Causal associations between dietary factors and colorectal cancer risk: a Mendelian randomization study.

Background: Previous epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive. Methods: We conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results. Results: MR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068-2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095-0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273-0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253-0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311-0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results. Conclusion: This study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.

Vesicoureteral reflux postoperative radical nephroureterectomy for upper urinary tract urothelial carcinoma: A case report.

Introduction: Primary Upper tract urothelial carcinoma (UTUC) is a rare subtype of urothelial carcinoma and has an unknown incidence and prevalence in Yemen. Radical nephroureterectomy (RNU) with bladder cuff removal is the standard treatment for UTUC. Case presentation: We present a 67-year-old male patient who developed grade II vesicoureteral reflux (VUR) on the left side of the urinary tract after undergoing right-sided RNU for non-invasive UTUC. Follow-up examinations at one-, three-, and six-month post-surgery revealed no evidence of kidney diseases. The patient's recovery has been satisfactory, and ongoing regular follow-ups are being maintained. Conclusion: Vigilant monitoring of VUR presence and effective management following RNU is crucial to minimize complications and preserve renal function. The underlying mechanisms linking VUR development and RNU remain unclear, necessitating further research.

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.

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.

Differentially expressed genes of esophageal tissue in male acute and chronic sleep deprivation mice.

Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.

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.

Global burden of inflammatory bowel disease 1990-2019: A systematic examination of the disease burden and twenty-year forecast.

BACKGROUND: Inflammatory bowel disease (IBD) is an idiopathic intestinal disease with various levels and trends in different countries and regions. Understanding the current burden and trends of IBD in various geographical locations is essential to establish effective strategies for prevention and treatment. We report the average annual percentage change (AAPC) and estimated annual percentage change (EAPC) in age-standardized rates (ASR) of IBD in different regions based on the Global Burden of Disease (GBD) study from 1990-2019, and the relationships between IBD and the human development index (HDI) and socio-demographic index (SDI). The prevalence trends of IBD were predicted by gender from 2019-2039. AIM: To comprehensively investigate IBD data, providing further insights into the management of this chronic disease. METHODS: We collected the information on the incidence of IBD from the GBD study from 1990-2019 to calculate the AAPC and EAPC in ASR of IBD in different regions. The relationships between IBD, HDI, and SDI were analyzed. The Nordpred and Bayesian age-period-cohort models were used to predict the prevalence trends of IBD by gender from 2019-2039, and the reliability of the results was validated. Statistics of all the data in this study were performed using R software (version 4.2.1). RESULTS: North America consistently had the highest IBD ASR, while Oceania consistently had the lowest. East Asia had the fastest average annual growth in ASR (2.54%), whereas Central Europe had the fastest decline (1.38%). Countries with a low age-standardized incidence rates in 1990 showed faster growth in IBD while there was no significant correlation in 2019. Additionally, IBD increased faster in countries with a low age-standardized death rates in 1990, whereas the opposite was true in 2019. Analysis of SDI and IBD ASR showed that countries with a high SDI generally had a higher IBD ASR. Finally, the projections showed a declining trend in the incidence of IBD from 2019-2039, but a gradual increase in the number of cases. CONCLUSION: As the global population increases and ages, early monitoring and prevention of IBD is important to reduce the disease burden, especially in countries with a high incidence of IBD.

Advances in experimental animal models of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with insidious early symptoms, easy metastasis, postoperative recurrence, poor drug efficacy, and a high drug resistance rate when surgery is missed, leading to a low 5-year survival rate. Research on the pathogenesis and drugs is particularly important for clinical treatment. Animal models are crucial for basic research, which is conducive to studying pathogenesis and drug screening more conveniently and effectively. An appropriate animal model can better reflect disease occurrence and development, and the process of anti-tumor immune response in the human body. This review summarizes the classification, characteristics, and advances in experimental animal models of HCC to provide a reference for researchers on model selection.

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.

The factors influencing the accuracy of pre-operative endoscopic ultrasonography assessment in endoscopic treatments for gastrointestinal tumors.

BACKGROUND: This retrospective study aimed to evaluate the factors influencing the accuracy of Endoscopic Ultrasonography (EUS) as a preoperative assessment for gastrointestinal tumors. METHODS: A total of 261 patients with 264 gastrointestinal tumors were enrolled in the study. The parameters of the gastrointestinal lesions examined under EUS and their pathology were recorded and analyzed. RESULTS: The accuracy of EUS for detecting intramucosal lesions and subepithelial lesions (SELs) were 83.6% and 91.4%, respectively. One hundred and ninety-four (73.5%) lesions originated from the mucous layer, as determined by pre-operation EUS examinations. The accuracy of EUS in predicting the correct T stage for intramucosal lesions in the gastric region, esophagus, and colorectum was 77%, 71.8%, and 84.6%, respectively. According to the Paris endoscopic classification, the distribution of macroscopic patterns was different between the EUS-pathology conformity and nonconformity groups (p = 0.018). In the nonconformity group, 48.6% of erosive lesions were classified as 0-IIc, 0-IIa + IIc, 0-IIc + IIa or 0-III macroscopic patterns compared with 26% patients in the conformity group (p = 0.025). Univariate analyses demonstrated that ulcerative lesions (OR = 7.516, 95% Confidence Interval [CI] 2.574-21.952, p < 0.001), location at the cardia of the stomach (OR = 3.619, 95%CI 1.076-12.168, p = 0.038), malignant tumor (OR = 2.920, 95%CI 1.339-6.368, p = 0.007) were significantly associated with EUS inaccuracy. Multivariate logistic regression analyses showed that ulcer was an independent risk factor associated with EUS inaccuracy, with odds ratios of 5.094 (95% CI: 1.641-15.807, p = 0.005). CONCLUSIONS: Our findings suggested that EUS is a reliable and easy-to-use diagnostic tool in decision-making regarding appropriate endoscopic treatment for gastrointestinal tumors. However, the diagnostic accuracy of EUS appeared questionable in the presence of ulceration.

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.

Brain-wide mapping of c-Fos expression with fluorescence micro-optical sectioning tomography in a chronic sleep deprivation mouse model.

Chronic sleep deprivation (SD) is a common problem for humans and can lead to many deleterious effects, including depression, anxiety, stroke, permanent cognitive deficits, stress, and other physiological diseases. It is vital to acquire information about the relevant neural activities at the whole-brain level to systematically explore the mechanisms of brain dysfunction related to SD. Expression of the immediate-early gene (IEG) Fos in the mouse brain has been widely used as a functional marker of brain activity in the field of neuroscience. However, most previous studies only analyzed the change of c-Fos in several specific brain regions using traditional research methods or in short-term SD model. Here, we applied c-Fos mapping through the fluorescence micro-optical sectioning tomography (fMOST) technique and AAV-PHP.eB to comprehensive analysis the state of cumulative activation across the whole brain in a mouse model of chronic SD. The chronic rapid eyes movement (REM) SD model was induced by moving mice to a separate holding area filled with water. The experimental period lasted for 6 h per day. The results showed that after 14 days of SD, the mice displayed anxiety-like behaviors in open field test and elevated plus maze test, and displayed depression-like behaviors in tail suspension test and the sucrose preference test. The c-Fos + cells were detected in a maximum of 230 brain regions. SD-induced stress model evoked c-Fos expression in several brain regions compared to the control group. In particular, the isocortex-cerebral cortex plate area, including the retrosplenial, anterior cingulate, agranular insular, gustatory, and parasubiculum, appear to be the most sensitive regions after chronic REM SD.

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.

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.

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).

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.

miR-4677-3p participates proliferation and metastases of gastric cancer cell via CEMIP-PI3K/AKT signaling pathway.

Gastric cancer is one of the top three leading causes of cancer-related death in the world. Evidence indicated that miR-4677-3p was dysregulated and involved in modulating invasion and migration in multiple types of cancer cells. The aim of this research is to explore the function and mechanism of miR-4677-3p in the development of gastric cancer. In this study, we discovered that miR-4677-3p was down-regulated in gastric cancer tissues and cells. Over-expression of miR-4677-3p suppressed the proliferation, migration and invasion of gastric cancer cells. Furthermore, miR-4677-3p directly bond to CEMIP 3'UTR region and inhibited CEMIP expression. CEMIP promoted cell proliferation, migration and invasion of gastric cancer cells via accelerating PI3K/AKT signaling pathway. siCEMIP or PI3K/AKT signaling inhibitor (Akti-1/2 and LY294002) partly reversed the effects of miR-4677-3p on the cellular growth and metastasis of gastric cancer. In general, miR-4677-3p regulated the development of gastric cancer through CEMIP-PI3K/AKT signaling pathway axis. This study verified the function and molecular mechanism of miR-4677-3p in gastric cancer cells, and may provide a potential diagnosis/prognosis target for patients with gastric cancer.

Topotecan-loaded thermosensitive nanocargo for tumor therapy: In vitro and in vivo analyses.

This study demonstrates the development of topotecan (TCN) loaded thermosensitive nanocargos (TCN-TS-NC) for intramuscular (IM) administration with enhanced antitumor activity. In this regards, TCN loaded temperature dependent solid lipid nanoparticles (SLNs) were prepared with micro-emulsion method, which were then incorporated into temperature sensitive poloxamer solution to develop TCN-TS-NC. The particle size, entrapment efficiency (%EE), zeta potential and transmission electron microscopy (TEM) analysis of the TCN-TS-NC were performed. Moreover, the inject-ability, release pattern, apoptosis, cellular uptake, pharmacokinetics and antitumor studies of the TCN-TS-NC were attained and compared with TCN solution and TCN-Emulgel (poloxamer solution containing TCN). At room temperature, the TCN loaded SLNs were solid and poloxamer solution remains liquid, however, TCN loaded SLNs melted to liquid and Emulgel converted into gel from, at body temperature, resulting controlled release of the incorporated drug. The TCN-TS-NC showed enhanced cellular uptake and better apoptosis. Similarly, it reduces Cmax and sustained its level for a significantly longer time in rats, as compared to the TCN-Emulgel and TCN solution. Moreover, a significantly improved antitumor activity was observed in TCN-TS-NC treated tumor bearing athymic nude mice when compared with the control, TCN solution and TCN-Emulgel applied mice. Thus, the TCN-TS-NC system showed control release of the drug with no initial fast effect. Furthermore, it enhanced the antitumor activity of TCN with comparatively no toxicity. It is therefore concluded that TCN-TS-NC could be a potentially more suitable drug delivery system for the delivery of TCN.