Randomized trial of transcutaneous auricular vagus nerve stimulation on patients with disorders of consciousness: A study protocol.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has recently been explored for the treatment of Disorders of consciousness (DoC) caused by traumatic brain injury. The evidence of taVNS during the consciousness recovery has been recently reported. However, the mechanism of taVNS in the recovery of consciousness is not clear. This study attempts to investigate the effectiveness of taVNS in DoC by means of Coma Recovery Scale-Revised (CRS-R), Magnetic resonance imaging (MRI), Electrophysiology (EEG), and Single-molecular array (Simoa). Methods/design: Nighty patients with DoC acquired brain injury are randomized into one of three groups receiving sham taVNS or active taVNS (just left and left or right), respectively. Each of the three groups will experience a 40 days cycle (every 10 days for a small period, baseline 2 weeks, intervention 2 weeks, 40 min per day, 5 days per week, then no intervention for 2 weeks, intervention 2 weeks, 40 min per day, and 5 days per week). Primary outcomes (CRS-R) will be recorded five times during every period. Secondary outcomes will be recorded at the first and at the last period [MRI, EEG, Phosphorylated tau (P-tau), and Neurofilament light chain (NFL)]. We will take notes the adverse events and untoward effects during all cycles. Discussion: Transcutaneous auricular vagus nerve stimulation as a painless, non-invasive, easily applied, and effective therapy was applied for treatment of patients with depression and epilepsy several decades ago. Recent progress showed that taVNS has behavioral effects in the consciousness recovery. However, there is no clinical evidence to support the effects of taVNS on brain activity. Therefore, we will design a randomized controlled trial to evaluate the effectiveness and safety of taVNS therapy for DoC, and explore neural anatomy correlated to taVNS during the consciousness recovery. Finally, this protocol also tests some biomarkers along with the recovery of consciousness. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2100045161. Registered on 9 April 2021.

Genome, transcriptome, and metabolome analyses provide new insights into the resource development in an edible fungus Dictyophora indusiata.

Dictyophora indusiata (Vent. Ex Pers.) Fisch. (DI) is an edible and medicinal fungus widely used in East Asian countries. However, during DI cultivation, the formation of fruiting bodies cannot be regulated, which leads to yield and quality losses. The present study performed a combined genome, transcriptome, and metabolome analysis of DI. Using Nanopore and Illumina sequencing approaches, we created the DI reference genome, which was 67.32 Mb long with 323 contigs. We identified 19,909 coding genes on this genome, of which 46 gene clusters were related to terpenoid synthesis. Subsequent transcriptome sequencing using five DI tissues (cap, indusia, mycelia, stipe, and volva) showed high expression levels of genes in the cap, indicating the tissue's importance in regulating the fruiting body formation. Meanwhile, the metabolome analysis identified 728 metabolites from the five tissues. Mycelium was rich in choline, while volva was rich in dendronobilin; stipe had monosaccharides as the primary component, and the cap was the main source of indole acetic acid (IAA) synthesis. We confirmed the importance of tryptophan metabolism for DI fruiting body differentiation based on KEGG pathway analysis. Finally, the combined multiomics analysis identified three new genes related to IAA synthesis of the tryptophan metabolic pathway in the cap, which may regulate DI fruiting body synthesis and improve DI quality. Thus, the study's findings expand our understanding of resource development and the molecular mechanisms underlying DI development and differentiation. However, the current genome is still a rough draft that needs to be strengthened.

Electronic cigarette knowledge, attitudes and use among students at a university in Hangzhou, China.

INTRODUCTION: Electronic cigarettes are increasingly popular worldwide, especially among youth. There is growing evidence of the negative health consequences of vaping. Our objective was to assess university students' knowledge and attitudes regarding electronic cigarettes (e-cigarettes), their use, as well as the associated influencing factors for their use. METHODS: The study involved an online cross-sectional survey conducted between November 2019 and March 2020 in a university in Hangzhou, China. A total of 563 students completed the questionnaire. Descriptive statistics were used to assess characteristics, knowledge, and attitudes; t-tests, χ2-tests and logistic regression models were used to identify factors associated with ever e-cigarette use. RESULTS: In all, 59.9% of respondents were female and the average age was 20.38 years (SD=1.32). Only 42.6% of the respondents thought that e-cigarettes contain nicotine, 31.1% thought e-cigarettes are tobacco products, and 8.2% of the students reported being ever e-cigarettes users. In regard to attitude, the average score of the students in the Safety dimension was 3.34 (SD=0.64), followed by the Restriction dimension (Mean=2.66, SD=0.83). Correlates of ever use included regions, friends' and roommates' ever e-cigarette use, and higher attitude score in the Supervision dimension. CONCLUSIONS: The university students' level of knowledge regarding e-cigarettes was not high, and their attitudes regarding e-cigarettes were not that supportive. Students' ever use of e-cigarettes at a university in Hangzhou was higher than for university students in other cities in China, but lower than for those in foreign countries.

Relationship between self-care compliance, trust, and satisfaction among hypertensive patients in China.

Introduction: Hypertension is a growing public health concern worldwide. It is a leading risk factor for all-cause mortality and may lead to complications such as cardiovascular disease, stroke, and kidney failure. Poor compliance of hypertensive patients is one of the major barriers to controlling high blood pressure. Compliance is not ideal among Chinese patients, and increasing patient self-care compliance with hypertension is necessary. Methods: This article analyzes the status of self-care compliance, trust, and satisfaction among Chinese hypertensive patients using cross-sectional data from Zhejiang Province. We use a multi-group structural equation model (MGSEM) to compare the interrelationships across genders. Results: The study's findings show that the average trust, satisfaction, and compliance scores are 3.92 ± 0.55, 3.98 ± 0.61, and 3.33 ± 0.41, respectively. Female patients exhibit higher average total scores for trust and compliance than male patients. The SEM results indicate that trust has a direct positive association with compliance [ß = 0.242, 95% CI: (0.068, 0.402)] and satisfaction [ß = 0.260, 95% CI: (0.145, 0.367)], while their satisfaction is not directly associated with compliance. The results of MGSEM show that trust has an indirect effect on compliance in the male group through satisfaction [ß = 0.051, P < 0.05, 95% CI: (0.012, 0.116)]. In the female group, trust has a direct effect on satisfaction [ß = 0.235, P < 0.05, 95% CI: (0.041, 0.406)] and compliance [ß = 0.319, P < 0.01, 95% CI: (0.086, 0.574)]. Discussion: This study reveals the mechanisms of self-care compliance, trust, and satisfaction among Chinese hypertensive patients. Its findings may serve as a reference for guiding primary healthcare providers to improve hypertension patients' compliance and implement gender-targeted health interventions.

WaveICA 2.0: a novel batch effect removal method for untargeted metabolomics data without using batch information.

INTRODUCTION: Untargeted metabolomics based on liquid chromatography-mass spectrometry is inevitably affected by batch effects that are caused by non-biological systematic bias. Previously, we developed a novel method called WaveICA to remove batch effects for untargeted metabolomics data. To detect batch effect information, the method relies on a batch label. However, it cannot be used in the scenario in which there is only one batch of data or the batch label is unknown. OBJECTIVES: We aim to improve the WaveICA method to remove batch effects for untargeted metabolomics data without using batch information. METHODS: We improved the WaveICA method by developing WaveICA 2.0 to remove batch effects for metabolomics data, and provided an R package WaveICA_2.0 to implement this method. RESULTS: The performance of the WaveICA 2.0 method was evaluated on real metabolomics data. For metabolomics data with three batches, the performance of the WaveICA 2.0 method was similar to that of the WaveICA method in terms of gathering quality control samples (QCSs) and subject samples together in principle component analysis score plots, increasing the similarity of QCSs, increasing differential peaks, and improving classification accuracy. For metabolomics data with only one batch, the WaveICA 2.0 method had a strong ability to remove intensity drift and reveal more biological information and outperformed the QC-RLSC and QC-SVRC methods in our study using our metabolomics data. CONCLUSION: Our results demonstrated that the WaveICA 2.0 method can be used in practice to remove batch effects for untargeted metabolomics data without batch information.

Attitude towards electronic cigarette and associated factors among college students in Zhejiang Province / 中国学校卫生

Objective@#To understand the attitude of college students in Zhejiang towards e cigarette and its influencing factors, so as to provide basis for making prevention and control strategies.@*Methods@#In September 2020, 10 colleges and universities in Zhejiang Province were selected to conduct an online survey by a combination of typical sampling method and convenience sampling method. A multivariable Logistic regression model was used to analyze the influencing factors.@*Results@#Among 884 subjects, 93 (10.52%) were positive about e-cigarettes, 310 (35.07%) thought e-cigarettes were harmless, 252 (28.51%) thought e-cigarettes were not addictive and 67 (7.58%) of respondents were using e-cigarettes. Multivariate Logistic regression analysis showed that gender, grade, cost of living, whether or not smoking e-cigarettes were harmful to college students attitudes towards e-cigarettes( OR =0.59, 0.47, 1.87, 0.34, 0.54, P <0.05).@*Conclusion@#College students in Zhejiang Province have a positive attitude towards electronics and are not active in avoiding the dangers of smoking. To make full use of the work of concentrated trainees in tobacco control, efforts should be made to break the positive image of e-cigarettes. Junior college students should be the prioritized population for intervention, and female students should not be neglected.

An immunophenotyping of renal clear cell carcinoma with characteristics and a potential therapeutic target for patients insensitive to immune checkpoint blockade.

Renal clear cell carcinoma (RCC) patients who do not achieve optimal control of progression with immune checkpoint blockade (ICB) should be further studied. Unsupervised consensus clustering was used to group 525 RCC patients based on two typical ICB pathways, CTLA-4 and pogrammed death 1 (PD-1)/programmed death-ligand 1 (PD-L1), as well as two new discovered regulators, CMTM6 and CMTM4. Three immune molecular subtypes (IMMSs) with different clinical and immunological characteristics were identified (type I, II, and III), among which there were more stage I and low-grade tumors in type I RCC than in type II and III. The proportion of males was highest in type II RCC. Overall survival of type II and III was similar (5.2 and 6 years) and statistically shorter than that of type I (7.6 years) before and after adjusting for age and gender. When conducting stratified analysis, our IMMSs were able to identify high-risk patients among middle-aged patients, males, and stage IV patients. Among the differentially expressed genes, approximately 84% were highly expressed in type II and III RCC. Genes related to ICB (CTLA-4, CD274, and PDCD1LG2) and cytotoxic lymphocytes (CD8A, GZMA, and PRF1) were all highly expressed in type II and III RCC. These results documented that patients with type II and III cancer may be more sensitive to anti-CTLA-4 therapy, anti-PD-1/PD-L1 therapy, and a combination of immunotherapies. High expression of CMTM4 in type I RCC (69%) and a statistically significant interaction of CD274 and CMTM6 indicated that CMTM4/6 might be new therapy targets for type I, who are resistant to ICB.

Proteomics of Uterosacral Ligament Connective Tissue from Women with and without Pelvic Organ Prolapse.

PURPOSE: Damage to the uterosacral ligaments is an important contributor to uterine and vaginal prolapse. The aim of this study is to identify differentially expressed proteins (DEPs) in the uterosacral ligaments of women with and without pelvic organ prolapse (POP) and analyze their relationships to cellular mechanisms involved in the pathogenesis of POP. EXPERIMENTAL DESIGN: Uterosacral ligament connective tissue from four patients with POP and four control women undergo iTRAQ analysis followed by ingenuity pathway analysis (IPA) of DEPs. DEPs are validated using Western blot analysis. RESULTS: A total of 1789 unique protein sequences are identified in the uterosacral ligament connective tissues. The expression levels of 88 proteins are significantly different between prolapse and control groups (≥1.2-fold, p < 0.05). IPA demonstrates the association of 14 DEPs with "Connective Tissue Function." Among them, fibromodulin, collagen alpha-1 (XIV) chain, calponin-1, tenascin, and galectin-1 appear most likely to play a role in the etiology of POP. CONCLUSIONS AND CLINICAL RELEVANCE: At least six proteins not previously associated with the pathogenesis of POP with biologic functions that suggest a plausible relationship to the disorder are identified. These results may be helpful for furthering the understanding of the pathophysiological mechanisms of POP.

A Community-Based Study of the Correlation of Hemorrhagic Stroke Occurrence with Meteorologic Factors.

BACKGROUND: Meteorologic variations may affect hemorrhagic stroke. Thus, the aim of this study was to explore the correlation of daily meteorologic factors with increased incidence of hypertensive intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) in a community-based study. METHODS: In a span of 2 years, 735 patients suffering from hypertensive ICH or SAH were enrolled in the study in Fularji District, Heilongjiang Province, China. Daily meteorologic data were obtained from the Bureau of Meteorology of Qiqihar. Daily meteorologic parameters with and without events were compared with hypertensive ICH and SAH, respectively. Logistic regression was used to assess the correlation of meteorologic factors with hypertensive ICH and SAH. RESULTS: Daily mean ambient temperature (AT) was statistically associated with the onset of primary hypertensive ICH (odds ratio [OR], .983; P < .001) and SAH (OR, .984; P = .046). After adjustment with AT variations, the occurrence of primary hypertensive ICH was not only influenced by daily mean AT (P = .0004) but also by the interaction between the mean temperature and its variation (P = .0082). Interestingly, there was no statistical association between meteorologic factors and recurrent hypertensive ICH. CONCLUSIONS: The higher incidence of primary hypertensive ICH in the late spring and early autumn was because of the influence of daily mean AT and its variation. When temperature changed, suddenly dropping in the hot weather or rising in the cold weather, the incidence of primary hypertensive ICH was also increased. Conversely, the incidence of SAH increased during days with lower temperature.

Increased ratio of neutrophil elastase to α1-antitrypsin is closely associated with liver inflammation in patients with nonalcoholic steatohepatitis.

An imbalance between neutrophil elastase (NE) and its inhibitor α1-antitrypsin (A1 AT) is known to contribute to the development of obesity-related inflammation. This study aimed to investigate the role of the NE-A1 AT system in the histological progression of non-alcoholic fatty liver disease (NAFLD), and to evaluate the ability of it to predict nonalcoholic steatohepatitis (NASH). A total of 252 adults (NAFLD group, n = 202; healthy group, n = 50) were recruited. Clinical biochemical characteristics, NE and A1 AT concentrations were measured in all subjects. Among the NAFLD group, 86 patients had previously undergone liver biopsy and information on histological characteristics was consequently available. The area under the receiver operating characteristic curve (AUC) was used to determine the predictive accuracy of the NE-A1 AT system for NASH. NAFLD patients had an elevated serum NE concentration and a reduced A1 AT level with consequent NE/A1 AT imbalance. NE increased in the early stage of steatosis, preceding the decline in A1 AT, dating from the onset of NASH (NAS 3-4), and subsequently NE/A1 AT increased in the presence of NASH. Nonetheless, this increase began to resolve as the disease state progressed to advanced fibrosis. A1 AT had a sensitivity (SEN) of 83.8% and a specificity (SP) of 83.3% with the optimal cut-off of -1459.43, NE/A1 AT had a SEN of 88.8% and a SP of 83.3% with cut-off of 0.363 to predict NASH. An increased NE: A1 AT ratio is closely associated with liver Inflammation in patients with NASH and could serve as a novel marker to predict NASH in humans.

Neutrophils Play a Crucial Role in the Early Stage of Nonalcoholic Steatohepatitis via Neutrophil Elastase in Mice.

Neutrophils infiltration in liver is one of the typical histological characteristics of nonalcoholic steatohepatitis (NASH) in both animal models and human subjects. This study was aimed to investigate the role of neutrophils in the process of NASH and its underling mechanisms. C57BL/6J mice were fed with either standard chow (SC) or methionine/choline-deficient (MCD) diet for 1, 2, 4, 8 weeks, respectively. C57BL/6J APOE(-/-) mice were fed with SC or high-fat high-cholesterol (HFHC) diet. Anti-Ly6G antibody was employed to deplete neutrophils and sivelestat was used to inhibit neutrophil elastase (NE). MCD-diet-receiving mice with neutrophil depletion had much lower serum ALT activity, liver inflammation, and mRNA levels of proinflammatory genes in the early stage of NASH (1 and 2 weeks) when compared to non-neutrophil-depleted mice. NE inhibitor sivelestat could recapitulate the effects of neutrophil depletion in APOE(-/-) mice fed with HFHC diet. As the disease progressed (4 and 8 weeks), neutrophil depletion did not lower serum ALT levels and liver lesions due to activation of Kupffer cells. Finally, we found neutrophils also affected anti-inflammation cytokine interleukin-1 receptor antagonist mRNA expression. Neutrophils play a crucial role in the early stage of NASH via NE.

Identification of potential biomarkers for ovarian cancer by urinary metabolomic profiling.

To evaluate the application of urinary metabolomics on discovering potential biomarkers for epithelial ovarian cancer (EOC), urine samples from 40 preoperative EOC patients, 62 benign ovarian tumor (BOT) patients, and 54 healthy controls were collected and analyzed with ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). Good separations were obtained for EOC vs BOT, EOC vs healthy controls analyzed by partial least-squares discriminant analysis, or principal component analysis. Twenty-two ascertained metabolomic biomarkers were found to be disturbed in several metabolic pathways among EOC patients, including nucleotide metabolism (pseudouridine, N4-acetylcytidine), histidine metabolism (L-histidine, imidazol-5-yl-pyruvate), tryptophan metabolism (3-indolelactic acid), and mucin metabolism (3'-sialyllactose and 3-sialyl-N-acetyllactosamine). In addition, the concentrations of some urinary metabolites of 18 postoperative EOC patients among the 40 EOC patients changed significantly compared with those of their preoperative condition, and four of them suggested recovery tendency toward normal level after surgical operation, including N4-acetylcytidine, pseudouridine, urate-3-ribonucleoside, and succinic acid. These metabolites would be highly postulated to be associated with EOC. In conclusion, our study demonstrated that urinary metabolomics analysis by UPLC-QTOF/MS, performed in a minimally noninvasive and convenient manner, possessed great potential in biomarker discovery for EOC.

Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide.

BACKGROUND: The effectiveness of near-infrared imaging (NIR) interrogation of epidermal growth factor receptor (EGFR) expression as a sensitive biomarker of oral squamous cell carcinoma (OSCC) response to arsenic trioxide therapy was studied in mice. MATERIAL AND METHODS: A431 OSCC in vitro were exposed to 0 µM, 0.5 µM, 2.5 µM, or 5 µM of As(2)O(3) for 0 h, 24 h, 48 h and 72 h. Confocal microscopy and flow cytometry confirmed EGFR expression and demonstrated a sensitivity dose-related signal decline with As(2)O(3) treatment. Next, mice with pharynx-implanted A431 cells received As(2)O(3) i.p. every 48 h at 0.0, 0.5, 2.5, or 5 mg/kg/day (n = 6/group) from day 0 to 10. An intravenous NIR probe, EGF-Cy5.5, was injected at baseline and on days 4, 8, and 12 for dynamic NIR imaging. Tumor volume and body weights were measured three times weekly. RESULTS: In vitro, A431 EGFR expression was well appreciated in the controls and decreased (p<0.05) with increasing As(2)O(3) dose and treatment duration. In vivo EGFR NIR tumor signal intensity decreased (p<0.05) in As(2)O(3) treated groups versus controls from days 4 to 12, consistent with increasing dosage. Tumor volume diminished in a dose-related manner while body weight was unaffected. Immunohistochemical staining of excised tumors confirmed that EGFR expression was reduced by As(2)O(3) treatment in a dose responsive pattern. CONCLUSION: This study demonstrates for the first time that OSCC can be interrogated in vivo by NIR molecular imaging of the EGFR and that this biomarker is effective for the longitudinal assessment of OSCC response to As(2)O(3) treatment.

Discrimination between malignant and benign ovarian tumors by plasma metabolomic profiling using ultra performance liquid chromatography/mass spectrometry.

BACKGROUND: Discrimination between epithelial ovarian cancer (EOC) and benign ovarian tumor (BOT) has always been difficult in clinical practice. We investigated the application of metabolomics in distinguishing EOC and BOT and tried to discover valuable biomarkers. METHODS: Plasma metabolomic profiling was performed using ultra-performance liquid chromatography mass spectrometry (UPLC/MS). Partial least-squares discriminant analysis was employed to classify EOC and BOT, and reveal their metabolic differences. The area under the receiver-operating characteristic curve (AUC) was utilized to evaluate the predictive performance of the metabolic profiles for external validation set. RESULTS: The metabolomic profiles consisting of 535 metabolites revealed a clear separation between EOC and BOT, with AUC of 0.86 for the external validation set. 6 metabolic biomarkers were identified, and the plasma concentrations of the 4 ascertained biomarkers (L-tryptophan, LysoPC(18:3), LysoPC(14:0), and 2-Piperidinone) were lower in EOC patients than those in BOT patients. Among them, tryptophan and LysoPC have been suspected to participate in cancer progression, and 2-Piperidinone might be a novel biomarker for EOC. CONCLUSIONS: Metabolomics could be used to discriminate EOC from BOT in clinical practice, and the identified metabolic biomarkers might be important on investigating the biological mechanisms of EOC.

The long-term efficacy of neoadjuvant chemotherapy followed by radical hysterectomy compared with radical surgery alone or concurrent chemoradiotherapy on locally advanced-stage cervical cancer.

OBJECTIVES: The purpose of this study was to compare the long-term survival of patients with locally advanced cervical cancer (stages IB2-IIB) treated with neoadjuvant chemotherapy followed by radical hysterectomy (hysterectomy plus pelvic lymph node dissection) (NACT + RS) with the survival of those treated with radical surgery (hysterectomy plus pelvic lymph node dissection) (RS) or concurrent chemoradiotherapy (CCRT). METHODS: A retrospective study was performed. Patients were followed up for 54 to 114 months (median, 82.8 months). All risk factors that may have affected the disease-free survival (DFS) and overall survival (OS) were assessed. RESULTS: From January 2000 to December 2005, 476 eligible patients were followed up. The 5-year DFS rates of the NACT + RS, RS, and CCRT groups were 85.00%, 77.44%, and 52.94%, respectively (P < 0.0001), whereas the 5-year OS rates were 88.67%, 80.21% and 64.37%, respectively (P < 0.0001). The NACT + RS group had significantly higher survival rates than both the RS (DFS: hazard ratio = 1.870, P = 0.0031; OS: hazard ratio = 1.813, P = 0.0175) and CCRT (DFS: hazard ratio = 3.535, P < 0.0001; OS: hazard ratio = 3.157, P < 0.0001) groups, while adjusting for the pathological type, clinical stage, tumor size (initial), and age. The 5-year DFS rate for patients receiving TP (paclitaxel and cisplatin) was 90.55%, and 71.70% for patients receiving PVB (cisplatin, vincristine, and bleomycin); the 5-year OS rates were 96.75% for TP and 70.09% for PVB, respectively. Patients receiving TP had a statistically significant improvement in both 5-year DFS and OS rates (P < 0.001). CONCLUSIONS: Neoadjuvant NACT + RS improves the long-term DFS and OS of patients with locally advanced cervical cancer stage IB2-IIB compared with RS alone and especially compared with CCRT. In the NACT + RS group, NACT with TP improves the long-term DFS and OS of patients compared with patients who had PVB chemotherapy regimen. These results may provide some useful information for clinicians to treat patients with locally advanced cervical carcinoma.

[Analysis of clinicopathologic features and prognosis in 2414 patients with rectal cancer].

OBJECTIVE: To explore the clinicopathologic factors associated with prognosis in patients with rectal cancer. METHODS: Clinicopathologic data of 2414 patients with rectal cancer, treated in the Affiliated Tumor Hospital of Harbin Medical University from May 1976 to December 2003, were analyzed retrospectively. Cox regression model was used to assess independent factors associated with prognosis. RESULTS: The median survival time was 58 months and the 5-year overall survival rate was 45.1%. Tumors were stage I( in 75.2%, stage II( in 48.1%, stage III( in 21.3%, and stage Ⅳ( in 8.8% of the patients. The 5-year overall survival rates during the three study periods were 41.2%(1976-1986), 43.0%(1987-1996), and 49.1%(1997-2003)(P<0.01). On univariate analysis, age, time at diagnosis, histological type, distant metastasis, type of surgery, intent of surgery, gross morphology, pathologic T stage, lymphatic invasion, bowel obstruction, and TNM stage showed statistically significant association with survival. Independent prognostic factors on multivariable analysis were gross tumor morphology chi-squared value(CV):68.744, pT(CV:81.344), lymphatic invasion(CV:42.951), bowel obstruction(CV:37.856) and TNM stage(CV:85.329). CONCLUSIONS: Survival in patients with rectal cancer is improved over time. TNM stage is the most important prognostic factor for survival in patients with rectal cancer.