Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501).

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.

Role of sestrins in metabolic and aging-related diseases.

Sestrins are a type of highly conserved stress-inducing protein that has antioxidant and mTORC1 inhibitory functions. Metabolic dysfunction and aging are the main risk factors for development of human diseases, such as diabetes, neurodegenerative diseases, and cancer. Sestrins have important roles in regulating glucose and lipid metabolism, anti-tumor functions, and aging by inhibiting the reactive oxygen species and mechanistic target of rapamycin complex 1 pathways. In this review, the structure and biological functions of sestrins are summarized, and how sestrins are activated and contribute to regulation of the downstream signal pathways of metabolic and aging-related diseases are discussed in detail with the goal of providing new ideas and therapeutic targets for the treatment of related diseases.

A COX2-targeting cancer-specific fluorescent probe for hydrogen sulfide detection in living cells, Caenorhabditis elegans, and zebrafish.

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.

Acute Pancreatitis in Pregnancy: A Propensity Score Matching Analysis and Dynamic Nomogram for Risk Assessment.

BACKGROUND: Acute pancreatitis is easily confused with abdominal pain symptoms, and it could lead to serious complications for pregnant women and fetus, the mortality was as high as 3.3% and 11.6-18.7%, respectively. However, there is still lack of sensitive laboratory markers for early diagnosis of APIP and authoritative guidelines to guide treatment. OBJECTIVE: The purpose of this study was to explore the risk factors of acute pancreatitis in pregnancy, establish, and evaluate the dynamic prediction model of risk factors in acute pancreatitis in pregnancy patients. STUDY DESIGN: Clinical data of APIP patients and non-pregnant acute pancreases patients who underwent regular antenatal check-ups during the same period were collected. The dataset after propensity matching was randomly divided into training set and verification set at a ratio of 7:3. The model was constructed using Logistic regression, least absolute shrinkage and selection operator regression, R language and other methods. The training set model was used to construct the diagnostic nomogram model and the validation set was used to validate the model. Finally, the accuracy and clinical practicability of the model were evaluated. RESULTS: A total of 111 APIP were included. In all APIP patients, hyperlipidemic pancreatitis was the most important reason. The levels of serum amylase, creatinine, albumin, triglyceride, high-density lipoprotein cholesterol, and apolipoprotein A1 were significantly different between the two groups. The propensity matching method was used to match pregnant pancreatitis patients and pregnant non-pancreatic patients 1:1 according to age and gestational age, and the matching tolerance was 0.02. The multivariate logistic regression analysis of training set showed that diabetes, triglyceride, Body Mass Index, white blood cell, and C-reactive protein were identified and entered the dynamic nomogram. The area under the ROC curve of the training set was 0.942 and in validation set was 0.842. The calibration curve showed good predictive in training set, and the calibration performance in the validation set was acceptable. The calibration curve showed the consistency between the nomogram model and the actual probability. CONCLUSION: The dynamic nomogram model we constructed to predict the risk factors of acute pancreatitis in pregnancy has high accuracy, discrimination, and clinical practicability.

The role of mitochondria in the resistance of melanoma to PD-1 inhibitors.

Malignant melanoma is one of the most common tumours and has the highest mortality rate of all types of skin cancers worldwide. Traditional and novel therapeutic approaches, including surgery, targeted therapy and immunotherapy, have shown good efficacy in the treatment of melanoma. At present, the mainstay of treatment for melanoma is immunotherapy combined with other treatment strategies. However, immune checkpoint inhibitors, such as PD-1 inhibitors, are not particularly effective in the clinical treatment of patients with melanoma. Changes in mitochondrial function may affect the development of melanoma and the efficacy of PD-1 inhibitors. To elucidate the role of mitochondria in the resistance of melanoma to PD-1 inhibitors, this review comprehensively summarises the role of mitochondria in the occurrence and development of melanoma, targets related to the function of mitochondria in melanoma cells and changes in mitochondrial function in different cells in melanoma resistant to PD-1 inhibitors. This review may help to develop therapeutic strategies for improving the clinical response rate of PD-1 inhibitors and prolonging the survival of patients by activating mitochondrial function in tumour and T cells.

[68Ga]Ga-FAPI-04 PET/CT on assessing Crohn's disease intestinal lesions.

BACKGROUND: Fibrosis and inflammation are major pathological changes of Crohn's disease (CD). Early detection and accurate severity evaluation of CD are critical for patient's prognosis. Endoscopy is widely used to evaluate CD progression. Herein, we evaluated the efficacy of [68Ga]Ga-FAPI-04 PET/CT to identify lesions and assess the progression of CD. METHODS: All CD patients received computed tomography enterography (CTE), [68Ga]Ga-FAPI-04 PET/CT examination, and ileocolonoscopy within 1 week. Two independent gastroenterologists computed the Crohn's disease activity index (CDAI) of all patients. Two radiology physicians assessed the CTE images separately, and the CTE scores were calculated. Lastly, two nuclear medicine physicians independently examined the [68Ga]Ga-FAPI-04 PET/CT images. Once the FAPI uptake of the intestinal segment was equal or higher relative to the liver (considered FAPI-positive), the target-to-background ratio (TBR) and global FAPI PET/CT score were computed, representing the independent intestinal activity and activity of all intestinal segments, respectively. Levels of fecal calprotectin (FCP) and C-reactive protein (CRP) were determined before the endoscopy. The Crohn's disease endoscopy index of severity (CDEIS) and the simple endoscopic score for Crohn's disease (SES-CD) were calculated during the endoscopy. Finally, all data were obtained and analyzed. RESULTS: There were 74 intestinal segments in 16 patients were assessed. [68Ga]Ga-FAPI-04 PET/CT identified 42 of 45 endoscopically lesioned segments (endoscopic lesions detection sensitivity: 93.3%), while CTE identified 39 of them (endoscopic lesions detection sensitivity: 86.7%). According to the receiver operating characteristic (ROC) analysis, [68Ga]Ga-FAPI-04 PET/CT showed better performance in the detection of endoscopic lesions compared with CTE (P < 0.05). The TBR was significantly associated with the CTE score (r = 0.81; (95% CI): 0.736-0.869; P < 0.0001) and SES-CD values (r = 0.86; (95% CI): 0.776-0.908; P < 0.0001). In addition, the global FAPI PET/CT score was significantly correlated with FCP (r = 0.52; 95% CI, 0.02-0.81; P = 0.039), CRP (r = 0.60; 95% CI, 0.13-0.85; P = 0.014), CDEIS (r = 0.55; 95% CI, 0.06-0.83; P = 0.028), and CDAI (r = 0.81; 95% CI, 0.50-0.93; P < 0.0001). CONCLUSION: In summary, [68Ga]Ga-FAPI-04 PET/CT correlated well with endoscopic, CTE, clinical, and biomarkers of CD. It was also highly sensitive in the detection of different classes of lesions in all intestinal segments, and unlike other examinations, this technique required no patient fasting or bowel preparation. Therefore, [68Ga]Ga-FAPI-04 PET/CT may be a promising method for assessing the activity of CD.

Gender differences of authors of major Hepatology society guidelines during the past 15 years.

BACKGROUND AND OBJECTIVE: Recent studies have shown that women are underrepresented as authors of medical research and clinical practice guidelines. This study aimed to evaluate gender disparities of authors of major hepatology guidelines. METHODS: We reviewed the hepatology guidelines published by the following major gastroenterology societies from January 2008 to September 2022: the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), American Association for the Study of Liver Diseases (AASLD), Asian-Pacific Association for the Study of the Liver (APASL), British Society of Gastroenterology (BSG), European Association for the Study of the Liver (EASL) and Korean Association for the Study of the Liver (KASL). We determined the topic and the gender of all authors of each guideline. The numbers of men authors, women authors and total authors were collected. The trends of women first authors, women senior authors and total women authors were assessed. A logistic regression analysis was performed to analyse the relationship between the gender of the first or senior author and related factors. RESULTS: We identified 103 hepatology guidelines published between January 2008 and September 2022 published by the AGA, ACG, AASLD, APASL, BSG, EASL, and KASL. The gender of 1096 of 1100 (99.6%) authors was determined. Therefore, a total of 1096 authors were included: 223 (20.3%) authors were women and 873 (79.7%) authors were men. Women comprised 14.6% of all first authors, and 20.4% of all senior authors were women. Only the AASLD had writing committees comprising more than 30% total women authors. The proportions of women senior authors and total women authors increased significantly during the study period (p < .05). Women first authors and women senior authors were more likely to publish guidelines with more women authors. Women first authors were less likely to be co-authors with men authors. CONCLUSIONS: Over the course of the past decade, the proportion of women authors of major hepatology guidelines has been low; however, this gender gap appears to be closing.

States and hotspots in Helicobacter pylori research from 2002 to 2021: A bibliometric analysis.

BACKGROUND: Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field. MATERIALS AND METHODS: Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis. RESULTS: 36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co-occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota. CONCLUSIONS: The United States has been the most productive and influential country on H. pylori research, and H. pylori-related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention.

Prediction of in-hospital Mortality of Intensive Care Unit Patients with Acute Pancreatitis Based on an Explainable Machine Learning Algorithm.

BACKGROUND AND AIM: Acute pancreatitis (AP) is potentially fatal. Therefore, early identification of patients at a high mortality risk and timely intervention are essential. This study aimed to establish an explainable machine-learning model for predicting in-hospital mortality of intensive care unit (ICU) patients with AP. METHODS: Data on patients with AP, including demographics, vital signs, laboratory tests, comorbidities, treatment, complication, and severity scores, were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU collaborative research database (eICU-CRD). Based on the data from MIMIC-IV, we used the least absolute shrinkage and selection operator algorithm to select variables and then established 9 machine-learning models and screened the optimal model. Data from the eICU-CRD were used for external validation. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, decision curve, and calibration plots were used to assess the models' efficacy. Shapley's additive explanation values were used to explain the model. RESULTS: Gaussian naive Bayes (GNB) model had the best performance on the data from MIMIC-IV, with an AUC, accuracy, sensitivity, and specificity of 0.840, 0.787, 0.839, and 0.792, respectively. The GNB model also performed well on the data from the eICU-CRD, with an AUC, accuracy, sensitivity, and specificity of 0.862, 0.833, 0.848, and 0.763, respectively. According to Shapley's additive explanation values, the top 4 predictive factors were maximum red cell distribution width, minimum saturation of blood oxygen, maximum blood urea nitrogen, and the Sequential Organ Failure Assessment score. CONCLUSION: The GNB model demonstrated excellent performance and generalizability in predicting mortality in ICU patients with AP. Therefore, it can identify patients at a high mortality risk.

Application of a Machine Learning Predictive Model for Recurrent Acute Pancreatitis.

BACKGROUND AND AIM: Acute pancreatitis is the main cause of hospitalization for pancreatic disease. Some patients tend to have recurrent episodes after experiencing an episode of acute pancreatitis. This study aimed to construct predictive models for recurrent acute pancreatitis (RAP). METHODS: A total of 531 patients who were hospitalized for the first episode of acute pancreatitis at the Affiliated Hospital of Southwest Medical University from January 2018 to December 2019 were enrolled in the study. We confirmed whether the patients had a second episode until December 31, 2021, through an electronic medical record system and telephone or WeChat follow-up. Clinical and follow-up data of patients were collected and randomly allocated to the training and test sets at a ratio of 7:3. The training set was used to select the best model, and the selected model was tested with the test set. The area under the receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, decision curve, and calibration plots were used to assess the efficacy of the models. Shapley additive explanation values were used to explain the model. RESULTS: Considering multiple indices, XGBoost was the best model. The area under the receiver operating characteristic curves, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model in the test set were 0.779, 0.763, 0.883, 0.647, 0.341, and 0.922, respectively. According to the Shapley additive explanation values, drinking, smoking, higher levels of triglyceride, and the occurrence of ANC are associated with RAP. CONCLUSION: The XGBoost model shows good performance in predicting RAP, which may help identify high-risk patients.

Remodeling morphology of the subluxated osteotomy vertebra in closing-opening wedge osteotomy in ankylosing spondylitis: would the anterior bony beak blunt?

INTRODUCTION: To investigate the remodeling morphology of subluxated osteotomy vertebra in ankylosing spondylitis (AS) patients with thoracolumbar kyphosis after single-level closing-opening wedge osteotomy (COWO). MATERIALS AND METHODS: Standing lateral radiographs were taken to evaluate sagittal parameters including lumbar lordosis (LL), C7 sagittal vertical axis (SVA), global kyphosis (GK), sacral slope (SS), and pelvic tilt (PT). Radiographic parameters of the osteotomy vertebra included osteotomized vertebra angle (OVA), sagittal translation (ST), anterior height (AH), posterior height (PH), and middle height (MH) of the osteotomy vertebrae. Furthermore, lateral projection area of the vertebral body was also measured to evaluate the remodeling of the osteotomy vertebrae. RESULTS: Sixty AS patients who underwent single-level lumbar COWO with a minimal 2-year follow-up were included. The cohort consisted of 54 males and 6 females with an average age of 36.6 years. All patients were divided into two groups according to the development of vertebral subluxation (VS): 15 in VS group (ST ≥ 5 mm), 45 in non-VS group (ST < 5 mm). There was significant difference in the correction of GK, SVA, and the loss of correction of SVA between AS patients with and without VS. Significant difference in vertebra-related parameters regarding AH and OVA was found between VS group and non-VS group (P < 0.05). CONCLUSIONS: After COWO, new bone formation narrowing the gap and adaptive resorption of the anterior bony beak at the osteotomy level during follow-up was surprisingly favorable. However, the ability of spinal canal remodeling is limited in patients complicated with VS.

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Inflammatory injury of the intestine is often accompanied by symptoms such as damage to intestinal mucosa, increased intestinal permeability, and intestinal motility dysfunction. Inflammatory factors spread throughout the body via blood circulation, and can cause multi-organ failure. Pyroptosis is a newly discovered way of programmed cell death, which is mainly characterized by the formation of plasma membrane vesicles, cell swelling until the rupture of the cell membrane, and the release of cell contents, thereby activating a drastic inflammatory response and expanding the inflammatory response cascade. Pyroptosis is widely involved in the occurrence of diseases, and the underlying mechanisms for inflammation are still a hot spot of current research. The caspase-1 mediated canonical inflammasome pathway of pyroptosis and caspase-4/5/8/11-mediated non-canonical inflammasome pathway are closely related to the occurrence and development of intestinal inflammation. Therefore, investigation of the signaling pathways and molecular mechanisms of pyroptosis in intestinal injury in sepsis, inflammatory bowel diseases, infectious enteristic, and intestinal tumor is of great significance for the prevention and treatment of intestinal inflammatory injury.

Does the thoracolumbar kyphosis secondary to ankylosing spondylitis affect the iliac trajectory of S2AI screw?

BACKGROUND: The study aimed to evaluate the influence of thoracolumbar kyphosis secondary to ankylosing spondylitis (AS) on parameters of S2AI trajectory and to compare the ideal S2AI trajectory with those of the non-deformity patients with AS, sagittal deformity patients without AS, and the normal population reported in literatures. METHODS: Sagittal parameters including global kyphosis (GK), pelvic tilt (PT) and sacral slope (SS) were measured. Besides, according to the simulated ideal S2AI trajectory on the CT images, trajectory parameters were measured including Sag angle, Tsv angle, Max-length, Sacral distance and Iliac width. Starting-point parameters were also measured including PSIS distance, Skin distance, Iliac wing and S2 midline. RESULTS: Ninety-four AS-related thoracolumbar kyphosis patients were included. After adjusting the age and gender, twenty non-deformity patients with AS and 20 sagittal deformity patients without AS were selected to compare with patients with AS-related thoracolumbar kyphosis, respectively. Sag angle in deformity patients with AS was smaller than other two groups (P < 0.001). No difference was found in Tsv angle and Sacral distance between AS patients with and without deformity. However, these two parameters were shown significant differences between deformity patients with AS and without AS. In deformity patients with AS, no significant differences were found in all parameters between genders Furthermore, there were strong correlations between PT and the bilateral Sag angle (P < 0.001). CONCLUSIONS: The thoracolumbar kyphosis secondary to AS affects the Sag angle of the ideal S2AI trajectory which was approximately 20° smaller than that in non-deformity patients with AS, sagittal deformity patients without AS, and the normal population. Additionally, the Tsv angle and the Sacral distance in AS patients with thoracolumbar kyphosis were about 10° and 10 mm larger than those in sagittal deformity patients without AS, and the normal population reported in literatures.

Sestrin 3 Protects Against Diet-Induced Nonalcoholic Steatohepatitis in Mice Through Suppression of Transforming Growth Factor ß Signal Transduction.

Sestrin 3 (Sesn3) belongs to the three-member sestrin protein family. Sestrins have been implicated in antioxidative stress, adenosine monophosphate-activated protein kinase and mammalian target of rapamycin signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied. In this work, we generated Sesn3 whole-body knockout and liver-specific transgenic mice to investigate the hepatic function of Sesn3 in diet-induced NASH. With only 4 weeks of dietary treatment, Sesn3 knockout mice developed severe NASH phenotype as characterized by hepatic steatosis, inflammation, and fibrosis. Strikingly, after 8-week feeding with a NASH-inducing diet, Sesn3 transgenic mice were largely protected against NASH development. Transcriptomic analysis revealed that multiple extracellular matrix-related processes were up-regulated, including transforming growth factor ß (TGF-ß) signaling and collagen production. Further biochemical and cell biological analyses have illustrated a critical control of the TGF-ß-mothers against decapentaplegic homolog (Smad) pathway by Sesn3 at the TGF-ß receptor and Smad3 levels. First, Sesn3 inhibits the TGF-ß receptor through an interaction with Smad7; second, Sesn3 directly inhibits the Smad3 function through protein-protein interaction and cytosolic retention. Conclusion: Sesn3 is a critical regulator of the extracellular matrix and hepatic fibrosis by suppression of TGF-ß-Smad3 signaling.

A decellularized porcine pulmonary valved conduit embedded with gelatin.

To prepare a tissue-engineered pulmonary valved conduit (PVC) with good tensile strength and biocompatibility. Sixty adult porcine PVCs were used to determine the optimal decellularization time. Five juvenile porcine decellularized PVCs and five juvenile porcine crosslinked PVCs were subsequently prepared according to the optimized decellularization and crosslinking methods. All PVCs were implanted into juvenile sheep for 8 months and then were harvested for staining. With a low concentration of detergent (0.25% Triton X-100+0.25% sodium deoxycholate), the decellularization effect on porcine PVCs was complete by 24 hours, and there was minimal damage to the matrix. Gelatin embedding and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) crosslinking improved the biomechanical properties of decellularized PVCs and reduced their immunogenicity. After implantation, the diameter and thickness of the PVCs in the decellularized and crosslinked groups increased significantly. In both groups, the conduits were unobstructed, with soft and smooth inner walls and without thrombosis, ulceration or neoplasia. The valves slightly degenerated with mild to moderate regurgitation. CD31-positive endothelial cells were visible on the inner surface of the conduits and valves. Scattered smooth muscle actin-positive cells were found in the middle layer of the conduit. The percentage of CD4- and CD68-positive cells and the calcium content were highest in decellularized porcine PVCs and lowest in ovine PVCs. The percentage of the matrix that was laminin-positive in decellularized and crosslinked porcine PVCs was lower than it was in ovine PVCs. Gelatin-embedded and EDC-crosslinked porcine PVCs can be "hosted" in sheep, with good biocompatibility, growth potential, and reduced calcification.

Cytotoxin-Associated Gene A-Positive Helicobacter pylori Promotes Autophagy in Colon Cancer Cells by Inhibiting miR-125b-5p.

OBJECTIVES: To investigate the effects of cytotoxin-associated gene A- (CagA-) positive Helicobacter pylori on proliferation, invasion, autophagy, and expression of miR-125b-5p in colon cancer cells. METHODS: Colon cancer cells were cocultured with H. pylori (CagA+) to analyze the effects of H. pylori on miR-125b-5p and autophagy. Colon cancer cells infected with H. pylori (CagA+) were mimicked by transfection of CagA plasmid. The effects of CagA on the proliferation, invasion, and autophagy of colon cancer cells were analyzed. Cell counting kit-8 (CCK-8), clone formation, and Transwell assays were used to detect cell viability, proliferation, and invasion ability, respectively. Proteins and miRNAs were detected by western blotting and qPCR, respectively. RESULTS: H. pylori (CagA+) inhibited expression of miR-125b-5p and promoted autophagy in colon cancer cells. MiR-125 b-5p was underexpressed in colon cancer cells after CagA overexpression. CagA promoted colon cancer cell proliferation, invasion, and autophagy. Overexpression of miR-125b-5p inhibited the proliferation, invasion, and autophagy of colon cancer cells and reversed the effects of CagA. CONCLUSION: H. pylori (CagA+) infection may promote the development and invasion of colon cancer by inhibiting miR-125b-5p.

[Effect of equal concentration of Helicobacter pylori suspension on gastric mucosa in mice by different gavage methods].

OBJECTIVE: To investigate the effects of equal concentration of Helicobacter pylori suspension on gastric mucosal infection in mice by different gavage methods. 
 Methods: Six-week-old male C57BL/6 mice were infected by a suspension of Brucella broth containing the same amount of NCTC11637 Helicobacter pylori suspension by A, B, C, and D methods. For method A, the mice were intragastrically administered with Helicobacter pylori suspension (0.2 mL per mouse), once two day for 5 times; for method B, the mice were intragastrically administered with Helicobacter pylori (0.2 mL per mouse) once a day for 5 times; for method C, the mice were perfused with 0.4 mL per mouse of Helicobacter pylori suspension on the first day, then once a day and 0.2 mL per mouse for 3 times; for method D, the mice were administrated with 0.4 mL per mouse Helicobacter pylori suspension on the first day, 0.2 mL per mouse every other day for 3 times. For method E, the mice received equal amounts of normal saline. The mice were killed at 2, 4, and 6 weeks after gavage. The gastric mucosa was detected by rapid urease test for Helicobacter pylori infection, and gastric mucosa was taken for HE staining to observe the degree of infection.
 Results: After 2 weeks of gavage, the infection rates of the mice in A, B, C, and D group were 33.3%, 50.0%, 66.7%, and 33.3%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. The infection rates of mice after 4 weeks of gavage in the A, B, C, and D groups were 50.0%, 83.3%, 83.3%, and 66.7%, respectively. The degree of inflammation infection was as following order: C group>B group>D group>A group>E group. After 6 weeks of gavage, the infection rate in A, B, C, and D groups was 100%, while the degree of inflammation infection was as following order: C group>D group>B group>A group>E group.
 Conclusion: At the acute stage of Helicobacter pylori infection, different gavage methods show different infection rates in mice, and the degree of inflammation is different. At the chronic stage, different gavage methods display the same infection rate in mice with different degree. The gavage method that 0.4 mL Helicobacter pylori suspension on the first day, then once a day and 0.2 mL for 3 times is most conducive to Helicobacter pylori colonization in the gastric mucosa of mice. This method can induce the the most seriou inflammatory infection and is beneficial to the successful establishment of the Helicobacter pylori infection model.

Roles of NMDA and dopamine in food-foraging decision-making strategies of rats in the social setting.

BACKGROUND: In highly complex social settings, an animal's motivational drive to pursue an object depends not only on the intrinsic properties of the object, but also on whether the decision-making animal perceives an object as being the most desirable among others. Mimetic desire refers to a subject's preference for objects already possessed by another subject. To date, there are no appropriate animal models for studying whether mimetic desire is at play in guiding the decision-making process. Furthermore, the neuropharmacological bases of decision-making processes are not well understood. In this study, we used an animal model (rat) to investigate a novel food-foraging paradigm for decision-making, with or without a mimetic desire paradigm. RESULTS: Faced with the choice of foraging in a competitive environment, rats preferred foraging for the desirable object, indicating the rats' ability for decision-making. Notably, treatment with the non-competitive N-methyl-D-aspartate receptor antagonist MK-801, but not with the dopamine D1 or D2 receptor antagonists, SCH23390 and haloperidol, respectively, suppressed the food foraging preference when there was a competing resident rat in the cage. None of these three antagonists affected the food-foraging preference for palatable food. Moreover, MK-801 and SCH23390, but not haloperidol, were able to abolish the desirable environment effect on standard food-foraging activities in complex social settings. CONCLUSIONS: These results highlight the concept that mimetic desire exerts a powerful influence on food-foraging decision-making in rats and, further, illustrate the various roles of the glutamatergic and dopaminergic systems in mediating these processes.

Differential roles of hippocampal glutamatergic receptors in neuropathic anxiety-like behavior after partial sciatic nerve ligation in rats.

BACKGROUND: Neuropathic pain evoked by nerve injury is frequently accompanied by deterioration of emotional behaviors, but the underlying signaling mechanisms remain elusive. Glutamate (Glu) is the major mediator of excitatory synaptic transmission throughout the brain, and abnormal activity of the glutamatergic system has been implicated in the pathophysiology of pain and associated emotional comorbidities. In this study we used the partial sciatic nerve ligation (PSNL) model of neuropathic pain in rats to characterize the development of anxiety-like behavior, the expression of glutamatergic receptors, and the phosphorylation of extracellular signal-regulated kinase (ERK) in the hippocampus, the region that encodes memories related to emotions. RESULTS: We found that the mechanical withdrawal threshold was significantly reduced and an anxiety-like behavior was increased as determined via open field tests and elevated plus-maze tests at 28 days after injury. No significant differences were found in the ratio of sucrose preference and immobility time detected by sucrose preference tests and forced swimming tests respectively, possibly due to the timing factor. The expression of N-methyl-D-aspartate (NMDA) receptor subtypes NR1 and NR2B, but not NR2A, GluR1, or GluR2 (the main subtype of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] receptor) in the hippocampus of injured rats was significantly reduced. Moreover, PSNL resulted in decreased phosphorylation of ERK1/2 in the hippocampus. Intriguingly, treatment with D-serine (a co-agonist of NMDA receptor, 1 g/kg intraperitoneally) reduced the anxiety-like behavior but not the mechanical hypersensitivity induced by PSNL. CONCLUSIONS: PSNL can induce significant anxiety-like but not depression-like behavior, and trigger down-regulation of NMDA but not AMPA receptors in the hippocampus at 28 days after injury.