[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

[Effect of laparoscopic novel W-H fundoplication in patients with proton pump inhibitor dependent gastroesophageal reflux disease].

Objective: To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). Methods: The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire. Results: A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P<0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation. Conclusions: The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

[The relationship between acid reflux and esophageal motility, esophagitis and cardiac morphology in gastroesophageal reflux disease].

Objective: To analyze the relationship between the severity of esophageal acid reflux and esophageal motility, esophageal mucosal injury and morphological anatomy of gastroesophageal junction (GEJ) in patients with gastroesophageal reflux disease (GERD). Methods: The clinicaldata of GERD patients who underwent 24 h pH-impedance monitoring, gastroscopy and high-resolution manometry (HRM) from January 2016 to January 2019 in the Gastroesophageal Surgery Department of PLA Rocket Force Characteristic Medical Center were retrospectively analyzed. The patients were divided into non-pathological acid reflux group, mild pathological acid reflux group and moderate to severe pathological acid reflux group according to the DeMeester score. The gender and age of each group were matched, with 60 cases in each group. Statistical analysiswas performed to analyze thedifferences in upper esophageal sphincter pressure, lower esophageal sphincter pressure (LES), LES length, length of ventral LES, percentage of ineffective swallowing, esophagitis, Hill grade of GEJ, and hiatus hernia (HH) in each group. The comparison and correlation analysis are also carried out between the groups. Results: The male-female ratio was 33/27, and the age was (57±13) years in each group. Non-parametric analysis showed that the LES pressure and the length of the ventral LES decreased with the severity of acid reflux, and there was a statistical difference (P= 0.033, P=0.015). The detection rate of HH by HRM increased significantly (χ(2)=0.001) as well. Esophagitis score increased with the severity of acid reflux and there was statistical difference (P<0.001).The detection rate of esophagitis increased significantly (χ(2)<0.001) as well. Hill grading score of GEJ increased with the severity of acid reflux, and there was statistical difference (P<0.001).The detection rate of HH by endoscopy increased significantly (χ(2)<0.001) as well. The correlation between DeMeester score and LES pressure, length of ventral LES, percentage of ineffective swallowing, esophagitis score, and Hill grade score were statistically significant (P<0.05). Conclusions: The esophageal low motility (such as low LES pressure) and anatomical abnormalities (abdominal esophageal shortening, GEJ flabbiness, and even HH formation) of the GEJ regionare significantly associated with the severity of acid reflux. These factors may be important causes of increased acid reflux. In addition, the aggravation of acid reflux can also increase the incidence and severity of esophagitis.

MiR-203 regulates JAK-STAT pathway in affecting pancreatic cancer cells proliferation and apoptosis by targeting SOCS3.

OBJECTIVE: Janus kinase (JAK)- signal transducer and transcriptional activator (STAT) pathway overactivation is closely related to tumorigenesis. Cytokine signal transduction inhibitor 3 (SOCS3) is a negative regulator of JAK-STAT. It is shown that miR-203 is significantly elevated in the pancreatic cancer tissues. The bioinformatics analysis revealed a targeted binding site between miR-203 and the 3'-UTR of SOCS3 mRNA. This study investigated the role of miR-203 in regulating SOCS3 expression and the proliferation and apoptosis of the pancreatic cancer cells. PATIENTS AND METHODS: Quantitative Real Time-PCR (qRT-PCR) was used to detect the expressions of miR-203 and SCOS3 mRNA in tumor tissues and paracancerous tissues. The Dual-Luciferase reporter gene assay was adopted to validate the target interaction between miR-203 and SOCS3. The PANC-1 cells were cultured in vitro and divided into miR-NC group and miR-203 inhibitor group followed by an analysis of the expressions of SOCS3, p-JAK2, and p-STAT3, cell apoptosis by flow cytometry, and cell proliferation by EdU staining. RESULTS: Compared with the adjacent tissues, miR-203 expression was significantly increased, while SOCS3 mRNA level was significantly declined in the tumor tissues of pancreatic cancer patients. There was a targeted regulatory relationship between miR-203 and SOCS3 mRNA. Compared with those in HPDE6-C7 cells, miR-203 level was upregulated, whereas SOCS3 mRNA and the protein expressions were reduced in pancreatic cancer PANC-1 and BXPC3 cells. The transfection of miR-203 inhibitor significantly increased SOCS3 mRNA and the protein levels, decreased p-JAK2 and p-STAT3 protein expressions, enhanced cell apoptosis, and inhibited cell proliferation in the pancreatic cancer PANC-1 cells. CONCLUSIONS: Increased miR-203 expression and reduced SOCS3 level are associated with the pathogenesis of pancreatic cancer. MiR-203 can regulate the proliferation and apoptosis of the pancreatic cancer cells by targeting the inhibited SOCS3 expression and regulating the JAK-STAT pathway activity.

[Relationship between the severity of reflux esophagitis and the esophageal motility features on high resolution manometry].

Objective: To analyze esophageal motility dysfunction in gastroesophageal reflux disease (GERD) with different severity of esophagitis, and the relationship between the esophageal motility dysfunction and the severity of esophagitis. Methods: GERD patients simultaneously undergone endoscopy and high-resolution manometry were divided into four groups: Non-esophagitis (Non-erosive gastroesophageal reflux disease, NERD) group, mild esophagitis group, moderate esophagitis group and severe esophagitis group. The gender and age were matched for each group, and every group consisted of 80 cases. Nonparametric test was used to analyze the differences in HRM parameters, such as upper esophageal sphincter (UES) pressure, lower esophageal sphincter (LES) pressure, LES length, LES-CD (crural diaphragm) separation distance, and the percentage of failed peristalsis of the four groups, and the differences between each two of the groups were also analyzed. Results: Nonparametric test showed that the LES pressure and length decreased with the severity of esophagitis, and there were statistical differences (P<0.001, P=0.030). The failed peristalsis percentage increased with the severity of esophagitis and the difference was statistically significant (P<0.001). The LES-CD separation distance was increased with the severity of esophagitis and had statistically significance (P<0.001). When comparing the differences between each two of the groups, there were significant differences (P<0.001, P=0.012, P<0.001, P<0.001) between NERD group and severe esophagitis group in the HRM parameters of the lower esophageal sphincter pressure, the LES length, the LES-CD separation distance, and the percentage of ineffective swallowing in the NERD and severe esophagitis group. The detection rate of HH was significantly increased from NERD to severe esophagitis, the detection rate of HH was 6.3% to 82.5% in gastoracopy and 16.3% to 45.0% in HRM, and the diagnostic consistency was fair (Kappa Value: 0.31). Conclusions: Hypo-dynamic state of esophageal and HH are the main motility characteristics of erosive gastroesophageal reflux disease, Esophageal motility abnormalities increase in parallel with the severity of GERD from NERD to severe esophagitis, these motility disorders may also play important roles in causing esophagitis.

[Zinc finger protein 521 suppresses osteogenic differentiation of rat mesenchymal stem cells by inhibiting the Wnt/beta-catenin signaling pathway].

Zinc finger protein 521 (Zfp521) is involved in a number of cellular processes in a variety of cells and tissues. In the present study, the effects of Zfp521 on osteogenic differentiation of rat mesenchymal stem cells (MSCs) were investigated. The results showed that, in rat MSCs, knocking down cellular Zfp521 by short hairpin RNA (shRNA) decreases cell proliferation while promoting ALP activity, calcium accumulation, and the expression of mRNA that encodes bone sialoprotein (BSP), osteocalcin (OCN) and Runx2. Furthermore, in Zfp521-depleted cells, the up-regulation of phospho-Wnt (p-Wnt) and beta-catenin expression levels was detected. However, over-expression of Zfp521 played the opposite role in proliferation and osteogenic differentiation of rat MSCs. To further demonstrate the functions of the Wnt/beta-catenin signaling in Zfp521 regulated-osteogenic differentiation, the activation of Wnt/beta-catenin was blocked with IWP-2 inhibitor. The suppression of the Wnt/beta-catenin pathway completely abrogated the effects of Zfp521 knockdown on osteogenic differentiation of rat MSCs. Therefore, we conclude that Zfp521 regulates osteogenic differentiation of rat MSCs through the suppression of the Wnt/beta-catenin signaling pathway.

[Laparoscopic reoperation for recurred antireflux surgery of gastroesophageal reflux disease].

OBJECTIVE: To investigate the safety and effectiveness of laparoscopic reoperation for patients with gastroesophageal reflux disease (GERD) recurred form previous anti-reflux surgery. METHODS: Totally 19 patients received laparoscopic reoperation for symptomatic and anatomic recurred GERD in Department of Gastroesophageal Reflux Disease, Rocket Force General Hospital from January 2008 to September 2015 were retrospectively analyzed. There were 12 male and 7 female patients. The average reoperation age was (48±14) years, the average duration of reoperation from original ones was (43±38) months. The patients underwent preoperative barium, endoscopy, manometry and 24-hour pH studies. Laparoscopic hiatal hernia repair plus fundoplication was carried out for reoperation. Gastroesophageal reflux related symptoms (reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation) before and after surgery were compared by a questionnaire. The patients' medication consumption, complications and satisfaction of the reoperation were investigated as well. The repeated measures analysis of variance was used for statistical comparison of data preoperatively and postoperatively. RESULTS: No major complication and death occurred. Six cases (32%) had complications such as diarrhea, increased passing wind, flatulence, dysphagia and abdominal pain. The GERD related symptom score of reflux, heartburn, chest pain, chough, wheezing, chest tightness and globus sensation all significantly decreased (F: 25.0 to 56.7; P: 0.000 to 0.001) after the reoperation, with 68% good outcome of all the patients. After a follow-up of (33±22) months after reoperation, 1 case had partial recurrence at the 3(rd) month after reoperation. For all the patients, 12 cases felt very satisfied or satisfied with the reoperation. CONCLUSION: Laparoscopic reoperation is generally effective with acceptable morbidity rates for patients with esophageal and extraesophageal symptoms recurred form previous hiatal repair and (or) fundoplication.

Five-year follow-up of a prospective study comparing laparoscopic Nissen fundoplication with Stretta radiofrequency for gastroesophageal reflux disease.

AIM: Laparoscopic Nissen fundoplication (LNF) and Stretta radiofrequency (RF) are used as main alternative strategies to manage medication-refractory GERD. This study was therefore prospectively evaluated outcomes of patients with refractory GERD 5 years after LNF or Stretta RF. METHODS: A total of 215 consecutive patients with refractory GERD underwent LNF (N.=102) and Stretta RF (N.=113) in our department between 2007 and 2008. They were followed-up for 5 years, during which the outcome measures including symptom scores of regurgitation, heartburn, chest pain, belching, hiccup, cough and asthma as well as the proton pump inhibitor (PPI) use and complications. RESULTS: Of the 215 patients, 179 patients following LNF (N.=87) or Stretta RF (N.=92) completed the designated 5-year follow-up and were included in the final analysis. At the end of 5-year follow-up, the post-treatment scores were statistically lower as compared with the pre-treatment scores in both groups, while the symptom improvements after Stretta were significantly lower than that after LNF (p < 0.05). Besides, 81 (91%) patients achieved complete PPI therapy independence after LNF, comparing with 47 (51.1%) after Stretta RF (P<0.05). No significant differences in post-treatment complications were observed except for the abdominal distention. CONCLUSION: Even though laparoscopic Nissen fundoplication and Stretta RF are capable of controlling GERD symptoms effectively and safely in selected patients, LNF could improve more in symptoms and PPI elimination.

Identification of ANAPC13 gene polymorphisms associated with body measurement traits in Bos taurus.

Body measurement traits, influenced by genes and environmental factors, play numerous important roles in the value assessment of productivity and economy. There has been some indication that ANAPC13 influences adult height. We used PCR-SSCP and DNA sequencing technology to identify polymorphisms in the ANAPC13 gene. A polymorphism in intron 1 (A > G at base 17) was identified and an additional polymorphic site (C > T at base 42) was also uncovered, which accompanied the previous polymorphism in more than 98% of the subjects. The two novel polymorphisms in exon 1 were assayed and potential associations with body measurement traits were evaluated in 404 individuals. Three genotypes were detected in the study group, named AACC, AGCT and GGTT. Significant differences were observed between genotypes AACC and AGCT for body length, withers height, hip height, hip width, heart girth, pin bone width. However, no associations were found among any genotypes and chest depth. We conclude that polymorphisms and mutations in non-coding regions of the ANAPC13 gene significantly affect body measurement traits.

The ansa subclavia: a review of the literature.

The ansa subclavia, subclavian loop, Vieussens' ansa or Vieussens' loop is a nerve cord that connects the middle cervical and inferior cervical sympathetic ganglia, forming a loop around the subclavian artery. The structure of the ansa subclavia is evolutionarily conserved from rats, guinea pigs, the porcine species and dogs to humans. A common application in physiological studies is to electrically stimulate the ansa subclavia in animal models as a robust protocol to modulate stimulatory cardiac sympathetic input. Despite a large number of physiological studies utilizing the ansa subclavia, only very brief descriptions have been devoted to it in standard anatomy texts. An extensive search found only one report in the English language literature concerning the anatomy of the ansa subclavia. The aim of this report, therefore, was to provide a comprehensive review of the clinical anatomy of the ansa subclavia and to discuss its potential physiological functions.

Essential functions of protein tyrosine phosphatases PTP2 and PTP3 and RIM11 tyrosine phosphorylation in Saccharomyces cerevisiae meiosis and sporulation.

Tyrosine phosphorylation plays a central role in eukaryotic signal transduction. In yeast, MAP kinase pathways are regulated by tyrosine phosphorylation, and it has been speculated that other biochemical processes may also be regulated by tyrosine phosphorylation. Previous genetic and biochemical studies demonstrate that protein tyrosine phosphatases (PTPases) negatively regulate yeast MAP kinases. Here we report that deletion of PTP2 and PTP3 results in a sporulation defect, suggesting that tyrosine phosphorylation is involved in regulation of meiosis and sporulation. Deletion of PTP2 and PTP3 blocks cells at an early stage of sporulation before premeiotic DNA synthesis and induction of meiotic-specific genes. We observed that tyrosine phosphorylation of several proteins, including 52-, 43-, and 42-kDa proteins, was changed in ptp2Deltaptp3Delta homozygous deletion cells under sporulation conditions. The 42-kDa tyrosine-phosphorylated protein was identified as Mck1, which is a member of the GSK3 family of protein kinases and previously known to be phosphorylated on tyrosine. Mutation of MCK1 decreases sporulation efficiency, whereas mutation of RIM11, another GSK3 member, specifically abolishes sporulation; therefore, we investigated regulation of Rim11 by Tyr phosphorylation during sporulation. We demonstrated that Rim11 is phosphorylated on Tyr-199, and the Tyr phosphorylation is essential for its in vivo function, although Rim11 appears not to be directly regulated by Ptp2 and Ptp3. Biochemical characterizations indicate that tyrosine phosphorylation of Rim11 is essential for the activity of Rim11 to phosphorylate substrates. Our data demonstrate important roles of protein tyrosine phosphorylation in meiosis and sporulation

A specific protein-protein interaction accounts for the in vivo substrate selectivity of Ptp3 towards the Fus3 MAP kinase.

The mitogen-activated protein kinases (MAPKs) play critical roles in many signal transduction processes. Several MAPKs have been found in Saccharomyces cerevisiae, including Fus3 in the mating pathway and Hog1 in the osmotic-stress response pathway. Cells lacking Fus3 or Hog1 activity are deficient in mating or adaptation to osmotic shock, respectively. However, constitutive activation of either Fus3 or Hog1 is lethal. Therefore, yeast cells have to tightly regulate both the activation and inactivation of Fus3 and Hog1 MAPKs, which are controlled mainly by phosphorylation and dephosphorylation. Previous studies have shown that Fus3 activity is negatively regulated by protein tyrosine phosphatase Ptp3. In contrast, the Hog1 MAPK is mainly dephosphorylated by Ptp2 even though the two phosphatases share a high degree of sequence similarity. To understand the mechanisms of MAPK regulation, we examined the molecular basis underlying the in vivo substrate specificity between phosphatases and MAPKs. We observed that the amino-terminal noncatalytic domain of Ptp3 directly interacts with Fus3 via CH2 (Cdc25 homology) domain conserved among yeast PTPases and mammalian MAP kinase phosphatases and is responsible for the in vivo substrate selectivity of the phosphatase. Interaction between Ptp3 and Fus3 is required for dephosphorylation and inactivation of Fus3 under physiological conditions. Mutations in either Ptp3 or Fus3 that abolish this interaction cause a dysregulation of the Fus3 MAPK. Our data demonstrate that the specificity of MAP kinase inactivation in vivo by phosphatases is determined by specific protein-protein interactions outside of the phosphatase catalytic domain.

Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae mating pheromone response is mediated by activation of a MAP kinase (Fus3p and Kss1p) signaling pathway. Pheromone stimulation causes cell cycle arrest. Therefore, inactivation of the Fus3p and Kss1p MAP kinases is required during recovery phase for the resumption of cell growth. We have isolated a novel protein tyrosine phosphatase gene, PTP3, as a negative regulator of this pathway. Ptp3p directly dephosphorylates and inactivates Fus3p MAP kinase in vitro. Multicopy PTP3 represses pheromone-induced transcription and promotes recovery. In contrast, disruption of PTP3 in combination with its homolog PTP2 results in constitutive tyrosine phosphorylation, enhanced kinase activity of Fus3p MAP kinase on stimulation, and delayed recovery from the cell cycle arrest. Both tyrosine phosphorylation and kinase activity of Fus3p are further increased by disruption of PTP3 and PTP2 in combination with MSG5, which encodes a dual-specificity phosphatase. Cells deleted for all three of the phosphatases (ptp2delta ptp3delta msg5delta) are hypersensitive to pheromone and exhibit a severe defect in recovery from pheromone-induced growth arrest. Our data indicate that Ptp3p is the major phosphatase responsible for tyrosine dephosphorylation of Fus3p to maintain a low basal activity; it also has important roles, along with Msg5p, in inactivation of Fus3p following pheromone stimulation. These data present the first evidence for a coordinated regulation of MAP kinase function through differential actions of protein tyrosine phosphatases and a dual-specificity phosphatase.