Biochemical analyses reveal new insights into RCAN1/Rcn1 inhibition of calcineurin.

Calcineurin is a serine/threonine protein phosphatase that is highly conserved from yeast to human and plays a critical role in many physiological processes. Regulators of calcineurin (RCANs) are a family of endogenous calcineurin regulators, which are capable of inhibiting the catalytic activity of calcineurin in vivo and in vitro. In this study, we first characterized the biochemical properties of yeast calcineurin and its endogenous regulator Rcn1, a yeast homolog of RCAN1. Our data show that Rcn1 inhibits yeast calcineurin toward pNPP substrate with a noncompetitive mode; and Rcn1 binds cooperatively to yeast calcineurin through multiple low-affinity interactions at several docking regions. Next, we reinvestigated the mechanism underlying the inhibition of mammalian calcineurin by RCAN1 using a combination of biochemical, biophysical, and computational methods. In contrast to previous observations, RCAN1 noncompetitively inhibits calcineurin phosphatase activity toward both pNPP and phospho-RII peptide substrates by targeting the enzyme active site in part. Re-analysis of previously reported kinetic data reveals that the RCAN1 concentrations used were too low to distinguish between the inhibition mechanisms [Chan B et al. (2005) Proc Natl Acad Sci USA 102, 13075]. The results presented in this study provide new insights into the interaction between calcineurin and RCAN1/Rcn1.

Reduction of eEF2 kinase alleviates the learning and memory impairment caused by acrylamide.

BACKGROUND: The impact of acrylamide (ACR) on learning and memory has garnered considerable attention. However, the targets and mechanisms are still unclear. RESULTS: Elongation factor 2 (eEF2) was significantly upregulated in the results of serum proteomics. Results from in vitro and in vivo experiments indicated a notable upregulation of Eukaryotic elongation factor 2 kinase (eEF2K), the sole kinase responsible for eEF2 phosphorylation, following exposure to ACR (P < 0.05). Subsequent in vitro experiments using eEF2K siRNA and in vivo experiments with eEF2K-knockout mice demonstrated significant improvements in abnormal indicators related to ACR-induced learning and memory deficits (P < 0.05). Proteomic analysis of the hippocampus revealed Lpcat1 as a crucial downstream protein regulated by eEF2K. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that eEF2K may play a role in the process of ACR-induced learning and memory impairment by affecting ether lipid metabolism. CONCLUSIONS: In summary, eEF2K as a pivotal treatment target in the mechanisms underlying ACR-induced learning and memory impairment, and studies have shown that it provides robust evidence for potential clinical interventions targeting ACR-induced impairments.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Incidence, prevention, risk factors, and prediction of venous thromboembolism in Chinese patients after colorectal cancer surgery: a prospective, multicenter cohort study.

BACKGROUND: Venous thromboembolism (VTE) is a common and serious complication after colorectal cancer (CRC) surgery. Few large-sample studies have reported VTE incidence and management status after CRC surgery in China. This study aimed to investigate the incidence and prevention of VTE in Chinese patients after CRC surgery, identify risk factors for developing VTE, and construct a new scoring system for clinical decision-making and care planning. METHODS: Participants were recruited from 46 centers in 17 provinces in China. Patients were followed up for 1 month postoperatively. The study period was from May 2021 to May 2022. The Caprini score risk stratification and VTE prevention and incidence were recorded. The predictors of the occurrence of VTE after surgery were identified by multivariate logistic regression analysis, and a prediction model (CRC-VTE score) was developed. RESULTS: A total of 1836 patients were analyzed. The postoperative Caprini scores ranged from 1 to 16 points, with a median of 6 points. Of these, 10.1% were classified as low risk (0-2 points), 7.4% as moderate risk (3-4 points), and 82.5% as high risk (≥5 points). Among these patients, 1210 (65.9%) received pharmacological prophylaxis, and 1061 (57.8%) received mechanical prophylaxis. The incidence of short-term VTE events after CRC surgery was 11.2% (95% CI 9.8-12.7), including deep venous thrombosis (DVT) (11.0%, 95% CI 9.6-12.5) and pulmonary embolism (PE) (0.2%, 95% CI 0-0.5). Multifactorial analysis showed that age (≥70 years), history of varicose veins in the lower extremities, cardiac insufficiency, female sex, preoperative bowel obstruction, preoperative bloody/tarry stool, and anesthesia time at least 180 min were independent risk factors for postoperative VTE. The CRC-VTE model was developed from these seven factors and had good VTE predictive performance ( C -statistic 0.72, 95% CI 0.68-0.76). CONCLUSIONS: This study provided a national perspective on the incidence and prevention of VTE after CRC surgery in China. The study offers guidance for VTE prevention in patients after CRC surgery. A practical CRC-VTE risk predictive model was proposed.

Rationale and design of a prospective, multicenter, cohort study on the evaluation of postoperative Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial).

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common complication after abdominal surgery. The incidence of VTE after colorectal malignancy is higher than that after general surgery. Although more attention has been paid to the prevention of VTE, there is still a large gap between clinical practice and guideline recommendation. Methods: The Venous ThromboEmbolism incidence in patients with ColoRectal Cancer (CRC-VTE trial) will be a prospective, multicenter, cohort study to determine the current status of the incidence, diagnosis, treatment, and prevention of VTE after colorectal cancer surgery in China, as well as to further improve the level of prevention and treatment of VTE events in these fragile patients. In this study, 1,217 patients will be enrolled at 40 centers in China and evaluated on VTE events and adverse events related to VTE prevention at 5-9 and 21-28 days after surgery. The primary outcome is the incidence of VTE events during the follow-up, and secondary outcome is the incidence of adverse events associated with VTE prevention. Discussion: This study will comprehensively evaluate the incidence and prevention of VTE after colorectal cancer surgery in China, balance the relationship between VTE prevention and bleeding adverse events, and the formulate a guideline for the prevention of VTE after colorectal surgery that might suitable for national conditions. Trial Registration: Clinical trial registration number NCT04588805 (The CRC-VTE trial).

Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics.

Mitochondria are indispensable for energy metabolism and cell signaling. Mitochondrial homeostasis is sustained with stabilization of mitochondrial membrane potential, balance of mitochondrial calcium, integrity of mitochondrial DNA, and timely clearance of damaged mitochondria via mitophagy. Mitochondrial dysfunction is featured by increased generation of mitochondrial reactive oxygen species, reduced mitochondrial membrane potential, mitochondrial calcium imbalance, mitochondrial DNA damage, and abnormal mitophagy. Accumulating evidence indicates that mitochondrial dysregulation causes oxidative stress, inflammasome activation, apoptosis, senescence, and metabolic reprogramming. All these cellular processes participate in the pathogenesis and progression of chronic respiratory diseases, including chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. In this review, we provide a comprehensive and updated overview of the impact of mitochondrial dysfunction on cellular processes involved in the development of these respiratory diseases. This not only implicates mechanisms of mitochondrial dysfunction for the pathogenesis of chronic lung diseases but also provides potential therapeutic approaches for these diseases by targeting dysfunctional mitochondria.

Factors associated with overall survival in early gastric cancer patients who underwent additional surgery after endoscopic submucosal dissection.

BACKGROUND: Controversy exists about the benefit of additional surgery after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). AIM: To examine risk factors for overall survival (OS) after additional surgery in patients with EGC who initially underwent ESD. METHODS: This was a retrospective analysis of patients with EGC who underwent additional surgery after ESD at the Beijing Friendship Hospital affiliated to Capital Medical University between August 2012 and August 2019. OS was the primary outcome. Lymph node metastasis and residual tumor were secondary outcomes. Logistic regression models and Kaplan-Meier curves were used for further analysis. RESULTS: Forty-two patients were evaluated, including 35 (83.3%) males and 7(16.7%) females. The mean age was 62 (range, 32-82) years. Male sex [hazard ratio (HR) = 21.906, 95% confidence interval (CI): 3.762-229.250; P = 0.039), T1b invasion (HR = 3.965, 95%CI: 1.109-17.432; P = 0.047), undifferentiated tumor (HR = 9.455, 95%CI: 0.946-29.482; P = 0.049), lymph node metastasis (HR = 2.126, 95%CI: 0.002-13.266; P = 0.031), and residual tumor (HR = 4.275, 95%CI: 1.049-27.420; P = 0.043) were independently associated with OS. The follow-up duration was 4-81 mo (median: 50.7 mo). OS was 77.0 ± 12.1 mo (95%CI: 53.3-100.7 mo). The 3-year and 5-year OS rates were 94.1% and 85%, respectively. CONCLUSION: Male sex, T1b invasion, undifferentiated tumor, lymph node metastasis, and residual tumor are independently associated with OS in patients with EGC who underwent additional surgery after ESD.

Verification of data in a nationwide transanal total mesorectal excision registry in China.

BACKGROUND AND OBJECTIVES: Transanal total mesorectal excision is a surgical procedure for mid- and low rectal cancer. The Chinese TaTME Registry Collaborative is a nationwide database collecting information on patients who have undergone this procedure. METHODS: Centers were invited by the registry committee to participate in a three-part data audit project: remote audits for data completeness and deviation values, onsite source verification of data accuracy, and an online survey of the characteristics of data managers. RESULTS: Twenty-three tertiary centers participated in this project. The median case volume registered by the centers was 51 (interquartile range, 25-89). The overall data completeness for 30 verified variables was 89.1%. Eight centers achieved a high data completeness rate (>95%). The source data of eight centers were verified onsite. The overall accuracy rate was 90.4% (85.3%-97.6% across centers). Postoperative complications, mortality, and proximal/distal resection margin involvement were accurately reported in >95% of cases. The data completeness rate was higher if the data manager was a surgeon/surgical resident (94.2% vs. 84.8%, p = 0.045). CONCLUSIONS: The completeness and accuracy of the data in the Chinese TaTME Registry Collaborative are acceptable. The quality of the data is highest when entered by colorectal surgeons and residents.

Gunsight Procedure Versus the Purse-String Procedure for Closing Wounds After Stoma Reversal: A Multicenter Prospective Randomized Trial.

BACKGROUND: Stoma reversal is associated with a high risk of wound infection. The gunsight and purse-string closure techniques are both effective alternatives for stoma reversal, but comparative studies are lacking. OBJECTIVE: The purpose of this study was to compare the gunsight procedure with the purse-string closure technique when closing wounds after loop stoma reversal. DESIGN: This was a nonblinded, multicenter prospective randomized study (clinicaltrials.gov No. NCT02053948). SETTINGS: The study was conducted at a general surgery unit of 7 tertiary academic medical centers. PATIENTS: A total of 143 patients undergoing loop stoma reversal were included in the study (72 in the gunsight group and 71 in the purse-string group) between November 2013 and December 2017. INTERVENTION: Patients were randomly assigned to undergo either gunsight or purse-string closure procedure. MAIN OUTCOME MEASURES: Primary outcome was wound healing time. Secondary outcomes were the incidence of surgical site infection, morbidity, and patient satisfaction. RESULTS: No differences were found between the 2 groups in terms of surgical site infection, intraoperative blood loss, and postoperative hospital stay. The gunsight procedure had a shorter wound healing time compared with the purse-string procedure (17 vs 25 d; p < 0.001). A patient satisfaction questionnaire showed that the gunsight group had a higher score level of patient satisfaction with respect to wound healing time (p < 0.001) and total patient satisfaction score (p = 0.01) than the purse-string group. LIMITATIONS: Treatment teams were not blinded, and there was operator dependence of techniques. CONCLUSIONS: The gunsight and purse-string techniques are effective procedures for stoma reversal and both have a low incidence of surgical site infection. The gunsight technique is associated with shorter wound healing time, higher levels of patient satisfaction with regard to healing time, and overall final score and is recommended as the closure technique of choice. See Video Abstract at http://links.lww.com/DCR/B319. EL PROCEDIMIENTO DE GUNSIGHT VERSUS EL PROCEDIMIENTO DE JARETA, PARA EL CIERRE DE HERIDAS, DESPUéS DE REVERSIóN DE ESTOMA: UN ENSAYO, MULTICéNTRICO, PROSPECTIVO Y RANDOMIZADO: La reversión de estoma está asociada con un alto riesgo de infección de la herida. Las técnicas de gunsight y de jareta, son eficaces alternativas en la reversión de estoma, pero faltan estudios comparativos.Comparar el procedimiento de gunsight con la técnica de jareta, después de la reversión de estoma en asa.Estudio multicéntrico, prospectivo y randomizado ciego (NCT02053948).Realizado en la unidad de cirugía general, de siete centros médicos académicos terciarios.Se incluyeron en el estudio, un total de 143 pacientes sometidos a reversión de estoma de asa (72 en el grupo de gunsight y 71 en el grupo de jareta) entre noviembre de 2013 y diciembre de 2017.Los pacientes fueron asignados aleatoriamente, para someterse a un procedimiento de cierre de gunsight o de jareta.El resultado primario fue el tiempo de cicatrización de la herida. Los resultados secundarios fueron la incidencia de infección del sitio quirúrgico, morbilidad y satisfacción del paciente.No se encontraron diferencias entre los dos grupos en términos de infección del sitio quirúrgico, pérdida de sangre intraoperatoria o estadía hospitalaria postoperatoria. El procedimiento de gunsight tuvo un tiempo más corto en la cicatrización de la herida, en comparación con el procedimiento de jareta (17 días frente a 25 días, p <0,001). Un cuestionario de satisfacción del paciente, mostró que el grupo de gunsight tenía una puntuación más alta en relación al tiempo de cicatrización de la herida (p <0.001) y la puntuación total en satisfacción del paciente (p = 0.01), que en el grupo de jareta.Los equipos de tratamiento quirúrgico, no fueron cegados y hubo en los cirujanos, dependencia en las técnicas.Las técnicas de gunsight y de jareta son procedimientos efectivos para la reversión de estoma y ambas tienen una baja incidencia de infección en el sitio quirúrgico. La técnica de gunsight está asociada con un tiempo más corto en cicatrización de heridas, mejores niveles en satisfacción del tiempo de cicatrización y en la puntuación general final. Se recomienda como la técnica de cierre de elección. Consulte Video Resumen en http://links.lww.com/DCR/B319. (Traducción-Dr Fidel Ruiz Healy).

An Analysis Scheme of Balancing Energy Consumption with Mobile Velocity Control Strategy for Wireless Rechargeable Sensor Networks.

Wireless Rechargeable Sensor Networks (WRSN) are not yet fully functional and robust due to the fact that their setting parameters assume fixed control velocity and location. This study proposes a novel scheme of the WRSN with mobile sink (MS) velocity control strategies for charging nodes and collecting its data in WRSN. Strip space of the deployed network area is divided into sub-locations for variant corresponding velocities based on nodes energy expenditure demands. The points of consumed energy bottleneck nodes in sub-locations are determined based on gathering data of residual energy and expenditure of nodes. A minimum reliable energy balanced spanning tree is constructed based on data collection to optimize the data transmission paths, balance energy consumption, and reduce data loss during transmission. Experimental results are compared with the other methods in the literature that show that the proposed scheme offers a more effective alternative in reducing the network packet loss rate, balancing the nodes' energy consumption, and charging capacity of the nodes than the competitors.

Utility of circulating tumor cells in stage II colorectal cancer patients undergoing curative resection.

BACKGROUND: The aim of this study was to determine whether circulating tumor cells (CTCs) have utility as a prognostic biomarker in stage II colorectal cancer (CRC), as well as a biomarker for the selection of patients for adjuvant chemotherapy. METHODS: CTCs were detected in peripheral blood samples obtained from 73 stage II CRC patients, using a negative enrichment and immune-fluorescence in situ hybridization (imFISH) staining method. The follow-up time ranged from 3.5 to 35.9 months, and the clinic-pathologic characteristics and recurrence free survival (RFS) were collected and analyzed. RESULTS: Seventy-three stage II CRC patients were included in this study. The positive rate of CTCs was 65.8% in all patients, 87.5% in recurrent patients and 59.6% in no recurrence patients. The mean RFS was 30.6 months for all patients, 28.7 months for CTC-positive patients and 34.0 months for CTC-negative patients (P=0.043). The mean RFS of CTC-positive and CTC-negative patients with adjuvant chemotherapy were not reached, and those without adjuvant chemotherapy were 27.7 and 33.4 months, respectively. CONCLUSIONS: The level of CTCs may be an effective prognostic factor to predict RFS in stage II CRC patients, and has potential in selecting stage II CRC patients for adjuvant chemotherapy.

Cigarette Smoke Reduces Fatty Acid Catabolism, Leading to Apoptosis in Lung Endothelial Cells: Implication for Pathogenesis of COPD.

Endothelial cell (EC) apoptosis contributes to cigarette smoke (CS)-induced pulmonary emphysema. Metabolism of glucose, glutamine, and fatty acid is dysregulated in patients with chronic obstructive pulmonary disease (COPD). Whether CS causes metabolic dysregulation in ECs leading to development of COPD remains elusive. We hypothesized that CS alters metabolism, resulting in apoptosis in lung ECs. To test this hypothesis, we treated primary mouse pulmonary microvascular ECs (PMVECs) with CS extract (CSE) and employed PMVECs from healthy subjects and COPD patients. We found that mitochondrial respiration was reduced in CSE-treated PMVECs and in PMVECs from COPD patients. Specifically, oxidation of fatty acids (FAO) was reduced in these cells, which linked to reduced carnitine palmitoyltransferase 1a (Cpt1a), an essential enzyme for carnitine shuttle. CSE-induced apoptosis was further increased when cells were treated with a specific Cpt1 inhibitor etomoxir or transfected with Cpt1a siRNA. L-Carnitine treatment augmented FAO but attenuated CSE-induced apoptosis by upregulating Cpt1a. CSE treatment increased palmitate-derived ceramide synthesis, which was reduced by L-carnitine. Although CSE treatment increased glycolysis, inhibiting glycolysis with 2-deoxy-d-glucose had no effects on CSE-mediated apoptosis in lung ECs. Conclusively, FAO reduction increases ceramide and apoptosis in lung ECs treated with CSE, which may contribute to the pathogenesis of COPD/emphysema.

Artificial intelligence system of faster region-based convolutional neural network surpassing senior radiologists in evaluation of metastatic lymph nodes of rectal cancer.

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION: www.chictr.org.cn (No. ChiCTR-DDD-17013842).

Enhanced Expression of TGFBI Promotes the Proliferation and Migration of Glioma Cells.

BACKGROUND/AIMS: Transforming growth factor beta-induced protein (TGFBI) is an extracellular matrix protein induced by TGF-ß. Previous studies have reported that the abnormal expression of TGFBI is related to the occurrence and development of some types of cancers, while the role of TGFBI in glioma is uncertain. METHODS: The association between TGFBI expression and the prognosis of patients with glioma was analyzed based on data obtained from The Cancer Genome Atlas database. TGFBI expression was analyzed in 3 normal human brains and 57 cases of human gliomas by immunohistochemistry followed by an evaluation of the relationships between TGFBI expression and clinic-pathological features. Furthermore, the RNA interference plasmid pSUPER-shTGFBI was constructed and transfected into U87 and U251 cells to explore the effect of short hairpin RNA against TGFBI (shTGFBI) on cell proliferation, migration, invasion and apoptosis. Western blot analysis was performed to examine the expression of proteins related to apoptosis and proteins in the PI3K/Akt signaling pathway. RESULTS: High TGFBI expression was found to be associated with poor prognosis in patients with glioblastoma multiforme. Immunohistochemistry showed that TGFBI expression was significantly higher in glioma tissue than in normal human brain tissues. The expression level of TGFBI showed no significant correlation with age, sex, lymph-node metastasis, or pathological grade. sh-TGFBI could inhibit proliferation, invasion and migration and induce apoptosis in U87 and U251 cells in vitro. Furthermore, the phosphorylation levels of AKT and mTOR declined significantly in sh-TGFBI transfected U81 and U251 cells when compared with control. CONCLUSION: TGFBI was up-regulated in glioma cells and played a promoting role in the growth and motility of U87 and U251 cells. These results suggested that TGFBI has the potential to be a diagnostic marker and to serve as a target for the treatment of gliomas.

Alcohol use in Hefei in relation to alcoholic liver disease: A multivariate logistic regression analysis.

BACKGROUND: An increase in alcohol consumption and related harmful effects has been reported among the elderly population in Asia. Of note, it is important to monitor patterns of alcohol use, and to establish a valid and reliable evaluation system when screening for risky consumption in this age group. OBJECTIVE: The aim of the current study was to evaluate the possible alcoholic liver disease (ALD) risk factors of a local population in elderly Chinese adults. METHODS: A questionnaire was sent to 3393 Chinese adults over 40 years old in Hefei. Alcohol consumption was determined based on the AUDIT questionnaire. ALD was defined by ALD diagnostic standards. Adjusted odds ratios and 95% confidence intervals (95% CI) derived from multiple logistic regression models were used to assess the relationship between ALD and sociodemographic variables. RESULTS: Among 2545 total interviewees, 448 (17.6%) reported a history of alcohol consumption in the previous 12 months. Of these drinkers, 46.7% were male and 53.3% were female. The overall Cronbach's alpha coefficient for AUDIT was 0.648. The rate of ALD was 6.83%. Alcohol abuse was significantly associated with ALD. In the logistical model, alcohol abuse was independently associated with ALD (OR = 6.17, 95% CI: 3.69-15.24; p < 0.01). CONCLUSIONS: Alcohol use, sex, age, and facial flushing were risk factors for ALD. These results provide important evidence for the prevention and therapy of ALD.

Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients.

Characterization, diagnosis, and treatment of colorectal cancers (CRC) is difficult due to limited biopsy information, impracticality of repeated biopsies, and cancer biomarker fallibility. Circulating tumor DNA (ctDNA) has recently been investigated as a non-invasive way to gain representative gene mutations in tumors, in addition to monitoring disease progression and response to treatment. We analyzed ctDNA mutations and concentrations in 47 early- and late-stage CRC patients using a targetted sequencing approach using a panel that covers 50 cancer-related genes. ctDNA mutations in 37 genes were identified in 93.6% of the patients (n=47). The results showed that TP53, PIK3CA, APC, and EGFR were the most frequently mutated genes. Stage IV patients had significantly higher ctDNA concentration than Stage I patients, and increased ctDNA concentration correlated with increased tumor size. Additionally, ctDNA detection was found to be a greater predictor of disease when compared with five known commonly used tumor biomarkers. The present study supports the use of ctDNA as a liquid biopsy to gain clinical tumor information that may facilitate early diagnosis and treatment and improve CRC patient prognosis.

[Feasibility and Safety of Enhanced Recovery after Surgery for Elderly Patients with Colorectal Cancer].

Objective To evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) in elderly patients with colorectal cancer (CRC).Methods A retrospective analysis was conducted on 230 CRC patients undergoing ERAS from January 2017 to January 2018. These subjects included 120 young patients (<70 years) and 110 elderly patients (≥70 years).The rates of ERAS compliance,anastomotic leakage,re-operation,and re-hospitalization,the mortality,and the average hospital stay were compared between these two groups.Results The elderly group had significantly higher incidences including diabetes (20.9% vs. 10.8%,P=0.045),heart disease (24.5% vs. 11.7%,P=0.039),respiratory diseases (20.0% vs. 10.0%,P=0.041),and hypertension (26.4% vs. 15.0%,P=0.035) than the young group. However,these two groups were not statistically significant in terms of ERAS compliance rate (79% in the young group vs. 74% in the elderly group,P=0.574),incidence of anastomotic leakage (2.5% vs. 1.8%,P=1.000),re-operation rate (1.7% vs. 2.7%,P=0.672),re-hospitalization rate (2.5% vs. 4.5%,P=0.484),mortality rate within 30 days after operation (1.7% vs. 2.7%,P=0.672). The average hospital stay was 5 days in the young group and 7 days in the elderly group (P=0.000).Conclusions Although the elderly patients tend to have poor general status,their ERAS compliance rate and main treatment indicators including incidence of anastomotic leakage,re-operation rate,re-hospitalization rate,and mortality rate within 30 days after surgery are not different from young patients. Thus,the ERAS program is safe and feasible for elderly CRC patients.

Laparoscopic-assisted Transanal Total Mesorectal Excision for Middle-Low Rectal Carcinoma: A Clinical Study of 19 Cases.

AIM: To explore the safety, feasibility and short-term outcomes of laparoscopic-assisted transanal total mesorectal excision (La-TaTME) of middle-low rectal carcinoma. MATERIALS AND METHODS: This retrospective research collected and analyzed the clinical data of 19 patients diagnosed with middle and low rectal carcinoma who underwent La-TaTME from August 2015 to February 2017. RESULTS: No case was converted to laparotomy. In none of the enrolled cases, did the circumferential resection margin test positive by histopathology examination. Also, there was no detected residual tumor at the proximal and distal resection margins. The rate of postoperative morbidity was 15.8% (Clavien-Dindo grade 2). During the follow-up period, no local recurrence or metastasis was observed. CONCLUSION: La-TaTME is a safe alternative to standard laparoscopic TME in middle-low rectal carcinoma when operated by an experienced colorectal surgeon. However, large-scaled randomized multi-centered comparative trials are still needed to further test its oncological effectiveness.

Explored Risk Factors for Lymph Node Metastasis with Siewert II/III Adenocarcinoma of the Gastroesophageal Junction.

AIM: To explore the risk factors and prognosis for lymphatic metastasis (LNM) in patients with Siewert II/III adenocarcinoma of the gastroesophageal junction (AEG). PATIENTS AND METHODS: This study retrospectively reviewed 49 patients with Siewert II/III AEG. Clinical characteristics and pathological features were analyzed by the Chi-square the and binary logistic regression. Survival data were analyzed using the Kaplan-Meier method. RESULTS: LNM frequency was found in lymph nodes No.1, No.2, No.3, No.7, No.11 and No.110. The results revealed that depth of infiltration, neoplasms by histological type and lymphatic embolus were independent risk factors for LNM. The 1- and 3-year survival of patients without LNM were both 100%, while patients with LNM had 70% and 60% survival, respectively. Although the differences were not statistically significant, survival rate with negative lymph nodes was higher than in patients with LNM. CONCLUSION: Total gastrectomy combined with D2 No.110 lymphadenectomy might improve the prognosis for LNM patients.