Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.

Exogenous hydrogen sulfide alleviates hepatic endoplasmic reticulum stress via SIRT1/FoxO1/PCSK9 pathway in NAFLD.

High-fat-induced endoplasmic reticulum (ER) stress has been the main reason for the occurrence and development of nonalcoholic fatty liver disease (NAFLD). Hydrogen sulfide (H2 S) produces a marked effect on regulating lipid metabolism and antioxidation, whose effects on ER stress of NAFLD are still unclear. Here, we studied the influence of exogenous H2 S on NAFLD and its potential mechanism. In vivo, NAFLD model was induced by high-fat diet (HFD) for 12 weeks, followed by intraperitoneal injection of exogenous H2 S intervention for 4 weeks. HepG2 cells exposure to lipid mixture (LM) were used as vitro model to explore the potential mechanism. We found exogenous H2 S significantly inhibited the hepatic ER stress and improved the liver fat deposition of HFD-fed mice. These similar results were also observed in HepG2 cells dealt with LM after exogenous H2 S treatment. Further mechanism studies showed exogenous H2 S strengthened the combination of FoxO1 with the PCSK9 promoter gene through SIRT1-mediated deacetylation, thereby inhibiting the PCSK9 expression to relieve the hepatic ER stress. However, SIRT1 knockout eliminated the effects of exogenous H2 S on FoxO1 deacetylation, PCSK9 inhibition, and remission of hepatic ER stress and steatosis. In conclusion, exogenous H2 S improved NAFLD by inhibiting hepatic ER stress through SIRT1/FoxO1/PCSK9 pathway. Exogenous H2 S and ER stress may be potential drug and target for the treatment of NAFLD, respectively.

The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

The standardized training and assessment system for magnetically controlled capsule gastroscopy (with video).

BACKGROUND AND AIM: To explore the feasibility of a standardized training and assessment system for magnetically controlled capsule gastroscopy (MCCG). METHODS: The results of 90 trainees who underwent the standardized training and assessment system of the MCCG at the First Affiliated Hospital of Xi'an Jiaotong University from May 2020 to November 2023 was retrospectively analyzed. The trainees were divided into three groups according to their medical backgrounds: doctor, nurse, and non-medical groups. The training and assessment system adopted the '7 + 2' mode, seven days of training plus two days of theoretical and operational assessment. The passing rates of theoretical, operational, and total assessment were the primary outcomes. Satisfaction and mastery of the MCCG was checked. RESULTS: Ninety trainees were assessed; theoretical assessment's passing rates in the three groups were 100%. The operational and total assessment passing rates were 100% (25/25), 97.92% (47/48), and 94.12% (16/17), for the doctor, nurse, and non-doctor groups respectively, with no significant difference (χ2 = 1.741, p = 0.419). No bleeding or perforation occurred during the procedure. Approximately, 96.00% (24/25), 95.83% (46/48), and 94.12% (16/17) of the doctor, nurse and non-medical groups anonymously expressed great satisfaction, respectively, without statistically significant difference (χ2 = 0.565, p = 1.000). The average follow-up time was 4-36 months, and 87 trainees (96.67%) had mastered the operation of the MCCG in daily work. CONCLUSIONS: Standardized training and assessment of magnetically controlled capsule endoscopists is effective and feasible. Additionally, a strict assessment system and long-term communication and learning can improve teaching effects.

NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling.

Hepatocellular carcinoma (HCC) is among the world's worst malignancies. Nuclear division cycle 1 (NDC1) is an essential membrane-integral nucleoporin, found in this study to be significantly increased in primary HCC. A multivariate analysis revealed that higher NDC1 expression was linked to worse outcome in HCC patients. Mouse xenograft tumors overexpressing NDC1 grew rapidly, and HCC cells overexpressing NDC1 showed enhanced proliferation, invasion, and migration in vitro. In contrast, knocking down NDC1 had the opposite effects in vitro. Furthermore, co-immunoprecipitation and liquid chromatograph mass spectrometer analyses revealed that NDC1 activated PI3K/AKT signaling by interacting with BCAP31. In summary, NDC1 and BCAP31 cooperate to promote the PI3K/AKT pathway, which is essential for HCC carcinogenesis. This suggests that NDC1 is predictive of prognosis in HCC.

RIPK2 promotes the progression of colon cancer by regulating BIRC3-mediated ubiquitination of IKBKG.

Colon cancer is a cancer with high morbidity and mortality worldwide. Receptor interacting serine/threonine kinase 2 (RIPK2) has been identified as a proto-oncogene, but its role in colon cancer is largely unknown. Herein, we found that RIPK2 interference could inhibit the proliferation and invasion of colon cancer cells, and promote apoptosis. Baculoviral IAP repeat containing 3 (BIRC3) is an E3 ubiquitin ligase, which was found highly expressed in colon cancer cells. Co-immunoprecipitation (Co-IP) experiments showed that RIPK2 could directly bind with BIRC3. Then, we demonstrated that RIPK2 overexpression promoted the expression of BIRC3, BIRC3 interference could eliminate RIPK2-dependent cell proliferation and invasion, and BIRC3 overexpression rescued the suppressive effect of RIPK2 interference on cell proliferation and invasion. We further identified IKBKG, an inhibitor of nuclear factor kappa B, as a ubiquitination substrate targeted by BIRC3. IKBKG interference could eliminate the inhibitory effect of BIRC3 interference on cell invasion. RIPK2 could promote BIRC3-mediated ubiquitination of IKBKG, inhibit the expression of IKBKG protein, and promote the expression of NF-κB subunits p50 and p65 proteins. In addition, DLD-1 cells transfected with sh-RIPK2 or/and sh-BIRC3 were injected into mice to establish a tumor xenograft model, and we found that administration of sh-RIPK2 or sh-BIRC3 impeded the growth of xenograft tumors in vivo, and co-administration displayed a better inhibitory effect. In general, RIPK2 promotes the progression of colon cancer by promoting BIRC3-mediated ubiquitination of IKBKG and activating the NF-κB signaling pathway.

USP14-mediated deubiquitination of SIRT1 in macrophage promotes fatty acid oxidation amplification and M2 phenotype polarization.

There is a trend of increasing young cases with gastric cancer globally. Sensitive early diagnosis methods and new therapeutic approaches are still the focus of clinical diagnosis and therapy of gastric cancer. USP14 plays an extensive role in tumor malignancy and fat metabolism regulation. However, researchers still have gaps in their knowledge of its substrates, which makes it difficult for deubiquitinases to become clinical targets. TAMs were isolated from tumor or polarized from primary THP1 cells by tumors cell lines under the control of IU1 and FAO inhibitor therapy. Cytokines controlled macrophages were compared to evaluate the capability to induce USP14 expression. Fatty acid uptake assay and OCR measurement were used to analyze macrophage metabolism. USP14 is found the correlation with tumor poor prognosis and poor immunophenotype in gastric cancer patients and mouse tumor models. Activation of USP14 determines elevated protein stability of SIRT1 and is required for activation of macrophage fatty acid oxidation and immunosuppressive phenotype. Although overexpression of USP14 is not sufficient to polarize macrophages to the M2 phenotype, inhibition of USP14 by IU1 in tumor-bearing mice disrupts the suppressive activity of cancer-promoting macrophages and effectively reshapes immune microenvironment characteristics. Our study provides evidence that a novel therapeutic strategy that targets to lipid metabolism of macrophages in tumors could be a potential option for emerging treatments for gastric cancer.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

HCG15 is a hypoxia-responsive lncRNA and facilitates hepatocellular carcinoma cell proliferation and invasion by enhancing ZNF641 transcription.

Hypoxia, one of the key features of the hepatocellular carcinoma (HCC) microenvironment, transcriptionally regulates the expression of mRNAs and non-coding RNAs via hypoxia-inducible factors (HIFs), thereby promoting tumor progression. However, hypoxia-responsive long non-coding RNAs (lncRNAs) in HCC required further investigation. We found that HLA complex group 15 (HCG15) was a new hypoxia-related lncRNA in HCC cells. Both hypoxia and HIF prolyl-hydroxylase inhibitor significantly increased HCG15 expression in HCC cells. At the same time, HIF-1α knockdown blocked hypoxia-induced the upregulation of HCG15. TCGA data revealed that HCG15 was markedly overexpressed and closely associated with the poor prognosis of HCC. HCG15 knockdown prominently suppressed the migration, invasion and proliferation of Hep3B and Huh7 cells. HCG15 overexpression markedly enhanced the proliferation and mobility of Huh7 cells. Zinc finger protein 641 (ZNF641) mRNA was frequently overexpressed and positively associated with HCG15 level in HCC samples from the TCGA database. Either HCG15 or upstream transcription factor 1 (USF1) silencing markedly reduced the ZNF641 level in HCC cells. RNA immunoprecipitation assay confirmed the interaction between HCG15 and USF1. Either HCG15 or USF1 knockdown prominently reduced the luciferase activity of reporter plasmid containing ZNF642 promoter. HCG15 knockdown remarkably abolished USF1-activated ZNF641 transcription in Hep3B cells. Finally, we confirmed that restoring ZNF641 expression remarkably abolished the effects of HCG15 knockdown on HCC cell migration, invasion and proliferation. Collectively, our study demonstrated that HCG15 was a new HIF-1 target gene and played a tumor-promoting role in HCC cells by enhancing USF1-mediated ZNF641 transcription.

Circ_0003570 Suppresses the progression of hepatocellular carcinoma through miR-182-5p/STARD13 regulatory axis.

BACKGROUND: Emerging evidence have revealed that circRNAs exert important biological effects in the development and progression of various diseases, including cancer. Our study aimed to elaborated the biological effects of hsa-circ_0003570 in hepatocellular carcinoma (HCC) development at the molecular level. RESULTS: The results of functional experiments showed that knockdown of circ_0003570 induced HCC cell growth, migration and invasion, whereas overexpression of circ_0003570 presented the opposite effects. In vivo experiments, xenograft tumors grown from circ-overexpressed cells had smaller tumor volume and weight than the control group. Further investigations suggested that circ_0003570 may function as a competing endogenous RNA via competitively binding miR-182-5p and thereby regulating the repression of downstream target gene STARD13, which were demonstrated by dual luciferase reporter assay and functional rescued experiments. CONCLUSIONS: Taken together, circ_0003570 suppresses the development of HCC by modulating miR-182-5p/STARD13 axis.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

Nomogram to predict cause-specific mortality of patients with rectal adenocarcinoma undergoing surgery: a competing risk analysis.

BACKGROUND: Rectal adenocarcinoma is one of major public health problems, severely threatening people's health and life. Cox proportional hazard models have been applied in previous studies widely to analyze survival data. However, such models ignore competing risks and treat them as censored, resulting in excessive statistical errors. Therefore, a competing-risk model was applied with the aim of decreasing risk of bias and thereby obtaining more-accurate results and establishing a competing-risk nomogram for better guiding clinical practice. METHODS: A total of 22,879 rectal adenocarcinoma cases who underwent primary-site surgical resection were collected from the SEER (Surveillance, Epidemiology, and End Results) database. Death due to rectal adenocarcinoma (DRA) and death due to other causes (DOC) were two competing endpoint events in the competing-risk regression analysis. The cumulative incidence function for DRA and DOC at each time point was calculated. Gray's test was applied in the univariate analysis and Gray's proportional subdistribution hazard model was adopted in the multivariable analysis to recognize significant differences among groups and obtain significant factors that could affect patients' prognosis. Next, A competing-risk nomogram was established predicting the cause-specific outcome of rectal adenocarcinoma cases. Finally, we plotted calibration curve and calculated concordance indexes (c-index) to evaluate the model performance. RESULTS: 22,879 patients were included finally. The results showed that age, race, marital status, chemotherapy, AJCC stage, tumor size, and number of metastasis lymph nodes were significant prognostic factors for postoperative rectal adenocarcinoma patients. We further successfully constructed a competing-risk nomogram to predict the 1-year, 3-year, and 5-year cause-specific mortality of rectal adenocarcinoma patients. The calibration curve and C-index indicated that the competing-risk nomogram model had satisfactory prognostic ability. CONCLUSION: Competing-risk analysis could help us obtain more-accurate results for rectal adenocarcinoma patients who had undergone surgery, which could definitely help clinicians obtain accurate prediction of the prognosis of patients and make better clinical decisions.

Colorectal Cancer Cell Differentiation Is Dependent on the Repression of Aerobic Glycolysis by NDRG2-TXNIP Axis.

BACKGROUND: Poorly differentiated colorectal cancers are more aggressive. Metabolism reprogramming is a significant hallmark in cancer, and aerobic glycolysis is common. However, how cancer cells reprogramming glucose metabolism contributes to cell differentiation was largely unknown. Previous studies have reported that tumor suppressor NDRG2 could promote colorectal cancers differentiation. AIMS: This study aims to demonstrate that NDRG2 promotes the differentiation of colorectal cancers, potentially through the inhibition of aerobic glycolysis via TXNIP induction. METHODS: Western blotting, qRT-PCR and immunohistochemical staining were used to detect the expression of related molecules. MTT assay was used to reflect cell viability and proliferation. Immunofluorescent assay was performed to identify the expression and distribution of molecules. Luciferase analysis and CHIP assays were used to investigate the mechanism. Bioinformatic analysis was performed to predict the relevance. RESULTS: In colorectal cancers, NDRG2 could inhibit cell proliferation, reduce glucose uptake and decrease expression of key glycolysis enzymes. Upregulated NDRG2 is associated with differentiated cancer. However, deletion of TXNIP, a classic glucose metabolism inhibitor, could obviously alter the function of NDRG2 in differentiation, glucose uptake, expression of key glycolysis enzymes and proliferation. Mechanistically, high glucose flux promotes the activity of TXNIP promoter. And NDRG2 promotes the occupancy of transcription factor Mondo A on TXNIP promoter, predominantly through the suppression of c-myc, which could complete with Mondo A binding to TXNIP promoter. In clinical samples, high expression of TXNIP indicates good prognosis and outcome. CONCLUSIONS: NDRG2-dependent induction of TXNIP is critical for the aerobic glycolysis during colorectal cancers differentiation.

High-power 450 nm blue diode laser for endoscopic mucosal resection/endoscopic submucosal dissection in the stomach: Preliminary results on a porcine model with a modified flexible endoscope.

BACKGROUND: Due to the precise vaporization of the novel 450 nm blue diode laser in soft tissues (i.e., bladder and colon) in our previous studies, porcine stomach tissues were applied here to certify its efficacy in endoscopic mucosal resection (ESR)/endoscopic submucosal dissection (ESD) for hypothetical lesions ex vivo and in vivo. MATERIALS AND METHODS: In an ex vivo study of ESR, 20 pieces of tissues (8 cm × 6 cm) from 7 fresh stomachs after spraying saline were vaporized with a three-dimensional scanning system using the blue diode laser at a maximum of 30 W, a different treatment speed and working distance (WD). In ex vivo ESD, 18 pieces of tissues from 6 fresh stomachs were used and the same laser parameters were used to perform the procedure. The depth, width, and coagulation of the laser vaporization were measured. Furthermore, the large scales (2.0 cm × 1.5 cm) for 18 hypothetical lesions of the gastric mucosa and submucosa of the 6 fresh stomachs were also resected with a modified flexible endoscope. In vivo, six hypothetical lesions of six porcine were vaporized by the novel blue laser, and the resultant lesions at the acute and chronic stages were assessed by the naked eye and hematoxylin and eosin staining. RESULTS: In the contact mode, more tissue was vaporized, and the thickness of the coagulation was stable when the WD was 0-2 mm, whose value varied from 0.33 to 1.73 mm. In the gastroscopy model, the mean thickness of coagulation from the mucosa was 0.67 mm, and a significant carbonization zone was not observed. In vivo, the laser beam could accurately act on the hypothetical target. No bleeding and clear vision were present in the procedure. After 3 weeks, tissue healing was well recovered after laser coagulation, resection, and submucosal dissection. CONCLUSIONS: In the present study, the novel 450 nm blue diode laser exhibited ideal vaporization and thinner coagulation thickness in the porcine stomach, which indicated that it could be alternately used as a new device for stomach lesions.

Endoscopic submucosal dissection treatment of metachronous early gastric adenocarcinoma in a case with diffuse large B-cell lymphoma.

Cases of primary gastric lymphoma complicated with gastric adenocarcinoma are rare in clinical practice. We report a case of metachronous early gastric adenocarcinoma diagnosed eight years after the onset of gastric diffuse large B-cell lymphoma (DLBCL) and treated with endoscopic submucosal dissection (ESD).

Activation of Toll-like receptor 2 enhances peripheral and tumor-infiltrating CD8+ T cell cytotoxicity in patients with gastric cancer.

BACKGROUND: Toll-like receptors (TLRs) play central roles in the initiation of innate immune response, and also control adaptive immunity activation. Thus, the aim of the study was to investigate the regulation of TLR activation to CD8+ T cells has not been fully elucidated in gastric cancer (GC). MATERIALS AND METHODS: Thirty-two GC patients and twenty-three healthy controls were enrolled. Expression profile of TLRs in peripheral and tumor-infiltrating CD8+ T cells was investigated. Purified CD8+ T cells were stimulated with Pam3Csk4, an agonist of TLR2, and cytotoxic and co-inhibitory molecules in CD8+ T cells was measured. Direct and indirect contact coculture system between CD8+ T cells and AGS cells was set up. Modulation of TLR2 activation to CD8+ T cells was assessed by measuring lactate dehydrogenase release and cytokine secretion. RESULTS: TLR2 mRNA and TLR2+ cell percentage was down-regulated in GC derived peripheral and tumor-infiltrating CD8+ T cells. CD8+ T cells from GC patients showed exhausted phenotype, which presented as decreased perforin/granzyme B, increased programmed death-1, and reduced cytotoxicity to AGS cells. TLR2 activation by Pam3Csk4 enhanced perforin and granzyme B expression in CD8+ T cells, however, did not affect either proinflammatory cytokine production or co-inhibitory molecules expression. Pam3Csk4 stimulation enhanced cytolytic activation of peripheral and tumor-infiltrating CD8+ T cells from GC, but not those from healthy individuals. CONCLUSION: The present data revealed an important immunomodulatory activity of TLR2 to CD8+ T cells in GC patients.

THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway.

Our research aims to identify the role of thrombospondin 4 (THBS4) in hepatocellular carcinoma (HCC). First, bioinformatic analysis was applied for detection the expression of THBS4 in HCC samples, and qRT-PCR and western blot were performed to explore the expression of THBS4 in HCC tissues and adjacent samples. Next, colony formation assay and cell viability assay were used to assess the function of THBS4 on HCC cells growth while transwell assay and scratch test were for metastasis. Meanwhile Xenograft tumor models were further conducted to verify the function of THBS4 in HCC. As for mechanism in deep, we investigated the influence of THBS4 on epithelial-mesenchymal transition (EMT) development and the interaction between THBS4 and integrin (ITG) family using multiple experiments, including western blot, immunofluorescence and immunoprecipitation (IP). As a result, our research discovered that the overexpression of THBS4 in both HCC patients' tissues and cell lines mediates HCC cells proliferation and metastasis in vitro and in vivo. In-depth, THBS4 regulated EMT progression and interacted with ITG family to modulate FAK/PI3K/AKT pathway. In conclusion, THBS4 as an oncogene interacts with integrinß1 (ITGB1) to regulate HCC development via FAK/PI3K/AKT pathway.

A new endoscopic technique for specific gastrointestinal stromal tumors: a retrospective cohort study.

OBJECTIVES: Surgical resection is recommended for treating gastrointestinal stromal tumors (GISTs) >20 mm. With the emergence of minimally invasive concept, endoscopic techniques are involved. We introduce a new endoscopic technique termed as endoscopic submucosal resection preserving serosa (ESR-PS) for GISTs ≥ 20 mm with mucosal erosion or ulcer locating at deep muscularis propria. METHODS: This retrospective cohort study collected patients at the endoscopy center of the First Affiliated Hospital of Xi'an Jiaotong University between January 2019 and 2021. The primary outcome was adverse events including pneumoperitoneum, fever and delayed bleeding. The second outcomes included en bloc resection complete en bloc resection, recurrence, operation time, hospital stay time after ESR-PS, postoperative indwelling gastric tube and postoperative eating. RESULTS: A total of 49 patients were included. One patient experienced pneumoperitoneum. All patients did not experienced fever or delayed bleeding after ESR-PS. All cases achieved en bloc resection and complete en bloc resection. The median operation time of ESR-PS was 49 min (range 43-71). The indwelling gastric tubes were given to patients for 1 d or 2 d after ESR-PS. After 1 d or 2 d, patients started oral diet, staying in hospital for a median of 4 (3-4) d after ESR-PS. During the follow-up time, recurrence was not found. CONCLUSIONS: Our study indicated that ESR-PS is a feasible, effective and safe technique for GISTs ≥ 20mm with mucosal erosion or ulcer locating at deep muscularis propria. More large, multi-center and prospective studies are needed to evaluate the effectiveness and safety of ESR-PS in the future.

Intraoperative localization of gastrointestinal tumors by magnetic tracer technique during laparoscopic-assisted surgery (with video).

BACKGROUND: Laparoscopic localization of gastrointestinal tumors has long been an important objective. This study aimed to evaluate the clinical application of a magnetic tracer technique during laparoscopic-assisted surgery. METHODS: Fifty-seven patients with gastrointestinal tumors, who voluntarily underwent endoscopic marking between May 2019 and May 2020, were enrolled. A magnetic ring was clamped onto tissues adjacent to the lesion and released during preoperative endoscopy. Then, another magnet ring or laparoscopic instrument was delivered to the wall of the digestive tract contralateral to the lesion and attracted, thus achieving accurate intraoperative localization. Observational evaluation included data regarding preoperative marking, intraoperative localization, operation, and safety. RESULTS: Fifty-six of the 57 (98.2%) patients with gastric tumors (n = 35), duodenal tumors (n = 1), and colorectal tumors (n = 20), successfully underwent marking, localization, and resection. The mean margins of proximal and distal resection of colorectal tumors were 106 and 78 mm, respectively. The mean (± SD) duration of endoscopic marking and laparoscopic localization for gastric/duodenal and colorectal tumors were 5.3 ± 0.3, 1.0 ± 0.1, 5.5 ± 0.4, and 1.0 ± 0.1 min, respectively. No complications occurred in 56 of the 57 patients. CONCLUSIONS: The magnetic tracer technique demonstrated promising potential as a localization method for gastrointestinal tumors, with superior safety, effectiveness, rapidity, and convenience.

Screening value for gastrointestinal lesions of magnetic-controlled capsule endoscopy in asymptomatic individuals.

BACKGROUND AND AIM: Most patients with gastric tumors and precancerous lesions are asymptomatic, which often results in delayed diagnosis and treatment. Compared with conventional gastroscopy and capsule endoscopy, magnetic-controlled capsule endoscopy is a non-invasive, effective, and cost-efficient diagnostic modality for gastric examination. We retrospectively investigated magnetic-controlled capsule endoscopy as a screening tool for gastrointestinal lesions (particularly gastric tumors and precancerous lesions) in asymptomatic individuals. METHODS: In this retrospective study, 1757 patients who voluntarily underwent magnetic-controlled capsule endoscopy between January and December 2019 at nine medical centers across Shaanxi province based on strict inclusion and exclusion criteria were enrolled. The primary outcomes were gastric tumor and precancerous lesion detection rates and procedural safety. RESULTS: The upper and lower gastrointestinal lesion detection rates were 98.35% (1728/1757) and 21.61% (78/361), respectively; 2.28% of patients were diagnosed with gastric tumors including gastric cancer (4/1757) and submucosal tumors (36/1757). Three types of precancerous lesions were found in 591 patients (33.64%), including chronic atrophic gastritis (23.16%), gastric polyp (10.98%), and gastric ulcer (2.96%). For patients aged over 40 years, the detection rate of precancerous lesions was higher (14.36% vs 42.58%, P < 0.001). No patient was diagnosed with small intestinal cancer. No adverse events occurred. CONCLUSIONS: Magnetic-controlled capsule endoscopy could be used as a promising novel screening modality for diagnosis of gastrointestinal lesions in asymptomatic individuals, specifically gastric tumors and precancerous lesions, with the advantages of safety, non-invasiveness, effectiveness, and cost-efficiency.