Rational Design of Liquid-Liquid Microdispersion Droplet Microreactors for the Controllable Synthesis of Highly Uniform and Monodispersed Dextran Microspheres.

Hydrogel microspheres are biocompatible materials widely used in biological and medical fields. Emulsification and stirring are the commonly used methods to prepare hydrogels. However, the size distribution is considerably wide, the monodispersity and the mechanical intensity are poor, and the stable operation conditions are comparatively narrow to meet some sophisticated applications. In this paper, a T-shaped stepwise microchannel combined with a simple side microchannel structure is developed to explore the liquid-liquid dispersion mechanism, interfacial evolution behavior, satellite droplet formation mechanism and separation, and the eventual successful synthesis of dextran hydrogel microspheres. The effect of the operation parameters on droplet and microsphere size is comprehensively studied. The flow pattern and the stable operation condition range are given, and mathematical prediction models are developed under three different flow regimes for droplet size prediction. Based on the stable operating conditions, a microdroplet-based method combined with UV light curing is developed to synthesize the dextran hydrogel microsphere. The highly uniform and monodispersed dextran microspheres with good mechanical intensity are synthesized in the developed microfluidic platform. The size of the microsphere could be tuned from 50 to 300 µm with a capillary number in the range of 0.006-0.742. This work not only provides a facile method for functional polymeric microsphere preparation but also offers important design guidelines for the development of a robust microreactor.

Acoustofluidic one-step production of plasmonic Ag nanoparticles for portable paper-based ultrasensitive SERS detection of bactericides.

SERS measurements for monitoring bactericides in dairy products are highly desired for food safety problems. However, the complicated preparation process of SERS substrates greatly impedes the promotion of SERS. Here, we propose acoustofluidic one-step synthesis of Ag nanoparticles on paper substrates for SERS detection. Our method is economical, fast, simple, and eco-friendly. We adopted laser cutting to cut out appropriate paper shapes, and aldehydes were simultaneously produced at the cutting edge in the pyrolysis of cellulose by laser which were leveraged as the reducing reagent. In the synthesis, only 5 µL of Ag precursor was added to complete the reaction, and no reducing agent was used. Our recently developed acoustofluidic device was employed to intensely mix Ag+ ions and aldehydes and spread the reduced Ag nanoparticles over the substrate. The SERS substrate was fabricated in 1 step and 3 min. The standard R6G solution measurement demonstrated the excellent signal and prominent uniformity of the fabricated SERS substrates. SERS detection of the safe concentration of three bactericides, including tetracycline hydrochloride, thiabendazole, and malachite green, from food samples can be achieved using fabricated substrates. We take the least cost, time, reagents, and steps to fabricate the SERS substrate with satisfying performance. Our work has an extraodinary meaning for the green preparation and large-scale application of SERS.

Efficacy, safety, and advantages of magnetic anchor-guided endoscopic submucosal dissection vs conventional endoscopic submucosal dissection: A retrospective paired cohort study.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS: Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS: Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION: MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.

USP29 activation mediated by FUBP1 promotes AURKB stability and oncogenic functions in gastric cancer.

BACKGROUND: Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. METHODS: The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. RESULTS: In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. CONCLUSIONS: These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.

The emerging role of USP29 in cancer and other diseases.

Reversible protein ubiquitination is a key process for maintaining cellular homeostasis. Deubiquitinases, which can cleave ubiquitin from substrate proteins, have been reported to be deeply involved in disease progression ranging from oncology to neurological diseases. The human genome encodes approximately 100 deubiquitinases, most of which are poorly characterized. One of the well-characterized deubiquitases is ubiquitin-specific protease 29 (USP29), which is often upregulated in pathological tissues and plays important roles in the progression of different diseases. Moreover, several studies have shown that deletion of Usp29 in mice does not cause visible growth and developmental defects, indicating that USP29 may be an ideal therapeutic target. In this review, we provide a comprehensive summary of the important roles and regulatory mechanisms of USP29 in cancer and other diseases, which may help us better understand its biological functions and improve future studies to construct suitable USP29-targeted therapy systems.

Identification of miRNA, lncRNA and circRNA associated with gastric cancer metabolism through sequencing and bioinformatics analysis.

Gastric cancer remains a highly prevalent malignancy worldwide with its molecular features poorly understood. To gain full insight into its genetic landscape, we performed whole-transcriptome sequencing on human tumors and adjacent non-tumors to predict the function of microRNA, long coding RNA, circular RNA, and mRNA, as well as estimate their correlation with gastric cancer characteristics through construction of ceRNA, WGCNA and PPI network. Functional enrichment analysis annotated nucleic acid binding, enzyme activity and binding related to differentially expressed miRNAs (dif-miRNAs); energy binding and enzyme binding related to dif-lncRNAs; protein binding and enzyme activity related to dif-circRNAs; protein digestion and absorption related to dif-mRNAs. The expression of key miR-135a-5p, lncRNAs-MSTRG.48856.1, ENST00000569981, MSTRG.22826.1, ENST00000564492, circRNAs-CCSER2, FNDC3B, CORO1C, FAM214A were validated by real-time PCR. The ceRNA network filtered 14 miRNAs, 30 lncRNAs, and 6 mRNA in the lncRNA-ceRNA axis and 8 miRNAs, 9 circRNAs, and 3 mRNA in the circRNA-ceRNA axis. Genes involved in ceRNA were annotated to be closely related to tumor material synthesis and metabolism. The WGCNA network filtered gene clusters related to TNM traits and extracted the hub genes CLDN10, CD177, newGene_35523, newGene_51201, CEACAM7, and newGene_46634. These genes were associated with cell proliferation, metabolism, and enzyme activity regulation. The PPI network analyzed the stable interaction relationships of the hub genes. Our research provides a valuable resource for understanding the molecular mechanisms of gastric cancer from the perspective of tumor metabolism.

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.

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.

The HN1/HMGB1 axis promotes the proliferation and metastasis of hepatocellular carcinoma and attenuates the chemosensitivity to oxaliplatin.

Hematological and neurological expressed 1 (HN1) is closely associated with the proliferation and metastasis of various tumors. However, the physiological functions and clinical significance of HN1 in hepatocellular carcinoma (HCC) remain indistinct. In this study, we investigated the role of HN1 in the pathogenesis of HCC and the underlying mechanism using clinical data from HCC patients, in vitro experiments utilizing HCC cell lines and in vivo animal models. We demonstrated that the overexpressed HN1 in HCC was correlated with patients' adverse outcomes. The gain and loss of function experiments indicated that HN1 could promote the proliferation, migration, and invasion of HCC cells in vitro. Furthermore, we found that HN1 knockdown sensitized HCC cells to oxaliplatin. Mechanically, HN1 prevented HMGB1 protein from ubiquitination and degradation via the autophagy-lysosome pathway, which was related to the interaction between HN1 protein and TRIM28 protein. In the nucleus, the downregulation of HMGB1 followed by HN1 knockdown resulted in increased DNA damage and cell death in the oxaliplatin-treated HCC cells. In the cytoplasm, HN1 regulated autophagy via HMGB1. Furthermore, HN1 knockdown in combination with HMGB1 overexpression restored the aggressive phenotypes of HCC cells and the sensitivity of these cells to oxaliplatin. HN1 knockdown inhibited the tumor growth and metastasis, and promoted the anticancer efficiency of oxaliplatin in vivo. In conclusion, our data suggest that the HN1/HMGB1 axis plays an important role in the development/progression and chemotherapy of HCC. Our findings indicate that the HN1/HMGB1 axis may be a promising therapeutic target for HCC treatment.

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.

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.

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.

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.

BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.

PURPOSE: Stemming from a myriad of genetic and epigenetic alterations, triple-negative breast cancer (TNBC) is tied to poor clinical outcomes and aspires for individualized therapies. Here we investigated the therapeutic potential of co-inhibiting integrin-dependent signaling pathway and BRD4, a transcriptional and epigenetic mediator, for TNBC. METHODS: Two independent patient cohorts were subjected to bioinformatic and IHC examination for clinical association of candidate cancer drivers. The efficacy and biological bases for co-targeting these drivers were interrogated using cancer cell lines, a protein kinase array, chemical inhibitors, RNAi/CRISPR/Cas9 approaches, and a 4 T1-Balb/c xenograft model. RESULTS: We found that amplification of the chromosome 8q24 region occurred in nearly 20% of TNBC tumors, and that it coincided with co-upregulation or amplification of c-Myc and FAK, a key effector of integrin-dependent signaling. This co-upregulation at the mRNA or protein level correlated with a poor patient survival (p < 0.0109 or p < 0.0402, respectively). Furthermore, we found that 14 TNBC cell lines exhibited high vulnerabilities to the combination of JQ1 and VS-6063, potent pharmacological antagonists of the BRD4/c-Myc and integrin/FAK-dependent pathways, respectively. We also observed a cooperative inhibitory effect of JQ1 and VS-6063 on tumor growth and infiltration of Ly6G+ myeloid-derived suppressor cells in vivo. Finally, we found that JQ1 and VS-6063 cooperatively induced apoptotic cell death by altering XIAP, Bcl2/Bcl-xl and Bim levels, impairing c-Src/p130Cas-, PI3K/Akt- and RelA-associated signaling, and were linked to EMT-inducing transcription factor Snail- and Slug-dependent regulation. CONCLUSION: Based on our results, we conclude that the BRD4/c-Myc- and integrin/FAK-dependent pathways act in concert to promote breast cancer cell survival and poor clinical outcomes. As such, they represent promising targets for a synthetic lethal-type of therapy against TNBC.

The Prognosis Analysis of Liver Cirrhosis with Acute Variceal Bleeding and Validation of Current Prognostic Models: A Large Scale Retrospective Cohort Study.

BACKGROUND: Acute variceal bleeding is a major cause of death in liver cirrhosis. This large scale retrospective cohort study aims to analyze the prognosis of patients with cirrhosis and acute variceal bleeding and to validate the current prognostic models. METHODS: Patients with cirrhosis and acute variceal bleeding were enrolled from Jan 2019 to March 2020. The independent prognostic factors for in-hospital death were identified by logistic regression analyses. Area under curves (AUCs) was compared among Child-Pugh, cirrhosis acute gastrointestinal bleeding (CAGIB) score, and model for end-stage liver disease (MELD) and neutrophil-lymphocyte ratio (NLR) scores. RESULTS: Overall, 379 patients with liver cirrhosis and acute variceal bleeding were consecutively evaluated. The majority of the patients were males (59.1%) and the mean age of all patients were 53.7 ± 1.3 years (range 14-89). Hepatitis B virus (HBV) was the most common underlying cause of liver cirrhosis (54.1%). 72 (19%) patients had hepatocellular carcinoma. Multivariate logistic regression analyses showed that age, HCC, WBC, total serum bilirubin, serum creatinine, and ALT were independently associated with in-hospital death. And the odds ratios (ORs) for in-hospital death were 1.066 (95% CI 1.017-1.118, P = 0.008), 7.19 (95% CI 2.077-24.893, P = 0.001), 1.123 (95% CI 1.051-1.201, P = 0.001), 1.014 (95% CI 1.005-1.023, P = 0.003), 1.012 (95% CI 1.004-1.021, P = 0.006), and 1.005 (95% CI 1.000-1.009, P = 0.036), respectively. In the whole cohort with HCC patients, the AUCs of Child-Pugh, CAGIB, MELD and NLR scores were 0.842 (95% CI 0.801-0.878), 0.840 (95% CI 0.799-0.876), 0.798 (95% CI 0.754-0.838), and 0.688 (95% CI 0.639-0.735), respectively. The differences were statistically significant between Child-Pugh and NLR scores (P = 0.0118), and between CAGIB and NLR scores (P = 0.0354). CONCLUSION: Child-Pugh and CAGIB scores showed better predictive performance for prognosis of patients with cirrhosis and acute variceal bleeding than NLR scores.

Telephone-Based Reeducation of Drug Administration for Helicobacterpylori Eradication: A Multicenter Randomized Controlled Study.

Poor adherence to treatment instructions may play an important role in the failure of Helicobacter pylori eradication. The aim of this study was to evaluate the effects of telephone-based reeducation on 14-day quadruple H. pylori eradication therapy. In total, 162 patients were randomly assigned (1 : 1) to either the intervention group (patients received telephone-based reeducation on the 4th, 7th, and 10th days of the course) or the control group (patients received instructions only at the time of getting the prescriptions). All patients received a 14-day quadruple H. pylori eradication therapy. The primary outcome was the H. pylori eradication rate. The secondary outcomes included the symptom relief rates and the incidence rates of adverse events. Seventy-five patients in the reeducation group and 74 patients in the control group completed the follow-up. The H. pylori eradication rate in the reeducation group was statistically higher than that in the control group (intention-to-treat: 72.8% vs. 50.6%, P = 0.006; per-protocol: 78.7% vs. 55.4%, P = 0.003). However, the symptom relief rates and the adverse event rates in these two groups were not significantly different. Overall, the results from this study suggest that telephone-based reeducation can be potentially applied to improve the H. pylori eradication rate in clinical practice, without significantly increasing the adverse effects.

TRPC1 exacerbate metastasis in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis.

Metastasis is frequently occurred in end-stage GC. Nevertheless, the initiation and progression of metastasis in GC remains unclear. The transient receptor potential canonical (TRPC) has been confirmed to be crucial for metastasis in many kinds of tumors, including GC. However, the molecular mechanisms regulating TRPC1 is unclear. Therefore, we investigated the role and mechanisms of TRPC1 in GC metastasis. We first evaluated the role of TRPC1 in GC by searching the public database, and tested the expression of TRPC1 in 50 paired GC tissues by qRT-PCR and IHC assays. Then, we generated BGC-823-shTRPC1 cells and MKN-45-TRPC1 cells to investigate the effects of TRPC1 on metastasis in vitro. For the mechanism study, we applied luciferase reporter assay, RNA pull-down assay, as well as RIP assay to validate the interation of ciRS-7, miR-135a-5p and TRPC1 in GC cells. This study, we showed that TRPC1 exacerbate EMT in gastric cancer via ciRS-7/miR-135a-5p/TRPC1 axis, and target TRPC1 could be beneficial for end-stage GC patients.

The Effect of Helicobacter pylori Eradication in Patients with Gastroesophageal Reflux Disease: A Meta-Analysis of Randomized Controlled Studies.

AIM: Helicobacter pylori infection has been established as a definite risk factor for gastric cancer. However, the consequence of H. pylori eradication on the progression of gastroesophageal reflux disease (GERD) remains controversial. The purpose of our study was to investigate the relationship between H. pylori eradication and the development of GERD. METHODS: A comprehensive, English literature search was performed from January 1990 to April 2019. Only randomized controlled trials (RCT) that evaluated the effect of H. pylori eradication on GERD were included. Meta-analysis of pooled OR was performed using Review Manger 5.1.7. RESULTS: Seventeen articles with 6,889 subjects (intention-to-treat) that fulfilled the inclusion criteria were finally included in the analysis. Of them, 8 RCTs have the similar study design and inclusion criterion, which included patients with H. pylori infection but without GERD at baseline. The OR for the development of erosive GERD after H. pylori eradication was 1.67 (95% CI 1.12-2.48, p = 0.01). The OR for the development of GERD-related symptoms after H. pylori eradication in eradication group compared with control group was 1.04 (95% CI 0.84-1.29, p = 0.71). In addition, 9 RCTs included patients with both baseline H. pylori infection and GERD. The OR for the healing rates and relapse rates after H. pylori eradication in the H. pylori eradication group vs. control group was 0.92 (95% CI 0.47-1.82, p = 0.82) and 1.12 (95% CI 0.60-2.09, p = 0.71), respectively. CONCLUSIONS: Our meta-analyses showed H. pylori eradication may lead to the development of new erosive GERD. However, eradication of H. pylori may affect neither the healing rates nor relapse rates of preexisting GERD.

Exosomal miR-106a derived from gastric cancer promotes peritoneal metastasis via direct regulation of Smad7.

Peritoneal metastasis develops in more than half of patients with gastric cancer but influencing factors are poorly characterized. Exosomes are increasingly recognized as a new mediator in cancer directional metastasis through the transfer of nucleic acids or proteins to neighboring or distant cells. The role of exosomes in peritoneal metastasis and whether it could establish pre-metastatic milieu are largely unknown. Here, we assessed the migration of gastric cancer (GC) cells and identified that PKH26-labeled exosomes from GC cells can be ingested by peritoneal mesothelial cells (MCs). Additionally, miRNA (miR-106a) that highly enriched in GC-derived exosomes (GC-exos) and essential for destroying the mesothelial barrier was demonstrated through the observation of the injury of the MCs including migratory enhancement and imbalance of apoptosis and proliferation. Moreover, either stimulating miR-106a or treatment with GC-exos could inhibit the expression of Smad7, accompanied by the concurrent elevated α-SMA and fibronectin in MCs. Silencing of miR-106a abolished GC-exos-induced gene expression in MCs. The MCs regain the viability, apoptosis reduction and Smad7 expression after rescue experiment conducted in miR-106a-enriched GC-exos. Xenograft model suggested that exosomal miR-106a had a potential to promote tumor growth through targeting Smad7. Collectively, we revealed that the delivery of miR-106a from GC-exos plays a crucial role in gastric cancer peritoneal metastasis.Abbreviations: MiR-106a: microRNA-106a; Smad7: small mothers against decapentaplegic 7; GC: gastric cancer; MCs: mesothelial cells; Exos: exosomes; HG: high-differentiated gastric cancer cells; LG: low-differentiated gastric cancer cells.

Role of lncRNA SNHG5 in the migration and invasion of hypoxia-induced hyhepa‐ tocellular carcinoma cells / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To explore the regulatory effect of long non-coding RNA (lncRNA) SNHG5 on invasion and migration of hypoxia-induced hepatocellular carcinoma (HCC) cells. Methods: A total of 20 pairs of cancer and para-cancerous tissue specimens resected from HCC patients in the First Affiliated Hospital of Xi'an Jiaotong University from January 2017 to June 2018, and human HCC cell lines (HepG2, MHCC-97L, MHCC-97H , Huh7) as well as immortalized human liver LO2 cells were collected for this study. Bioinformatics methods were used to analyze the binding sites between hypoxia-inducible factor 1α (HIF-1α) and SNHG5. pCMVHIF-1α and shRNA-SNHG5 (sh-SNHG5) plasmids were transfected into HCC cells, respectively. qPCR was used to detect the expres‐ sion level of SNHG5 in HCC tissues and hypoxia-induced HCC cells. Western botting was used to detect the expression level of HIF-1α protein in HCC cells, and Transwell chamber method was used to detect the migration and invasion ability of HCC cells after SNHG5 si‐ lence under normoxia and hypoxia condition. Results: Compared with para-cancerous tissues and immortalized human liver LO2 cells, the expression of SNHG5 was significantly up-regulated in HCC tissues and cell lines (all P<0.01). Hypoxia promoted the expression level of SNHG5 in HCC cells, and its mechanism might be related to the combination of hypoxia-activated HIF-1α and SNHG5 promoter to promote its transcription. Hypoxia promoted the invasion and migration ability of HepG2 and MHCC-97L cells (all P< 0.01), but knockdown of SNHG5 significantly inhibited the invasion and migration ability of HepG2 and MHCC-97L cells under hy‐ poxic conditions (all P<0.01). Conclusion: SNHG5 is highly expressed in HCC tissues and cell lines and plays an important role in the invasion and migration of HCC cells induced by hypoxia.