Improving Bowel Function Recovery and Quality of Life in Han Chinese Patients with Spinal Cord Injuries: A Quantitative Assessment-Based Nursing Intervention Study.

BACKGROUND Neurological bowel dysfunction (NBD) due to spinal cord injuries (SCIs) is common and significantly impacts patients' quality of life. This study evaluated the efficacy of quantitative assessment-based nursing interventions on bowel function recovery, quality of life, and caregivers' satisfaction with SCI patients with NBD. MATERIAL AND METHODS The study included 418 SCI patients with NBD. Patients were categorized into 3 cohorts: quantitative assessment-based nursing intervention (QN, n=114), conventional nursing intervention (CN, n=125), or no nursing intervention (DN, n=189). The 3 cohorts were followed over a 6-month period. RESULTS At 6 months post-intervention, patients in the QN and CN cohorts showed significant reductions in symptoms of fecal incontinence, constipation, and abdominal distension compared to the DN cohort. Additionally, defecation time decreased significantly in the QN and CN cohorts compared to both initial measures and the DN cohort. Notably, patients in the QN cohort demonstrated substantial improvement in overall quality of life scores compared to baseline, CN, and DN cohorts. The QN cohort also reported marked improvement in caregivers' satisfaction, surpassing that of caregivers in the CN and DN cohorts. CONCLUSIONS Six months of quantitative assessment-based nursing interventions significantly improved bowel function, quality of life, and caregiver satisfaction in SCI patients with NBD. This intervention appears beneficial for managing NBD in SCI patients and improving their quality of life and caregiver satisfaction.

Integrated meta-omics study on rapid tylosin removal mechanism and dynamics of antibiotic resistance genes during aerobic thermophilic fermentation of tylosin mycelial dregs.

For efficient treatment of tylosin mycelial dregs (TMDs), rapid tylosin removal mechanism and dynamics of ARGs during TMDs fermentation were investigated using integrated meta-omics (genomics, metaproteomics and metabolomics) and qPCR approaches. The results showed that over 86% of tylosin was degraded on day 7 regardless of the type of bulking agents. The rapid removal of tylosin was mainly attributed to de-mycarose reaction (GH3) and esterase hydrolysis (C7MYQ7) of Saccharomonospora, and catalase-peroxidase oxidation of Bacillus (A0A077JB13). In addition, the moisture content and mobile genetic elements were vital to control the rebound of ARGs. The removal efficiency of antibiotic resistant bacteria (Streptomyces, Pseudomonas, norank_f__Sphingobacteriaceae, and Paenalcaligenes) and Intl1 (98.8%) in fermentation treatment TC21 with corncob as the bulking agent was significantly higher than that in other three treatments (88.3%). Thus, appropriate bulking agents could constrain the abundance of antibiotic resistant bacteria and Intl1, which is crucial to effectively reduce the resistance.

Novel endoscopic management for small gastric submucosal tumors: A single-center experience (with video).

BACKGROUND AND AIMS: To explore the novel treatment of small gastric submucosal tumors (SMTs) originating from the muscularis propria layer (SMT-MPs), we utilized endoscopic band ligation (EBL) with a precut of the covering mucosa. METHODS: From Jan. 2012 to Dec. 2019, 111 patients with 124 gastric SMT-MPs were treated by precutting EBL. The clinical characteristics, operation duration, postoperative adverse events, and follow-up profiles were retrospectively collected. RESULTS: A total of 124 tumors from 111 patients were successfully treated by precutting EBL. No adverse events, including perforation and major bleeding, were observed. Furthermore, 93 patients (83.8%) underwent endoscopic surveillance postoperatively, and during the follow-up period, no local recurrence was detected. CONCLUSIONS: Precutting EBL appears to be a safe and simple method for removing gastric SMT-MPs < 16 mm (mainly indicated for potentially malignant GISTs), but further studies with longer follow-up are needed to assess the radicality of this intervention.

MARK2 inhibits the growth of HeLa cells through AMPK and reverses epithelial-mesenchymal transition.

Microtubule affinity-regulating kinases (MARKs; MARK1, MARK2, MARK3 and MARK4) act directly downstream of LKB1, the multitasking tumor-suppressor kinase, and thereby mediate its biological effects. Current understanding of the function of MARKs is greatly restricted to regulation of cell polarity. However, whether or how MARKs contribute to cellular growth control remains largely unknown. In the present study, we utilized an inducible lentiviral expression system that allows rapid MARK expression in LKB1-deficient HeLa cells, and characterized additional functions of MARKs: overexpression of MARK2 in HeLa cells resulted in a decrease in cell growth, inhibition of colony formation and arrest in G1 cell cycle phase, with AMPK as the putative downstream effector upregulating the expression of p21 and p16. MARK2 was found to play a role in F-actin reorganization and to contribute to reversal of epithelial­mesenchymal transition (EMT) as exemplified in the case of HeLa cells that exhibited phenotypic changes, reduced cell migration and invasion. Our findings unveil the coordinated regulation of cell growth and EMT mediated by MARK2, and also provide new insights into the mechanisms underlying the anti-metastatic activity of MARK2.

LKB1 expression reverses the tumorigenicity of L02 cells.

The tumor-suppressor liver kinase B1 (LKB1), a highly conserved and ubiquitously expressed protein kinase, plays a critical role in tumorigenesis. In the present study, we revealed that human hepatic L02 cells had severely impaired endogenous LKB1 expression as gauged by western blot, northern blot and RT-PCR analyses. Stable ectopic expression of LKB1 in L02 cells resulted in decreased cell growth, hypophosphorylation of Rb, and marked attenuation of colony formation on soft agar. Inoculation of L02 cells into immunocompromised mice resulted in the development of subcutaneous tumors, which could be completely abrogated by ectopic LKB1 expression. The tumors that formed in the mouse model recapitulated the histopathological features of hepatocellular carcinoma under the microscope. Our results jointly suggest that severely compromised endogenous LKB1 expression in the L02 cell line may confer to L02 cells tumor-initiating capacities in vivo and in vitro, and ectopic LKB1 expression antagonizes the tumorigenic properties of L02 cells. Our findings imply that caution may be needed to interpret the results obtained on the widely used human hepatic L02 cell line. The L02 cell line may be a new model to define the cellular mechanisms of liver transformation, and to unravel the molecular mechanisms underlying the growth suppressive effect of LKB1.

Wireless esophageal pH capsule for patients with gastroesophageal reflux disease: a multicenter clinical study.

AIM: To investigate the feasibility and safety of pH capsule to monitor pH in patients with gastroesophageal reflux disease (GERD). METHODS: Ninety-one patients with symptoms suggestive of GERD were enrolled in this study, 46 of whom were randomized to the pH capsule group; the remaining 45 patients used the conventional catheter and pH capsule simultaneously. The pH data and traces were recorded via automatic analysis, and capsule detachment was assessed using X-ray images. All of the patients were required to complete a questionnaire regarding tolerance with the capsule. RESULTS: The capsules were successfully attached on the first attempt, and no early detachment of the capsules was observed. Compared to the 24-h pH data recorded with the conventional catheter, the data collected with the pH capsule showed no significant differences in 24-h esophageal acid exposure. The measurements of esophageal acid exposure over 24 h collected with the two devices showed a significant correlation (r(2) = 0.996, P < 0.001). Capsule detachment occurred spontaneously in 89 patients, and 2 capsules required endoscopic removal due to chest pain. The capsule was associated with less interference with daily activity. CONCLUSION: The wireless pH capsule provides a feasible and safe method for monitoring gastroesophageal reflux and therefore may serve as an important tool for diagnosing GERD.

Exogenous activation of LKB1/AMPK signaling induces G1 arrest in cells with endogenous LKB1 expression.

The tumor suppressor protein LKB1 is a serine/threonine kinase that plays a critical role in cell proliferation, and its inactivation has been linked to tumorigenesis in various cancer types. Current understanding of the LKB1 function is largely restricted to results from experiments on LKB1­deficient cancer cells, while the regulation and activity of endogenous LKB1 has been rarely investigated. In a previous study, we showed that LKB1 knockdown in two healthy cell lines accelerates cell cycle progression through the G1/S checkpoint by inhibition of the p53 and p16 pathways. In the present study, we examined the effects of overexpression of LKB1 on two healthy and one cancer cell line. Administration of exogenous LKB1 activated LKB1/AMPK signaling and arrested the cell cycle at the G1 phase in an LKB1-dependent manner. G1 arrest induced by LKB1 was accompanied by the downregulation of cyclin D1 and cyclin D3, and the upregulation of p53, p21 and p16, while no differences were detected for CDK4, CDK6, cyclin E, p15 and p27. These results indicated that exogenous activation of LKB1/AMPK signaling inhibits the G1/S cell cycle transition, even in cells with an endogenous expression of LKB1. Findings of the present study extend earlier observations on LKB1­inactivated neoplastic cells and provide novel insights into the growth-inhibitory effects of LKB1.

Clinical utility and tolerability of JSPH-1 wireless esophageal pH monitoring system.

BACKGROUND: Wireless esophageal pH monitoring system is an important approach for diagnosis of gastroesophageal reflux disease (GERD), the aim of this study is to test the tolerability and utility of the first wireless esophageal pH monitoring system made in China, and evaluate whether it is feasible for clinical application to diagnose GERD. METHODS: Thirty patients from Department of Gastroenterology of The First Affiliated Hospital of Chongqing Medical University who were suspected GERD underwent JSPH-1 pH capsule. The capsule was placed 5 cm proximal to the squamocolumnar junction (SCJ) by endoscopic determination, the data was recorded consecutively for 48 hours. Then all pH data was downloaded to a computer for analysis. The discomforts reported by patients were recorded. RESULTS: 30 patients were placed JSPH-1 pH capsule successfully and completed 24-hour data recording, 29 patients completed 48-hour data recording. One patient complained of chest pain and required endoscopic removal. No complications and interference of daily activities were reported during data monitoring or follow-up period. 48-hour pH monitoring detected 15 patients of abnormal acid exposure, on day1 detected 9 patients, the difference had statistical significance (P<0.01). Positive symptom index (SI) was identified in 3 patients with normal pH data in both 24-hours. In total, 48-hour monitoring increased diagnosis of GERD in 9 patients. CONCLUSION: 48-hour esophageal pH monitoring with JSPH-1 wireless pH monitoring system is safe, well tolerated and effective. It can be feasible for clinical application to diagnose GERD.

Attenuated Salmonella typhimurium carrying TRAIL and VP3 genes inhibits the growth of gastric cancer cells in vitro and in vivo.

BACKGROUND: Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) and apoptin (VP3) of chicken anemia virus can selectively induce apoptosis in human tumor cell lines by two different pathways. Salmonella not only delivers functional genes to mammalian cells but also possesses antitumor activity and therefore could be adopted as a novel vector for anticancer therapy. MATERIALS AND METHODS: TRAIL and VP3 genes were cloned into a pBudCE4.1 vector and delivered by attenuated Salmonella typhimurium into gastric cancer cells, and their expression and antitumor effects in nude mice were monitored by Western blot, fluorescence microscopy, MTT assay, TUNEL staining, and immunohistochemistry. RESULTS: pBud-VP3 and pBud-TRAIL-VP3 plasmids were constructed to express TRAIL and apoptin in gastric cancer cells, leading to inhibition of cancer cell proliferation after 48 hours (P < 0.05). TRAIL and VP3 genes in pBudCE4.1 vector were also successfully delivered by attenuated S. typhimurium into gastric cancer cells in vivo, in which both TRAIL and apoptin were expressed. In vivo data indicated that S. typhimurium carring pBud-TRAIL-VP3 induced significant cell growth inhibition and tumor regression (P < 0.05). Moreover, expression of TRAIL and apoptin increased the expression of caspase-3 and caspase-9, resulting in enhanced apoptosis. CONCLUSION: Delivery of TRAIL and VP3 genes by attenuated S. typhimurium can significantly inhibit the growth of gastric cancer cells in vitro and in vivo.

[Overexpression of adiponectin prevents hepatocyte steatosis].

OBJECTIVE: To investigate the effect of adiponectin on hepatocyte steatosis. METHODS: L02 cells were transfected with pEGFP-N1-AdipoQ, a plasmid encoding pEGFP-adiponectin fusion protein, or pEGFP-N1. Lipid droplets in the hepatocytes were observed by oil red staining at 72 h. The contents of TG, FFA and glycerol in hepatocytes were measured. RESULTS: Compared to cells transfected with pEGFP-N1-AdipoQ plasmid, much more lipid droplets were observed in cells transfected with pEGFP-N1 plasmid. TG, FFA and glycerol contents in L02 cells and L02/pEGFP-N1 cells were significantly higher than those in L02/pEGFP-N1-AdipoQ cells. CONCLUSIONS: Overexpression of adiponectin prevent hepatocyte steatosis.

Endogenous LKB1 knockdown accelerates G(1)/S transition through p53 and p16 pathways.

The tumor suppressor LKB1 is inactivated in 90% of Peutz-Jeghers cancer syndrome, 30-40% of non-small cell lung carcinoma, and a variety of other cancers, indicating the loss of LKB1 activity is a critical step in oncogenesis. However, current understanding of LKB1 function is largely limited to the results from cancer cells, and how LKB1 inactivation initiates malignant transformation in normal cells remains unclear. Here we ablated endogenous expression of LKB1 in two normal cell lines: human embryonic kidney 293T cells (HEK-293T cells) and human umbilical vein endothelial cells (HUVECs) by LKB1-specific short hairpin RNAs. Downregulation of endogenous LKB1 lead to a facilitated G(1)/S transition, accompanied by a concomitant increase in Rb phosphorylation (Ser(807/811)). Furthermore, reduced expression of p53 and p16 was observed in LKB1 ablated cells, while no differences were detected for cyclin D1 and cyclin E. These results jointly suggest that endogenous LKB1 knockdown accelerates cell cycle progression through G(1)/S checkpoint in HEK-293T cells and HUVECs, which is at least in part, mediated by decline of p53 and p16 pathways. Our findings provided a plausible mechanism by which loss of LKB1 expression in normal cells contributes to the formation of malignancies.

[Anti-tumor effect of eukaryotic expressing plasmid containing soluble tumor necrotic factor-related apoptosis inducing ligand combined with human angiostatin Kringle (1 - 3) genes on human gastric cancer xenografts in nude mice].

OBJECTIVE: To investigate the anti-tumor effect of eukaryotic expressing plasmid containing human angiostatin Kringle (1 - 3) [hAG (K1-3)] combined with soluble tumor necrotic factor-related apoptosis inducing ligand (sTRAIL) genes on human gastric cancer xenografts in nude mice. METHODS: Recombinant plasmids of pBud-hAG and pBud-hAG-TRAIL were constructed by subcloning technique. Twenty nude BALB/c mice were inoculated with human gastric cancer cells of the line BGC-823 subcutaneously into the back. One week later after the appearance of implanted tumors the mice were randomly divided into 4 groups with pBud-hAG, pBud-hAG-TRAIL, pBud blank plasmid, and normal saline (NS) injected into the tumors respectively once the other day for 7 times. The size of tumor was observed. 7 days later the mice were killed with their tumors taken out. RT-PCR was used to detect the expression of hAG and sTRAIL. The microvessel density (MVD) of tumor was observed and recorded by detecting the protein of CD34 with immunohistochemistry on the microscopy. RESULTS: The MVD of tumor in the pBud-hAG-TRAIL and pBud-hAG groups were (4.8 +/- 0.9)/HP and (4.6 +/- 1.2)/HP respectively, significantly lower than those of the pBud and NS groups [(17.4 +/- 2.4)/HP and (18.2 +/- 2.7)/HP respectively, all P < 0.05], but there was no significant difference between the pBud-hAG-TRAIL and pBud-hAG groups. mRNA expression and protein expression of sTRAIL and hAG were positive in the pBud-hAG-TRAIL and pBud-hAG groups. The tumor volumes of tumors of the pBud-hAG-TRAIL and pBud-hAG groups were (1.325 +/- 0.012) cm(3) and (1.862 +/- 0.017) cm(3) respectively, both significantly lower than those of the pBud and NS groups [(3.637 +/- 0.032) cm(3) and (3.521 +/- 0.028) cm(3) respectively, all P < 0.05]. CONCLUSION: Angiostatin inhibits tumor angiogenesis through inhibiting the growth of vascular endothelial cells, and TRAIL induces tumor cell apoptosis. hAG (K1-3) combined with TRAIL can inhibit tumor growth more efficiently.

Removal of chloride ion from aqueous solution by ZnAl-NO(3) layered double hydroxides as anion-exchanger.

The layered double hydroxides (LDHs) containing nitrate as the interlayer anion has a high anion-exchange capacity in the presence of appropriate anions. In the light of this, ZnAl-NO(3) LDHs have been employed to remove chloride ion from aqueous solution in a batch mode. The influences of conditions for chloride ion uptake, including dosage of LDHs, pH of aqueous solution, and temperature on anion-exchange have been investigated, respectively. The thermodynamic parameters including Gibbs free energy (DeltaG(0)), standard enthalpy change (DeltaH(0)), and standard entropy change (DeltaS(0)) for the process were calculated using the Langmuir constants. It was found from kinetics test that the pseudo-second order kinetics model could be used to well describe the uptake process. An E(a) value of 10.27 kJ/mol provides evidence the anion-exchange process. The explanation of anion-exchange phenomenon has also been supported by X-ray diffraction and FT-IR spectra.

RNA interference-mediated silencing of the Hsp70 gene inhibits human gastric cancer cell growth and induces apoptosis in vitro and in vivo.

AIMS AND BACKGROUND: The role of heat shock protein (HSP) 70 in gastric cancer has been extensively examined in many studies for the past decade. It has been demonstrated that over-expression of Hsp70 might play important role in malignant transformation and maintenance of malignant phenotypes. Therefore, silencing the Hsp70 gene could be applicable in molecular therapies of human gastric cancer. Herein, we designed a small interfering RNA targeting Hsp70 to knock down its expression and investigated its effect on cell proliferation and apoptosis in a gastric cancer cell line. METHODS: Two plasmids (phsp1-siRNA, phsp2-siRNA), along with a negative control (phsp3-siRNA), were created using a genic recombination technique. BGC823 cell lines were used to perform experiments. Western blotting and RT-PCR were used to detect Hsp70 expression in vitro and in vivo. Cell morphology was observed under light microscope. Cell cycle and apoptosis were analyzed by flow cytometry and acridine orange/ethidium bromide double stain, and cell proliferative activity was measured by alamarblue assay. In all experiments, a negative control served as a baseline measure. RESULTS: We successfully constructed phsps-siRNA plasmids and transfected them into BGC823 cells. RT-PCR and western blotting revealed that the expression of Hsp70 was down-regulated in transfection groups compared with the control group. Flow cytometric analysis indicated that less S-phase fraction accumulated in small interfering RNA transfected cells than in parental cells and the cells transfected with empty vector. CONCLUSIONS: Our results demonstrated that RNAi against Hsp70 could effectively knock down gene expression, inhibit growth of cancer cells, induce cell cycle arrest and increase cell apoptosis in vitro and in vivo. Hsp70 might serve as a therapeutic target for human gastric cancer.

Comparison of esomeprazole enteric-coated capsules vs esomeprazole magnesium in the treatment of active duodenal ulcer: a randomized, double-blind, controlled study.

AIM: To evaluate the efficacy and tolerability of two different preparations of esomeprazole in healing duodenal ulcers. METHODS: A total of 60 patients with active duodenal ulcers were enrolled and randomized to receive esomeprazole enteric-coated capsules (40 mg) or esomeprazole magnesium (40 mg), once daily, for 4 consecutive wk, with ulcer healing being monitored by endoscopy. Safety and tolerability were also assessed. RESULTS: Fifty seven patients completed the whole trial. The ulcer healing rates at the end of wk 2 were 86.7% and 85.2% in the esomeprazole enteric-coated capsules and esomeprazole magnesium groups, respectively (P = 0.8410), and reached 100% at the end of wk 4 in both groups. Symptom relief at the end of wk 2 was 90.8% in the esomeprazole enteric-coated capsules group and 86.7% in the esomeprazole magnesium group (P = 0.5406); at the end of wk 4 symptom relief was 95.2% and 93.2%, respectively (P = 0.5786). Adverse events occurred in 16.7% of the esomeprazole enteric-coated capsules group and 14.8% of the esomeprazole magnesium group (P = 1.0000). CONCLUSION: The efficacies of esomeprazole enteric-coated capsules and esomeprazole magnesium in healing duodenal ulcer lesions and relieving gastrointestinal symptoms are equivalent. The tolerability and safety of both drugs were comparable.

Calcium dependence of proteinase-activated receptor 2 and cholecystokinin-mediated amylase secretion from pancreatic acini.

Pancreatic acini secrete digestive enzymes in response to a variety of secretagogues including CCK and agonists acting via proteinase-activated receptor-2 (PAR2). We employed the CCK analog caerulein and the PAR2-activating peptide SLIGRL-NH(2) to compare and contrast Ca(2+) changes and amylase secretion triggered by CCK receptor and PAR2 stimulation. We found that secretion stimulated by both agonists is dependent on a rise in cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) and that this rise in [Ca(2+)](i) reflects both the release of Ca(2+) from intracellular stores and accelerated Ca(2+) influx. Both agonists, at low concentrations, elicit oscillatory [Ca(2+)](i) changes, and both trigger a peak plateau [Ca(2+)](i) change at high concentrations. Although the two agonists elicit similar rates of amylase secretion, the rise in [Ca(2+)](i) elicited by caerulein is greater than that elicited by SLIGRL-NH(2). In Ca(2+)-free medium, the rise in [Ca(2+)](i) elicited by SLIGRL-NH(2) is prevented by the prior addition of a supramaximally stimulating concentration of caerulein, but the reverse is not true; the rise elicited by caerulein is neither prevented nor reduced by prior addition of SLIGRL-NH(2). Both the oscillatory and the peak plateau [Ca(2+)](i) changes that follow PAR2 stimulation are prevented by the phospholipase C (PLC) inhibitor U73122, but U73122 prevents only the oscillatory [Ca(2+)](i) changes triggered by caerulein. We conclude that 1) both PAR2 and CCK stimulation trigger amylase secretion that is dependent on a rise in [Ca(2+)](i) and that [Ca(2+)](i) rise reflects release of calcium from intracellular stores as well as accelerated influx of extracellular calcium; 2) PLC mediates both the oscillatory and the peak plateau rise in [Ca(2+)](i) elicited by PAR2 but only the oscillatory rise in [Ca(2+)](i) elicited by CCK stimulation; and 3) the rate of amylase secretion elicited by agonists acting via different types of receptors may not correlate with the magnitude of the [Ca(2+)](i) rise triggered by those different types of secretagogue.

Protection against acute pancreatitis by activation of protease-activated receptor-2.

Protease-activated receptor-2 (PAR-2) is a widely expressed tethered ligand receptor that can be activated by trypsin and other trypsin-like serine proteases. In the exocrine pancreas, PAR-2 activation modulates acinar cell secretion of digestive enzymes and duct cell ion channel function. During acute pancreatitis, digestive enzyme zymogens, including trypsinogen, are activated within the pancreas. We hypothesized that trypsin, acting via PAR-2, might regulate the severity of that disease, and to test this hypothesis, we examined the effect of either genetically deleting or pharmacologically activating PAR-2 on the severity of secretagogue-induced experimental pancreatitis. We found that experimental acute pancreatitis is more severe in PAR-2(-/-) than in wild-type mice and that in vivo activation of PAR-2, achieved by parenteral administration of the PAR-2-activating peptide SLIGRL-NH2, reduces the severity of pancreatitis. In the pancreas during the early stages of pancreatitis, the MAPK ERK1/2 is activated and translocated to the nucleus, but nuclear translocation is reduced by activation of PAR-2. Our findings indicate that PAR-2 exerts a protective effect on pancreatitis and that activation of PAR-2 ameliorates pancreatitis, possibly by inhibiting ERK1/2 translocation to the nucleus. Our observations suggest that PAR-2 activation may be of therapeutic value in the treatment and/or prevention of severe clinical pancreatitis, and they lead us to speculate that, from a teleological standpoint, PAR-2 may have evolved in the pancreas as a protective mechanism designed to dampen the injurious effects of intrapancreatic trypsinogen activation.