SALL1 promotes proliferation and metastasis and activates phosphorylation of p65 and JUN in colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most usual malignant tumors, and its incidence continues to rise. Our purpose was to explore the function and potential regulatory mechanisms of SALL1, a differentially methylated gene in CRC, in vivo and in vitro. METHODS: Firstly, methylation differential gene SALL1 in CRC was screened and validated. SALL1 overexpression plasmids or SALL1 siRNAs were transfected in HT-29 and SW480 cells. Moreover, 10 µM T-5224 was added in SALL1-overexpressed CRC cells. CCK-8, flow cytometry and transwell assays were utilized to assess cell proliferation, cycle, migration, and invasion, respectively. Then CRC organoids were cultured. Next, HT-29 and SW480 cells transfected with SALL1 overexpression lentivirus were analyzed by transcriptome sequencing. Finally, in vivo tumorigenesis was used to analyze the effect of SALL1 overexpression on subcutaneous tumorigenesis in nude mice. RESULTS: The methylation level of CpG island in SALL1 promoter was increased in CRC tissues and could distinguish tumor tissues. Overexpression of SALL1 accelerated proliferation, migration and invasion of HT-29 and SW480 cells, and silencing of SALL1 attenuated proliferation, migration and invasion of HT-29 and SW480 cells. Through analysis and validation, we found that overexpression of SALL1 also could upregulate p-p65 and p-JUN expressions. Besides, c-Fos/activator protein (AP)- 1 inhibitor (T-5224) could reverse the induction of CRC progression by SALL1 overexpression. In vivo, we also proved that overexpression of SALL1 significantly increased tumor volume, tumor weight, and p-JUN expression. CONCLUSIONS: SALL1 could promote the proliferation, migration, and invasion of CRC cells and activate phosphorylation of p65 and JUN.

Effective switching of an all-solid-state mode-locked laser by a graphene modulator.

Although sophisticated novel saturable absorber materials are available for the development of ultrafast lasers, innovative approaches and devices play an increasingly important role in continuously adjusting mode-locked lasers with electrical gating. In this study, electrically switched operational regimes of an Nd:YVO4 all-solid-state mode-locked laser with a high modulation ratio (from 900 ns to 15 ps) are demonstrated for the first time. The laser can automatically switch multiple operation regimes with the assistance of electrical signals using techniques such as Q-switching, Q-switched mode-locking (QML), and continuous-wave mode-locking (CWML). The device is operated at an ultralow electrical modulation power (0.1 nW) to generate sub 15 ps pulses with a high average output power (as much as 800 mW) from a mode-locked laser operating at 1064 nm. The results verify the reversible switching of the operational regimes from QML to CWML and provide a basis for exploring their applications in electro-optical devices.

Effect of Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial.

Background and Aims: The clinical efficacy of fecal microbiota transplantation (FMT) in patients with non-alcoholic fatty liver disease (NAFLD) and the variant effects of FMT on lean and obese NAFLD patients remain elusive. Our study aimed to determine the clinical efficacy and safety of FMT for patients with NAFLD, elucidating its different influences on lean and obese patients with NAFLD. Methods: We performed a randomized and controlled clinical trial. Patients in the non-FMT group were administered oral probiotics. In the FMT group, patients were randomized to receive FMT with donor stool (heterologous) via colonoscopy, followed by three enemas over 3 days. Both groups were also required to maintain a healthy diet and keep regular exercise for more than 40 min every day. They returned to the hospital for reexamination 1 month after treatment. Results: FMT can decrease the fat accumulation in the liver by improving the gut microbiota dysbiosis, thus attenuating fatty liver disease. Significant differences in the clinical features and gut microbiota between lean and obese NAFLD patients were unveiled. Moreover, FMT had better effects on gut microbiota reconstruction in lean NAFLD than in obese NAFLD patients. Conclusions: FMT could successfully improve the therapeutic effects on patients with NAFLD, and its clinical efficacy was higher in lean NAFLD than in obese NAFLD patients.

Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.

Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population. Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared. Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term. Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.

Dynamic control of the mode-locked fiber laser using a GO/PS modulator.

This Letter proposes a novel, to the best of our knowledge, transistor-like optical fiber modulator composed of graphene oxide (GO) and polystyrene (PS) microspheres. Unlike previously proposed schemes based on waveguides or cavity enhancement, the proposed method can directly enhance the photoelectric interaction with the PS microspheres to form a light local field. The designed modulator exhibits a distinct optical transmission change (62.8%), with a power consumption of <10 nW. Such low power consumption enables electrically controllable fiber lasers to be switched in various operational regimes, including continuous wave (CW), Q switched mode-locked (QML), and mode-locked (ML). With this all-fiber modulator, the pulse width of the mode-locked signal can be compressed to 12.9 ps, and the corresponding repetition rate is 21.4 MHz.

Pre-treatment Eckardt score is a simple factor for predicting one-year peroral endoscopic myotomy failure in patients with achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel treatment for achalasia with excellent outcomes. But the predictor for treatment failure is not well defined. This study was aimed to prospectively investigate the factors for predicting failed POEM. METHODS: From June 2011 to May 2015, a total of 115 achalasia patients treated by POEM were included for the retrospective cohort study from Nanfang Hospital and the First People's Hospital of Yunnan Province. Patients were followed up with Eckardt score, high-resolution manometry and endoscope. POEM failure was defined as primary failure (Eckardt score failed to decrease to 3 or below) and recurrences (decrease of Eckardt score to 3 or below, then rise to more than 3) during one-year follow-up. Univariate and multivariate Cox regression analyses were performed to assess the predictive factor. For the associated factor, receiver operating characteristic curve (ROC) was utilized to determine the cutoff value of the predicting factor. RESULTS: The failure rate of POEM after 1 year was 7.0% (8/115), including 5 primary failure cases and 3 recurrences. Multivariate analysis showed higher pre-treatment Eckardt score was the single independent factor associated with POEM failure [9.5 (6-12) vs. 7 (2-12), odds ratio (OR) 2.24, 95 confidence interval (95% CI) 1.39-3.93, p = 0.001]. The cutoff value (Eckardt score ≥9) had 87.5 sensitivity (95% CI 47.3-99.7%) and 73.8% specificity (95% CI 64.4-81.9%) for predicting failed POEM. CONCLUSIONS: Pre-treatment Eckardt score could be a predictive factor for failed POEM. Eckardt score ≥9 was associated with high sensitivity and specificity for predicting POEM failure.

Comparison of conventional versus Hybrid knife peroral endoscopic myotomy methods for esophageal achalasia: a case-control study.

OBJECTIVE: Peroral endoscopic myotomy (POEM) has been developed to treat achalasia as a novel less invasive modality. We aimed to compare the efficacy and safety of conventional knife versus Hybrid knife (HK) during POEM procedure. MATERIALS AND METHODS: Between June 2012 and July 2014, 31 patients underwent POEM using HK in our department (HK group), and 36 patients underwent POEM using conventional method (injection needle and triangular tip [TT] knife, TT group). Procedure-related parameters, symptom relief, adverse events were compared between two groups. RESULTS: There were no significant differences in the age, sex and other baseline characteristics between the two groups. The mean procedural time was significantly shorter in HK group than TT group (53.0 ± 17.2 vs. 67.6 ± 28.4 min, p = 0.015). The mean frequency of devices exchange was 4.7 ± 1.7 in HK group and 10.9 ± 1.8 in TT group (p = 0.000). No serious adverse events occurred postoperatively in both groups. At one-year follow-up, a total of 94% treatment success was achieved in all patients (93.5% in HK group and 94.4% in TT group, p = 0.877). CONCLUSION: HK in POEM can shorten the procedural time, and achieve similar treatment success compared to conventional TT knife.

Myotomy of Distal Esophagus Influences Proximal Esophageal Contraction and Upper Esophageal Sphincter Relaxation in Patients with Achalasia After Peroral Endoscopic Myotomy.

BACKGROUND/AIMS: The motility change after peroral endoscopic myotomy (POEM) in achalasia is currently focused on lower esophageal sphincter (LES). This study aims to investigate the correlation of motility response between distal and proximal esophagus after POEM. METHODS: A total of 32 achalasia patients who received POEM and high-resolution manometry (HRM) were included for analysis. Eckardt score was used to assess symptom improvement. HRM was applied for studying motility. Main parameters analyzed were (1) LES: resting pressure (restP), 4-second integrated relaxation pressure; (2) esophageal body (EB): contractile integral of distal segment with myotomy (CI-DM) and proximal segment without myotomy (CI-PNM); and (3) upper esophageal sphincter (UES): relaxation pressure (UES-RP). RESULTS: There were 6 type I, 17 type II, and 9 type III achalasia patients included for analysis. (1) Eckardt score, LES tone, CI-DM, CI-PNM and UES-RP were reduced remarkably after POEM (P< 0.001). (2) no significant correlation was noted between LES tone and contractile intergral of EB. (3) a positive linear correlation of CI-DM and CI-PNM changes was detected (P< 0.001). (4) the change of UES-RP was positively correlated with the change of contractile integral of EB (P< 0.001). CONCLUSIONS: Myotomy of the distal esophagus would attenuate proximal EB contraction and assist UES relaxation in achalasia patients after POEM.

Factors predicting the technical difficulty of peroral endoscopic myotomy for achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) has been described as a novel treatment for esophageal achalasia. Owing to its technical difficulty, POEM is not widely performed. This study was aimed to prospectively assess the factor predicting technical difficulty of POEM in a single center with large volume cases. METHODS: A total of 105 cases of achalasia treated by POEM from April 2011 to September 2014 were analyzed. Difficult cases of POEM were defined as procedure time ≥90 min and occurrence of adverse events, including mucosal perforation, pneumothorax, and major bleeding. Univariate and multivariate logistic regression analyses were performed to assess the predictive factors of difficult POEM. RESULTS: POEM was successfully completed in all the patients, and no one was converted to laparoscopy. The number of cases with procedure time ≥90 min was 17. Mucosal perforations occurred in six (5.7 %) patients during submucosal tunnel creation, major bleeding occurred in seven (6.7 %) patients, and pneumothorax occurred in six (5.7 %) patients immediately after procedure. All the complications were managed conservatively. No other intraoperative and immediate postoperative complications, including infections and pneumoperitoneum, occurred. Multivariate analysis showed that early period (odds ratio [OR] 4.173, 95 % confidence interval [95 % CI] 1.36-6.829, P = 0.023) and triangular tip knife ([OR] 6.712, [95 % CI] 1.479-30.460, P = 0.014) were independent factors associated with technical difficulty regarding longer procedure time (procedure time ≥90 min). CONCLUSION: POEM is safe for the treatment of esophageal achalasia. Triangular tip knife and early period were independent risk factors for longer procedural time.

Usefulness of peroral endoscopic myotomy for treating achalasia in children: experience from a single center.

INTRODUCTION: Achalasia is a rare esophageal motility disorder in the pediatric population. Peroral endoscopic myotomy (POEM) has been demonstrated to be effective and safe for the treatment of achalasia as a novel endoscopic technique, but data involving its utility in pediatric patients are limited. We aimed to assess the safety and efficacy of POEM for pediatric patients with achalasia. MATERIALS AND METHODS: Between July 2012 and August 2014, five consecutive pediatric patients (2 female and 3 male, with a median age of 15 years) with achalasia underwent POEM in our center. Diagnosis was based on symptoms, manometry, radiology and endoscopy. Preoperative and postoperative symptoms scores, and manometry outcomes were recorded and analyzed. RESULTS: Procedure was performed successfully in all patients, and the median time required for the procedure was 50 min (range 40-90 min). There were no mortalities and no serious intraoperative and postoperative complications. The median length of myotomy was 8 cm (range 6-11 cm). During a median follow-up period of 18 months, treatment success (Eckardt score ≤3) was achieved in all patients. There was a significant improvement of symptoms relief, dysphagia score and lower esophageal sphincter pressure decrease after POEM. No patient developed gastroesophageal reflux disease. CONCLUSION: Our study suggests that POEM is a safe and effective technique for treating pediatric achalasia. Further studies with long-term follow-up in large-volume pediatric patients are warranted to clearly define the durability of the procedure.