GWAS combined with QTL mapping reveals the genetic loci of leaf morphological characters in Nicotiana tabacum.

BACKGROUND: Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. RESULTS: In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. CONCLUSIONS: These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Impact of Social Capital on Health Behaviors of Middle-Aged and Older Adults in China-An Analysis Based on CHARLS2020 Data.

To actively respond to the challenges posed by population aging, people are paying more and more attention to healthy behavioral lifestyles, and the impact of social capital as an informal system on health behaviors cannot be ignored. This paper explores the impact of social capital on health behaviors of middle-aged and older adults based on 2020 CHARLS data. Using binary logistic regression models, we discussed the association between social capital and five health behaviors. The results suggest that structural social capital significantly increases physical activity and physical examination behaviors among middle-aged and older adults but also decreases the probability of abstinence behaviors. Cognitive social capital increases the probability that middle-aged and older adults will have a reasonable amount of sleep and physical activity. However, it also decreases the probability that smoking cessation behaviors will occur. Further attention needs to be paid to the role of social capital, the creation of a harmonious social environment and the enhancement of social trust, the strengthening of communities and grass-roots social organizations, and the provision of more platforms for the participation of middle-aged and older adults in social activities, to improve the quality of the healthy lives of middle-aged and older adults and, in turn, to promote the establishment of healthy behaviors.

A Radiological-Radiomics model for differentiation between minimally invasive adenocarcinoma and invasive adenocarcinoma less than or equal to 3 cm: A two-center retrospective study.

OBJECTIVE: To develop a Radiological-Radiomics (R-R) combined model for differentiation between minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) of lung adenocarcinoma (LUAD) and evaluate its predictive performance. METHODS: The clinical, pathological, and imaging data of a total of 509 patients (522 lesions) with LUAD diagnosed by surgical pathology from 2 medical centres were retrospectively collected, with 392 patients (402 lesions) from center 1 trained and validated using a five-fold cross-validation method, and 117 patients (120 lesions) from center 2 serving as an independent external test set. The least absolute shrinkage and selection operator (LASSO) method was utilized to filter features. Logistic regression was used to construct three models for predicting IA, namely, Radiological model, Radiomics model, and R-R model. Also, receiver operating curve curves (ROCs) were plotted, generating corresponding area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: The R-R model for IA prediction achieved an AUC of 0.918 (95 % CI: 0.889-0.947), a sensitivity of 80.3 %, a specificity of 88.2 %, and an accuracy of 82.1 % in the training set. In the validation set, this model exhibited an AUC of 0.906 (95 % CI: 0.842-0.970), a sensitivity of 79.9 %, a specificity of 88.1 %, and an accuracy of 81.8 %. In the external test set, the AUC was 0.894 (95 % CI: 0.824-0.964), a sensitivity of 84.8 %, a specificity of 78.6 %, and an accuracy of 83.3 %. CONCLUSION: The R-R model showed excellent diagnostic performance in differentiating MIA and IA, which can provide a certain reference for clinical diagnosis and surgical treatment plans.

Long-term oncological outcomes of transanal versus laparoscopic total mesorectal excision for mid-low rectal cancer: a retrospective analysis of 2502 patients.

BACKGROUND: Transanal total mesorectal resection (taTME) has recently emerged as a promising surgical approach for the treatment of mid-low rectal cancer. However, there is limited evidence on the long-term survival outcomes associated with taTME. This retrospective study aimed to compare the overall survival (OS), disease-free survival (DFS), and cancer-specific survival of taTME and laparoscopic TME (laTME) in patients with mid-low rectal cancer. MATERIALS AND METHODS: From July 2014 to June 2022, a total of 3627 patients were identified from two prospective cohorts: the laparoscopic rectal surgery cohort and the CNTAES cohort. To balance the baseline characteristics between the taTME and laTME groups, propensity score matching (PSM) was performed. RESULTS: A total of 2502 patients were included in the study. Prior to PSM, the laTME group comprised 1853 patients, while the taTME group comprised 649 patients. The 5-year OS (82.9% vs. 80.4%, P =0.202) and 5-year DFS (74.4% vs. 72.5%, P =0.167) were comparable between the taTME and laTME groups. After PSM, the taTME group showed no statistically significant difference in the 5-year OS (83.1% vs. 79.2%, P =0.101) and 5-year DFS (74.8% vs. 72.1%, P =0.135) compared to the laTME group. Subgroup analysis further suggested that taTME may potentially reduce the risk of death [hazard ratio 0.652; (95% CI, 0.452-0.939)] and disease recurrence [hazard ratio 0.736; (95% CI, 0.562-0.965)] specifically in patients with low rectal cancer. CONCLUSION: In this study, taTME demonstrated comparable oncologic safety to laTME in patients with mid-low rectal cancer. Moreover, the results indicate that taTME may confer potential survival benefits for patients with low rectal cancer.

Does vitamin D have a potential role in precocious puberty? A meta-analysis.

Background: Precocious puberty, one of the common pediatric endocrine system diseases, has been related to reduced adult height, adverse psychological outcomes and long-term health consequences. Previous findings have found that low levels of vitamin D appear to be associated with the characteristics of precocious puberty such as early menarche. However, the effect of vitamin D on precocious puberty remains controversial. Methods: The published literature was searched from PubMed, Web of Science, Cochrane Library, MEDLINE, EMBASE, CNKI, Wan Fang and VIP databases up to October 2022. A randomized effect model was used to perform a meta-analysis to evaluate differences in vitamin D concentration between precocious puberty subjects and normal subjects, the risk of precocious puberty in subjects with low vitamin D levels, and the effect of supplementation of vitamin D on subjects with precocious puberty on medication. Results: Our study found that precocious puberty subjects had lower serum vitamin D levels than the normal population (standardized mean difference (SMD) = -1.16 ng ml-1 and 95% confidence interval (CI) = -1.41 and -0.91 ng ml-1). Meanwhile, the lower level of vitamin D was associated with the risk of precocious puberty (odd ratio (OR) = 2.25 and 95% CI = 1.66 and 3.04). Moreover, compared with gonadotropin-releasing hormone analogue (GnRHa) intervention alone, subjects receiving GnRHa + vitamin D intervention had significantly lower luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol levels and bone age, and higher predicted adult height (PAH). Conclusions: Vitamin D may have a potential role in precocious puberty and more data from large clinical trials are needed to confirm the findings.

Morbidity, Mortality, and Pathologic Outcomes of Transanal Versus Laparoscopic Total Mesorectal Excision for Rectal Cancer Short-term Outcomes From a Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine the morbidity, mortality, and pathologic outcomes of transanal total mesorectal resection (taTME) versus laparoscopic total mesorectal excision (laTME) among patients with rectal cancer with clinical stage I to III rectal cancer below the peritoneal reflection. BACKGROUND: Studies with sufficient numbers of patients allowing clinical acceptance of taTME for rectal cancer are lacking. Thus, we launched a randomized clinical trial to compare the safety and efficacy of taTME versus laTME. METHODS: A randomized, open-label, phase 3, noninferiority trial was performed at 16 different hospitals in 10 Chinese provinces. The primary endpoints were 3-year disease-free survival and 5-year overall survival. The morbidity and mortality within 30 days after surgery, and pathologic outcomes were compared based on a modified intention-to-treat principle; this analysis was preplanned. RESULTS: Between April 13, 2016, and June 1, 2021, 1115 patients were randomized 1:1 to receive taTME or laTME. After exclusion of 26 cases, modified intention-to-treat set of taTME versus laTME groups included 544 versus 545 patients. There were no significant differences between taTME and laTME groups in intraoperative complications [26 (4.8%) vs 33 (6.1%); difference, -1.3%; 95% confidence interval (CI), -4.2% to 1.7%; P =0.42], postoperative morbidity [73 (13.4%) vs 66 (12.1%); difference, 1.2%; 95% CI, -2.8% to 5.2%; P =0.53), or mortality [1 (0.2%) vs 1 (0.2%)]. Successful resection occurred in 538 (98.9%) versus 538 (98.7%) patients in taTME versus laTME groups (difference, 0.2%; 95% CI, -1.9% to 2.2%; P >0.99). CONCLUSIONS: Experienced surgeons can safely perform taTME in selected patients with rectal cancer.

Sensitivity and specificity of magnetic resonance imaging in routine diagnosis of pulmonary lesions: a comparison with computed tomography.

Background: State-of-the-art thoracic magnetic resonance imaging (MRI) plays a complementary role in the assessment of pulmonary nodules/masses which potentially indicate to cancer. We aimed to evaluate the sensitivity and specificity of MRI in diagnosis of pulmonary nodules/masses. Methods: Sixty-eight patients with computed tomography (CT)-detected pulmonary nodules/masses underwent 3T MRI (T1-VIBE, T1-starVIBE, T2-fBLADE turbo spin-echo, and T2-SPACE). The detection rate was calculated for each of the different subgroups of pulmonary nodules according to lung imaging reporting and data system (Lung-RADS). The four MRI sequences were compared in terms of detection rate and image quality-signal to noise ratio (SNR), contrast to noise ratio (CNR) and 5-point scoring scale. Agreement of lesion size measurement between CT and MRI was assessed by intraclass correlation coefficient (ICC). The picture-SNR, lesion-SNR and CNR of each sequence were analyzed by Mann-Whitney U test. Results: In total, 232 pulmonary lesions were detected by CT. The CT showed 86 solid nodules (SNs) <6 mm, 15 SNs between 6-8 mm, 35 SNs between 8-15 mm, and 52 SNs between 15-30 mm. The T1-VIBE, T1-starVIBE, T2-fBLADE TSE and T2-SPACE sequences accurately detected 141 SNs (141/188, 75%/83.3%), 150 SNs (150/188, 79.8%/100%), 166 SNs (166/188, 88.3%/66.7%) and 169 SNs (169/188, 89.9%/53.3%), respectively. Four ground glass nodules (GGNs) (4/6) were detected by T2-fBLADE TSE. Twelve part-solid nodules (PSNs) (12/22) were detected by T1-VIBE and 20 PSNs (20/22) by T2-SPACE. A total of 100 lesions (2.2±1.4 cm, 0.8-7.3 cm) were accurately detected and measured by the four MRI sequences with ICC >0.96. The picture-SNR, lesion-SNR and CNR by T1-starVIBE were higher than those by T1-VIBE (P<0.001). The lesion-SNR and CNR by T2-fBLADE TSE were higher than those by T2-SPACE (P=0.006, 0.038). 86% of images by T1-starVIBE, 92% by T2-fBLADE TSE, 90% by T2-SPACE and 93% by T1-VIBE were scored 3 or more. Conclusions: MRI achieves high sensitivity and specificity for different type of pulmonary nodules detection and is an effective alternative to CT as a diagnostic tool for pulmonary nodules.

Serum metabolomics reveals an innovative diagnostic model for salivary gland tumors.

An early diagnosis of salivary gland tumors (SGTs) and determination of their malignancy are conducive to developing individualized therapeutic strategies and thus improving prognosis. The aim of this study was to investigate the difference of serum metabolic profiles in patients with SGTs to better understand the mechanism of this disease and disease risk stratification. We used ultrahigh-performance liquid chromatography Q Exactive mass spectrometry and multivariate statistical analyses to conduct a comprehensive analysis of serum metabolites in a population with normal control and SGTs. 32 differentially expressed metabolites were identified, while the level of serine and lactic acid were investigated to gradually upregulate in benign SGTs and malignant SGTs. Then, the expression of serine and lactic acid were assessed in validation cohort using multiple reaction monitoring (MRM) based targeted metabolite analysis. A risk score formula based on the amount of serine and lactic acid was developed and explored to be significantly related to benign SGTs and malignant SGTs in discovery and validation cohort. Our work highlights the possible use of the risk score assessment based on the serum metabolites not only reveal in the early diagnosis of SGTs but also assist in enhancing current therapeutic strategies in the clinic.

Applying a CT texture analysis model trained with deep-learning reconstruction images to iterative reconstruction images in pulmonary nodule diagnosis.

OBJECTIVE: To investigate the feasibility and accuracy of applying a computed tomography (CT) texture analysis model trained with deep-learning reconstruction images to iterative reconstruction images for classifying pulmonary nodules. MATERIALS AND METHODS: CT images of 102 patients, with a total of 118 pulmonary nodules (52 benign, 66 malignant) were retrospectively reconstructed with a deep-learning reconstruction (artificial intelligence iterative reconstruction [AIIR]) and a hybrid iterative reconstruction (HIR) technique. The AIIR data were divided into a training (n = 96) and a validation set (n = 22), and the HIR data were set as the test set (n = 118). Extracted texture features were compared using the Mann-Whitney U test and t-test. The diagnostic performance of the classification model was analyzed with the receiver operating characteristic curve (ROC), the area under ROC (AUC), sensitivity, specificity, and accuracy. RESULTS: Among the obtained 68 texture features, 51 (75.0%) were not influenced by the change of reconstruction algorithm (p > 0.05). Forty-four features were significantly different between benign and malignant nodules (p < 0.05) for the AIIR dataset, which were selected to build the classification model. The accuracy and AUC of the classification model were 92.3% and 0.91 (95% confidence interval [CI], 0.74-0.90) with the validation set, which were 80.0% and 0.80 (95% CI, 0.68-0.86) with the test set. CONCLUSION: With the CT texture analysis model trained with deep-learning reconstruction (AIIR) images showing favorable diagnostic accuracy in discriminating benign and malignant pulmonary nodules, it also has certain applicability to the iterative reconstruction (HIR) images.

Transanal total mesorectal excision combined with intersphincteric resection has similar long-term oncological outcomes to laparoscopic abdominoperineal resection in low rectal cancer: a propensity score-matched cohort study.

Background: Transanal total mesorectal excision (taTME) or intersphincteric resection (ISR) has recently proven to be a valid and safe surgical procedure for low rectal cancer. However, studies focusing on the combination of these two technologies are limited. This study aimed to evaluate perioperative results, long-term oncologic outcomes, and anorectal functions of patients with low rectal cancer undergoing taTME combined with ISR, by comparing with those of patients undergoing laparoscopic abdominoperineal resection (laAPR). Methods: After 1:1 propensity score matching, 200 patients with low rectal cancer who underwent laAPR (n = 100) or taTME combined with ISR (n = 100) between September 2013 and November 2019 were included. Patient demographics, clinicopathological characteristics, oncological outcomes, and anal functional results were analysed. Results: Patients in the taTME-combined-with-ISR group had less intraoperative blood loss (79.6 ± 72.6 vs 107.3 ± 65.1 mL, P = 0.005) and a lower rate of post-operative complications (22.0% vs 44.0%, P < 0.001) than those in the laAPR group. The overall local recurrence rates were 7.0% in both groups within 3 years after surgery. The 3-year disease-free survival rates were 86.3% in the taTME-combined-with-ISR group and 75.1% in the laAPR group (P = 0.056), while the 3-year overall survival rates were 96.7% and 94.2%, respectively (P = 0.319). There were 39 patients (45.3%) in the taTME-combined-with-ISR group who developed major low anterior resection syndrome, whereas 61 patients (70.9%) had good post-operative anal function (Wexner incontinence score ≤ 10). Conclusion: We found similar long-term oncological outcomes for patients with low rectal cancer undergoing laAPR and those undergoing taTME combined with ISR. Patients receiving taTME combined with ISR had acceptable post-operative anorectal function.

Transanal versus Laparoscopic Total Mesorectal Excision in Male Patients with Low Tumor Location after Neoadjuvant Therapy: A Propensity Score-Matched Cohort Study.

Background: Since Sylla and Lacy successfully reported the transanal total mesorectal excision in 2010, taTME was considered to have the potential to overcome some problematic laparoscopic cases in male, low advanced rectal cancer. However, the evidence is still lacking. This study compared the short and long outcomes of taTME with laTME in these "challenging" patients to explore the advantages of taTME among the patients. Method: After propensity score matching analysis, 106 patients were included in each group from 325 patients who met the including standard. Statistical analysis was used to compare the differences of perioperative outcomes, histopathological results, and survival results between taTME and laTME groups. Results: The mean time of pelvic operation in the taTME group was significantly shorter than in the laTME group (62.2 ± 14.2 mins vs 81.1 ± 18.9 mins, P = 0.003). The complication incidence rate and the rate of protective loop ileostomy in the taTME group were significantly lower than those in the laTME group (19.8% vs 38.7%, P = 0.003 and 70.8% vs 92.5%, P < 0.001). In long-term result, there was no significant difference between the two groups for 3-year OS (87.3% vs 85.4%, P = 0.86) or 3-year DFS (74.9% vs 70.1%, P = 0.92). The 2-year cumulative local recurrence rate was similar between the two groups (1.1% vs 5.8%, P = 0.22). Conclusion: This study demonstrated that taTME might reduce the incidence of postoperative complications, especially of anastomotic leakage in these "challenging" patients. taTME may be considered to have clear advantages for "challenging" patients.

Neoadjuvant PD-1 blockade with toripalimab, with or without celecoxib, in mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancer (PICC): a single-centre, parallel-group, non-comparative, randomised, phase 2 trial.

BACKGROUND: PD-1 blockade is highly effective in patients with mismatch repair-deficient or microsatellite instability-high metastatic colorectal cancer. The role of single-agent PD-1 blockade in the neoadjuvant setting for resectable mismatch repair-deficient or microsatellite instability-high colorectal cancer remains unclear. We investigated the efficacy and safety of PD-1 blockade with toripalimab, with or without the COX-2 inhibitor celecoxib, as neoadjuvant treatment for mismatch repair-deficient or microsatellite instability-high, locally advanced, colorectal cancers. METHODS: The PD-1 Inhibitor in Microsatellite Instability Colorectal Cancer (PICC) trial was a single-centre, open-label, parallel-group, non-comparative, randomised, phase 2 study undertaken at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China). Eligible patients were aged 18-75 years, had histologically confirmed mismatch repair-deficient or microsatellite instability-high colorectal cancer, had clinical stage T3-T4 or any T with lymph node positivity (N+), Eastern Cooperative Oncology Group performance score of 0 or 1, and adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1), without any stratification or balanced blocking, to receive toripalimab 3 mg/kg intravenously on day 1, with or without celecoxib 200 mg orally twice daily from day 1 to 14 of each 14-day cycle, for six cycles before surgical resection. Adjuvant treatment with toripalimab with or without celecoxib was permitted at the investigators' discretion. The primary endpoint was the proportion of patients with pathological complete response, defined as tumours without any viable tumour cells in the resected primary tumour sample and all sampled regional lymph nodes. All efficacy and safety analyses were assessed in the modified intention-to-treat population, which included all patients who were randomly assigned to treatment and who received at least one dose of toripalimab. This trial is registered with ClinicalTrials.gov, NCT03926338, and is ongoing. FINDINGS: Between May 1, 2019, and April 1, 2021, 53 patients were screened, of whom 34 were randomly assigned to either the toripalimab plus celecoxib group (n=17) or the toripalimab monotherapy group (n=17). As of data cutoff (Aug 10, 2021), median follow-up was 14·9 months (IQR 8·8-17·0). All patients received study treatment and underwent surgical resection; there were no treatment-related surgical delays. All 34 patients had an R0 resection (>1 mm resection margin). 15 of 17 patients (88% [95% CI 64-99]) in the toripalimab plus celecoxib group and 11 of 17 patients (65% [38-86]) in the toripalimab monotherapy group had a pathological complete response. All patients continued to receive adjuvant toripalimab with or without celecoxib for a total perioperative duration of 6 months and were alive and free of recurrence at data cutoff. During neoadjuvant treatment, ten (59%) patients in the toripalimab plus celecoxib group and ten (59%) in the toripalimab monotherapy group had grade 1-2 treatment-related adverse events. Only one (3%) of 34 patients, who was in the toripalimab plus celecoxib group, had a grade 3 or higher treatment-related adverse event during the neoadjuvant phase, which was grade 3 increased aspartate aminotransferase levels. In the adjuvant phase, only one (3%) of 34 patients, who was in the toripalimab monotherapy group, had a grade 3 or higher treatment-related adverse events, which was grade 3 increased aspartate aminotransferase and alanine aminotransferase levels. INTERPRETATION: Neoadjuvant toripalimab with or without celecoxib could be a potential therapeutic option for patients with mismatch repair deficient or microsatellite instability-high, locally advanced, colorectal cancer. This treatment was associated with a high pathological complete response rate and an acceptable safety profile, which did not compromise surgery. Longer term follow-up is needed to assess effects on survival-related endpoints. FUNDING: The National Key R&D Program of China, the National Natural Science Foundation of China, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Identification and Validation of PLOD2 as an Adverse Prognostic Biomarker for Oral Squamous Cell Carcinoma.

BACKGROUND: Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a key enzyme that catalyzes the hydroxylation of lysine, plays a crucial role in the progression of several solid tumors. However, its spatial expression profile and prognostic significance in oral squamous cell carcinoma (OSCC) have not been revealed. MATERIALS: Mass spectrometry was used to explore amino acid perturbations between OSCC tumor tissues and paired normal tissues of 28 patients. Then, PLOD2 mRNA and protein levels were assessed using several public databases and 18 pairs of OSCC patients' tissues. Additionally, PLOD2 spatial expression profiles were investigated in 100 OSCC patients by immunohistochemistry and its diagnostic and prognostic values were also evaluated. Lastly, gene set enrichment analysis (GSEA) was used to investigate the potential functions of PLOD2 in OSCC. RESULTS: Lysine was significantly elevated in OSCC tissues and could effectively distinguish tumor from normal tissues (AUC = 0.859, p = 0.0035). PLOD2 mRNA and protein levels were highly increased in tumor tissues of head and neck squamous cell carcinoma (HNSCC) (p < 0.001) and OSCC compared with those in nontumor tissues (p < 0.001). Histopathologically, PLOD2 was ubiquitously expressed in tumor cells (TCs) and fibroblast-like cells (FLCs) of OSCC patients but absent in tumor-infiltrating lymphocytes (TILs). Patients with highly expressed PLOD2 in TCs (PLOD2TCs) and FLCs (PLOD2FLCs) showed poor differentiation, a worse pattern of invasion (WPOI) and more lymph node metastasis (LNM), contributing to higher postoperative metastasis risk and poor survival time. However, PLOD2FLCs rather than PLOD2TCs was an independent risk factor for survival outcomes in OSCC patients. Molecularly, GSEA demonstrated highly expressed PLOD2 was mainly enriched in epithelial-mesenchymal transformation (EMT), TGF-beta signaling and hypoxia pathway, which are associated with poor clinical outcomes of OSCC patients. CONCLUSIONS: PLOD2 was a poor prognostic biomarker for OSCC patients and may affect the metastasis of OSCC through EMT pathway. These findings might shed novel sights for future research in PLOD2 targeted OSCC therapy.

Pulmonary Epithelioid Hemangioendothelioma: Imaging and Clinical Features.

OBJECTIVE: The aim of this study was to analyze the computed tomography (CT), fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), and clinical findings of pulmonary epithelioid hemangioendothelioma. METHODS: Eighteen patients were included. We reviewed CT and PET/CT features and clinical information. Spearman correlation analysis was used to reveal the correlation between lesion size and maximum standardized uptake values (SUVmax). RESULTS: Eleven patients complained of different symptoms. The serum levels of tumor markers were elevated in 8 patients (44.4%). Multiple lesions were shown in 14 cases (77.8%). Eleven cases (61.1%) presented as bilateral multiple perivascular lesions. The size of the largest nodule was less than 20 mm in diameter in 11 cases (61.1%). Eleven cases underwent PET/CT examination, and 8 cases (72.7%) had increased FDG uptake. There was a positive correlation (Spearman correlation coefficient, 0.56; P = 0.009) between lesion size and SUVmax. Extrapulmonary involvement was shown in 7 cases, including the liver and bone. CONCLUSIONS: Pulmonary epithelioid hemangioendothelioma on CT scan usually showed multiple bilateral perivascular lung nodules, generally measuring less than 20 mm in diameter. Lesions usually showed increased FDG uptake on PET/CT scans. There was a positive correlation between lesion size and SUVmax. The liver and bone were the most frequently involved extrapulmonary organs.

Distinct Genomic Landscape of Colorectal Mucinous Carcinoma Determined via Comprehensive Genomic Profiling: Steps to a New Treatment Strategy.

Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC. HER2 amplification and TP53 and APC mutation rates were lower, whereas SMAD4, PIK3CA, ACVR2A, KMT2D, LRP1, TGFBR2, GRIN2A, BRAF V600E, PTEN, and BRCA2 mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF- pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.

Transanal vs laparoscopic total mesorectal excision for rectal cancer: a multicenter randomized phase III clinical trial (TaLaR trial) protocol.

BACKGROUND: Total mesorectum excision (TME) is considered the standard surgical procedure for rectal-cancer treatment. Transanal TME (taTME) is a new procedure to treat low rectal cancer. Some published studies have proven that taTME can provide a better-quality resected specimen in low-rectal-cancer patients in comparison to the transabdominal procedure, yet long-term outcomes must be investigated. We designed this non-inferiority trial (TaLaR trial) to compare short-term and long-term outcomes between taTME and laparoscopic TME (lapTME) for rectal cancer. METHODS: The TaLaR trial is a phase III open-labeled multicenter randomized-controlled trial. Patients who are diagnosed with rectal cancer with no more than T3N2 stage, and with the tumor location below the peritoneal reflection by magnetic resonance imaging scan, digital rectal examination, or colonoscopy, qualify for this study. After calculating, a total of 1,114 patients (557 per group) will be randomly allocated to either the taTME or the lapTME group. Primary endpoints are the 3-year disease-free survival (DFS) rate and the 5-year overall survival (OS) rate. Secondary endpoints include specimen quality, perioperative results, pelvic and anal function, and quality of life. DISCUSSION: The TaLaR trial is expected to clarify whether taTME can achieve comparable oncological outcomes, as well as improve specimen quality and recovery conditions in rectal-cancer patients compared with lapTME.

Construction of a SNP Fingerprinting Database and Population Genetic Analysis of Cigar Tobacco Germplasm Resources in China.

Cigar tobacco is an important economic crop that is widely grown around the world. In recent years, varietal identification has become a frequent problem in germplasm preservation collections, which causes considerable inconvenience and uncertainty in the cataloging and preservation of cigar germplasm resources, in the selection of parental lines for breeding, and in the promotion and use of high quality varieties. Therefore, the use of DNA fingerprints to achieve rapid and accurate identification of varieties can play an important role in germplasm identification and property rights disputes. In this study, we used genotyping-by-sequencing (GBS) on 113 cigar tobacco accessions to develop SNP markers. After filtering, 580,942 high-quality SNPs were obtained. We used the 580,942 SNPs to perform principal component analysis (PCA), population structure analysis, and neighbor joining (NJ) cluster analysis on the 113 cigar tobacco accessions. The results showed that the accessions were not completely classified based on their geographical origins, and the genetic backgrounds of these cigar resources are complex and diverse. We further selected from these high-quality SNPs to obtained 163 SNP sites, 133 of which were successfully converted into KASP markers. Finally, 47 core KASP markers and 24 candidate core markers were developed. Using the core markers, we performed variety identification and fingerprinting in 216 cigar germplasm accessions. The results of SNP fingerprinting, 2D barcoding, and genetic analysis of cigar tobacco germplasm in this study provide a scientific basis for screening and identifying high-quality cigar tobacco germplasm, mining important genes, and broadening the basis of cigar tobacco genetics and subsequent breeding work at the molecular level.

Transanal and transabdominal combined endoscopic resection of rectal stenosis and anal reconstruction based on transanal endoscopic technique.

OBJECTIVE: To propose a method for the resection of the rectal anastomotic stenosis and anal reconstruction based on the transanal endoscopic technique through a transanal and transabdominal combined endoscopic resection, and to verify its clinical effectiveness. METHODS: Thirty-eight patients with anastomotic stenosis were admitted to the Sixth Affiliated Hospital, Sun Yat-sen University, China, from January 2016 to September 2019. Patients were divided into an experimental group (17 patients) and a control group (21 patients) subjected to the removal of the intestinal stenosis followed by anal reconstruction, they underwent transanal and transabdominal endoscopic surgery and traditional transabdominal surgery, respectively. Data on intraoperative blood loss, operation time, postoperative recovery, and prognosis were collected. RESULTS: (1) The median intraoperative blood loss was approximately 100 ml, without conversion to laparotomy during the surgery and intraoperative complications. The safety of the surgical operation was improved. (2) The operation time was shortened compared to previous reports, and the median operative time was 193 min. The average time of transanal endoscopic dissociation to the retroperitoneal fold was 76 min. (3) Laparoscopic assistance was carried out on 14 of the17 patients, and the incision was reduced. (4) The short-term curative effect was quite satisfactory, without permanent stoma. The average time to recover food intake after the surgery was 1.5 days. The average ambulation time was 3 days. Within 30 days after the surgery, one case suffered anastomotic leakage and then underwent refunctioning stoma through a second surgery. One patient suffered from intestinal obstruction, and the condition was improved through a conservative treatment. One case experienced delayed abdominal wound healing. CONCLUSION: The transanal and transabdominal endoscopic resection of the rectal anastomotic stenosis and anal reconstruction reduced the difficulty of the surgery, improved its safety, shortened the operation time, decreased the operative complications, and enabled patients to recover well after surgery.

Transanal Total Mesorectal Excision in Mid-Low Rectal Cancer: Evaluation of the Learning Curve and Comparison of Short-term Results With Standard Laparoscopic Total Mesorectal Excision.

BACKGROUND: Ever since transanal total mesorectal excision was introduced by Sylla and Lacy in 2010, it has become more popular among colorectal surgeons. However, some surgeons hesitate to use it, because this novel approach differs greatly from laparoscopic total mesorectal excision and requires a long learning curve. OBJECTIVE: This study analyzed the learning curve of transanal total mesorectal excision procedure and compared the different phases of transanal total mesorectal excision with laparoscopic total mesorectal excision. DESIGN: This is retrospective case-control study. SETTINGS: We used data from the approved colorectal cancer database of the Sixth Affiliated Hospital of Sun Yat-sen University. PATIENTS: The patients involved in this study underwent transanal total mesorectal excision performed by a single surgeon (L.K.) or underwent laparoscopic transanal total mesorectal excision performed by experienced surgeons. INTERVENTIONS: Transanal or laparoscopic resection of mid-low rectal cancer was conducted. MAIN OUTCOMES MEASURES: Perioperative complication and resection margin were measured. RESULTS: A total of 342 patients were included in both groups. The learning curve of transanal total mesorectal excision was divided into 3 phases. Data show that demographics and tumor characteristics were not significantly different between the matched groups. Indeed, during phase 1, only operative time was longer than in the laparoscopic group, whereas, during phase 2, results from the transanal group were comparable with the laparoscopic group. Results show that, during phase 3, operative time, intraoperative blood loss, and postoperative hospital stay were all lower than in the laparoscopic group. Local recurrence occurred in 3 patients during phase 1 and in 1 patient during phase 2. LIMITATIONS: This study was a small retrospective study and focused on just 1 surgeon performing transanal total mesorectal excision. CONCLUSIONS: Short-term and histopathologic outcomes are similar compared between a transanal group and matched laparoscopic group. Transanal total mesorectal excision also provided good oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B450. ESCISIN MESORRECTAL TOTAL TRANSANAL EN EL CNCER DE RECTO MEDIOBAJO EVALUACIN DE LA CURVA DE APRENDIZAJE Y COMPARACIN DE RESULTADOS A CORTO PLAZO CON TME LAPAROSCPICA ESTNDAR: ANTECEDENTES:Desde que Sylla y Lacy introdujeron la escisión mesorrectal total transanal en 2010, se ha vuelto más popular entre los cirujanos colorrectales. Sin embargo, algunos cirujanos dudan en utilizarlo, porque este nuevo método difiere mucho de la escisión mesorrectal total laparoscópica y requiere una larga curva de aprendizaje.OBJETIVO:Este estudio analizó la curva de aprendizaje del procedimiento de escisión mesorrectal total transanal y comparó las diferentes fases de la escisión mesorrectal total transanal con la escisión mesorrectal total laparoscópica.DISEÑO:Este es un estudio retrospectivo de casos y controles.ENTORNO CLINICO:Utilizamos base de datos de cáncer colorrectal aprobada del Sexto Hospital Afiliado de la Universidad Sun Yat-sen (Guangzhou, China).PACIENTES:Los pacientes involucrados en este estudio fueron sometidos a escisión mesorrectal total transanal realizada por un solo cirujano (LK) o se sometieron a escisión mesorrectal total transanal laparoscópica realizada por cirujanos experimentados.INTERVENCIONES:Resección transanal o laparoscópica de cáncer de recto medio-bajo.PRINCIPALES MEDIDAS DE VOLARCION:complicación perioperatoria y margen de resección.RESULTADOS:Se incluyó un total de 342 pacientes en ambos grupos. La curva de aprendizaje de la escisión mesorrectal total transanal se dividió en tres fases. Los datos muestran que las características demográficas y tumorales no fueron significativamente diferentes entre los grupos emparejados. De hecho, durante la fase 1, solo el tiempo operatorio fue más largo que en el grupo laparoscópico. Mientras que durante la fase 2, los resultados del grupo transanal fueron comparables a los del grupo laparoscópico. Los resultados muestran que durante la fase 3, el tiempo operatorio, la pérdida de sangre intraoperatoria y la estancia hospitalaria postoperatoria fueron menores que en el grupo laparoscópico. La recurrencia local ocurrió en 3 pacientes durante la fase 1 y en 1 paciente durante la fase 2.LIMITACIONES:Este estudio fue un estudio retrospectivo pequeño y se centró en un solo cirujano que realizaba la escisión mesorrectal total transanal.CONCLUSIÓN:Los resultados a corto plazo e histopatológicos son similares en comparación entre el grupo transanal y el grupo laparoscópico emparejado. La escisión mesorrectal total transanal también proporcionó buenos resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B450.

Identification and Validation of HOTAIRM1 as a Novel Biomarker for Oral Squamous Cell Carcinoma.

ORAL squamous cell carcinoma (OSCC) is a malignant tumor with the highest incidence among tumors involving the oral cavity maxillofacial region, and is notorious for its high recurrence and metastasis potential. Long non-coding RNAs (lncRNAs), which regulate the genesis and evolution of cancers, are potential prognostic biomarkers. This study identified HOTAIRM1 as a novel significantly upregulated lncRNA in OSCC, which is strongly associated with unfavorable prognosis of OSCC. Systematic bioinformatics analyses demonstrated that HOTAIRM1 was closely related to tumor stage, overall survival, genome instability, the tumor cell stemness, the tumor microenvironment, and immunocyte infiltration. Using biological function prediction methods, including Weighted gene co-expression network analysis (WGCNA), Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA), HOTAIRM1 plays a pivotal role in OSCC cell proliferation, and is mainly involved in the regulation of the cell cycle. In vitro, cell loss-functional experiments confirmed that HOTAIRM1 knockdown significantly inhibited the proliferation of OSCC cells, and arrested the cell cycle in G1 phase. At the molecular level, PCNA and CyclinD1 were obviously reduced after HOTAIRM1 knockdown. The expression of p53 and p21 was upregulated while CDK4 and CDK6 expression was decreased by HOTAIRM1 knockdown. In vivo, knocking down HOTAIRM1 significantly inhibited tumor growth, including the tumor size, weight, volume, angiogenesis, and hardness, monitored by ultrasonic imaging and magnetic resonance imaging In summary, our study reports that HOTAIRM1 is closely associated with tumorigenesis of OSCC and promotes cell proliferation by regulating cell cycle. HOTAIRM1 could be a potential prognostic biomarker and a therapeutic target for OSCC.