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BACKGROUND: Pyloroplasty is an effective surgery for gastroparesis. However, some patients fail to improve after pyloric drainage and may require subsequent gastric electric stimulation. There is a paucity of data on the efficacy of gastric stimulator as an adjunct to failed pyloroplasty. This study aimed to describe our experience with pyloroplasty, determine the efficacy of gastric stimulator for failed pyloroplasty, and compare the final outcomes of those who required pyloroplasty with and without gastric stimulator for gastroparesis. METHODS: Records of patients who underwent primary pyloroplasty for gastroparesis at our institution were reviewed. Patients with poor symptomatic improvement after pyloroplasty underwent subsequent gastric stimulator. Symptoms were assessed using the gastroparesis cardinal symptom index (GCSI) preoperatively and after each surgery. Severe gastroparesis was defined as GCSI total score ≥3. Outcomes were assessed after pyloroplasty in all patients and after stimulator in patients who failed pyloroplasty. Final outcomes were then compared between those who did and did not require adjunct gastric stimulator. RESULTS: The study population consisted of 104 patients (89.4% females) with a mean (SD) age of 42.2 years (11) and body mass index of 26.9 kg/m2 (7). Gastroparesis etiologies were 71.2% idiopathic, 17.3% diabetic, and 11.5% postsurgical. At 18.7 months (12) after pyloroplasty, there was a decrease in the GCSI total score (3.5 [1] to 2.7 [1.2]; P = .0012) and the rate of severe gastroparesis (71.9%-29.3%; P < .0001). Gastric emptying scintigraphy (GES) 4-hour retention decreased (36.5 [24] to 15.3 [18]; P = .0003). Adjunct gastric stimulator was required by 30 patients (28.8%) owing to suboptimal outcomes with no improvement in GCSI (P = .201) or GES (P = .320). These patients were younger (40.5 [10.6] vs 49.6 [15.2] years; P = .0016), with higher baseline GCSI total scores (4.3 [0.7] vs 3.7 [1.1]; P < .001) and more severe gastroparesis (100% vs 55.6%; P < .001). All other preoperative characteristics were similar. At 21.7 months (15) after gastric stimulator, there was improvement in GCSI (4.1 [0.7] to 2.6 [1.1]; P < .0001), severe gastroparesis (100%-33.3%; P < .0001), and GES 4-hour retention (21.2 [22] to 7.6 [10]; P = .054). Before gastric stimulator, those who failed pyloroplasty had significantly worse GCSI (P = .0009) and GES (P = .048). However, after gastric stimulator, GCSI and GES improved and were comparable with those who only required pyloroplasty (P > .05). CONCLUSION: Pyloroplasty improved gastroparesis symptoms and gastric emptying, yet 28% failed, requiring gastric stimulator. Younger patients and those with preoperative GCSI scores ≥3 were more likely to fail. Gastric stimulator improved outcomes after failed pyloroplasty, with comparable final GCSI and GES with those who did not fail.

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OBJECTIVE: To evaluate and compare magnetic sphincter augmentation (MSA) device sizing protocols on postoperative outcomes and dysphagia. SUMMARY BACKGROUND DATA: Among predictors of dysphagia after MSA, device size is the only factor that may be modified. Many centers have adopted protocols to increase device size. However, there is limited data on the impact of MSA device upsizing protocols on the surgical outcomes. METHODS: Patients who underwent MSA were implanted with 2 or 3-beads above the sizing device's pop-off point (POP). Clinical and objective outcomes >1-year after surgery were compared between patients implanted with POP+2-vs-POP+3 sizing protocols. Multiple subgroups were analyzed for benefit from upsizing. Pre- and postoperative characteristics were compared between size patients received, regardless of protocol. RESULTS: A total of 388 patients were implanted under POP+2 and 216 under POP+3. At a mean of 14.2(7.9) months pH normalization was 73.6% and 34.1% required dilation, 15.9% developed persistent dysphagia, and 4.0% required removal. Sizing protocol had no impact on persistent dysphagia ( P =0.908), pH normalization ( P =0.822), or need for dilation ( P =0.210) or removal ( P =0.191). Subgroup analysis found that upsizing reduced dysphagia in patients with <80 percent peristalsis (10.3-vs-31%, P =0.048) or DCI >5000 (0-vs-30.4%, P =0.034). Regardless of sizing protocol, as device size increased there was a stepwise increase in percent male sex ( P <0.0001), BMI>30 ( P <0.0001), and preoperative hiatal hernia>3 cm ( P <0.0001), LA grade C/D esophagitis ( P <0.0001), and DeMeester score ( P <0.0001). Increased size was associated with decreased pH-normalization ( P <0.0001) and need for dilation ( P =0.043) or removal ( P =0.014). CONCLUSIONS: Upsizing from POP+2 to POP+3 does not reduce dysphagia or affect other MSA outcomes; however, patients with poor peristalsis or hypercontractile esophagus do benefit. Regardless of sizing protocol, preoperative clinical characteristics varied among device sizes, suggesting size is not a modifiable factor, but a surrogate for esophageal circumference.

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INTRODUCTION AND OBJECTIVES: Cholangiocarcinoma (CCA) is characterized by early distant invasion and metastasis, whereas the underlying mechanism is still obscure. Increasing evidence shows that collagen type Ι alpha 1 (COL1A1) is a gene associated with the progression of multiple diseases. Here, we attempted to investigate the role of COL1A1 in CCA. MATERIALS AND METHODS: The expression of COL1A1 between tumor tissues and adjacent normal tissues obtained from CCA patients was detected by Western blot and immunofluorescence, followed by analysis of its clinical significance. Then, the biological effects of COL1A1 overexpression or knockdown on CCA cells were evaluated in vitro and in vivo. Finally, molecular mechanism of COL1A1 in regulating the invasion and metastasis of CCA cells was determined by a series of experiments. RESULTS: COL1A1 expression was significantly higher in CCA pathological tissues than in corresponding adjacent normal tissues. Analysis of 83 CCA patients showed that higher expression of COL1A1 was correlated with poorer patient prognosis. Notably, overexpression or knockdown experiments revealed that COL1A1 contributed to the migration and invasion, as well as epithelial-to-mesenchymal transition (EMT), in CCA cells. Further investigations demonstrated that matrix metalloproteinase-2 (MMP2) promoted COL1A1 upregulation via the integrin alpha Ⅴ pathway, therefore affecting ECM remodelling and inducing EMT in CCA cells. Moreover, COL1A1 expression was positively related to PD-1 and PD-L1 in CCA, and COL1A1 increased PD-L1 expression by activating the NF-κB pathway. CONCLUSIONS: COL1A1 plays an important role in regulating CCA progression and may act as a promising biomarker and therapeutic target for CCA.

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BACKGROUND: Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. STUDY DESIGN: This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. RESULTS: The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). CONCLUSIONS: This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.

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OBJECTIVE: To evaluate the impact of MSA on lower esophageal sphincter (LES) and esophageal body using high resolution impedance manometry. BACKGROUND: MSA is an effective treatment in patients with gastroesophageal reflux disease, but there is limited data on its impact on esophageal functional physiology. METHODS: Patients who underwent MSA were approached 1-year after surgery for objective foregut testing consists of upper endoscopy, esophagram, high resolution impedance manometry, and esophageal pH-monitoring. Postoperative data were then compared to the preoperative measurements. RESULTS: A total of 100 patients were included in this study. At a mean follow up of 14.9(10.1) months, 72% had normalization of esophageal acid exposure. MSA resulted in an increase in mean LES resting pressure [29.3(12.9) vs 25(12.3), P < 0.001]. This was also true for LES overall length [2.9(0.6) vs 2.6(0.6), P = 0.02] and intra-abdominal length [1.2(0.7) vs 0.8(0.8), P < 0.001]. Outflow resistance at the EGJ increased after MSA as demonstrated by elevation in intrabolus pressure (19.6 vs 13.5 mmHg, P < 0.001) and integrated relaxation pressure (13.5 vs 7.2, P < 0.001). MSA was also associated with an increase in distal esophageal body contraction amplitude [103.8(45.4) vs 94.1(39.1), P = 0.015] and distal contractile integral [2647.1(2064.4) vs 2099.7(1656.1), P < 0.001]. The percent peristalsis and incomplete bolus clearance remained unchanged ( P = 0.47 and 0.08, respectively). CONCLUSIONS: MSA results in improvement in the LES manometric characteristics. Although the device results in an increased outflow resistance at the EGJ, the compensatory increase in the force of esophageal contraction will result in unaltered esophageal peristaltic progression and bolus clearance.

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Bombyx mori gloverin A2 (BMGlvA2) is an induced antimicrobial insect protein isolated from Bombyx mori. This study was conducted to explore the effect and potential mechanisms of BMGlvA2 on inflammatory responses and cellular functions in intestinal epithelial cells (IPEC-J2) exposure to enterotoxigenic E. coli (ETEC). IPEC-J2 cells pretreated with or without BMGlvA2 (12.5 µg/mL) were challenged by ETEC K88 (1×106 CFU/well) or culture medium. We show that BMGlvA2 pretreatment increased the cell viability and improved the distribution and abundance of tight junction protein ZO-1 in IPEC-J2 cells exposure to ETEC (P < 0.05). Interestingly, BMGlvA2 not only decreased the expression levels of inflammatory cytokines such as the tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), but also decreased the expression level of Caspase3 and the apoptosis rate in the ETEC-challenged cells (P < 0.05). Importantly, BMGlvA2 decreased the protein abundances of two critical inflammation-associated signaling proteins, phosphorylated nuclear factor-kappa-B inhibitor alpha (p-IκBα) and phosphorylated nuclear factor-kappa B (p-NF-κB), in the ETEC-challenged cells. These results indicate that BMGlvA2 attenuates ETEC-induced inflammation in the IPEC-J2 cells by regulating the NF-κB signaling pathway, resulting in decreased secretion of inflammatory cytokine and reduced cell apoptosis.

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BACKGROUND: The performance and durability of various types of fundoplication are variable when stratified by disease severity. To date, magnetic sphincter augmentation (MSA) has not been evaluated in this context. We designed this study to determine the efficacy of MSA in the treatment of severe GERD. STUDY DESIGN: Guided by previous studies, a DeMeester score (DMS) ≥ 50 was used as a cutoff point to define severe reflux disease. Subjects were divided into 2 groups using this cutoff, and outcomes of severe cases were compared with those with less severe disease (DMS < 50). RESULTS: A total of 334 patients underwent MSA. Patients with severe disease had a higher mean preoperative DMS compared with those with mild to moderate GERD (79.2 [53.2] vs 22.8 [13.7], p < 0.0001). At a mean postoperative follow-up of 13.6 (10.4) months, there was no difference between the mean GERD Health-Related Quality of Life (HRQL) total scores in patients with severe disease compared with those with less severe GERD (8.8 [10] vs 9.2 [10.8], p = 0.9204). Postoperative mean DMS was not different between groups (17.3[23.0] vs 14.1[33.9], p = 0.71), and there was no difference in the prevalence of esophagitis (p = 0.52). Patients with severe disease were less likely to be free from use of proton pump inhibitors after surgery (85% vs 93.1%, p = 0.041). There were similar rates of postoperative dysphagia (10% vs 14%, p = 0.42) and need for device removal (3% vs 5%, p = 0.7463). CONCLUSIONS: MSA is an effective treatment in patients with severe GERD and leads to significant clinical improvement across the spectrum of disease severity, with few objective outcomes being superior in patients with mild-to-moderate reflux disease.

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BACKGROUND: Magnetic sphincter augmentation (MSA) is a promising surgical treatment for patients with GERD. The aim of this study was to evaluate the outcomes of MSA in a large cohort of patients with GERD and to determine the factors predicting a favorable outcome. METHODS: This was a retrospective review of prospectively collected data of 553 patients who underwent MSA at our institution in a 5-year period. Preoperative clinical, endoscopic, manometric, and pH data were used in a univariate analysis. This was followed by a regression multivariable analysis to determine the factors predicting a favorable outcome. Favorable outcome was defined as freedom from proton pump inhibitors and ≥50% improvement in Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) total score. RESULTS: At a mean (SD) follow-up of 10.3 (10.6) months after MSA, 92.7% of the patients were free of proton pump inhibitor use and 84% reported at least 50% improvement in their GERD-HRQL total score. The GERD-HRQL total score was improved from a mean (SD) baseline value of 33.8 (18.7) to 7.2 (9.0) (p < 0.001) and 76.1% of the patients had normalization of their esophageal acid exposure. Independent predictors of a favorable outcome after MSA included age younger than 45 years (odds ratio [OR] 4.2; 95% CI, 1.1 to 15.2; p = 0.0305), male sex (OR 2.5; 95% CI, 1.1 to 5.7; p = 0.0301), GERD-HRQL total score >15 (OR 7.5; 95% CI, 3.3 to 16.8; p < 0.0001), and abnormal DeMeester score (OR, 2.6; 95% CI, 1.1 to 5.7; p = 0.0225). CONCLUSIONS: In this largest single-institution series, we demonstrate that MSA implantation is associated with very good clinical and objective outcomes. Age younger than 45 years, male sex, GERD-HRQL total score >15, and abnormal DeMeester score are the 4 preoperative factors predicting a favorable outcome and can be used in patient counseling and MSA use.

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This experiment was conducted to evaluate the effects of dietary protein and net energy (NE) levels on growth performance, nutrient digestibility, nitrogen metabolism, and faecal microbiota of growing-finishing pigs. Eighteen crossed barrows were randomly allocated into one of three dietary treatments: high protein + high NE diet, low protein + high NE diet, and low protein + low NE diet. The whole experiment lasted 90 days and was divided into three phases (phase I: 25-50 kg; phase II: 50-75 kg; phase III: 75-105 kg). All pigs were individually housed in a metabolism cage and subjected to four-day total faeces and urine collection period at the end of each phase. There was no significant difference in growth performance, nutrient digestibility, serum total protein, and albumin concentrations of pigs among the dietary treatments. Compared with the high protein + high NE diet, pigs fed low protein + high NE and low protein + low NE diets had lower N intake, urine N, and total N excretion in each phase. At the end of the experiment, pigs fed the low protein + high NE and low protein + low NE diets had lower blood urea nitrogen, serum NH3-N concentrations, faecal pH value, faecal NH3-N concentration, and faecal Escherichia coli count than those fed the high protein + high NE diet. However, there was no significant difference in all of the above indexes between low protein + high NE and low protein + low NE diets. Decreasing the dietary protein content by 3.5 percentage units has no adverse effects on growth performance and nutrient digestibility of pigs while significantly reduces N excretion and faecal Escherichia coli count. Moreover, further decreasing dietary NE level in the low-protein diet by 0.35-0.5 MJ/kg does not affect growth performance, nutrient digestibility, N excretion, blood profiles, and faecal Escherichia coli count of pigs.(AU)

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Background: Xylanases are considered one of the most important enzymes in many industries. However, their low thermostability hampers their applications in feed pelleting, pulp bleaching, and so on. The main aim of this work was to improve the thermostability of Trichoderma ressei xylanase 2 (Xyn2) by introducing disulfide bonds between the N-terminal and α-helix and the ß-sheet core. Results: In this work, two disulfide bonds were separately introduced in the Xyn2 to connect the N-terminal and α-helix to the ß-sheet core of Xyn2. The two disulfide bonds were introduced by site-directed mutagenesis of the corresponding residues. The half-life of the mutants Xyn2C14­52 (disulfide bond between ß-sheets B2 and B3) and Xyn2C59­149 (disulfide bond between ß-sheets A5 and A6) at 60°C was improved by approximately 2.5- and 1.8-fold compared to that of the wild type Xyn2. In addition, the enzyme's resistance to alkali and acid was enhanced. Conclusion: Our results indicated that the connection of the N-terminal and α-helix to the ß-sheet core is due to the stable structure of the entire protein.

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