eight mouse cell lines respectively. Those m6A peaks were further classified into mRNA and lncRNA groups. To better understand the potential function of m6A, we then mapped m6A peaks in different subcellular components and gene regions. Among those human m6A modification, 190,050 and 150,900 peaks were identified in cancer and non-cancer cells, respectively. Finally, all results were integrated and imported into a visualized cell-dependent m6A database CVm6A. We believe the specificity of CVm6A could significantly contribute to the research for the function and regulation of cell-dependent m6A modification in disease and development.

Establishment and characterization of a new cell line derived from human colorectal laterally spreading tumor.

AIM: To study the molecular mechanism of laterally spreading tumor (LST), a cell line [Laterally Spreading Tumor-Rectum 1 (LST-R1)] was derived and the characteristics of this cell line were investigated. METHODS: A new cell line (LST-R1) originated from laterally spreading tumor was established. Properties of the cell line were characterized using scanning and transmission electron microscopy, immunohistochemistry method, cytogenetic analysis and nude mice xenograft experiments. In vitro invasion assay, cDNA microarray and Western blotting were used to compare the difference between the LST-R1 and other colorectal cancer cell lines derived from prudent colon cancer. RESULTS: Our study demonstrated that both epithelial special antigen (ESA) and cytokeratin-20 (CK20) were expressed in LST-R1. The cells presented microvilli and tight junction with large nuclei. The karyotypic analysis showed hyperdiploid features with structural chromosome aberrations. The in vivo tumorigenicity was also demonstrated in nude mice xenograft experiments. The invasion assay suggested this cell line has a higher invasive ability. cDNA microarray and Western blotting show the loss of the expression of E-cadherin in LST-R1 cells. CONCLUSION: We established and characterized a colorectal cancer cell line, LST-R1 and LST-R1 has an obvious malignant tendency, which maybe partially attributed to the changes of the expression of some adhesion molecules, such as E-cadherin. It is also a versatile tool for exploring the original and progressive mechanisms of laterally spreading tumor and the early colon cancer genesis.