Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Higher oxidative balance score is associated with lower kidney stone disease in US adults: a population-based cross-sectional study.

PURPOSE: Oxidative balance stress (OBS) was an important indicator for assessing exposure to oxidative stress related to diet and lifestyle. The purpose of this study was to explore the relationship between OBS and kidney stone disease (KSD). METHODS: Secondary dataset analysis was performed by the study from six survey cycles (2007-2018) in the National Health and Nutrition Examination Survey (NHANES). OBS was the exposure factor and ever had kidney stone (yes or no) was the outcome. Weighted univariate or multivariate logistic regression models were used to estimate the associations. RESULTS: The prevalence of KSD among participants was 8.6%. OBS showed a significant negative correlation with KSD (OR: 0.98, 95% CI 0.96-0.999), 35% reduction in KSD in the highest OBS quartile compared to the lowest OBS quartile. Dietary OBS was significantly negatively correlated with KSD (OR: 0.98, 95% CI 0.96-0.9998), but not with lifestyle OBS. In addition, OBS had a negative correlation with KSD in females (OR: 0.97, 95% CI 0.94-0.996), non-diabetic participants (OR: 0.98, 95% CI 0.96-0.99), and hypertensive participants (OR: 0.96, 95% CI 0.93-0.99), but OBS was not observed to be associated with KSD in gout participants. Interestingly, this relationship existed in participants aged 30-60 years and a ratio of family income to poverty (PIR) of 1.3-3.5 (all P value < 0.05). CONCLUSION: Our study revealed that OBS was negative associated with KSD, and high OBS might be a protective factor in KSD. Targeting one of the components of OBS might be beneficial.

Antioxidant diet/lifestyle could mitigate the adverse impacts of urinary polycyclic aromatic hydrocarbons on lung function.

BACKGROUND: Extant research has demonstrated a correlation between exposure to polycyclic aromatic hydrocarbons (PAHs) and impaired lung function. The maintenance of an antioxidant-rich diet/lifestyle positively benefits pulmonary health. However, the potential ameliorative impact of an antioxidant-based diet/lifestyle on PAH-induced detrimental effects remains unclear. METHODS: The study drew upon cross-sectional data encompassing 1615 participants derived from the National Health and Nutrition Examination Survey 2007 to 2012. To gauge the maintenance of an antioxidant-rich diet/lifestyle, we employed Oxidative Balance Score (OBS) that incorporates sixteen nutrients and four lifestyle factors. Lung function was evaluated using percent-predicted Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1), FEV1/FVC, and fractional exhaled nitric oxide (FENO). Our analytical approach entailed the utilization of weighted linear models. RESULTS: Our analysis unveiled interaction effects between urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and OBS concerning lung function. A one-unit increase in ∑OH-PAH (sum of eight OH-PAHs) was linked to a -0.75% reduction (95% CI: -1.28, -0.22) in FEV1/FVC. Individuals exhibiting low OBS displayed a marked decrease in FEV1/FVC (mean difference = -1.10%; 95% CI: -1.82, -0.39) for each unit increase in ∑OH-PAH, whereas no significant associations were discerned for those with medium or high OBS. Further stratification by gender yielded consistent results. The correlation between ∑OH-PAH and FENO proved statistically significant among participants with low OBS (P = 0.002) and medium OBS (P = 0.001), but non-significant for those with high OBS. Parallel findings emerged when examining percent-predicted FEV1 and FVC. CONCLUSIONS: In conclusion, our study underscores the existence of statistically significant interactions between OH-PAHs and the maintenance of an antioxidant-rich diet and lifestyle concerning lung function. These findings underscore the pivotal role of maintaining an antioxidant-based diet and lifestyle in mitigating the adverse impacts of PAH exposure on lung function.

Higher oxidative balance score was associated with decreased risk of erectile dysfunction: a population-based study.

BACKGROUND: Erectile dysfunction (ED) is a prevalent condition that is thought to be significantly impacted by oxidative stress. The oxidative balance score (OBS) has been built to characterize the state of antioxidant/pro-oxidant balance. There is less known regarding the relationship of OBS with ED. METHODS: This study conducted cross-sectional analyses on 1860 males who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. OBS was constructed by the 16 dietary components and 4 lifestyle factors. Self-reported ED was defined as men who indicated that they "never" or "sometimes" could achieve or keeping an erection adequate for satisfactory intercourse. Multivariate logistic regression models were applied to examine the association between OBS and the risk of ED. RESULTS: Among 1860 participants, the median OBS was 20 (IQR 15-26), and OBS was lower in males with ED vs. those without ED (P = 0.001). The results of our analyses indicated a negative correlation between OBS and ED among male subjects. Specifically, each one-unit increase in the continuous OBS was relate to 3% reduction in the odds of ED after full adjustment. Moreover, when extreme OBS quartiles were compared, the adjusted odds ratio (95% confidence interval) for the 4th OBS category was 0.53 (0.32 to 0.88) after full adjustment (P for trend < 0.05). There was also statistical significance in the relationships between dietary/lifestyle OBS with ED, and the association between lifestyle OBS and ED may be even tighter. For each unit increase in lifestyle OBS, the odds of ED decreased by 11% after full adjustment. CONCLUSION: Higher OBS was associated with reduced risk of ED in U.S. males. These findings suggested that adopting an antioxidant-rich diet and engaging in antioxidant-promoting lifestyle behaviors may contribute to a lower incidence of ED. These results provided recommendations for a comprehensive dietary and lifestyle antioxidants for ED patients.

Risk factors and predicting nomogram for the clinical deterioration of non-severe community-acquired pneumonia.

BACKGROUND: Currently, there remains insufficient focus on non-severe community-acquired pneumonia (CAP) patients who are at risk of clinical deterioration, and there is also a dearth of research on the related risk factors. Early recognition of hospitalized patients at risk of clinical deterioration will be beneficial for their clinical management. METHOD: A retrospective study was conducted in The First Affiliated Hospital of Wenzhou Medical University, China, spanning from January 1, 2018 to April 30, 2022, and involving a total of 1,632 non-severe CAP patients. Based on whether their condition worsened within 72 h of admission, patients were divided into a clinical deterioration group and a non-clinical deterioration group. Additionally, all patients were randomly assigned to a training set containing 75% of patients and a validation set containing 25% of patients. In the training set, risk factors for clinical deterioration in patients with non-severe CAP were identified by using LASSO regression analysis and multivariate logistic regression analysis. A nomogram was developed based on identified risk factors. The effectiveness of the nomogram in both the training and validation sets was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS: Age, body mass index (BMI), body temperature, cardiovascular comorbidity, respiratory rate, LDH level, lymphocyte count and D-dimer level were identified as risk factors associated with the clinical deterioration of non-severe CAP within 72 h of admission. The area under curve (AUC) value of the nomogram was 0.78 (95% CI: 0.74-0.82) in the training set and 0.75 (95% CI: 0.67-0.83) in the validation set. Furthermore, the calibration curves for both the training and validation sets indicated that the predicted probability of clinical deterioration aligned with the actual probability. Additionally, DCA revealed clinical utility for the nomogram at a specific threshold probability. CONCLUSION: The study successfully identified the risk factors linked to the clinical deterioration of non-severe CAP and constructed a nomogram for predicting the probability of deterioration. The nomogram demonstrated favorable predictive performance and has the potential to aid in the early identification and management of non-severe CAP patients at elevated risk of deterioration.

Genome-Wide Analysis of the Oat (Avena sativa) HSP90 Gene Family Reveals Its Identification, Evolution, and Response to Abiotic Stress.

Oats (Avena sativa) are an important cereal crop and cool-season forage worldwide. Heat shock protein 90 (HSP90) is a protein ubiquitously expressed in response to heat stress in almost all plants. To date, the HSP90 gene family has not been comprehensively reported in oats. Herein, we have identified twenty HSP90 genes in oats and elucidated their evolutionary pathways and responses to five abiotic stresses. The gene structure and motif analyses demonstrated consistency across the phylogenetic tree branches, and the groups exhibited relative structural conservation. Additionally, we identified ten pairs of segmentally duplicated genes in oats. Interspecies synteny analysis and orthologous gene identification indicated that oats share a significant number of orthologous genes with their ancestral species; this implies that the expansion of the oat HSP90 gene family may have occurred through oat polyploidization and large fragment duplication. The analysis of cis-acting elements revealed their influential role in the expression pattern of HSP90 genes under abiotic stresses. Analysis of oat gene expression under high-temperature, salt, cadmium (Cd), polyethylene glycol (PEG), and abscisic acid (ABA) stresses demonstrated that most AsHSP90 genes were significantly up-regulated by heat stress, particularly AsHSP90-7, AsHSP90-8, and AsHSP90-9. This study offers new insights into the amplification and evolutionary processes of the AsHSP90 protein, as well as its potential role in response to abiotic stresses. Furthermore, it lays the groundwork for understanding oat adaptation to abiotic stress, contributing to research and applications in plant breeding.

Hepatocellular carcinoma cells remodel the pro-metastatic tumour microenvironment through recruitment and activation of fibroblasts via paracrine Egfl7 signaling.

BACKGROUND: The tumour microenvironment consists of a complex and dynamic milieu of cancer cells, including tumour-associated stromal cells (leukocytes, fibroblasts, vascular cells, etc.) and their extracellular products. During invasion and metastasis, cancer cells actively remodel the tumour microenvironment and alterations of microenvironment, particularly cancer-associated fibroblasts (CAFs), can promote tumour progression. However, the underlying mechanisms of the CAF formation and their metastasis-promoting functions remain unclear. METHODS: Primary liver fibroblasts and CAFs were isolated and characterized. CAFs in clinical samples were identified by immunohistochemical staining and the clinical significance of CAFs was also analysed in two independent cohorts. A transwell coculture system was used to confirm the role of HCC cells in CAF recruitment and activation. qRT-PCR, western blotting and ELISA were used to screen paracrine cytokines. The role and mechanism of Egfl7 in CAFs were explored via an in vitro coculture system and an in vivo mouse orthotopic transplantation model. RESULTS: We showed that CAFs in hepatocellular carcinoma (HCC) are characterized by the expression of α-SMA and that HCC cells can recruit liver fibroblasts (LFs) and activate them to promote their transformation into CAFs. High α-SMA expression, indicating high CAF infiltration, was correlated with malignant characteristics. It was also an independent risk factor for HCC survival and could predict a poor prognosis in HCC patients. Then, we demonstrated that EGF-like domain multiple 7 (Egfl7) was preferentially secreted by HCC cells, and exhibited high potential to recruit and activate LFs into the CAF phenotype. The ability of Egfl7 to modulate LFs relies upon increased phosphorylation of FAK and AKT via the receptor ανß3 integrin. Strikingly, CAFs activated by paracrine Egfl7 could further remodel the tumour microenvironment by depositing fibrils and collagen and in turn facilitate HCC cell proliferation, invasion and metastasis. CONCLUSION: Our data highlighted a novel role of Egfl7 in remodelling the tumour microenvironment: it recruits LFs and activates them to promote their transformation into CAFs via the ανß3 integrin signaling pathway, which further promotes HCC progression and contributes to poor clinical outcomes in HCC patients. Video Abstract.

Comparison of open, laparoscopic, and robotic left colectomy for radical treatment of colon cancer: a retrospective analysis in a consecutive series of 211 patients.

BACKGROUND: Robotic surgery has been widely used in the radical treatment of colonic cancer. However, it is unclear what advantages the robotic approach offers over other approaches in left colectomy. This study aims to explore the advantage of robotic surgery in left colectomy by comparing open, laparoscopic, and robotic surgery. METHODS: A retrospective analysis was performed on the clinical data of patients with radical left colectomy for colon cancer who were admitted to the Department of General Surgery, The First Affiliated Hospital of Nanchang University, from November 2012 to November 2017. Two hundred eleven patients included were divided into the open surgery group (OS, n=49), laparoscopic surgery group (LS, n=92), and robotic surgery group (RS, n=70) according to surgical techniques. The clinicopathologic data were collected for clinical outcome assessment. Finally, the clinical value of RS in radical left colectomy was further evaluated by propensity score matching (PSM) analysis. RESULTS: Three groups were similar in demographics and clinical characteristics. Compared with OS, LS and RS groups had better intraoperative and perioperative clinical outcomes. Moreover, the RS group exhibited the minimum operative times, length of stay (LOS), and evaluated blood loss. LS and RS also exhibited less perioperative and postoperative long-term complications. Three groups showed similar postoperative pathological outcomes. The overall survival and disease-free survival were also similar among the three groups (all P > 0.05). Cox regression analysis showed surgical approach was not a prognostic factor for overall survival (P = 0.671) and disease-free survival (P = 0.776). PSM analysis of RS and LS by clinical characteristics showed RS showed shorter operation time (P < 0.001) and LOS for patients without complications (P = 0.005). However, no significant differences were found in perioperative and long-term postoperative complications, pathological outcomes, overall survival, and disease-free survival. CONCLUSIONS: Among three techniques for radical left colectomy, LS and RS had significant advantages over OS in short-term clinical outcomes, and no significant differences were found in overall, disease-free survival, local recurrence, and distant metastasis incidence. Moreover, RS shows better perioperative clinical outcomes but without compromising survival compared with LS.

Male urogenital function after robot-assisted and laparoscopic total mesorectal excision for rectal cancer: a prospective cohort study.

BACKGROUND: Urogenital dysfunction is recognized as a serious complication affecting patient quality of life after rectal cancer surgery to treat rectal cancer; however, the studies focus on the urogenital function after robot-assisted rectal cancer surgery compared to laparoscopic surgery are limited. METHODS: Male patients undergoing robotic total mesorectal excision (R-TME) or laparoscopic total mesorectal excision (L-TME) were prospectively enrolled. The International Prostate Symptom Score (IPSS) and the five-item version of the International Index of Erectile Function (IIEF-5) scale were used to compare the urogenital function of the two groups preoperatively and 3, 6, and 12 months postoperatively. RESULTS: Eighty-nine patients who planned to undergo R-TME and L-TME were prospectively enrolled; 77 patients of these patients (86.5%) completed all questionnaires at all time points and were thus included in the final analysis. Of the included patients, 38 underwent R-TME and 39 underwent L-TME. There was no significant difference in age, BMI, American Society of Anesthesiologists (ASA) score, tumor location, neoadjuvant therapy, operation method, postoperative pathological results and adjuvant therapy between the two groups. Preoperative urogenital function was similar in both groups; however, the IPSS was significantly lower in R-TME patients than that in T-TME patients at 6 months and 12 months [(7.82 ± 2.25 vs. 9.95 ± 3.01, P = 0.006; 7.62 ± 2.5 vs. 9.12 ± 2.64, P = 0.012)]. IIEF-5 scores decreased 3 months after R-TME and L-TME surgery (14.87 ± 3.27 vs. 13.92 ± 3.62, p = 0.231) and then gradually increased; at 12 months, IIEF-5 scores were comparable to those at baseline in both groups. IIEF-5 scores were higher in R-TME patients than those in L-TME patients at 6 months (18.55 ± 3.45 vs. 16.75 ± 3.26, P = 0.021), but there was no significant difference between the two groups at 12 months (21.22 ± 3.06 vs. 19.95 ± 3.03, P = 0.071). CONCLUSIONS: The robotic approach for TME was associated with more rapid restoration of male urogenital function than the laparoscopic approach.

Comparative Metabolomic Studies of Siberian Wildrye (Elymus sibiricus L.): A New Look at the Mechanism of Plant Drought Resistance.

Drought is one of the most important factors affecting plant growth and production due to ongoing global climate change. Elymus sibiricus has been widely applied for ecological restoration and reseeding of degraded grassland in the Qinghai-Tibetan Plateau (QTP) because of its strong adaptability to barren, salted, and drought soils. To explore the mechanism of drought resistance in E. sibiricus, drought-tolerant and drought-sensitive genotypes of E. sibiricus were used in metabolomic studies under simulated long-term and short-term drought stress. A total of 1091 metabolites were detected, among which, 27 DMs were considered to be the key metabolites for drought resistance of E. sibiricus in weighted gene co-expression network analysis (WGCNA). Ten metabolites, including 3-amino-2-methylpropanoic acid, coniferin, R-aminobutyrate, and so on, and 12 metabolites, including L-Proline, L-histidine, N-acetylglycine, and so on, showed differential accumulation patterns under short-term and long-term drought stress, respectively, and thus, could be used as biomarkers for drought-tolerant and drought-sensitive E. sibiricus. In addition, different metabolic accumulation patterns and different drought response mechanisms were also found in drought-tolerant and drought-sensitive genotypes of E. sibiricus. Finally, we constructed metabolic pathways and metabolic patterns for the two genotypes. This metabolomic study on the drought stress response of E. sibiricus can provide resources and a reference for the breeding of new drought-tolerant cultivars of E. sibiricus.

Genomic survey sequencing, development and characterization of single- and multi-locus genomic SSR markers of Elymus sibiricus L.

BACKGROUND: Siberian wildrye (Elymus sibiricus L.) attracts considerable interest for grassland establishment and pasture recovery in the Qinghai-Tibet Plateau (QTP) due to its excellence in strong stress tolerance, high nutritional value and ease to cultivate. However, the lack of genomic information of E. sibiricus hampers its genetics study and breeding process. RESULTS: In this study, we performed a genome survey and developed a set of SSR markers for E. sibiricus based on Next-generation sequencing (NGS). We generated 469.17 Gb clean sequence which is 58.64× of the 6.86 Gb estimated genome size. We assembled a draft genome of 4.34 Gb which has 73.23% repetitive elements, a heterozygosity ratio of 0.01% and GC content of 45.68%. Based on the gnomic sequences we identified 67,833 SSR loci and from which four hundred were randomly selected to develop markers. Finally, 30 markers exhibited polymorphism between accessions and ten were identified as single-locus SSR. These newly developed markers along with previously reported 30 ones were applied to analyze genetic polymorphism among 27 wild E. sibiricus accessions. We found that single-locus SSRs are superior to multi-loci SSRs in effectiveness. CONCLUSIONS: This study provided insights into further whole genome sequencing of E. sibiricus in strategy selection. The novel developed SSR markers will facilitate genetics study and breeding for Elymus species.

Comparison of robotic and laparoscopic rectal cancer surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: Robotic and laparoscopic surgery for rectal cancer has been applied in the clinic for decades; nevertheless, which surgical approach has a lower rate of postoperative complications is still inconclusive. Therefore, the aim of this meta-analysis was to compare the postoperative complications within 30 days between robotic and laparoscopic rectal cancer surgery based on randomized controlled trials. METHODS: Randomized controlled trials (until May 2020) that compared robotic and laparoscopic rectal cancer surgery were searched through PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, and China Biology Medicine disc (CBMdisc). Data regarding sample size, clinical and demographic characteristics, and postoperative complications within 30 days, including overall postoperative complications, severe postoperative complications (Clavien-Dindo score ≥ III), anastomotic leakage, surgical site infection, bleeding, ileus, urinary complications, respiratory complications, conversion to open surgery, unscheduled reoperation, perioperative mortality, and pathological outcomes, were extracted. The results were analyzed using RevMan v5.3. RESULTS: Seven randomized controlled trials that included 507 robotic and 516 laparoscopic rectal cancer surgery cases were included. Meta-analysis showed that the overall postoperative complications within 30 days [Z = 1.1, OR = 1.18, 95% CI (0.88-1.57), P = 0.27], severe postoperative complications [Z = 0.22, OR = 1.12, 95% CI (0.41-3.07), P = 0.83], anastomotic leakage [Z = 0.96, OR = 1.27, 95% CI (0.78-2.08), P = 0.34], surgical site infection [Z = 0.18, OR = 1.05, 95% CI (0.61-1.79), P = 0.86], bleeding [Z = 0.19, OR = 0.89, 95% CI (0.27-2.97), P = 0.85], ileus [Z = 1.47, OR = 0.66, 95% CI (0.38-1.15), P = 0.14], urinary complications [Z = 0.66, OR = 1.22, 95% CI (0.67-2.22), P = 0.51], respiratory complications [Z = 0.84, OR = 0.64, 95% CI (0.22-1.82), P = 0.40], conversion to open surgery [Z = 1.73, OR = 0.61, 95% CI (0.35-1.07), P = 0.08], unscheduled reoperation [Z = 0.14, OR = 0.91, 95% CI (0.26-3.20), P = 0.89], perioperative mortality [Z = 0.28, OR = 0.79, 95% CI (0.15-4.12), P = 0.78], and pathological outcomes were similar between robotic and laparoscopic rectal surgery. CONCLUSION: Robotic surgery for rectal cancer was comparable to laparoscopic surgery with respect to postoperative complications within 30 days.

No beneficial effect on survival but a decrease in postoperative complications in patients with rectal cancer undergoing robotic surgery: a retrospective cohort study.

BACKGROUND: Robotic surgery has been taken as a new modality to surpass the technical limitations of conventional surgery. Here we aim to compare the oncologic outcomes of patients with rectal cancer receiving robotic vs. laparoscopic surgery. METHODS: Data from patients diagnosed with rectal cancer between March 2011 and December 2018 were obtained for outcome assessment at the First Affiliated Hospital of Nanchang University. All patients were separated into two groups: a robot group (patients receiving robotic surgery, n = 314) and a laparoscopy group (patients receiving laparoscopic surgery, n = 220). The primary endpoint was survival outcomes. The secondary endpoints were the general conditions of the operation, postoperative complications and pathological characteristics. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) at years 1, 3 and 5 were 96.6%, 88.7%, and 87.7% vs. 96.7%, 88.1%, and 78.4%, and 98.6%, 80.2-, and 73.5% vs. 96.2-, 87.2-, and 81.1% in the robot and laparoscopy groups, respectively (P > 0.05). In the multivariable-adjusted analysis, robotic surgery was not an independent prognostic factor for OS and DFS (P = 0.925 and 0.451, respectively). With respect to the general conditions of the operation, patients in the robot group had significantly shorter operation times (163.5 ± 40.9 vs. 190.5 ± 51.9 min), shorter times to 1st gas passing [2(1) vs. 3(1)d] and shorter hospital stay days [7(2) vs. 8(3)d] compared to those in the laparoscopy group (P < 0.01, respectively). After the operation, the incidence of short- and long-term complications in the robot group was significantly lower than that in the laparoscopy group (15.9% vs. 32.3%; P < 0.001), especially for urinary retention (1.9% vs. 7.3%; 0.6% vs. 4.1%, P < 0.05, respectively). With regard to pathological characteristics, TNM stages II and III were more frequently observed in the robot group than in the laparoscopy group (94.3% vs. 83.2%, P < 0.001). No significant difference were observed in lymph nodes retrieved, lymphovascular invasion and circumferential resection margin involvement between the two groups (P > 0.05, respectively). CONCLUSIONS: This monocentre retrospective comparative cohort study revealed short-term advantages of robot-assisted rectal cancer resection but similar survival compared to conventional laparoscopy.

Robotic-assisted versus conventional laparoscopic-assisted total gastrectomy with D2 lymphadenectomy for advanced gastric cancer: short-term outcomes at a mono-institution.

BACKGROUND: Robotic-assisted surgery, a developed technology, is becoming more and more accepted by surgeons. However, the comparison between robotic-assisted total gastrectomy (RATG) and conventional laparoscopy-assisted total gastrectomy (LATG) for advanced gastric cancer (AGC) is seldom reported, or usually the sample sizes reported are small. The current research was designed to compare the short-term outcomes of RATG and LATG with D2 lymphadenectomy for AGC in a mono-institution from China. METHODS: A total of 205 patients from June 2015 to October 2018 were included in this study. Among them, 106 patients underwent LATG, and 99 patients underwent RATG. The patients' clinicopathological characteristics, surgical performance and short-term outcomes were retrospectively analyzed. RESULTS: The clinicopathological characteristics showed no difference between the LATG group and the RATG group. However, compared with the LATG group, the operation time was longer (P = 0.000), and the operative blood loss (P = 0.000) and the volume of abdominal drainage was less (P = 0.000) in the RATG group. Moreover, the RATG took less time to remove abdominal drainage tube than LATG (P = 0.000). The plasma levels of CRP at 72 h post-operation was lower (P = 0.000), and the number of retrieved lymph nodes was more (P = 0.000) in the RATG group. Nevertheless, the postoperative length of stay (P = 0.890), the time to first flatus (P = 0.448), the postoperative complication (P = 0.915) and the visual analogue pain score at 24 h post-operation (P = 0.457) were comparable between the two groups. CONCLUSIONS: RATG with D2 lymphadenectomy shows safety and feasibility for AGC and could be served as an alternative treatment for AGC in the future.

Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway.

Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC.

Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

UNLABELLED: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide because of metastasis. Epithelial-mesenchymal transition (EMT) is widely considered to be crucial to the invasion-metastasis cascade during cancer progression. Actin-like 6A (ACTL6A) is initially verified important for cell proliferation, differentiation, and migration. In this study, we find that ACTL6A plays an essential role in metastasis and EMT of HCC. ACTL6A expression is up-regulated in HCC cells and tissues. A high level of ACTL6A in HCCs is correlated with aggressive clinicopathological features and is an independent poor prognostic factor for overall and disease-free survival of HCC patients. Ectopic expression of ACTL6A markedly promotes HCC cells migration, invasion, as well as EMT in vitro and promotes tumor growth and metastasis in the mouse xenograft model. Opposite results are observed when ACTL6A is knocked down. Mechanistically, ACTL6A promotes metastasis and EMT through activating Notch signaling. ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, in HCC cells. Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)-box 2 (SOX2) expression and then activate Notch1 signaling. CONCLUSIONS: ACTL6A promotes metastasis and EMT by SOX2/Notch1 signaling, indicating a prognostic biomarker candidate and a potential therapeutic target for HCC.

High expression of partitioning defective 3-like protein is associated with malignancy in colorectal cancer.

Partitioning defective 3-like protein is a novel cell polarity protein. Recently, partitioning defective 3-like protein has been demonstrated with tumor-promoting function by disrupting tight junction, inhibiting tumor suppressor liver kinase B1, and maintaining mammary stem cells. For the first time, we studied partitioning defective 3-like protein expression in malignant colorectal cancer. We used immunohistochemistry scoring system to evaluate partitioning defective 3-like protein expression in 196 colorectal cancer tissues and 33 adjacent normal tissues. We found that colorectal cancer tissues had much stronger partitioning defective 3-like protein immunoreactivity than normal tissues, and colorectal cancer patients with positive partitioning defective 3-like protein expression were characterized with higher cancer stages, metastasis, poor tumor differentiation, larger tumor size, as well as high levels of colorectal cancer markers carcinoembryonic antigen and cancer antigen 19-9. Besides, partitioning defective 3-like protein overexpression was independently predictive of lower survival rate in colorectal cancer patients, even after adjusting the influence of cofactors. Moreover, we also found that partitioning defective 3-like protein was associated with rapid growing colorectal cancer, while knockdown of partitioning defective 3-like protein expression largely inhibited cancer cell proliferation. Our study provided the first evidence that partitioning defective 3-like protein was overexpressed in colorectal cancer and associated with disease malignancy. Also, partitioning defective 3-like protein may serve as a promising prognostic marker and a potential therapeutic target for colorectal cancer treatment. Further study is necessary to understand the regulatory mechanism of partitioning defective 3-like protein in colorectal cancer and the feasibility of its application in clinic.

H2.0-like homeobox 1 acts as a tumor suppressor in hepatocellular carcinoma.

H2.0-like homeobox 1 (HLX1) is a homeobox transcription factor gene expressed primarily in cytotrophoblast cell types in the early pregnancy human placenta and involved in the development of enteric nervous system. However, the biological function of HLX1 in hepatocellular carcinoma (HCC) remains unclear. In the present study, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, western blot, and immunohistochemical staining were used to examine the expression level of HLX1 in a total of 125 cases of HCC tissues and their matched adjacent nontumorous tissues (ANLTs), and its correlation with clinical features of HCC patients was analyzed. Our findings showed that the expression level of HLX1 was significantly reduced in HCCs compared to ANLTs. Besides, it was also remarkably downregulated in HCC cell lines compared to normal liver cell line. We further found that the HLX1 level was significantly associated with the tumor size (p = 0.016), tumor number (p = 0.004), vascular invasion (p = 0.031), Edmondson-Steiner grade (p = 0.041), tumor-node-metastasis (TNM) stage (p < 0.001), and Barcelona clinic liver cancer (BCLC) stage (p = 0.008). Moreover, HLX1 was an independent risk factor for overall survival (OS, p = 0.020) and disease-free survival (DFS, p = 0.024) of HCC patients. In vitro experiments showed that overexpression of HLX1 markedly suppressed the invasion, migration, proliferation, and colony formation of HCC cells; in contrast, downregulation of HLX1 significantly promoted the invasion, migration, proliferation, and colony formation of HCC cells. In vivo study indicated that overexpression of HLX1 significantly inhibited the tumorigenic capacity of HCC cells in nude mice. Based on these findings, we suggest that HLX1 acts as a tumor suppressor in HCC.

MicroRNA-188-5p suppresses tumor cell proliferation and metastasis by directly targeting FGF5 in hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the detailed molecular mechanisms underlying HCC progression are still not completely clear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyze the expression and function of a metastasis-associated miRNA named miR-188-5p in HCC. METHODS: miRNA array analysis was performed to search for metastasis-associated miRNAs in HCC. miR-188-5p expressions in tumor tissues and adjacent non-tumorous liver tissues of HCC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analyzed by Western blot and immunohistochemistry. Luciferase reporter assays was used to validate the target of miR-188-5p. The effect of miR-188-5p on HCC progression was studied in vitro and in vivo. RESULTS: miR-188-5p was significantly decreased in HCC and its expression levels were highly correlated with multiple nodules, microvascular invasion, overall and disease-free survival of HCC. Ectopic expression of miR-188-5p suppressed HCC cell proliferation and metastasis in vitro and in vivo. Fibroblast growth factor 5 (FGF5) was identified as a major target of miR-188-5p. Enforced expression of miR-188-5p inhibited the expression of FGF5 significantly and the restoration of FGF5 expression reversed the inhibitory effects of miR-188-5p on HCC cell proliferation and metastasis. CONCLUSIONS: These findings collectively demonstrate a tumor suppressor role of miR-188-5p in HCC progression via targeting FGF5, suggesting that miR-188-5p could serve as a potential prognostic biomarker and therapeutic target for HCC.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.