Comparison of the use of a spiral nasojejunal tube and transendoscopic enteral tubing in washed microbiota transplantation via the mid-gut route.

Background: Methods for washed microbiota transplantation (WMT) through the mid-gut include transendoscopic enteral tubing (TET) and manual spiral nasojejunal tube (SNT) placement have not been studied. Methods: This prospective interventional study was performed at a single centre. Patients were divided into the SNT and mid-gut TET groups based on their conditions and wishes. In the SNT group, an SNT was passively inserted into the stomach, and abdominal X-rays were taken within 24 h to confirm tube placement in the small intestine. In the mid-gut TET group, mid-gut TET was placed in the small intestine for gastroscopy. Data on the clinical efficacy of WMT, intubation time, cost, overall comfort score, adverse reactions, etc., were collected from the two groups. Results: Sixty-three patients were included in the study (SNT group (n = 40) and mid-gut TET group (n = 23)). The clinical efficacy of WMT in the SNT and mid-gut TET groups was 90 % and 95.7 %, respectively (P = 0.644). Compared with the mid-gut TET group, the SNT group showed a shorter operation time (120 s vs. 258 s, P = 0.001) and a lower average cost (641.7 yuan vs. 1702.1 yuan, P = 0.001). There was no significant difference in the overall comfort score or the incidence of common discomfort symptoms between the two groups. Conclusion: The different implantation methods have different advantages; compared with mid-gut TET placement, manual SNT placement provides some benefits.

Ability of lactulose breath test results to accurately identify colorectal polyps through the measurement of small intestine bacterial overgrowth.

BACKGROUND: While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps. AIM: To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results. METHODS: A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays. RESULTS: H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group (P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66. CONCLUSION: The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

Differentiation between alcohol-associated cirrhosis and hepatitis B-associated cirrhosis based on hepatic complications and psychological symptoms.

Background: The prognosis of and occurrence of complications in patients with different clinical features of cirrhosis differ, and cirrhosis with different etiologies has varying clinical characteristics. The aim of this study was to describe the liver function markers, hepatic complications, and psychological features differentiating patients with hepatitis B virus (HBV) infection-related and alcohol-related cirrhosis. Materials and Methods: This was a retrospective and observational study that analyzed the medical data of inpatients with alcohol-related or HBV infection-related cirrhosis from May 2014 to May 2020. Markers of liver function, portal hypertension, and psychological symptoms were compared between the two groups. Results: Patients with alcohol-related cirrhosis showed higher Self-Rating Anxiety Scale scores and prevalence of hypoproteinemia, fatty liver, and depression than those with HBV infection-related cirrhosis (all P < 0.05). After adjustment for potential confounders, patients with alcohol-related cirrhosis also showed higher risks of increased total cholesterol (odds ratio [OR] =2.671, 95% confidence interval [CI]: 1.160-6.151, P = 0.021), increased high-density lipoprotein-cholesterol (OR = 2.714, 95% CI: 1.009-7.299, P = 0.048), and fatty liver (OR = 2.713, 95% CI: 1.002-7.215, P = 0.048); however, splenomegaly and splenectomy were significantly associated with HBV infection-related cirrhosis (OR = 2.320, 95% CI: 1.066-5.050, P = 0.034). Conclusion: Patients with alcohol-related cirrhosis were more likely to develop hyperlipidemia, fatty liver, and psychological symptoms, whereas those with HBV-related cirrhosis had a higher risk of splenomegaly.

Serum Lactate Dehydrogenase Is a Sensitive Predictor of Systemic Complications of Acute Pancreatitis.

Background: Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease that can cause various complications, including systemic inflammatory response syndrome (SIRS), pleural effusion, ascitic fluid, myocardial infarction, and acute kidney injury (AKI). However, there is still a lack of rapid and effective indicators to assess the disease. The aim of this study was to investigate the associations of high serum lactate dehydrogenase (LDH) levels with AP severity and systemic complications. Methods: AP patients treated from July 2014 to December 2020 were retrospectively enrolled. They were divided into elevated (n = 93) and normal (n = 143) LDH groups. Their demographic data, clinical data, hospital duration, and hospital expenses were analyzed. Linear and binary logistic regression analyses were used to determine whether elevated LDH is a risk factor for AP severity and complications after adjusting for confounders. Results: There were significant differences in AP severity scores (Ranson, MODS, BISAP, APACHE II, and CTSI), hospital duration, hospital expenses, and the incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI) between the elevated and normal LDH groups. After adjusting for confounders, elevated LDH was associated with AP severity scores and hospital duration and expenses (based on linear regression analyses) and was a risk factor for the occurrence of AP complications and interventions, that is, diuretic and vasoactive agent use (based on binary logistic regression analyses). Conclusions: Elevated LDH is associated with high AP severity scores and high incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI).

Effects of Washed Microbiota Transplantation on Serum Uric Acid Levels, Symptoms, and Intestinal Barrier Function in Patients with Acute and Recurrent Gout: A Pilot Study.

INTRODUCTION: Gut dysbiosis has been reported to be closely associated with gout. Washed microbiota transplantation (WMT) is considered as an effective way to restore a healthy gut microbiota with less adverse events than the conventional fecal microbiota transplantation. In this study, we aimed to evaluate the effects of WMT on serum uric acid levels, symptoms, and the intestinal barrier function in patients with acute and recurrent gout. METHODS: We performed a pilot study of WMT for acute and recurrent gout. The primary outcome was the changes in the serum uric acid level and gout symptoms. The secondary outcomes included the changes in levels of diamine oxidase (DAO), D-lactic acid, and endotoxin. RESULTS: Eleven patients received WMT treatment. The averaged serum uric acid levels in patients with gout reduced after WMT (p = 0.031), accompanied with a decrease in the frequency and duration time of acute gout flares (p < 0.01). The levels of DAO, D-lactic acid, and endotoxin were higher in patients than in healthy donors (p < 0.05). After WMT treatment, the levels of DAO and endotoxin decreased (p < 0.05). CONCLUSIONS: WMT is effective for reducing serum uric acid levels and improving gout symptoms in patients with gout and contributes to improve their impaired intestinal barrier function.

Efficacy and Safety of Washed Microbiota Transplantation to Treat Patients with Mild-to-Severe COVID-19 and Suspected of Having Gut Microbiota Dysbiosis: Study Protocol for a Randomized Controlled Trial.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is often accompanied by gastrointestinal symptoms, which are related to gut microbiota dysbiosis (GMD). Whether washed microbiota transplantation (WMT) is an effective treatment for COVID-19 patients suspected of having GMD by restoring the gut microbiota is unknown. This study is designed to explore the efficacy and safety of WMT in COVID-19 patients suspected of having GMD. METHODS: This is a randomized, multicenter, single-blind prospective study. COVID-19 patients suspected of having GMD will be randomly divided to receive routine treatment only or to receive routine treatment and WMT. The frequency of WMT will be once a day for three consecutive days. Laboratory and imaging examinations will be performed at admission, 1 and 2 weeks after treatment, and on the day of discharge. Then a telephone follow-up will be conducted at 1st week, 2nd week, and 6th month after discharge. The clinical efficacy and safety of WMT in COVD-19 patients suspected of having GMD and the effects of WMT on the organ function, homeostasis, inflammatory response, intestinal mucosal barrier function, and immunity of the patients will be evaluated. RESULTS: By following the proposed protocol, WMT is expected to be efficacious and safe for the treatment of COVID-19 patients suspected of having GMD, and the therapeutic effect is expected to be associated with improvement of the intestinal mucosal barrier function, inflammatory response, and immunity. CONCLUSION: The findings from this study may offer a new approach for the prevention and treatment of COVID-19 patients suspected of having GMD.

Changes in oral flora of patients with functional dyspepsia.

To explore the changes in oral flora in people with functional dyspepsia (FD). Unstimulated saliva was collected from 21 FD patients diagnosed according to the Rome IV criteria and from 12 healthy controls (HCs) for 16SrRNA sequencing. The pH of saliva samples and community periodontal index (CPI) were tested. The prevalence of small intestinal bacterial overgrowth (SIBO) was obtained by the methane-and hydrogen-based breath test. At the phylum level, FD patients had a higher relative abundance of Spirochaetes and a lower relative abundance of Fusobacteria, TM7 and Proteobacteria than HCs (p < 0.01). In the saliva, Kingella and Abiotrophia genus levels showed significant changes between the FD and HC groups (p < 0.01). Salivary species level marker Intermedia was significantly different between FD and HC groups (p < 0.01). The oral pH of FD patients was higher than that of HCs (p < 0.01). The mean CPI of the FD group was 1.52 and that of the HC group was 0.17 (p < 0.01). Moreover, 71.4% of the FD group was positive for SIBO. The oral flora of FD patients was different from that of HCs. Spirochaetes, Kingella, Abiotrophia, and Intermedia may be diagnostic indicators of FD.

Washed microbiota transplantation reduces proton pump inhibitor dependency in nonerosive reflux disease.

BACKGROUND: The pathogenesis of gastroesophageal reflux disease (GERD) is closely associated with the intestinal bacteria composition and their metabolites. AIM: To investigate whether washed microbiota transplantation (WMT) improves symptoms of nonerosive reflux disease (NERD) with proton pump inhibitor (PPI) dependency. METHODS: Patients with recurrent NERD and PPI dependency at the First Affiliated Hospital of Guangdong Pharmaceutical University from 2017 to 2018 were included and divided into a WMT or PPI group treated with PPI with/without WMT. The endpoint was NERD symptom frequency evaluated 1 mo after WMT using reflux disease questionnaire (RDQ) and GERD questionnaire (GERDQ) scores, remission time, PPI dose, and the examination of intestinal mucosal barrier function. RESULTS: In the WMT (n = 15) and PPI (n = 12) groups, the total remission rate at 1 mo after treatment was 93.3% vs 41.7%. Compared with the PPI group, the WMT group showed better results in GERDQ (P = 0.004) and RDQ (P = 0.003) and in remission months (8 vs 2, P = 0.002). The PPI dose was reduced to some extent for 80% of patients in the WMT group and 33.3% in the PPI group. In 24 patients, intestinal mucosal barrier function was examined before treatment, and changes in the degree of damage were observed in 13 of these patients after treatment. Only one of the 15 patients had minor side effects, including a mushy stool two or three times a day, which resolved on their own after 1 wk. CONCLUSION: This study is the first to demonstrate that WMT may be safe and effective for relieving NERD symptoms and reducing PPI dependency and recurrence.

The Efficacy of Washed Microbiota Transplantation on Helicobacter pylori Eradication: A Pilot Study.

AIM: The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication. METHODS: Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up 13C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined. RESULTS: A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without (13.00 ± 6.97vs.8.31 ± 3.733; P = 0.02). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication. CONCLUSION: H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.

Multi-donor multi-course faecal microbiota transplantation relieves the symptoms of chronic hemorrhagic radiation proctitis: A case report.

RATIONALE: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model. PATIENT CONCERNS: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection. DIAGNOSES: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis. INTERVENTIONS: The patient was treated with a total of 4 individual courses of FMT. OUTCOMES: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors. LESSONS: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.

Hair regrowth following fecal microbiota transplantation in an elderly patient with alopecia areata: A case report and review of the literature.

BACKGROUND: Alopecia areata is a hair loss disease associated with genetics, autoimmunity, and other factors. There is an intriguing link between alopecia areata and gut dysbiosis. Fecal microbiota transplantation (FMT) has been recommended to treat Clostridium difficile (previously known as Clostridioides difficile) infection, and has also shown potentials in the treatment of inflammatory bowel disease, irritable bowel syndrome, and non-alcohol fatty liver disease. CASE SUMMARY: An 86-year-old man, with a history of sigmoid colon carcinoma, suffered from recurrent abdominal pain and distension, and diarrhea for six months, with inappetence. At admission, he was also diagnosed with depression. Upon physical examination, the patient presented with a 1.5 cm × 2.0 cm alopecia areata on his right occiput. Due to the negative results of laboratory testing, capsule endoscopy, and colonoscopy, the patient was diagnosed with noninfectious diarrhea, depressive disorder, and patchy alopecia areata. Considering that noninfectious diarrhea in the elderly patient was mainly caused by gut dysbiosis, he was given six rounds of FMT. His diarrhea improved remarkably one month after FMT, with improved appetite and disappearance of abdominal pain, distension, and depressive symptoms. Surprisingly, he reported new hair growth on the affected region of his scalp, with some of his white hair gradually turning to black, without taking any other therapies for alopecia areata before and after FMT. CONCLUSION: FMT might act as a potential therapy for patients who suffer from alopecia areata. Large and well-designed studies are required to confirm the role of FMT in alopecia areata.

Cardioprotection via the skin: nociceptor-induced conditioning against cardiac MI in the NIC of time.

Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9-T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.

Type 2 Diabetes Mellitus Is Associated with More Serious Small Intestinal Mucosal Injuries.

BACKGROUND: Clinical and experimental research has revealed that diabetes mellitus (DM) is characterized by intestinal hypomotility, gut microbial dysbiosis, increased gut permeability, microcirculation disorders, circulatory changes, and dysfunction of intestinal stem cells, which may be linked to inflammation of intestinal mucosa. However, the relationship between type 2 DM (T2DM) and macroscopic small intestinal mucosal injuries is still unclear. Therefore, we retrospectively studied capsule endoscopy data to determine the relationship between T2DM and small intestinal mucosal injuries. MATERIALS AND METHODS: We compared the records of 38 T2DM patients with those of 152 non-DM patients for small intestinal mucosal injuries. Different types of mucosal injuries and Lewis scores were compared between T2DM and non-DM patients. The relationships between patients with or without different types of diabetic complications and the Lewis score was assessed. Moreover, the relationships between insulin resistance and Lewis score, between HbA1c and Lewis score, were also both assessed. RESULTS: The prevalence of a villous edema in subjects with T2DM was significantly higher than in those without DM (P < 0.001), but incidence of ulcers was not different (P = 1.000). With T2DM, the Lewis score was also significantly higher (P = 0.002). In addition, subjects with diabetic nephropathy showed significantly higher Lewis scores than patients without diabetic nephropathy (P = 0.033). In Pearson's correlation tests, the homeostasis model assessment of insulin resistance (HOMA-IR) value was correlated positively with the Lewis score (γ = 0.175, P = 0.015), but no statistical correlation was found between HbA1c level and Lewis score (γ = 0.039, P = 0.697). CONCLUSIONS: Subjects with T2DM, especially those with diabetic nephropathy, have higher Lewis scores and more serious small intestinal mucosal lesions.

[Effect of Qingyi Granule on HMGB1 Expression in Liver and Renal Tissues of Severe Acute Pancreatitis Rats].

OBJECTIVE: To explore the effect of Qingyi Granule (QYG) on high mobility group box-1 (HMGB1) expressions in liver and renal tissues of severe acute pancreatitis (SAP) rats. METHODS: Fifty-four Sprague-Dawley (SD) rats were divided into the sham-operation (SO) group, the SAP group, and the QYG group according to random digits table. Rats in the SAP group were induced by injecting 5% sodium taurocholate (STC). Liver and renal pathological changes were observed by HE staining. Serum contents of amylase (AMS), MDA, IL-1, and HMGB1 were detected by ELISA. HMGB1 protein expressions in liver and renal tissues were tested by immunohistochemistry. HMGB1 mRNA expressions in liver and renal tissues were detected by reversed transcription PCR. RESULTS: The pathological scores, serum levels of AMS, MDA, IL-1 and HMGB1, and protein and mRNA HMGB1 expressions in liver and renal tissues were increased more obviously in the SAP group than in the SO group (P < 0.05, P < 0.01). All of them could be down-regulated by QYG intervention, with the most significant effect seen at 72 h (P < 0.05, P < 0.01) in a time-effect relationship. CONCLUSIONS: HMGB1 participated in SAP complicated liver and renal injuries. QYG could effectively inhibit HMGB1 expressions, thereby attenuating SAP complicated liver and renal injuries.

Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response.

AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group received an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, Tat-NBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1beta and TNF-alpha mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1beta and TNF-alpha protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1beta mRNA, IL-1beta protein, TNF-alpha mRNA and TNF-alpha protein, whereas significantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-kappaB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-kappaB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has anti-inflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS.

Nuclear factor kappa B: a marker of chemotherapy for human stage IV gastric carcinoma.

AIM: To detect the nuclear factor kappa B (NF-kappaB) condition in human stage IV gastric carcinoma patients and to explore the correlation between NF-kappaB activation and survival of these patients after chemotherapy. METHODS: Expression of NF-kappaB-p65 was determined by immunohistochemical analysis. Activity of NF-kappaB DNA-binding in carcinoma tissue was detected by electrophoretic mobility shift assay. Kaplan-Meier survival analysis was performed to show the relation between NF-kappaB and progression-free survival (PFS) or overall survival (OS) of the patients. RESULTS: The positive expression rate of NF-kappaB-p65 in 60 gastric cancer tissue samples was 76.7% (46/60). The expression of NF-kappaB-p65 was reduced in adjacent carcinoma and normal tissue samples. Electrophoretic mobility shift assay (EMSA) analysis showed a strong activation of NF-kappaB in cancer tissue samples. A survival difference was found in NF-kappaB-p65 positive and negative patients. NF-kappaB-p65 expression was negative in cancer tissue samples (n=14). PFS was 191.40+/-59.88 d and 152.93+/-16.99 d, respectively, in patients with positive NF-kappaB-p65 expression (n=46) (P=0.4028). The survival time of patients with negative and positive NF-kappaB-p65 expression was 425.16+/-61.61 d and 418.85+/-42.98 d, respectively (P=0.7303). Kaplan-Meier analysis showed no significant difference in PFS or OS. The 46 patient tissue which positive NF-kappaB-p65 expression was found in the tissue samples from the 46 patients whose PFS and OS were 564.89+/-75.94 d and s 352.37+/-41.32 d, respectively (P=0.0165). CONCLUSION: NF-kappaB is activated in gastric carcinoma tissue, which is related to the OS after chemotherapy.

Sialic acid contributes to hyperexcitability of dorsal root ganglion neurons in rats with peripheral nerve injury.

Axonal injury of the dorsal root ganglion (DRG) neurons may alter the synthesis of certain membrane proteins that are responsible for the development of abnormal hyperexcitability. The external domains of most of these membrane proteins are sialylated. Because sialic acid carries heavy negative charges, the increase of sialylated proteins may increase neurons' negative surface charges, which will have predictable effects on the voltage-gated channels, and affect the excitability of injured neurons. Using intracellular electrophysiological recording, we demonstrated that following chronic constriction injury (CCI) of the sciatic nerve, Aalpha/beta DRG neurons become hyperexcitable, as indicated by a more depolarized resting membrane potential (Vm) and a lowered threshold current (TIC). More interestingly, the excitability of injured DRG neurons was reduced substantially when the extracellular sialic acid was removed by pretreatment with neuraminidase. The Vm was less depolarized and the TIC increased robustly as compared to the CCI neurons without neuraminidase treatment. However, desialylation of normal, intact neurons had no significant effect on the Vm and less effect on the TIC. Our results suggest that the hyperexcitability of injured sensory neurons may be associated with increased negatively charged sialic acid residues on the surface of the neuronal somata.

Sialic acid contributes to generation of ectopic spontaneous discharges in rats with neuropathic pain.

Ectopic spontaneous discharges (ESD) of teased myelinated fibers were recorded from the sciatic nerve proximal to the site of 'chronic constriction nerve injury' in the rat. Ca(2+), Mg(2+), Mn(2+), Ni(2+), La(3+) and some positively charged organic compounds (hexamethonium and poly-lysine) when applied topically to the injured site abolished or significantly reduced the rate of ESD. After enzymatic removal of sialic acid by neuraminidase (2 units/ml), the ESD was silenced in 11, reduced in four and unchanged in four of 19 fibers. However, divalent cations failed to depress the reappeared ESD evoked by 4-aminopyridine in the desialylated silenced fibers. Moreover, the mean incidence of ESD was significantly reduced after neuraminidase treatment. These results indicate that an increase in negative charges on the external membrane surface of injured neuron caused by sialylation is a key factor in ESD generation.