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.

[Expression and Clinical Significance of ATP Citrate Lyase in Hepatocellular Carcinoma].

Objective To investigate the role of ATP citrate lyase(ACLY)in the development of hepatocellular carcinoma(HCC)and the impact of this enzyme on the immune microenvironment of HCC.Methods We utilized the University of Alabama at Birmingham Cancer Data Analysis Portal and the Gene Expression Profiling Interactive Analysis to identify the changes in ACLY expression and prognosis across different tumor types from The Cancer Genome Atlas.With HCC as the disease model,we analyzed the ACLY expression in HCC samples from the gene expression database.Furthermore,we collected the clinical specimens from HCC patients to verify the mRNA and protein levels of ACLY.In addition,we conducted transcriptome sequencing after knocking down the expression of ACLY to analyze the differentially expressed genes and investigated the impact of ACLY expression interference on cell proliferation and other functions.Finally,we explored the correlations of ACLY with immune cells and immune infiltration in the tumor microenvironment,new antigens,and immune checkpoint genes.Results ACLY expression was significantly up-regulated in solid tumors including HCC(all P<0.05),and high ACLY expression was associated with overall survival rate in HCC(P=0.005).Furthermore,high ACLY expression affected the presence of immune cells(e.g.,tumor-associated fibroblasts)and the expression of genes involved in lipid metabolism(all P<0.05).Conclusions ACLY is closely related to the occurrence and development of HCC and lipid metabolism abnormalities.Moreover,it has a specific impact on the immune microenvironment of HCC.

Single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles in breast cancer.

BACKGROUND: In order to explore the surgical safety and the reliability of axillary staging of single-port endoscopic-sentinel lymph node biopsy, we combined it with indocyanine green that was excited by near-infrared fluorescence endoscopy and carbon nanoparticles as a tracer and compared this method to conventional open sentinel lymph node biopsy. METHODS: This is a retrospective and observational study, there were 20 patients in each group and the total sample size was 60: Group 1, single-port endoscopic-sentinel lymph node biopsy combined with indocyanine green and carbon nanoparticles; Group 2, single-port endoscopic-sentinel lymph node biopsy with carbon nanoparticles only; Group 3, conventional sentinel lymph node biopsy with indocyanine green and carbon nanoparticles. Sentinel lymph node detection and upper extremity function were determined to measure the safety and efficacy of the novel single-port endoscopic-sentinel lymph node biopsy (SPE-SLNB) technique to the standard conventional sentinel lymph node biopsy technique. RESULTS: The detection rate of sentinel lymph nodes was 100% in Group 1, 100% in Group 2, and 95% in Group 3. There were no significant differences in upper arm function and pain scores between the three groups. CONCLUSION: The novel technique of combining indocyanine green and carbon nanoparticles with single-port endoscopic-sentinel lymph node biopsy achieved a similar detection rate and mean number of sentinel lymph nodes as conventional sentinel lymph node biopsy. Traditional open surgery requires two different incisions for breast surgery and SLNB. While the most important advantage of SPE-SLNB is that two procedures can be effectively performed through a single-port in the axilla Therefore, for patients who meet the indications, single-port endoscopic-sentinel lymph node biopsy is as safe and reliable as conventional sentinel lymph node biopsy but has the aesthetic advantage of only one incision.

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.

Preservation of left colic artery in laparoscopic colorectal operation: The benefit challenge.

BACKGROUND: During laparoscopic resection for colorectal cancer, there is controversy regarding whether the left colic artery (LCA) should be preserved at its origin. AIM: To investigate the prognostic significance of preservation of the LCA in colorectal cancer surgery. METHODS: Patients were divided into two groups. The high ligation (H-L) technique (refers to ligation performed 1 cm from the beginning of the inferior mesenteric artery) group consisted of 46 patients, and the low ligation (L-L) technique (refers to ligation performed below the initiation of the LCA) group consisted of 148 patients. Operative time, blood loss, lymph nodes with tumor invasion, postoperative complications and recovery time, recurrence rate, and 5-year survival rate were compared between the two groups. RESULTS: The average number of lymph nodes detected in postoperative pathological specimens was 17.4/person in the H-L group and 15.9/person in the L-L group. There were 20 patients (43%) with positive lymph nodes (lymph node metastasis) in the H-L group and 60 patients (41%) in the L-L group. No statistical differences were found between the groups. Complications occurred in 12 cases (26%) in the H-L group and in 26 cases (18%) in the L-L group. The incidences of postoperative anastomotic complications and functional urinary complications were significantly lower in the L-L group. The 5-year survival rates in H-L and L-L groups were 81.7% and 81.6%, respectively, and relapse-free survival rates were 74.3% and 77.1%, respectively. The two groups were similar statistically. CONCLUSION: Complete mesenteric resection combined with lymph node dissection around the inferior mesenteric artery root while preserving the LCA is a beneficial surgical approach during laparoscopic resection for colorectal cancer.

RUNX2 Reverses p53-Induced Chemotherapy Resistance in Gastric Cancer.

Objective: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance. Methods: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed. Results: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer. Conclusion: RUNX2 is a possible target for platinum-based chemotherapy resistance.

Single-port nipple-sparing subcutaneous mastectomy with immediate prosthetic breast reconstruction for breast cancer.

INTRODUCTION: This study compares the perioperative results, aesthetic outcome and oncologic safety of single-port insufflation endoscopic nipple-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (SIE-NSM-IRPI) with those of conventional open-nipple and areola-sparing subcutaneous mastectomy combined with immediate reconstruction using prosthesis implantation (C-NSM-IRPI). METHODS: In this retrospective cohort study, 64 early-stage breast cancer patients were divided into SIE-NSM-IRPI (n = 38) and C-NSM-IRPI (n = 26) groups. Perioperative results (operation time, intraoperative blood loss, incision length, drainage duration, and recent complications) were then compared between the two groups. Differences in satisfaction with the breasts, psychosocial well-being, physical well-being (chest) and sexual well-being were analyzed according to the BREAST-Q scale, and survival outcomes were also compared. RESULTS: The median follow-up time was 51.5 months. The incision length of SIE-NSM-IRPI was shorter than that of C-NSM-IRPI (P < 0.001). SIE-NSM-IRPI achieved the same detection rate and median number of sentinel lymph nodes as C-NSM-IRPI (3.00vs. 4.00, P = 0.780). The incidence of prosthesis removal due to infection or prosthesis exposure in the SIE-NSM-IRPI group was lower than that in the C-NSM-IRPI group (P = 0.015). Satisfaction with breasts (82.00vs.59.00, P < 0.001), psychosocial well-being (93.00vs.77.00, P = 0.001) and physical well-being (chest) (89.00vs.82.00, P < 0.001) scores were higher in the SIE-NSM-IRPI group. There were no significant differences between the two groups in disease-free survival (hazard ratio = 0.829, 95% confidence interval = 0.182-3.779) and overall survival (hazard ratio = 1.919, 95% confidence interval = 0.169-21.842). CONCLUSION: In this selected cohort of patients with early breast cancer, SIE-NSM-IRPI was comparable to C-NSM-IRPI, considering oncologic safety and detection of sentinel lymph nodes. It had a lower incidence of prosthesis removal, shorter incision length, and was associated with better patient satisfaction with the breasts. More random clinical trials of this novel approach in a larger cohort of Chinese patients with an extended follow-up period are needed in the future.

Comparing outcomes of single-port insufflation endoscopic breast-conserving surgery and conventional open approach for breast cancer.

BACKGROUND: In the surgical treatment of breast cancer, the goal of surgeons is to continually create and improve minimally invasive surgical techniques to increase patients' quality of life. Currently, routine breast-conserving surgery is often performed using two obvious incisions. Here, we compare the clinical efficacy and aesthetic outcomes of a novel technique using one incision, called 'single-port insufflation endoscopic breast-conserving surgery' (SIE-BCS), vs. conventional breast-conserving surgery (C-BCS) in patients with early-stage breast cancer. METHODS: A total of 180 patients with stage I or stage II breast cancer participated in this study, of whom 63 underwent SIE-BCS and 117 underwent C-BCS. Logistic regression analysis was conducted to assess the risk of local recurrence and metastasis. Aesthetic outcomes were evaluated using the BREAST-Q scale. RESULTS: The mean operation time was significantly longer for SIE-BCS (194.9 ± 71.5 min) than for C-BCS (140.3 ± 56.9 min), but the mean incision length was significantly shorter for SIE-BCS than for C-BCS (3.4 ± 1.2 cm vs. 8.6 ± 2.3 cm). While both surgeries yielded similar BREAST-Q ratings for satisfaction with breasts and sexual well-being, SIE-BCS was associated with significantly better ratings for physical well-being (chest area) and psychological well-being. Additionally, SIE-BCS was associated with decreased rates of adverse effects of radiation. The preliminary analysis showed that SIE-BCS did not increase the risk of local recurrence or metastasis. CONCLUSION: The novel single-port insufflation endoscopic assisted BCS technique is feasible, safe, and improves patients' postoperative comfort and psychological well-being, as compared to the conventional technique.

Altered Brain Structural Reorganization and Hierarchical Integrated Processing in Obesity.

The brain receives sensory information about food, evaluates its desirability and value, and responds with approach or withdrawal. The evaluation process of food in the brain with obesity may involve a variety of neurocircuit abnormalities in the integration of internal and external information processing. There is a lack of consistency of the results extant reported for aberrant changes in the brain with obesity that prohibits key brain alterations to be identified. Moreover, most studies focus on the observation of neural plasticity of function or structure, and the evidence for functional and structural correlations in the neuronal plasticity process of obesity is still insufficient. The aims of this article are to explore the key neural structural regions and the hierarchical activity pattern of key structural nodes and evaluate the correlation between changes in functional modulation and eating behavior. Forty-two participants with obesity and 33 normal-weight volunteers were recruited. Gray matter volume (GMV) and Granger causality analysis (GCA) were performed using the DPARSF, CAT12, and DynamicBC toolbox. Compared with the normal weight group, the obesity group exhibited significantly increased GMV in the left parahippocampal gyrus (PG). The obesity group showed decreased causal inflow to the left PG from the left orbitofrontal cortex (OFC), right calcarine, and bilateral supplementary motor area (SMA). Decreased causal outflow to the left OFC, right precuneus, and right SMA from the left PG, as well as increased causal outflow to the left middle occipital gyrus (MOG) were observed in the obesity group. Negative correlations were found between DEBQ-External scores and causal outflow from the left PG to the left OFC, and DEBQ-Restraint scores and causal inflow from the left OFC to the left PG in the obesity group. Positive correlation was found between DEBQ-External scores and causal outflow from the left PG to the left MOG. These results show that the increased GMV in the PG may play an important role in obesity, which may be related to devalued reward system, altered behavioral inhibition, and the disengagement of attentional and visual function for external signals. These findings have important implications for understanding neural mechanisms in obesity and developing individual-tailored strategies for obesity prevention.

Dendritic cell combination therapy reduces the toxicity of triptolide and ameliorates colitis in murine models.

Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we designed an approach to target DCs in vitro to avoid the direct exposure of organs to TP. Our results revealed that DCs pretreated with TP (DCTP) exerted satisfactory therapeutic effects in mice with colitis, resulting in improved colonic inflammation and alleviated local lesion damage. In addition, no obvious toxicity was observed. DCTP also reshaped the immune milieu by decreasing CD4+ T cell numbers and increasing regulatory T cell numbers in the spleen, mesenteric lymph nodes, peripheral blood and colon; these effects were further confirmed in vitro. Downregulation of CD80/86, ICAM-1, MHCI, TLR2/4, TNF-α, and IL-6 expression and upregulation of programmed cell death ligand 1 (PDL1) and IL-10 expression were observed, indicating that DCs were converted into tolerogenic DCs. In conclusion, DCTP can effectively reduce toxicity and alleviate colonic inflammation and local lesion damage in mice with colitis. The immune mechanism underlying the effects of DCTP included the conversion of DCs into tolerogenic DCs and the alteration of T cell differentiation to produce immunoinhibitory rather than immunostimulatory T cells.

Inflammation-related indicators to distinguish between gastric stromal tumors and leiomyomas: A retrospective study.

BACKGROUND: Gastric leiomyomas and gastric stromal tumors are the most common types of gastric tumors encountered. In recent years, the incidence of the two types of tumors has been increasing, but the differential diagnosis is still a challenge in clinical work. However, as there are many reports on stromal tumors and inflammation-related indicators are gradually being paid attention to as important factors in predicting tumor prognosis, the two main purposes of this study were to explore the inflammation-related differences between the two types of tumors and to develop a nomogram as a predictive model. AIM: To explore the differences in platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte mononuclear cell ratio (LMR), and SII between the two types of tumors, and simultaneously create the nomogram model. METHODS: This study enrolled 88 patients in the gastric stromal tumor group and 56 patients in the gastric leiomyoma group, and the relevant data of the two groups were entered into the system for an integrated analysis. The primary objective of this study was to identify the differences in the inflammation index between the two types of tumors. RESULTS: There were statistically significant differences between the two groups in sex, age, and tumor location. In comparison, gastric leiomyomas seem to be more common in women, young patients, and gastric cardia, which is in line with our previous research; the groups showed the following statistical differences: PLR (158.2% vs 134.3%, P = 0.028), NLR (2.35 vs 1.68, P = 0.000), LMR (5.75 vs 10.8, P = 0.004), and SII (546.2 vs 384.3, P = 0.003). The results of the multivariate logistic regression analysis showed that sex, age, tumor location, and LMR were independent risk factors for the identification of the two types of tumors. After considering the risk factors selected by the above analysis into the predictive model, a predictive model for distinguishing gastrointestinal stromal tumors from gastric leiomyomas was established as the nomogram. CONCLUSION: Gastric leiomyomas and gastric stromal tumors are not only different in factors such as age of the patient, but also in inflammatory indicators such as LMR and PLR. We have established a predictive model related to the laboratory indicators and are looking forward to further research conducted in this clinical area.

Current indications for endoscopic submucosal dissection of early gastric cancer.

The development of endoscopic treatment technology has further promoted the minimally invasive treatment of early gastric cancer (EGC). Endoscopic treatment has achieved better therapeutic effects in terms of safety and prognosis and is the preferred treatment method for patients who meet the indications for endoscopic treatment. However, the consequent problem is that some patients receiving endoscopic treatment may undergo non-curative resection, and the principle of follow-up management for non-curative resection patients deserves further attention. In addition, there are still debates on how to improve the accuracy of clinical staging, select a reasonable treatment method for patients who meet the expanded indications for endoscopic treatment, manage patients with positive endoscopic surgical margins, conduct research on function-preserving surgery, and manage the treatment of EGC under the current situation in China. Consequently, we aim to review current indications for endoscopic submucosal dissection of EGC in order to better inform treatment options.

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.

circGFRA1 affects the sensitivity of triple-negative breast cancer cells to paclitaxel via the miR-361-5p/TLR4 pathway.

In recent years, the role of circular RNAs (circRNAs) in tumours has attracted widespread attention. Some circRNAs have been reported to play a role in triple-negative breast cancer (TNBC). However, circRNAs have rarely been reported in terms of TNBC resistance. This study aimed to clarify that circGFRA1 affects the sensitivity of TNBC cells to paclitaxel (PTX) by the miR-361-5p/TLR4 pathway. Compared with the non-PTX-resistant TNBC cell line MDA-MB-231, the expression of circGFRA1 in the PTX-resistant TNBC cell line MDA-MB-231.PR was significantly increased. The small hairpin RNA-mediated circGFRA1 knockdown inhibited the resistance of TNBC cells to PTX. RNA pull-down assay and luciferase reporter gene assay confirmed the binding between circGFRA1 and miR-361-5p and between miR-361-5p and TLR4. It has been proven that circGFRA1 knockdown can inhibit the resistance of TNBC cells to PTX by promoting the expression of miR-361-5p, and subsequently reduce the expression of TLR4.

Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR-Hippo-YAP pathway.

The long-term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.

Hierarchical integrated processing of reward-related regions in obese males: A graph-theoretical-based study.

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.

LncRNA KCNQ1OT1 is a key factor in the reversal effect of curcumin on cisplatin resistance in the colorectal cancer cells.

The development of cisplatin resistance is a common cause of cancer recurrence in colorectal cancer (CRC). Though many studies have reported the oncogenic function of long non-coding RNA (LncRNA) KCNQ1OT1 in multiple cancers, few studies explored its role in cisplatin resistance of CRC. Curcumin is a natural phenolic compound extracted from turmeric, which can effectively suppress cisplatin resistance in CRC. This study aims to expound the role of KCNQ1OT1 in cisplatin resistance in CRC cells and whether KCNQ1OT1 participates in the reversal effect of curcumin on cisplatin resistance in CRC. The interplay between KCNQ1OT1 and miR-497 was determined using RNA pull-down assay and dual-luciferase reporter gene assay. The combination of B-cell lymphoma 2 (Bcl-2) and miR-497 was confirmed using dual-luciferase reporter gene assay. Compared with CRC cell line HCT8, the cisplatin-resistant CRC cell line HCT8/DDP exhibited a higher expression level of KCNQ1OT1. Functionally, the silence of KCNQ1OT1 suppressed proliferation and boosted apoptosis in HCT8/DDP cells. Subsequently, we found that KCNQ1OT1 could act as a sponge of miR-497 and remove the suppressive effect of miR-497 on Bcl-2 expression. Curcumin treatment restrained proliferation and facilitated apoptosis in HCT8/DDP cells. While KCNQ1OT1 overexpression removed the effect of curcumin on HCT8/DDP cells via miR-497/ Bcl-2 axis. Finally, the in vivo experiments showed that the inhibitory effect of curcumin on the growth of cisplatin-resistant CRC cells was reserved by the ectopic expression of KCNQ1OT1. In conclusion, KCNQ1OT1 aggravated cisplatin resistance in CRC cells via the miR-497/Bcl-2 axis. Administration of curcumin could effectively downregulate KCNQ1OT1 expression, thus reversing cisplatin resistance in CRC cells.