Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

Analysis of bowel function, urogenital function, and long-term follow-up outcomes associated with robotic and laparoscopic sphincter-preserving surgical approaches to total mesorectal excision in low rectal cancer: a retrospective cohort study.

OBJECTIVE: The present study comparatively analyzed short-term clinical effectiveness and long-term follow-up endpoints associated with robotic-assisted sphincter-preserving surgery (RAS) and laparoscopic-assisted sphincter-preserving surgery (LAS) when used to treat low rectal cancer. METHOD: Within such a single-center retrospective cohort analysis, low rectal cancer patients that underwent RAS (n=200) or LAS (n=486) between January 2015 and beginning of July 2018 were enrolled. RESULTS: The mean operative durations in the RAS and LAS cohorts were 249±64 min and 203±47 min, respectively (P<0.001). Temporary ileostomy rates in the RAS and LAS cohorts were 64.5% and 51.6% (P = 0.002). In addition, major variations across such cohorts regarding catheter removal timing, time to liquid intake, time to first leaving bed, and length of hospitalization (all P<0.001). This distal resection margin distance within the RAS cohort was diminished in comparison to LAS cohort (P=0.004). For patients within the LAS cohort, the time required to recover from reduced urinary/female sexual function was > 6 months post-surgery (P<0.0001), whereas within the RAS cohort this interval was 3 months (P<0.0001). At 6 months post-surgery, male sexual function within RAS cohort was improved in comparison to LAS cohort (P<0.001). At 6 months post-surgery, Wexner scores revealed similar results (P<0.001). No major variations within overall or disease-free survival were identified across these cohorts at 3 or 5 years post-surgery. CONCLUSION: Robotic sphincter-preserving surgery is a safe and effective surgical technique in low rectal patients in terms of postoperative oncological safety and long-term endpoints. And the RAS strategy provides certain additional benefits with respect to short-term urogenital/anorectal functional recovery in treated patients compared to LAS.

A new method of robot-assisted laparoscopic repair of perineal hernia after abdominoperineal resection: a case report.

INTRODUCTION: Perineal hernia is a protrusion of the pelvic floor which contains intra-abdominal viscera. The occurrence of perineal hernia after abdominoperineal resection (APR) is rare, but it has been reported in recent years that the incidence of perineal hernia after rectal cancer surgery has increased. This has been attributed to a shift towards extralevator abdominoperineal resection, together with more frequent and long-term use of neoadjuvant therapy. PRESENTATION OF CASE: Here, we report a patient with perineal hernia 5 years after APR surgery for rectal cancer. We decided to perform robot-assisted laparoscopic surgery on this patient using the da Vinci Surgical System. The perineal hernia was repaired by primary closure with the placement of a non-absorbable synthetic mesh as reinforcement for the pelvic floor. No complications occurred during the operation, and the patient was discharged on the third day after the operation. Clinical follow-up proceeded at the designated time intervals without difficulties. DISCUSSION: The recurrence rates of perineal hernia are still very high, and due to poor view, suturing, and mesh placement in the deep pelvis, surgeons face many challenges. Many methods have been described, but there is still no consensus as to the optimal repair technique for perineal hernia. CONCLUSION: Perineal hernias can be repaired with robot-assisted laparoscopy. Furthermore, compared with the open and laparoscopic methods, suturing and mesh placement are easier with the robot approach.

The correlation between NEDD4L and HIF-1α levels as a gastric cancer prognostic marker.

NEDD4L (neural precursor cell expressed developmentally down-regulated 4-like) protein is a member of ubiquitin ligases Nedd4 family. Although studies have shown that Nedd4L may act as a tumor suppressor in various cancers, including gastric cancer (GC), its clinical significance and the diagnostic value in GC is not well defined. HIF-1α (hypoxia inducible factor family of transcription factors) is actively involved in the metabolism of many tumors, although the relationship between its expression levels and clinical significance in GC still need to be established. In this study, the level of HIF-1α and NEDD4L mRNA and protein in 25 freshly frozen GC- and matched normal-tissues were determined by western blot and quantitative PCR (qPCR). Additionally, immunohistochemistry assay was performed to measure the protein level of NEDD4L and HIF-1α in 124 GC and 25 normal control tissues. We observed that the NEDD4L mRNA and protein levels decreased significantly (P < 0.001) in GC tissues, while that of HIF-1α increased (P < 0.001), and they both were associated with a poor prognosis, as was the case in patients with lower NEDD4L and higher HIF-1α expression (P < 0.001). On correlation analysis, a significantly negative relationship (r = 0.288, P < 0.01) was revealed between NEDD4L and HIF-1α expressions. Multivariate analysis revealed that co-expression of NEDD4L (P < 0.05) and HIF-1α (P < 0.001) were independent predictors of GC prognosis. Thus, the correlation of NEDD4L and HIF-1α levels may act as a prognostic marker of GC.

Knockdown of IARS2 suppressed growth of gastric cancer cells by regulating the phosphorylation of cell cycle-related proteins.

The purpose of the article is to investigate the role of IARS2 in proliferation, apoptosis, and cell cycle of gastric cancer (GC) cells in vitro. The IARS2-shRNA lentiviral vector was established and used to infect the GC cell line AGS. qRT-PCR and Western blot were employed to determine the efficiency of IARS2 knockdown. The effects of IARS2 knockdown on cell proliferation, cell clone formation, and cell cycle were assessed by MTT assay, colony formation assay, and flow cytometer analysis, respectively. Finally, a PathScan Antibody Array Kit was used to detect the expression levels of cell cycle-related proteins after IARS2 knockdown in AGS cells to elucidate the underlying mechanisms. Compared with negative control group, IARS2 was significantly knocked down by transfection with lentivirus encoding shRNA of IARS2 in AGS cells. IARS2 knockdown significantly inhibited the proliferation and colony formation ability and induced cycle arrest at G2/M phase of AGS cells. IARS2 knockdown significantly decreased the expression levels of phosphorylation of (p-Smad2), p-SAPK/JUK, cleavage-Caspase-7, and p-TAK1, but increased the expression levels of p-53 and cleavage-PARP in AGS cells compared to shCtrl group. We demonstrated that IARS2 knockdown inhibits proliferation, suppresses colony formation, and causes cell cycle arrest in AGS cells. We also found that IARS2 regulates key molecules of cell apoptosis-related signaling pathway.

Robotic total gastrectomy with π-shaped esophagojejunostomy using a linear stapler as a novel technique.

OBJECTIVE: To evaluate the intraoperative and short-term postoperative outcomes of a novel robotic intracorporeal π-shaped esophagojejunostomy (EJS) after D2 total gastrectomy (TG) using the Da Vinci robotic surgical system for intracorporeal anastomosis after TG. BACKGROUND: Intracorporeal π-shaped EJS, using a linear stapler, was recently reported for laparoscopic total gastrectomy in patients with gastric cancer. However, robotic intracorporeal π-shaped EJS using a linear stapler has not been reported. This report aimed to describe the use of a novel technique for π-shaped EJS using the Da Vinci robotic system. METHODS: Robotic intracorporeal π-shaped esophagojejunostomy after total gastrectomy was performed in 11 consecutive patients diagnosed with early gastric cancer, and their perioperative outcomes were analyzed. RESULTS: All the operations were successful without conversion to open or laparoscopic surgery and postoperative complications. The total number of patients was 11 (7 males and 4 females). The mean age of the patients was 63.36 ± 10.56 years old. Seven patients were diagnosed with cardia cancer, 3 patients were diagnosed with gastric body cancer, and 1 patient was diagnosed with gastric antrum cancer. The patients' mean proximal resection margin was 3.18 ± 1.17 cm, the distal resection margin was 6.18 ± 1.40 cm, the mean length of the incision was 4.55 ± 0.69 cm, the mean operative time was 287.27 ± 30.69 min, the mean day of first flatus was 3.27 ± 0.79 days, the mean day of the start of diet was 2.91 ± 0.94 days, the mean postoperative hospital stay was 11.45 ± 5.13 days, and the mean operative blood loss was 47.27 ± 31.33 ml. No complications were observed during anastomosis, and the median anastomosis time was 19.5 min. The mean number of lymph node dissections was 17.91 ± 4.59, the mean number of positive lymph nodes was 0.45 ± 0.69, all patients were diagnosed with stage I-II gastric cancer, and the mean maximum diameter of the tumor was 2.67 ± 1.30 cm. All the patients had a smooth hospital discharge. CONCLUSION: A novel robotic gastrectomy with intracorporeal π-shaped EJS for esophagojejunal anastomosis described and shows acceptable resulted. This technique has the potential to offer better short-term surgical outcomes and overcomes the drawbacks of laparoscopy with a decreased risk of complications during and after surgery.

miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1.

BACKGROUND: The aberrant expression of microRNA-140-5p (miR-140-5p) has been described in gastric cancer (GC). However, the role of miR-140-5p in GC remains unclear. In this study, the prognostic relevance of miR-140-5p in GC was investigated and YES1 was identified as a novel target of miR-140-5p in regulating tumor progression. METHODS: miR-140-5p level was determined in 20 paired frozen specimens through quantitative real-time PCR, and analyzed in tissue microarrays through in situ hybridization. The target of miR-140-5p was verified through a dual luciferase reporter assay, and the effects of miR-140-5p on phenotypic changes in GC cells were investigated in vitro and in vivo. RESULTS: Compared with that in adjacent normal tissues, miR-140-5p expression decreased in cancerous tissues. The downregulated miR-140-5p in 144 patients with GC was significantly correlated with the reduced overall survival of these patients. miR-140-5p could inhibit GC cell proliferation, migration and invasion by directly targeting 3'-untranlated region of YES1. miR-140-5p could also remarkably reduce the tumor size in GC xenograft mice. CONCLUSIONS: miR-140-5p serves as a potential prognostic factor in patients with GC, and miR-140-5p mediated YES1 inhibition is a novel mechanism behind the suppressive effects of miR-140-5p in GC.

Down regulation of Thrombospondin2 predicts poor prognosis in patients with gastric cancer.

BACKGROUND: Thrombospondins (THBSs) are a family of multidomain and secreted matricellular Ca(2+)-binding glycoproteins which has at least five members encoded by independent genes. As a THBSs family member, Thrombospondin2 (THBS2) has been reported to regulate angiogenesis. Nevertheless, the functions and clinical significance of THBS2 still remains unclear in gastric cancer. METHODS: The mRNA and protein expression levels of THBS2 were assessed in 14 paired of gastric cancer specimens and corresponding normal mucosas using quantitative real-time PCR and western blot analysis. Immunohistochemistry of THBS2 and CD34 on population-based tissue microarrays consisting of 129 gastric cancer cases were used to evaluate the prognostic significance of THBS2 and microvessel density (MVD) of each sample. Survival analyses were performed by Kaplan-Meier method and Cox's proportional hazards model. Colony formation assay, endothelial cell tube formation assay, cell migration assay and apoptosis analysis in MKN-45 and SGC-7901 cell lines were carried out to evaluate the effects of THBS2 on gastric cancer in vitro. RESULTS: 85.71% (12 of 14) gastric cancer tissues expressed remarkably lower THBS2 in both mRNA and protein levels than the corresponding normal controls. Consistently, tissue microarray (TMA) results showed THBS2 levels were also inhibited in gastric cancer tissues compared with the normal controls. Moreover, we observed that patients with higher levels of THBS2 were significantly correlated with more favourable prognosis while decreased THBS2 expression were associated with poorer histological grades of gastric cancer. Additionally, our in vitro experiments further demonstrated that overexpression of THBS2 could impede both the proliferation rate and the tube formation of Human umbilical vein endothelial cells (HUVECs) in MKN-45 and SGC-7901 cell lines. CONCLUSION: Our study suggests THBS2 is aberrantly expressed in gastric cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of gastric cancer.

Genetic correlation, shared loci, but no causality between bipolar disorder and inflammatory bowel disease: A genome-wide pleiotropic analysis.

BACKGROUND AND AIMS: The comorbidity between bipolar disorder (BD) and inflammatory bowel disease (IBD) has been widely reported in observational studies. However, unclear whether this comorbidity reflects a shared genetic architecture. METHODS: Leveraging large-scale genome-wide association study (GWAS) summary statistics of BD, IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), we performed a genome-wide pleiotropic analysis to estimate heritability and genetic correlation, identify pleiotropy loci/genes, and explore the shared biological pathway. Mendelian randomization (MR) studies were subsequently employed to infer whether the potential causal relationship is present. RESULTS: We found a positive significant genetic correlation between BD and IBD (rg = 0.10, P = 7.00 × 10-4), UC (rg = 0.09, P = 2.90 × 10-3), CD (rg = 0.08, P = 6.10 × 10-3). In cross-trait meta-analysis, a total of 29, 24, and 23 independent SNPs passed the threshold for significant association between BD and IBD, UC, and CD, respectively. We identified five novel pleiotropy genes including ZDHHC2, SCRN1, INPP4B, C1orf123, and BRD3 in both BD and IBD, as well as in its subtypes UC and CD. Pathway enrichment analyses revealed that those pleiotropy genes were mainly enriched in several immune-related signal transduction pathways and cerebral disease-related pathways. MR analyses provided no evidence for a causal relationship between BD and IBD. CONCLUSION: Our findings corroborated that shared genetic basis and common biological pathways may explain the comorbidity of BD and IBD. These findings further our understanding of shared genetic mechanisms underlying BD and IBD, and potentially provide points of intervention that may allow the development of new therapies for these co-occurrent disorders.

Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

The efficacy of immunotherapy against colorectal cancer (CRC) is impaired by insufficient immune cell recruitment into the tumor microenvironment. Our study shows that targeting circDNA2v, a circular RNA commonly overexpressed in CRC, can be exploited to elicit cytotoxic T cell recruitment. circDNA2v functions through binding to IGF2BP3, preventing its ubiquitination, and prolonging the IGF2BP3 half-life, which in turn sustains mRNA levels of the protooncogene c-Myc. Targeting circDNA2v by gene silencing downregulates c-Myc to concordantly induce tumor cell senescence and the release of proinflammatory mediators. Production of CXCL10 and interleukin-9 by CRC cells is elicited through JAK-STAT1 signaling, in turn promoting the chemotactic and cytolytic activities of CD8+ T cells. Clinical evidence associates increased circDNA2v expression in CRC tissues with reductions in CD8+ T cell infiltration and worse outcomes. The regulatory relationship between circDNA2v, cellular senescence, and tumor-infiltrating lymphocytes thus provides a rational approach for improving immunotherapy in CRC.

Lysine-specific Demethylase 6A Upregulates Cadherin-1 and Accelerates Gastric Cancer Growth.

BACKGROUND: Gastric cancer (GC) ranks fifth among all common malignancies globally. Genetic research has revealed several genes that are frequently dis-regulated in GC, such as lysine-specific demethylase 6A (KDM6A) and cadherin-1 (CDH1). OBJECTIVE: This study aimed to examine the expression profile and role of KDM6A in GC, as well as the molecular pathway involved. METHODS: The expression profile and overall survival data of KDM6A were retrieved from the TCGA database. Expression levels of KDM6A were also measured in GC patient samples and compared with those of healthy controls. Furthermore, stable silencing of KDM6A was introduced into the GC cell line NCI-N87, followed by assessments of cell proliferation, migration and invasion, in the xenograft mouse model. The metastatic status of mice injected with NCI-N87 cells was also analyzed. RESULTS: In patients diagnosed with GC, KDM6A was upregulated. Silencing KDM6A reduced the proliferation, migration and invasion of cells, as well as the growth of xenograft tumors. KDM6A knockdown also inhibited metastatic behaviors of injected NCI-N87 cells, as well as elevated CDH1 expression, leading to reversed epithelial-mesenchymal transition. CONCLUSION: KDM6A serves as an oncogene in GC and exerts its pro-tumor functions by repressing the expression of CDH1.

FIT links c-Myc and P53 acetylation by recruiting RBBP7 during colorectal carcinogenesis.

Colorectal cancer (CRC) poses one of the most serious threats to human health worldwide, and abnormally expressed c-Myc and p53 are deemed the pivotal driving forces of CRC progression. In this study, we discovered that the lncRNA FIT, which was downregulated in CRC clinical samples, was transcriptionally suppressed by c-Myc in vitro and promoted CRC cell apoptosis by inducing FAS expression. FAS is a p53 target gene, and we found that FIT formed a trimer with RBBP7 and p53 that facilitated p53 acetylation and p53-mediated FAS gene transcription. Moreover, FIT was capable of retarding CRC growth in a mouse xenograft model, and FIT expression was positively correlated with FAS expression in clinical samples. Thus, our study elucidates the role of the lncRNA FIT in human colorectal cancer growth and provides a potential target for anti-CRC drugs.

Targeting TLK2 inhibits the progression of gastric cancer by reprogramming amino acid metabolism through the mTOR/ASNS axis.

Several recent studies have suggested that TLKs are related to tumor progression. However, the function and mechanism of action of TLK2 in gastric cancer (GC) remain elusive. In this study, TLK2 was found to be significantly upregulated in patients with GC and was identified as an independent prognostic factor for GC. Consistently, TLK2 knockdown markedly reduced the aggressiveness of GC, whereas its overexpression had the opposite effect. IP-MS revealed that the effects of TLK2 on GC were mainly associated with metabolism reprogramming. TLK2 knockdown suppressed amino acid synthesis by downregulating the mTORC1 pathway and ASNS expression in GC cells. Mechanistically, mTORC1 directly interacts with the ASNS protein and inhibits its degradation. Further experiments validated that the ASNS protein was degraded via ubiquitination instead of autophagy. Inhibiting and activating the mTORC1 pathway can upregulate and downregulate ASNS ubiquitination, respectively, and the mTORC1 pathway can reverse the regulatory effects of TLK2 on ASNS. Furthermore, TLK2 was found to regulate the mRNA expression of ASNS. TLK2 directly interacted with ATF4, a transcription factor of ASNS, and promoted its expression. The kinase inhibitor fostamatinib significantly inhibited the proliferative, invasive, and migratory capabilities of GC cells by inhibiting TLK2 activity. Altogether, this study reveals a novel functional relationship between TLK2 and the mTORC1/ASNS axis in GC. Therefore, TLK2 may serve as a potential therapeutic target for GC.

Application of Laparoscopic Gastric Jejunum Uncut Roux-en-Y Anastomosis.

Background: Uncut Roux-en-Y gastrojejunostomy, recently developed in China, is useful in the treatment of distal gastric cancer. This study is aimed at comparing laparoscopic gastric jejunum uncut Roux-en-Y anastomosis with conventional anastomosis in the surgical treatment of distal gastric malignancy. Methods: In this retrospective study, the clinical data of 178 patients and their follow-up records were analyzed. 112 cases (uncut group) were the observation group for stomach jejunum uncut Roux-en-Y anastomosis, the control group for the stomach, 66 cases (conventional group) were for jejunum Roux-en-Y anastomosis and Billroth I and Billroth II anastomosis. A comparison between the two groups was conducted based on the general situation of the patients, TNM stage, and one-year survival rate. Results: There was no significant difference reported between the two groups in terms of the general situation and TNM stage. A comparison on postoperative complications between the two groups revealed that the postoperative bleeding was 0.9% and 6.1%, the bile reflux gastritis was 1.8% and 9.1%, the anastomotic leakage was 0.0% and 3.0%, the delayed gastric emptying was 0.9% and 7.6%, and the overall complications was at 3.6% and 25.8%, which was significantly lower in the observation group than in the control group, and the difference was statistically significant. Notably, there was no significant difference in 1-year survival rate between the two groups. Conclusion: Laparoscopic gastric jejunal uncut Roux-en-Y anastomosis significantly reduces the risk of postoperative complications of the digestive tract. Its operation is easy and exhibits an effective curative effect.

Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues.

Purpose: Hypoxia-inducible factor-1alpha (HIF-1A) is a transcription factor that plays an "angiogenic switch" role especially under hypoxia microenvironment in solid tumor. However, the functions and clinical significance of HIF-1A in gallbladder cancer (GBC) are still controversial, and it has not been studied in normal gallbladder tissues. In this study, we sought to clarify the role of sub-cellular localization of HIF-1A expression in GBC and normal gallbladder tissues. Methods: The expressions of HIF-1A and CD34 in 127 GBC and 47 normal gallbladder tissues were evaluated by immunohistochemistry. Cox's proportional hazards model analysis and Kaplan-Meier method analysis were used to assess the correlations between these factors and clinicopathological features and prognosis. Results: HIF-1A was expressed in both cytoplasm and nucleus of GBC and normal control tissues, and was significantly correlated with microvessel density (MVD). GBC tissues with positive nuclear HIF-1A expression had higher MVD compared to that with positive cytoplasmic HIF-1A expression; however, in normal gallbladder tissues, samples with positive cytoplasmic HIF-1A had higher MVD compared to that with positive nuclear HIF-1A expression. Moreover, GBC with nuclear HIF-1A expression tended to be more poorly differentiated and had larger tumor size compared to that with cytoplasm HIF-1A expression. Furthermore, GBC patients with nuclear HIF-1A positive were significantly correlated with worse overall survival (OS) compared with cytoplasmic HIF-1A positive. Multivariate Cox regression analysis identified lymph node metastasis and nuclear HIF-1A expression to be independent prognostic parameter in GBC. Conclusions: Our findings provide evidence for the first time that HIF-1A is expressed in normal gallbladder tissues. Nuclear HIF-1A and cytoplasm HIF-1A plays different roles in GBC and normal gallbladder tissues.

Circ_0005927 Inhibits the Progression of Colorectal Cancer by Regulating miR-942-5p/BATF2 Axis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common aggressive neoplasms worldwide. Circular RNAs (circRNAs) have been involved in the biological process of CRC. This study aimed to explore the effects of circ_0005927 on CRC progression and underneath mechanism. MATERIALS AND METHODS: The expression of circ_0005927, microRNA-942-5p (miR-942-5p) and basic leucine zipper ATF-like transcription factor 2 (BATF2) was detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression of BATF2 was determined by Western blot. The effects among circ_0005927, miR-942-5p and BATF2 on cell colony-forming ability, apoptosis and migratory and invasive abilities were revealed by cell colony formation, flow apoptosis and transwell assays, respectively. The associated relationship between miR-942-5p and circ_0005927 or BATF2 was predicted by Circinteractome or TargetScan online database, and identified by dual-luciferase reporter or RNA immunoprecipitation (RIP) assay. The impacts of circ_0005927 overexpression on tumor growth in vivo were investigated by in vivo tumor formation assay. RESULTS: Circ_0005927 expression and the mRNA and protein expression of BATF2 were dramatically downregulated, while miR-942-5p expression was obviously upregulated in CRC tissues or cells compared with control groups. Circ_0005927 overexpression repressed cell colony-forming ability, migration and invasion, whereas induced cell apoptosis in CRC; however, these impacts were hindered by miR-942-5p mimic or BATF2 knockdown. Furthermore, circ_0005927 was a sponge of miR-942-5p, and miR-942-5p bound to BATF2. In addition, circ_0005927 overexpression repressed tumor growth in vivo. CONCLUSION: Circ_0005927 suppressed cell colony-forming ability, migration and invasion, and promoted cell apoptosis by sponging miR-942-5p to induce BATF2 in CRC. The possible mechanism provides a theoretical basis for the study of circRNA-directed therapy for CRC.

Exosomal miR-183-5p Shuttled by M2 Polarized Tumor-Associated Macrophage Promotes the Development of Colon Cancer via Targeting THEM4 Mediated PI3K/AKT and NF-κB Pathways.

BACKGROUND: Abnormal accumulation of macrophages in the colon cancer (CC) contribute to its progression. miR-183-5p has been confirmed as an oncogene in CC and this article explores the effect and mechanism of exosomal miR-183-5p enriched by M2-polarized tumor-associated macrophages (TAM) on CC cells. METHODS: The human macrophage THP1 was induced to M2 polarization through IL-4 and IL-13 treatment. Exosomes in THP1 were isolated through ultracentrifugation, and the miR-183-5p expression in macrophages and exosomes was verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The miR-183-5p inhibitors and mimics were applied to down-regulate and upregulate miR-183-5p in macrophages, respectively. Meanwhile, CC cell lines LoVo and SW480 were treated with the macrophage conditioned medium and exosomes, respectively. CC cells' proliferation, invasion, and apoptosis were tested by the cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry (FCM), Transwell assay, and xenograft assay, respectively. The profiles of thioesterase superfamily member 4 (THEM4), Akt, and NF-κB were compared by Western blotting (WB). RESULTS: The miR-183-5p level in M2-TAM and M2-TAM-derived exosomes was significantly increased. Meanwhile, M2-TAM and M2-TAM-derived exosomes significantly facilitated CC cell proliferation and invasion and dampened apoptosis. Overexpression of miR-183-5p in M2-TAM aggravated M2-TAM-mediated promotive effects on CC cells, with down-regulating miR-183-5p reversed M2-TAM-mediated tumor-promotive effects. Mechanically, miR-183-5p targeted THEM4 and inhibited its mRNA and protein expression. Overexpressing THEM4 abated miR-183-5p-mediated carcinogenic effects and inactivates Akt and NF-κB pathways in CC cells. Overall, this article elaborated that exosomal miR-183-5p shuttled by M2-TAM mediated Akt/NF-κB pathway to accelerate CC progression through targeting THEM4.

A novel method for π-shaped esophagojejunostomy and double-tract reconstruction (DTR) as an alternative in totally laparoscopic or robotic proximal gastrectomy for treating upper third proximal early gastric cancer.

This study evaluated the impact of a new intracorporeal π-shaped esophagojejunostomy (EJS) and double-tract reconstruction (DTR) in totally laparoscopic and totally robotic proximal gastrectomy (TLPG or TRPG) for treating upper third early gastric cancer (U-EGC) in terms of intraoperative and short-term postoperative outcomes. Early proximal gastric cancer patients were identified based on a prospectively established database. From January 2017 to December 2018, these patients underwent intracorporeal π-shaped EJS and DTR after totally laparoscopic (n = 8) or robotic (n = 4) proximal gastrectomy (PG). We recorded and analyzed the baseline characteristics and surgical outcomes, including postoperative complications for these patients. No severe postoperative complications were observed following the operational procedures. Twelve patients (seven male and five female) diagnosed with cardia cancer (Siewert II and III) were enrolled, of which eight underwent the totally laparoscopic proximal gastrectomy (TLPG), and four underwent the totally robotic proximal gastrectomy (TRPG). The mean operative time, blood loss, day of the start of the diet, and postoperative hospital stay was 235.54 ± 20.79 min, 50.65 ± 35.44 mL, 3.85 ± 0.65 days, and 12.45 ± 3.24 days, respectively. All patients presented with a diagnosis of stage I gastric cancer. The mean number of lymph node dissections and the maximum tumor diameter was 13.91 ± 4.63 and 2.18 ± 0.73 cm, respectively. After the operational procedure, using the iodoethylene contrast reagent, we observed that a large proportion of iodoethylene contrast agents entered the jejunum directly, and a small proportion entered the jejunum through the duodenum. Surgeons followed up with ten patients for more than 12 months and the remaining two patients for more than 24 months. None of the patients showed any signs of anastomotic stenosis or reflux esophagitis or anemia symptoms. This study presents a novel method for π-shaped EJS and DTR as an alternative in TLPG or TRPG for treating proximal early gastric cancer, and it offers better short-term postoperative and intraoperative surgical outcomes.

A case of COVID-19 patient with the diarrhea as initial symptom and literature review.

Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.

The outcomes of bariatric surgery on rheumatoid arthritis disease activity: a prospective cohort study.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Overweight and obesity can aggravate disease activity and clinical outcome in patients with RA. However, the role of bariatric surgery in inducing weight loss in the treatment of RA has not been confirmed. In this 12-month prospective cohort study, RA patients with obesity who were referred to our hospital were included. Thirty-two patients were classified into the bariatric surgery group according to the patient's decision after a comprehensive assessment of surgery indications, and 33 patients received only pharmacotherapy for RA. At the 12-month follow-up, the response rates of ACR20, ACR50 and ACR70 were 75.0% vs. 51.5%, 53.1% vs. 39.4% and 31.3% vs. 21.2% in the bariatric surgery and non-surgery groups, respectively (all p < 0.05); the mean DAS28-ESR, DAS28-CRP and cDAI scores were 1.5 ± 0.9 vs. 2.4 ± 1.4, 1.2 ± 0.9 vs. 2.2 ± 1.7 and 9.5 ± 6.8 vs. 15.8 ± 12.5, respectively, in surgical patients compared to non-surgical patients (all p < 0.05). Compared to baseline, after 12 months, a significant reduction was observed in the use of leflunomide, biological agents, combination treatments, and NSAIDs in both groups (p < 0.05 or p < 0.01). However, there was no difference in medication use between the 2 groups either at baseline or at the 12-month follow-up (all p > 0.05). Compared to non-surgical patients, in RA patients with obesity, weight loss after bariatric surgery was associated with lower disease activity. Medication tapering for RA in patients who underwent bariatric surgery was not superior to that in non-surgical patients.