Weight Loss During Neoadjuvant Therapy Is Associated With Poor Response Among the Patients With Gastrointestinal Cancer: A Propensity Score Matching Analysis.

PURPOSE: The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients. METHODS: From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared. RESULTS: A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable. CONCLUSION: BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.

Mesorectal reconstruction with pedicled greater omental transplantation to relieve low anterior resection syndrome following total intersphincteric resection in patients with ultra-low rectal cancer.

BACKGROUND: Total intersphincteric resection (ISR) is the ultimate anus-preserving surgery for patients with ultra-low rectal cancer (ULRC), which can result in various degrees of anorectal dysfunction. Known as low anterior resection syndrome (LARS), it seriously affects the postoperative quality of life of patients. The aim of this study was to discuss the value of mesorectal reconstruction with pedicled greater omental transplantation (PGOT) to relieve LARS following total ISR in patients with ULRC, hoping to provide new ideas and strategies for the prevention and improvement of LARS. METHODS: We retrospectively analyzed hospitalization data and postoperative anorectal function of 26 ULRC patients, who were met inclusion and exclusion criteria in our center from January 2015 to February 2022. And combined with the results of anorectal manometry and rectal magnetic resonance imaging (MRI) defecography of some patients, we assessed comprehensively anorectal physiological and morphological changes of the patients after surgery, and their correlation with LARS. RESULTS: In this study, 26 patients with ULRC were enrolled and divided into observation group (n = 15) and control group (n = 11) according to whether PGOT was performed. There were no significant differences in surgical results such as operative time, intraoperative blood loss and postoperative complications between the two groups (P > 0.05). Postoperative follow-up showed that patients in both groups showed severe LARS within 3 months after surgery, but from the 3rd month after surgery, LARS in both groups gradually began to decrease, especially in the observation group, which showed faster recovery and better recovery, with statistically significant difference (P < 0.001). Through anorectal manometry, the mean rectal resting pressure in the observation group was significantly lower than that in the control group (P = 0.010). In addition, the postoperative thickness of the posterior rectal mesenterium in the observation group was significantly higher than that in the control group (P = 0.001), and also higher than the preoperative level (P = 0.018). Moreover, rectal MRI defecography showed that the neo-rectum had good compliance under the matting of greater omentum, and its intestinal peristalsis was coordinated. CONCLUSIONS: ULRC patients, with the help of greater omentum, coordinated their neo-rectum peristalsis after total ISR and recovery of LARS was faster and better. PGOT is expected to be an effective strategy for LARS prevention and treatment of ULRC patients after surgery and is worthy of clinical promotion.

Advantages of total proctocolectomy with straight ileoanal anastomosis plus pedicled omental transposition for familial adenomatous polyposis: a preliminary study.

PURPOSE: To achieve excellent postoperative bowel function in familial adenomatous polyposis (FAP) patients, it is important to reconstruct the digestive tract. The aim of this study is to preliminarily discuss the advantages of total proctocolectomy with straight ileoanal anastomosis (TPC-SIAA) plus pedicled omental transposition for FAP. METHODS: A retrospective study was carried out in two hospitals analysing data for FAP patients who underwent surgical treatments between 2015 and 2021. Perioperative outcomes and early and mid-term anal functions were analysed. RESULTS: After excluding 4 patients who underwent total proctocolectomy with permanent ileostomy, 10 patients were enrolled in the study. Among the 10 patients, 3 received TPC-SIAA plus pedicled omental transposition, 3 received total proctocolectomy with ileal pouch-anal anastomosis (TPC-IPAA), and 4 received total colectomy with ileal pouch-rectal anastomosis (TC-IPRA). Except for one case conversion to laparotomy, laparoscopic surgery was performed for the other cases. The incidence of early postoperative complications was apparently higher with pouch anastomosis (57.1%) than straight anastomosis (0%). Frequencies of bowel movement and low anterior resection syndrome (LARS) score were higher for TPC-SIAA than the other two surgical procedures in the early term; over time, however, the frequencies of bowel movement and LARS score both showed a decreasing trend. In addition, combined with anorectal pressure detection and magnetic resonance imaging defecography at the 3rd month after TPC-SIAA plus pedicled omental transposition, defecation coordination was good. The dynamics and receptivity of the new rectum tended to be as expected. CONCLUSION: Although the three surgical procedures are safe and feasible surgical options for FAP, TPC-SIAA plus pedicled omental transposition is more consistent with intestinal physiology, with good intestinal compliance, and anal function tended to be as expected over time. Nevertheless, more extensive studies are needed to confirm these benefits.

Feasibility and advantages analyses of wedge resection without mesentery detached approach applied to closure of loop ileostomy.

OBJECTIVES: To evaluate the feasibility and advantages of wedge resection plus transverse suture without mesentery detached approach applied to loop ileostomy closure by analyzing the surgical data and the incidence of postoperative complications of patients undergoing this procedure. METHODS: We performed a retrospective analysis of the hospitalization data of patients who underwent ileostomy closure surgery and met the research standards from January 2017 to April 2021 in Guangxi Medical University Cancer Hospital; all surgeries were performed by the same surgeon. The perioperative data were statistically analyzed by grouping. RESULTS: In total, 65 patients were enrolled in this study, with 12 in the wedge resection group, 35 in the stapler group, and 18 in the hand suture group. There was no significant difference in operation time between the wedge resection group and stapler group (P > 0.05), but both groups had shorter operation time than that in the hand suture group (P < 0.05). The postoperative exhaustion time of wedge resection group was earlier than that of the others, and cost of surgical consumables in the wedge resection group was significantly lower than that in the stapler group, all with statistically significant differences (P < 0.05). By contrast, there were no statistically significant differences in postoperative complication incidences among the three groups. CONCLUSIONS: The wedge resection plus transverse suture without mesentery detached approach is safe and easy for closure of loop ileostomy in selected patients, and the intestinal motility recovers rapidly postoperatively. It costs less surgical consumables, and is particularly suitable for the currently implemented Diagnosis-Related Groups payment method.

Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients.

BACKGROUND: KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. METHODS: 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. RESULTS: NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. CONCLUSIONS: KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.

Comparison between 3-dimensional and 2-dimensional endoscopic thyroidectomy for benign and malignant lesions: a meta-analysis.

BACKGROUND: The use of 3-dimensional (3D) endoscopic thyroidectomy (ET) has been increasing, but its feasibility and safety have not been well documented for thyroidectomy. Hence, to systematically investigate the comparative outcomes during 3D-ET and 2-dimensional (2D) ET for benign and malignant lesions, we conducted this meta-analysis. METHODS: Based on the PRISMA guidelines, a systematic database search of the PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases was performed. The eligible studies were published in English and Chinese up to October 2020. The major endpoints evaluated were procedure time, blood loss, postoperative drainage, postoperative hospitalization, postoperative complications, total number of lymph node dissections (LNDs), and total cost. RESULTS: A total of 15 relevant studies including 1190 patients (583 for 3D-ET and 607 for 2D-ET) compared the application of 3D and 2D laparoscopic systems in thyroid surgery, of which 8 were endoscopic benign thyroidectomy (EBT) and 7 were endoscopic malignant thyroidectomy (EMT). Our meta-analysis indicated that 3D-ET generally had advantages over 2D-ET in terms of procedure time (P = 0.000), blood loss (P = 0.000), postoperative drainage (P = 0.000), postoperative complications (P = 0.000), and LNDs (P = 0.006). However, there were no significant differences between the two systems in terms of total cost (P = 0.245) or postoperative hospitalization (P = 0.068). Subgroup analysis showed consistency of the overall outcomes in each subset, but a shorter postoperative hospitalization in 3D-EBT was revealed. CONCLUSIONS: Compared to 2D-ET, 3D endoscopic thyroidectomy is an efficient, safe, and reliable method with better depth perception and stereoscopic vision, and an equally satisfactory outcome. More clinical RCTs with long-term follow-up are required to reproduce these promising results.

Analysis of presacral tissue structure in LARS and the prevention of LARS by reconstruction of presacral mesorectum with pedicled greater omentum flap graft.

BACKGROUND: The greater omentum has played a unique biological role in regenerative surgery. The aim of our study was to alter the anterior sacral structure by filling the anterior sacral space with the greater omentum and evaluate its effect on the low anterior resection syndrome (LARS) after total mesorectal excision (TME) surgery for low rectal cancer. METHODS: We retrospectively collected clinical data of patients with primary low rectal cancer who underwent TME and ileostomy closure in our hospital from March 2018 to March 2020. Spearman correlation analysis was conducted to analyze the correlation between postoperative mesorectal fascia (MRF) thickness and LARS score. Subsequently, we prospectively used a tipped greater omental flap graft to reconstruct the anterior rectal sacral structures (MRF reconstruction) in 17 patients and compared LARS scores and rectal compliance (RC) at week 12 after closure of the ileostomy in both groups. RESULTS: There were 47 patients with No-MRF reconstruction (31 males, mean age 60.68 ± 9.21 years) and 17 with MRF reconstruction (10 males, mean age 49.82 ± 14.74 years). Correlation analysis indicated that MRF thickness and RC were negatively correlated with LARS severity (p < 0.05). The LARS score of patients with MRF reconstruction at 12 weeks was significantly better than that of those with No-MRF reconstruction (32.97 ± 2.65 vs. 26.94 ± 1.52, p = 0.001), and the RC of MRF reconstruction were lower (2.80 ± 0.55 vs. 3.67 ± 0.38, p = 0.001). In addition, MRF reconstruction and No-MRF reconstruction have the similar incidence of postoperative complications (p = 0.156). No hemorrhage or necrosis of the greater omentum flap was observed in any of the patients. CONCLUSIONS: Greater omentum flap transplantation can significantly improve the symptoms of LARS at 12 weeks after ileostomy closure and we expect it to become a new surgical procedure for the treatment of low rectal cancer.

MicroRNA-1284 inhibits proliferation and induces apoptosis in SGC-7901 human gastric cancer cells.

OBJECTIVES: To explore the functional effects of miR-1284 on gastric cancer cells. RESULTS: Overexpression of miR-1284 significantly reduced SGC-7901 cell proliferation, but improved apoptosis. However, miR-1284 suppression displayed the inversed impacts. Furthermore, the protein levels of p27, Bax, procaspase-3 and active caspase-3 were up-regulated by miR-1284 overexpression, but were down-regulated by miR-1284 suppression. The level of Bcl-2 was down-regulated by miR-1284 overexpression, while it was up-regulated by miR-1284 suppression. The level of p21 was unaffected. CONCLUSION: These results suggest that miR-1284 overexpression might be a suppressor for gastric cancer via controlling of cell proliferation and apoptosis.

E2F-1 promotes DAPK2-induced anti-tumor immunity of gastric cancer cells by targeting miR-34a.

Activation of the transcription factor E2F-1 gene is a negative event in dendritic cell (DC) maturation process. Down-regulation of E2F1 causes immaturity of DC thereby stopping antigen production which in turn leads to inhibition of immune responses. E2F-1-free stimulates the NF-kB signaling pathway, leading to activation of monocytes and several other transcription factor genes. In the study, we report that down-regulation of E2F-1 in DCs promote anti-tumor immune response in gastric cancer (GC) cells through a novel mechanism. DCs were isolated from peripheral blood mononuclear cells. E2F-1 small interfering RNA (E2F-1-shRNA) induced down-regulation of E2F-1 mRNA and protein expression in DCs. Furthermore, we identified the E2F-1-shRNA targeted the CD80, CD83, CD86, and MHC II molecules, promoted their expression, and induced T lymphocytes proliferation activity and up-regulation of IFN-I³ production and GC cell killing effect, which significantly correlated with the cytotoxic T lymphocytes activated by E2F-1-shRNA DCs. The higher expression of miR-34a was found which was significantly correlated with the DC enhancing anti-tumor immunity against gastric cancer cell, and miR-34a potently targeted DAPK2 and Sp1, both of which were involved in the deactivation of E2F-1. Moreover, in E2F-1-DC-down-regulation in mice, GC transplantation tumors displayed down-regulation of Sp1, DAPK2, Caspase3, and Caspase7 and progressed to anti-tumor immunity. Collectively, our data uncover an E2F-1-mediated mechanism for the control of DC anti-tumor immunity via miR-34a-dependent down-regulation of E2F-1 expression and suggest its contribution to GC immunotherapy.

Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation.

This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography.

BACKGROUND: Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM: To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS: We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS: In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION: MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Invasion characteristics and clinical significance of tumor-associated macrophages in gastrointestinal Krukenberg tumors.

Background: Tumor-associated macrophages (TAMs) have been used as potential drug targets in preclinical research and clinical trials of various cancers. However, their distribution in Krukenberg tumors (KTs) remains unclear. We investigated the expression and prognostic value of TAMs in patients with gastrointestinal cancer with KTs. Methods: The infiltration of various types of TAMs was detected in surgical tissues of 35 patients with KTs using immunohistochemical staining. The level of infiltration of TAMs in tumor nests (TN), tumor stroma (TS), and invasive margin (IM) areas was evaluated. The Kaplan-Meier method and univariate/multivariate Cox regression risk models were used to analyze the relationship between the degree of TAMs invasion and overall survival (OS) and progression-free survival (PFS). Results: The distribution of TAMs exhibited spatial heterogeneity between TN, TS, and IM regions in primary tumor (PT) and KT tissues. TAMs infiltrated in the TN had greater prognostic value and were barely influenced by preoperative neoadjuvant therapy, despite similar grades of invasion in PT and KT tissues. Moreover, the number of CD68+ TAMs in TN of KT tissues was an independent risk factor affecting patient OS, whereas tumor resection scope might be an independent risk factor affecting patient PFS. Conclusions: In view of the close relationship between TAMs, the tumor microenvironment and patient prognosis, targeting TAMs combined with chemotherapy is expected to become a new approach for the treatment of patients with KTs.

Effect of Esophagus-Remnant Stomach Anterior Wall Anastomosis on Postoperative Reflux and Nutritional Status in Patients with Early- and Intermediate-Stage Proximal Gastric Cancer.

Purpose: To compare and analyze the incidence of postoperative reflux esophagitis (RE) in patients with early- and intermediate-stage proximal gastric cancer after proximal gastrectomy plus esophagus-remnant stomach anterior wall anastomosis with proper spacing between the reserved anastomotic stoma and the stump of the remnant stomach versus total gastrectomy plus Roux-en-Y anastomosis and to analyze the advantages and disadvantages of these anastomosis approaches. Methods: Hospitalization data of 23 patients with early- and intermediate-stage proximal gastric cancer were retrospectively analyzed. They were divided into an observation group who underwent proximal gastrectomy plus esophagus-remnant stomach anterior wall anastomosis with proper spacing between the reserved anastomotic stoma and the stump of the remnant stomach and a control group who underwent total gastrectomy plus Roux-en-Y anastomosis. Quality observation indicators were compared between the two groups. Results: There was no statistically significant difference between the groups in the number of lymph nodes cleared or the recurrence rate at 12 months postoperatively. The incidence of postoperative RE was significantly lower in the observation group (25%) than in the control group (80%). The operation time, postoperative length of hospital stay, appetite change, body mass index, and hemoglobin level at 6 months postoperatively were significantly better in the observation group than in the control group (P < .05). Conclusion: Proximal gastrectomy plus esophagus-remnant stomach anterior wall anastomosis with proper spacing between the reserved anastomotic stoma and the stump of the remnant stomach can be used as a preferred surgical procedure for early- and mid-stage proximal gastric cancer.

Effects of Chinese Martial Arts on Motor Skills in Children between 5 and 6 Years of Age: A Randomized Controlled Trial.

Children's motor skills can be fully developed only by the appropriate stimulation of physical activities and the environment, and the poor development of motor skills greatly increases the risk of cognitive impairment, obesity, and movement coordination disorder. This study aimed to examine the effects of Chinese martial arts on the motor skills of preschool children aged 5−6 years through a randomized controlled trial. A total of 87 children aged 5−6 years served as participants in a martial arts sensory teaching group (MAST, n = 29), a martial arts traditional teaching group (MATT, n = 29), and a free activity group (FA, n = 29). The interventions were conducted twice weekly for a total of 10 weeks, with each session lasting 30 min. Children's motor skills were assessed before and after the intervention using the Movement Assessment Battery for Children (MABC-2). The results indicated that the balance index scores in the MAST (p < 0.001) and MATT (p = 0.014) groups were significantly higher than those in the FA and that the MAST score was significantly higher than the MATT (p = 0.004). Meanwhile, the MAST was significantly higher in total scores on motor skills when compared to the FA (p = 0.039), and the MAST showed significantly higher scores on manual dexterity when compared to both the MATT (p = 0.021) and FA (p = 0.011). Chinese martial arts can significantly improve the balance ability of preschool children, and the MAST method was found to be better than that of the MATT. Meanwhile, the MAST had good potential for the development of preschool children's manual dexterity and their overall level of motor skills.

Anatomy of Subpancreatic Transverse Colon Vessel and Its Clinical Significance: An Observational Study.

Purpose: To observe and count the probability of presence and the anatomy of the vessel arising via the inferior margin of the pancreas and traveling within the transverse mesocolon, and analyze its clinical significance. Methods: Patients who underwent radical operation for transverse colon cancer or descending colon cancer from January 2020 to November 2021 and a nonspecific cadaver were included in this study. We observed and recorded intraoperatively for the probability of presence and the anatomy of the vessel arising via the inferior margin of the pancreas and traveling within the transverse mesocolon. And its property was determined by tissue slice. Results: A total of 84 patients were included, of which, the vessel was observed in 72 (85.7%) patients, and its property was confirmed by tissue slice of one patient after surgery. The vessel was also observed in a nonspecific cadaver. Originating from transverse pancreatic artery, often one, occasionally two, rarely three vessels arose via the inferior margin of pancreas and supplied the left transverse colon. Artery and vein parallel ran, and it was difficult to separate them due to their small diameter, but the vessels may thicken under certain conditions for increasing blood supply. Conclusion: The vessel, which is not yet reported and named in the literature, can be called the subpancreatic transverse colon vessel, which has a high probability of presence in humans and may be of great significance to human physiological anatomy, surgery, and oncology, and deserves recognition and attention from surgeons.

MicroRNA-766-3p-mediated downregulation of HNF4G inhibits proliferation in colorectal cancer cells through the PI3K/AKT pathway.

Nuclear receptors (NRs) are a class of transcription factors that play a pivotal role in carcinogenesis, but their function in colorectal cancer (CRC) remains unclear. Here, we investigate the role NRs play in CRC pathogenesis. We found that hepatocyte nuclear factor 4 gamma (HNF4G; NR2A2), hepatocyte nuclear factor 4α (HNF4A; NR2A1), and retinoid-related orphan receptor γ (RORC; NR1F3) were significantly upregulated in CRC tissues analyzed by GEPIA bioinformatics tool. The expression of HNF4G was examined in CRC samples and cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. Increased expression of HNF4G was strongly associated with high tumor-node-metastasis stage and poor prognosis. Moreover, overexpression of HNF4G significantly promoted the proliferation of CRC cells in vitro. Next, we found that HNF4G promoted CRC proliferation via the PI3K/AKT pathway through targeting of GNG12 and PTK2. In addition, HNF4G was verified as a direct target of microRNA-766-3p (miR-766-3p). miR-766-3p inhibited the proliferation of CRC cells by targeting HNF4G in vitro and in vivo. Collectively, our study indicates that miR-766-3p reduces the proliferation of CRC cells by targeting HNF4G expression and thus inhibits the PI3K/AKT pathway. Therefore, development of therapies which target the miR-766-3p/HNF4G axis may aid in the treatment of CRC.

Oncology Outcomes of Total Mesorectal Excision with Preservation of Both the Superior Rectum Artery and Left Colonic Artery for Upper-Rectal and Sigmoid Colon Cancers: A Meta-Analysis.

Background: Total mesorectal resection (TME) has become the standard surgical procedure for resection of colorectal cancer tumors. We presented a systematic meta-analysis to evaluate the surgical outcomes of laparoscopic TME surgery with preservation or nonpreservation of both the superior rectum artery (SRA) and left colonic artery (LCA) for upper-rectal and sigmoid colon cancers. Methods: The comparative studies were systematically searched on PubMed, Science Direct, Web of Science, Wanfang Data, and China National Knowledge Infrastructure (CNKI) up to April 2021. Primary outcomes were oncology outcomes. And secondary outcomes involved surgical outcomes of interest and postoperative recovery. Results: Five relevant studies with a total of 761 patients undergoing laparoscopic TME surgery were eligible for meta-analysis. Three hundred seven patients received TME with preservation of both SRA and LCA (Group A), and 454 received TME surgery alone (Group B), respectively. Our results indicated that Group A had a less total postoperative complications (P = .000), lower anastomotic leakage rate (P = .002), shorter length of stay (P = .008), and longer operative time (P = .002). However, there was no significant difference between the two groups in terms of lymph node dissections (P = .188), intraoperative bleeding (P = .474), the first postoperative defecation (P = .943), recurrence rate (P = .547), and conversive rate (P = .504). Conclusions: Based on our meta-analysis, laparoscopic TME surgery with preservation of both the SRA and LCA for upper-rectal and sigmoid colon cancers may significantly receive better clinical and surgical outcomes. More well-designed large sample studies are required to replicate the short-term benefits and long-term oncologic outcomes.

Indole-3-carbinol enhances the resolution of rat liver fibrosis and stimulates hepatic stellate cell apoptosis by blocking the inhibitor of κB kinase α/inhibitor of κB-α/nuclear factor-κB pathway.

Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the clearance of activated HSC by apoptosis is associated with the resolution of liver fibrosis. The development of strategies that promote this process in a selective way is therefore important. We evaluated the effects of indole-3-carbinol (I3C), a nutritional component derived from vegetables from the Brassica family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of I3C were monitored in three rat models of liver fibrosis induced by porcine serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line. The results showed that I3C treatment significantly reduced the number of activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C reduced hepatocyte degeneration and necrosis, accelerated collagen degradation, and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the expression ratio of Bax to Bcl-2. High-throughput protein array analysis indicated that the tumor necrosis factor-α/nuclear factor-κB (NF-κB) signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and electrophoretic mobility-shift assay confirmed that I3C inhibited the phosphorylation of inhibitor of κB kinase α and inhibitor of κB-α and NF-κB DNA binding activity. In conclusion, I3C could promote the reverse process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro, which indicates the use of I3C as a potential therapeutic agent in liver fibrosis treatment.