Potential Risk Factors of Disorders of Gut-Brain Interaction in Undergraduates and Postgraduates: Partially Mediated by Life Stress and Lifestyle.

INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.

[Research progress of three-dimensional bioprinting technology in auricle repair and reconstruction].

Objective: To review the research progress on the application of three-dimensional (3D) bioprinting technology in auricle repair and reconstruction. Methods: The recent domestic and international research literature on 3D printing and auricle repair and reconstruction was extensively reviewed, and the concept of 3D bioprinting technology and research progress in auricle repair and reconstruction were summarized. Results: The auricle possesses intricate anatomical structure and functionality, necessitating precise tissue reconstruction and morphological replication. Hence, 3D printing technology holds immense potential in auricle reconstruction. In contrast to conventional 3D printing technology, 3D bioprinting technology not only enables the simulation of auricular outer shape but also facilitates the precise distribution of cells within the scaffold during fabrication by incorporating cells into bioink. This approach mimics the composition and structure of natural tissues, thereby favoring the construction of biologically active auricular tissues and enhancing tissue repair outcomes. Conclusion: 3D bioprinting technology enables the reconstruction of auricular tissues, avoiding potential complications associated with traditional autologous cartilage grafting. The primary challenge in current research lies in identifying bioinks that meet both the mechanical requirements of complex tissues and biological criteria.

FOSL1 knockdown ameliorates DSS-induced inflammation and barrier damage in ulcerative colitis via MMP13 downregulation.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Fos-related antigen 1 is highly expressed in mild UC and affects the maintenance and delayed recurrence of inflammatory bowel disease. Therefore the present study aimed to investigate the role of Fos-like antigen-1 (FOSL1) in UC. Use of the JASPAR database predicted the possible interaction of FOSL1 and the MMP13 promoter. FOSL1 and MMP13 mRNA and protein expression levels in dextran sodium sulfate (DSS)-induced HT29 cells and colon tissues of a UC mice model were determined using reverse transcription-quantitative PCR and western blotting, respectively. MMP13 promoter activity was determined using the dual-luciferase reporter assay, the relationship between FOSL1 and MMP13 promoter was determined using chromatin immunoprecipitation, inflammatory factor levels were quantified using ELISA, cell monolayer permeability analysis was performed using transepithelial electrical resistance measurements and tight junction protein expression levels were determined by western blotting. After constructing a UC mice model, mice colonic injury was determined with the quantification of colon length, H&E staining and disease activity index. The results demonstrated that FOSL1 and MMP13 were upregulated in DSS-induced HT29 cells and tissues. FOSL1 was also determined to be bound to the MMP13 promoter region and was demonstrated to upregulate MMP13 expression levels. Furthermore, FOSL1 knockdown inhibited DSS-induced inflammation and barrier damage in HT29 cells via MMP13 downregulation. FOSL1 knockdown also ameliorated colonic injury, inflammation and barrier damage in the tissues of the UC mice model via MMP13 downregulation. Overall, FOSL1 knockdown was demonstrated to potentially ameliorate DSS-induced inflammatory injury and protect the intestinal barrier integrity in the UC mice model via MMP13 downregulation.

Omentin-1 attenuates inflammation and barrier damage in DSS-induced ulcerative colitis in mice by inhibiting endoplasmic reticulum stress.

Ulcerative colitis (UC) is a diffuse inflammatory disease that occurs in the mucosa of the colon and rectum. Research illustrated that omentin-1 level was significantly lower in the serum of patients with UC. This study systematically examines the emerging roles of omentin-1 in UC and its related mechanisms. Omentin-1 level in dextran sulfate sodium (DSS)-induced mice was examined by Western blot and RT-PCR. The expressions of endoplasmic reticulum (ER) stress-related proteins were detected adopting Western blot with or without the addition of ER stress inducer tunicamycin (TM) in colitis mice. Subsequently, in DSS-induced UC mice, colonic damage was determined by HE staining, body weight, colon length, and disease activity index (DAI). Inflammation and barrier damage were examined by ELISA and Western blot. Cell apoptosis in colon tissues was examined by TUNEL and Western blot. Omentin-1 expressed lowly in DSS-induced colon tissues of UC mice, and its overexpression inhibited ER stress. Additionally, overexpression of omentin-1 also inhibited DSS-induced colon damage, inflammation, barrier damage and cell apoptosis in UC mice; however, these changes were partly abolished by TM administration. In conclusion, omentin-1 attenuates DSS-induced inflammation and barrier damage in UC mice by inhibiting ER stress, suggesting omentin-1 may be a useful target for the treatment of UC.

Transcription factor paired related homeobox 1 (PRRX1) activates matrix metalloproteinases (MMP)13, which promotes the dextran sulfate sodium-induced inflammation and barrier dysfunction of NCM460 cells.

Paired related homeobox 1 (PRRX1) is a newly identified transcription factor that regulates the expression of various genes. We aimed to investigate the roles of PRRX1 and Matrix metalloproteinases (MMP)13 in dextran sulfate sodium (DSS)-induced inflammation and barrier dysfunction of NCM460 cells. PRRX1 expression in the mucosal tissues of patients with ulcerative colitis was analyzed using the GSE87466 microarray. PRRX1 and MMP13 expression was examined using Western blotting and RT-qPCR following the exposure of the NCM460 cells to DSS. The JASPAR database was used to predict the binding sites of PRRX1 to the MMP13 promoter, which was verified by luciferase reporter and chromatin immunoprecipitation assays. MMP13 expression was then detected following PRRX1 silencing or overexpression. The levels of inflammatory factors were determined using ELISA. Finally, the expression of intestinal barrier function-related proteins was evaluated using Western blotting and cellular permeability was detected by Transepithelial electrical resistance. PRRX1 was upregulated in the mucosal tissue samples of patients with UC. DSS induction upregulated PRRX1 and MMP13 expression. PRRX1 bound to the promoter of MMP13, which was further supported by the decreased expression of MMP13 observed following PRRX1 knockdown and its increased expression following PRRX1 overexpression. Furthermore, PRRX1 deletion decreased TNF-α, IL-1ß and IL-6 levels in the DSS-challenged NCM460 cells, which were subjected to MMP13 overexpression. Moreover, PRRX1 silencing upregulated ZO-1, occludin and claudin-1 expression and elevated the TEER value, whereas MMP13 overexpression attenuated these effects. Collectively, PRRX1 activates MMP13, which in turn promotes the DSS-induced inflammation and barrier dysfunction of NCM460 cells.

Silencing LncRNA-DANCR attenuates inflammation and DSS-induced endothelial injury through miR-125b-5p.

BACKGROUND: LncRNA-DANCR is involved in inflammation and acts as a major contributor to colon cancer. The effects and mechanism of LncRNA-DANCR were first investigated in a DSS-induced colitis model in vivo and vitro. MATERIAL AND METHODS: Sprague-Dawley rats were given DSS to induce the colitis model. TNF-α, IL-1ß, IL-6 levels and expression of intestinal adhesion proteins ZO-1 and MUC2 in colon tissues and DSS-induced NCM460 cells were measured using corresponding kits. A hematoxylin and eosin (H&E) staining assay was performed to evaluate colon tissue pathology conditions. Protein expression levels in DSS-induced NCM460 cells were evaluated by Western blotting, and cell apoptosis was detected using a TUNEL assay. Gene levels in DSS-induced NCM460 cells were evaluated by PCR. The StarBase online tool was used to predict the LncRNA-DANCR target. The LncRNA-DANCR target was verified using a luciferase reporter assay. RESULTS: LncRNA-DANCR was up-regulated in DSS-induced groups of rats. TNF-α, IL-1ß and IL-6 expression was significantly increased in DSS-induced groups of rats and cells. Zo-1 and MUC2 expression levels were decreased in DSS-induced groups of rats. Silencing LncRNA-DANCR reduced inflammation, cell apoptosis and up-regulated ZO-1, MUC2 and Claudin-1 in DSS-induced cells. MiR-125b-5p was the downstream LncRNA-DANCR target. All LncRNA-DANCR effects in the colitis model were reversed by the miR-125b-5p inhibitor. CONCLUSION: LncRNA-DANCR/miR-125b-5p, which may act as a regulatory axis in inflammation, apoptosis and barrier function dysregulation, can provide an essential reference for the development of new drugs in colitis treatment.

Nonsurgical Secondary Prophylaxis of Esophageal Variceal Bleeding in Cirrhotic Patients: A Systematic Review and Network Meta-analysis.

INTRODUCTION: The aim of this study was to evaluate the effectiveness of nonsurgical secondary prophylaxis interventions for esophageal varices (EV) rebleeding in cirrhotic patients using network meta-analysis. MATERIALS AND METHODS: Secondary prophylaxis of EV rebleeding in cirrhosis is searched on PubMed, Embase, and the Cochrane Library databases. The quality of literatures was extracted by 2 independent investigators according to the requirements of Cochrane Handbook for Systematic Reviews of Interventions, Version 5.0.0. Meta-analysis was performed on Review Manager 5.3 software for the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality; and STATA 15.1 software was used for network meta-analysis. RESULTS: In all, 57 randomized controlled trials were reviewed. Endoscopic band ligation (EBL)+argon plasma coagulation has not been recommended by guidelines, and it is rarely used; the number of existing studies and the sample size are small. Considering poor stability of the combined results, these studies were excluded; 55 literatures were included. In terms of reducing the incidence of rebleeding, transjugular intrahepatic portosystemic shunt (TIPS) surface under the cumulative ranking curve (SUCRA) (94.3%) was superior to EBL+endoscopic injection sclerotherapy (EIS) (84.4%), EIS+ß-blockers (77.9%), EBL (59.8%), EBL+ß-blockers+isosorbide-5-mononitrate (52.7%), EBL+ß-blockers (51.4%), EIS (34.2%), ß-blockers+isosorbide-5-mononitrate (23.7%), ß-blockers (20.8%), and placebo (0.8%). In reducing rebleeding-related mortality, TIPS SUCRA (87.2%) was more efficacious than EBL+EIS (83.5%), EIS (47.9%), EBL+ß-blockers (47.4%), ß-blockers (41.8%), EBL (34.5%), and placebo (7.6%). In reducing overall mortality, TIPS SUCRA (81.1%) was superior to EBL+EIS (68.9%), EIS+ß-blockers (59.2%), EBL+ß-blockers (55.4%), EIS (48.8%), EBL (48.7%), ß-blockers (34.2%), placebo (3.6%). CONCLUSIONS: TIPS was more effective in reducing the incidence of cirrhosis EV rebleeding, rebleeding-related mortality, and overall mortality in cirrhosis. Combined with the above results, TIPS is more likely to be recommended as a secondary prophylaxis intervention for EV in cirrhosis.

Growth differentiation factor 11 is involved in isoproterenol­induced heart failure.

The present study aimed to investigate the potential effects of growth differentiation factor 11 (GDF11) on isoproterenol (ISO)­induced heart failure (HF) and identify the underlying molecular mechanisms. A rat model of HF was induced in vivo by intraperitoneally administering ISO (5 mg/kg/day) for 7 days. After 4 weeks following establishment of the HF model, hemodynamic analysis demonstrated that ISO induced a significant increase in the left ventricular end­diastolic pressure and a decrease in the left ventricular systolic pressure and maximum contraction velocity. The plasma levels of myocardial injury markers, including lactate dehydrogenase (LDH), creatine kinase (CK), CK­muscle/brain which were determined using the corresponding assay kits and plasma brain natriuretic peptide which was detected by an ELISA kit, an important biomarker of HF, increased following ISO treatment. Furthermore, levels of GDF11 expression and protein, which were estimated using reverse transcription­quantitative polymerase chain reaction and an ELISA kit in plasma and western blotting in the heart tissue, respectively, significantly increased following ISO treatment. To demonstrate the effects of ISO on GDF11 production in cardiomyocytes, H9C2 cells (a cardiomyoblast cell line derived from embryonic rat heart tissue) were treated with ISO (50 nM) for 24 h in vitro; it was revealed that GDF11 protein and mRNA expression levels significantly increased following ISO treatment. In addition, recombinant GDF11 (rGDF11) administered to ISO­treated H9C2 cells resulted in decreased proliferation, which was detected via a CCK­8 assay, and increased LDH levels and cell apoptosis of cells, which was determined using Caspase­3 activity and Hoechst 33258 staining. Additionally, rGDF11 increased the levels of reactive oxygen species and malondialdehyde due to the upregulation of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) following rGDF11 treatment. Conversely, GDF11 knockdown reduced ISO­induced apoptosis by inhibiting oxidative stress injury. The results suggested that GDF11 production was upregulated in ISO­induced rats with HF and in ISO­treated H9C2 cells, and that rGDF11 treatment increased ISO­induced oxidative stress injury by upregulating Nox4 in H9C2 cells.

Anti-depressive effect of Shuangxinfang on rats with acute myocardial infarction: Promoting bone marrow mesenchymal stem cells mobilization and alleviating inflammatory response.

Bone marrow mesenchymal stem cells (BM-MSCs) are recruited to injured site for cardiac self-repairing in acute myocardial infarction (AMI), but the spontaneous mobilization of BM-MSCs is insufficient for self-repairing. Inflammation initiated by necrosis cardiomyocytes induced cardiac remodeling and depression. Given the anti-inflammatory effects of BM-MSCs and the inextricably relationship among inflammation, ventricular remodeling and depression following AMI, methods focused on enhancing BM-MSCs mobilization are promising. Shuangxinfang (Psycho-cardiology Formula, PCF) is a classical traditional Chinese medicine prescription. In this study, we explored its psycho-cardiology effects in rats with AMI and explore its potential mechanism. Our results showed PCF inhibited inflammation caused by injured myocardium, improved heart function and depression developed from myocardial infarction, and these might partly attribute to the higher BM-MSCs mobilization efficiency promoted by PCF.

Chaihulonggumulitang Shows Psycho-cardiology Therapeutic Effects on Acute Myocardial Infarction by Enhancing Bone Marrow Mesenchymal Stem Cells Mobilization.

Ischemic myocardium initiates the mobilization and homing of bone marrow mesenchymal stem cells (BM-MSCs) to promote myocardial regeneration after acute myocardial infarction (AMI). Inflammation caused by necrotic cardiomyocytes induce major pathological changes (cardiac remodeling and myocardial apoptosis) as well as anxiety disorder. This process may be inhibited by the differentiation and paracrine effects of BM-MSCs. However, the spontaneous mobilization of BMSCs is insufficient to prevent this effect. Given the anti-inflammatory effects of BM-MSCs, ventricular remodeling and anxiety following AMI, methods focused on enhancing BMSCs mobilization are promising. BFG is a classical traditional Chinese prescription medicine and has been proved effective in treating AMI and reducing anxiety, but the potential mechanism of its function remains unknown. In the present study, we explored the effects of Chaihulonggumulitang (BFG) on AMI and anxiety in vivo and in vitro. We also tested its effects in promoting BMSCs mobilization and alleviating inflammation. Our data showed that the classical Chinese prescription BFG promoted BM-MSCs mobilization, inhibited inflammatory response, and improved heart damage and anxiety developed from AMI. Thus, we provided an underlying mechanism of BFG function in psycho-cardiology conditions such as AMI.

Effects of Tianmagouteng particles on brain cognitive function in spontaneously hypertensive rats with hyperactivity of liver-yang: A [F-18] FDG micro-PET imaging study.

OBJECTIVE: To collect visualized proof of Tianmagouteng particles (TMGTP) in alleviating cognitive dysfunction and to explore its effects on brain activity in spontaneously hypertensive rats (SHRs) with hyperactivity of liver-yang (Gan Yang Shang Kang, GYSK). METHODS: Sixteen SHRs were randomized into treatment group and non-treatment. The SHR with GYSK was induced by gavaging aconite decoction (10mL/kg at 0.2g/mL). After the SHR models were prepared, the rats in the treatment group were administered TMGTP (10mL/kg) once a day for 14days.The rats in the non-treatment group or normal rats (control group) received an equivalent volume of saline. Morris water maze test was conducted before and after the treatment to observe cognitive function. Fluorine 18-deoxy glucose [F-18]FDG micro-PET brain imaging scans was performed after treatment. Data were analyzed with two-sample t-test (P<0. 001) using SPM2 image analysis software. RESULTS: Compared with the non-treatment group, the escape latency significantly decreased but the frequency of entrance into the target zone significantly increased in the treatment group. Consistent with the alteration of cognitive functions, TMGTP induced strong brain activity in the following sites: right dorsolateral nucleus and ventrolateral nucleus of thalamus, amygdala, left met thalamus, cerebellum leaflets, original crack, front cone crack, loop-shaped leaflets; but deactivation of right medial frontal gyrus, bilateral corpus callosum, hippocampus, and left dentate gyrus. CONCLUSION: TMGTP could alleviate cognitive dysfunction in SHRs with GYSK, which was possibly by inducing alteration of glucose metabolism in different brain regions with corresponding functions.

The difference between Asian and Western in the effect of LDL-C lowering therapy on coronary atherosclerotic plaque: a meta-analysis report.

BACKGROUND: The different effects of LDL-C levels and statins therapy on coronary atherosclerotic plaque between Western and Asian remain to be settled. METHODS: PubMed, EMBASE, and Cochrane databases were searched from Jan. 2000 to Sep. 2014 for randomized controlled or blinded end-points trials assessing the effects of LDL-C lowering therapy on regression of coronary atherosclerotic plaque (CAP) in patients with coronary heart disease by intravascular ultrasound. The significance of plaques regression was assessed by computing standardized mean difference (SMD) of the volume of CAP between the baseline and follow-up. RESULTS: Twenty trials (ten in the West and ten in Asia) were identified. For Westerns, Mean lowering LDL-C by 49.4% and/or to level 61.9 mg/dL in the group of patients with baseline mean LDL-C 123.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.156 mm(3), 95% CI -0.248 ~ -0.064, p = 0.001). LDL-C lowering by rosuvastatin (mean 40 mg daily) could significantly decrease the volumes of CAP at follow up. For Asians, Mean lowering LDL-C by 36.1% and/or to level 84.0 mg/dL with baseline mean LDL-C 134.2 mg/dL could significantly reduce the volume of CAP at follow up (SMD -0.211 mm(3), 95% CI -0.331 ~ -0.092, p = 0.001). LDL-C lowering by rosuvastatin (mean 14.1 mg daily) and atorvastatin (mean 18.9 mg daily) could significantly decrease the volumes of CAP at follow up. CONCLUSIONS: There was a different effect of LDL-C lowering on CAP between Westerns and Asians. For regressing CAP, Asians need lower dosage of statins or lower intensity LDL-C lowering therapy than Westerns.

Epidemiology characteristics of constipation for general population, pediatric population, and elderly population in china.

Objective. To acquire more data about the epidemiologic characteristics of constipation in different kinds of populations in China. Methods. Using "constipation" and "China" as search terms; relevant papers were searched from January 1995 to April 2014. Data on prevalence, gender, diagnostic criteria, geographical area, educational class, age, race, and physician visit results were extracted and analyzed. Results. 36 trials were included. Prevalence rates of constipation in elderly population (18.1%) and pediatric population (18.8%) were significantly higher than that in general population (8.2%). Prevalence of constipation defined by non-Rome criteria was higher than that by Rome criteria in general population. Prevalence rates of constipation were different for different geographical area. People with less education were predisposed to constipation. In pediatric population, prevalence of constipation was the lowest in children aged 2-6 years. Prevalence of constipation in ethnic minorities was higher than that in Han people. People with constipation were predisposed to FD, haemorrhoid, and GERD. Only 22.2% patients seek medical advice in general population. Conclusions. In China, prevalence of constipation was lower compared with most of other countries. The factors including female gender, diagnostic criteria, geographical area, age, educational class, and race seemed to have major effects on prevalence of constipation.

[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].

OBJECTIVE: To observe the effect of electrocupuncture (EA) intervention at different time-points of post-modeling on behavior and hippocampal monoamine neurotransmitter noradrenalin (NE), dopamine (DA) and 5-hydroxytrypamine (5-HT) contents in vascular dementia (VD) mice, so as to study its mechanism underlying improvement of VD. METHODS: A total of 60 Kunming mice were randomized into sham-operation control (n = 20), VD model (n = 20), EA-day (D)-1 (EA treatment was given from the 1st day on after modeling, n = 10), EA-D-3 (EA was given from the 3rd day on after modeling, n = 10) groups. VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. EA (2 Hz/80 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14),"Zusanli" (ST 36) and "Geshu"(BL 17) for 10 min, once daily for 15 days. Hippocampal NE, DA and 5-HT contents were assayed by fluorospectrophotometry. The mouse's learning-memory ability was assessed by step-down tests. RESULTS: In comparison with the sham-operation control group, the learning-memory ability (marked increase of reaction time and error times, decrease of step-down latency) was apparently lowered in the model group (P < 0.01). The hippocampal NE, DA and 5-HT contents were significantly lower in the model group than in the sham-operation group (P < 0.01). Compared with the model group, the mice's learning-memory ability (marked decrease of reaction time and error times, increase of step-down latency) was significantly increased in EA intervention groups (P < 0.01), and hippocampal NE, DA and 5-HT levels were significantly increased (P < 0.01), and the effect of EA-D-3 group was obviously better than that of the EA-D-1 group (P < 0.05, P < 0.01). CONCLUSION: EA can improve the VD mice's learning-memory ability, which is closely related to its effects in up-regulating hippocampal NE, DA and 5-HT contents, and the effect of later EA intervention after modeling is better.

Esophageal Motility in the Supine and Upright Positions for Liquid and Solid Swallows Through High-resolution Manometry.

BACKGROUND/AIMS: Most recent studies using high-resolution manometry were based on supine liquid swallows. This study was to evaluate the differences in esophageal motility for liquid and solid swallows in the upright and supine positions, and to determine the percentages of motility abnormalities in different states. METHODS: Twenty-four asymptomatic volunteers and 26 patients with gastroesophageal reflux disease underwent high-resolution manometry using a 36-channel manometry catheter. The peristalses of 10 water and 10 steamed bread swallows were recorded in both supine and upright positions. Integrated relaxation pressure, contractile front velocity, distal latency (DL) and the distal contractile integral (DCI) were investigated and comparisons between postures and boluses were analyzed. Abnormal peristalsis of patients was assessed applying the corresponding normative values. RESULTS: In total, 829 swallows from healthy volunteers and 959 swallows from patients were included. (1) The upright position provided lower integrated relaxation pressure, shorter DL and weaker DCI than the supine position. (2) In the comparison of liquid swallows, the mean for contractile front velocity was obviously reduced while DL and DCI were increased in solid swallows. (3) The supine position detected more hypotensive peristalsis than the upright position. The upright position provided more rapid and premature contraction than the supine position but there was no statistically significant difference. CONCLUSIONS: Supine solid swallows occur with more hypotensive peristalsis. Analysis should be based on normative values from the corresponding posture and bolus.