Establishment of a modified Kyoto classification scoring model and its significance in the diagnosis of Helicobacter pylori current infection.

BACKGROUND AND AIMS: We aimed to establish a modified model of the Kyoto classification score and verify its accuracy for predicting Helicobacter pylori (HP) infection during endoscopy. METHODS: Patients who underwent gastroscopy from June 2020 to March 2021 were included in this study. Atrophy, intestinal metaplasia, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, xanthoma, map-like redness, fundic gland polyp, and regular arrangement of collecting venules (RAC) were recorded according to the Kyoto classification of gastritis. The HP infection status of participants was determined by a 13C breath test, anti-HP antibody, and histopathologic hematoxylin and eosin staining. The modified Kyoto classification scoring model was established based on univariate analysis and logistic regression analysis. The modified scoring model was used to judge the status of HP infection in patients undergoing gastroscopy from July to September 2021 and to evaluate the accuracy of the prediction. RESULTS: Of 667 participants in the derivation dataset, 326 cases had HP infection and 341 cases did not. Atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, and spotty redness were associated with HP current infection. Thus, a new scoring model, termed the modified Kyoto classification scoring model, was constructed that included atrophy, hypertrophy of the gastric fold, nodularity, diffuse redness, sticky mucus, spotty redness, fundic gland polyp, and RAC as indicators. To test the model, 808 subjects, including 251 HP-positive patients, comprised the validation dataset. CONCLUSIONS: The modified Kyoto classification scoring model improved the accuracy of endoscopic determination of HP current infection and has clinical application potential in the Chinese population.

Discovery and SAR of 4-aminopyrrolidine-2-carboxylic acid correctors of CFTR for the treatment of cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive disease resulting from mutations on both copies of the CFTR gene. Phenylalanine deletion at position 508 of the CFTR protein (F508del-CFTR) is the most frequent mutation in CF patients. Currently, the most effective treatments of CF use a dual or triple combination of CFTR correctors and potentiators. In triple therapy, two correctors (C1 and C2) and a potentiator are employed. Herein, we describe the identification and exploration of the SAR of a series of 4-aminopyrrolidine-2-carboxylic acid C2 correctors of CFTR to be used in conjunction with our existing C1 corrector series for the treatment of CF.

Transcutaneous Electrical Acustimulation Improved the Quality of Life in Patients With Diarrhea-Irritable Bowel Syndrome.

BACKGROUND AND AIM: Patients with diarrhea-dominant irritable bowel syndrome (IBS-D) experience abdominal pain and reduced quality of life and need effective treatments. This study aimed to evaluate whether transcutaneous electrical acustimulation (TEA) at two acupuncture points, LI4 and ST36, could improve pain and quality of life of patients with IBS-D. MATERIALS AND METHODS: A total of 42 patients with IBS-D who met the Rome IV criteria were randomly divided into two groups: TEA and sham-TEA. TEA was performed through acupoints Hegu (LI4) and Zusanli (ST36) for one hour twice daily for one month, using previously established parameters; sham-TEA was delivered in the same way as TEA but without actual electrical current stimulation. RESULTS: The sham-TEA group showed a significantly higher rate of drop-out than the TEA group (29% vs 0%, p = 0.021). TEA, but not sham-TEA, significantly improved quality of life (before: 78.55 ± 9.62, after: 85.97 ± 9.49, p < 0.0001). Both TEA and sham-TEA reduced abdominal pain; however, TEA was more potent than sham-TEA (p = 0.014). The IBS symptom severity scale score was reduced by both TEA and sham-TEA. Autonomic functions assessed by plasma norepinephrine and pancreatic polypeptide were not altered with TEA, nor was interleukin 10 or interleukin 6. CONCLUSIONS: TEA at LI4 and ST36 improves abdominal pain and quality of life of patients with IBS-D, probably mediated by mechanisms other than autonomic function or inflammatory cytokines.

Biological Characterization of F508delCFTR Protein Processing by the CFTR Corrector ABBV-2222/GLPG2222.

Cystic fibrosis (CF) is the most common monogenic autosomal recessive disease in Caucasians caused by pathogenic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (CFTR). Significant small molecule therapeutic advances over the past two decades have been made to target the defective CFTR protein and enhance its function. To address the most prevalent defect of the defective CFTR protein (i.e., F508del mutation) in CF, two biomolecular activities are required, namely, correctors to increase the amount of properly folded F508delCFTR levels at the cell surface and potentiators to allow the effective opening, i.e., function of the F508delCFTR channel. Combined, these activities enhance chloride ion transport yielding improved hydration of the lung surface and subsequent restoration of mucociliary clearance. To enhance clinical benefits to CF patients, a complementary triple combination therapy consisting of two corrector molecules, type 1 (C1) and type 2, with additive mechanisms along with a potentiator are being investigated in the clinic for maximum restoration of mutated CFTR function. We report the identification and in vitro biologic characterization of ABBV-2222/GLPG2222 (4-[(2R,4R)-4-({[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-(difluoromethoxy)-3,4-dihydro-2H-chromen-2-yl]benzoic acid),-a novel, potent, and orally bioavailable C1 corrector developed by AbbVie-Galapagos and currently in clinical trials-which exhibits substantial improvements over the existing C1 correctors. This includes improvements in potency and drug-drug interaction (DDI) compared with 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid (VX-809, Lumacaftor) and improvements in potency and efficacy compared with 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-[1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(1-hydroxy-2-methylpropan-2-yl)indol-5-yl]cyclopropane-1-carboxamide (VX-661, Tezacaftor). ABBV-2222/GLPG2222 exhibits potent in vitro functional activity in primary patient cells harboring F508del/F508del CFTR with an EC50 value <10 nM. SIGNIFICANCE STATEMENT: To address the most prevalent defect of the defective CFTR protein (i.e., F508del mutation) in cystic fibrosis, AbbVie-Galapagos has developed ABBV-2222/GLPG2222, a novel, potent, and orally bioavailable C1 corrector of this protein. ABBV-2222/GLPG2222, which is currently in clinical trials, exhibits potent in vitro functional activity in primary patient cells harboring F508del/F508del CFTR and substantial improvements over the existing C1 correctors.

Internet and WeChat used by patients with Crohn's disease in China: a multi-center questionnaire survey.

BACKGROUND: Currently, WeChat is widely used in disease education for patients with Crohn's disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. METHODS: In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. RESULTS: Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn's and Colitis Foundation (CCCF) (73%), "IBD Academic Officer" (21%) and "IBD in love" (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients' expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). CONCLUSIONS: WeChat has become a major source of information for IBD education in China, but the content of WeChat didn't fully meet patients' expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients' demands.

The correlation between histological gastritis staging- 'OLGA/OLGIM' and serum pepsinogen test in assessment of gastric atrophy/intestinal metaplasia in China.

BACKGROUND: Serum pepsinogen (PG) test, as an indicator of gastric mucosal atrophy, reflects the functional and morphologic status of gastric mucosal and it is suggested to serve as a useful predictive marker for patients with gastric cancer (GC). The available classifications of gastritis, known as the Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastritis Intestinal Metaplasia (OLGIM), integrating the severity and topography of atrophy/intestinal metaplasia (IM), have been gradually accepted and used in screening for GC in recent years. GOALS: To assess whether serum pepsinogen test, including PGI, PGII, PGI/PGII and gastrin-17 (G-17) could reflect the extent and topography of gastric mucosal atrophy/IM. Furthermore, to discuss the relationship between OLGA/OLGIM staging system and serum pepsinogen test in assessment of gastric atrophy/IM. METHODS: The OLGA/OLGIM ranks the gastric staging according to both the topography and the severity of gastric atrophy/IM. A retrospective study was conducted with 331 patients who underwent endoscopy with consecutive biopsy sampling and reassessed according to OLGA/OLGIM staging system. Serum pepsinogen test, including PGI, PGII, PGI/PGII and G-17, as well as serological Helicobacter pylori (Hp) antibody were also measured. Results were presented as gastritis stage, serum pepsinogen level and Hp status. Baseline characteristics were compared using analysis of variance (ANOVA) test for continuous data and Pearson's χ2 test for categorical data. A logistic regression model was used for the correlation analysis between OLGA/OLGIM and serological pepsinogen test. RESULTS: A total of 177 non-atrophic gastritis and 154 atrophic gastritis were analyzed, among which 40 were antrum atrophy, 32 were corpus atrophy and 82 were pan-atrophy. All patients were assessed applying the OLGA/OLGIM criteria with a mean age of 54.7 ± 10.8 years. Patients among OLGA/OLGIM Stage III-IV were presented with a lower level of serum PGI and PGI/PGII (p < .05), especially for Stage IV (p = .01). For both Hp-positive patients and Hp-negative patients according to OLGA system, PGI/PGII level correlated inversely with the rising stage (p = .022; p = .028). As for OLGIM system, similar difference can be seen in PGI/PGII level in either Hp-positive patients, or Hp-negative patients (p = .036; p = .013). In addition, the percentage of G-17 <1 pmol/L combined with PG-negative in antrum atrophy group was much higher than that of non-atrophy group and corpus atrophy group (25 versus 15.8 versus 6.3%) (p = .029). The proportion of G-17 > 15 pmol/L combined with PG-positive was apparently higher in corpus atrophy group, compared with other two groups (25 versus 11.3 versus 8.1%) (p = .023). Logistic regression modeling showed there exist significant connections between OLGA/OLGIM stages and serum pepsinogen test in patient stratification for gastric mucosal atrophy assessment (p < .001, p < .001). CONCLUSIONS: Serum pepsinogen test has a strong correlation with OLGA/OLGIM gastritis stage and could provide important information in assessment of atrophy/intestinal metaplasia.

The distribution of active ß-glucosidase-producing microbial communities in composting.

The composting ecosystem is a suitable source for the discovery of novel microorganisms and secondary metabolites. Cellulose degradation is an important part of the global carbon cycle, and ß-glucosidases complete the final step of cellulose hydrolysis by converting cellobiose to glucose. This work analyzes the succession of ß-glucosidase-producing microbial communities that persist throughout cattle manure - rice straw composting, and evaluates their metabolic activities and community advantage during the various phases of composting. Fungal and bacterial ß-glucosidase genes belonging to glycoside hydrolase families 1 and 3 (GH1 and GH3) amplified from DNA were classified and gene abundance levels were analyzed. The major reservoirs of ß-glucosidase genes were the fungal phylum Ascomycota and the bacterial phyla Firmicutes, Actinobacteria, Proteobacteria, and Deinococcus-Thermus. This indicates that a diverse microbial community utilizes cellobiose. The succession of dominant bacteria was also detected during composting. Firmicutes was the dominant bacteria in the thermophilic phase of composting; there was a shift to Actinomycetes in the maturing stage. Proteobacteria accounted for the highest proportions during the heating and thermophilic phases of composting. By contrast, the fungal phylum Ascomycota was a minor microbial community constituent in thermophilic phase of composting. Combined with the analysis of the temperature, cellulose degradation rate and the carboxymethyl cellulase and ß-glucosidase activities showed that the bacterial GH1 family ß-glucosidase genes make greater contribution in cellulose degradation at the later thermophilic stage of composting. In summary, even GH1 bacteria families ß-glucosidase genes showing low abundance in DNA may be functionally important in the later thermophilic phase of composting. The results indicate that a complex community of bacteria and fungi expresses ß-glucosidases in compost. Several ß-glucosidase-producing bacteria and fungi identified in this study may represent potential indicators of composting in cellulose degradation.

Biological characteristics of molecular subtypes of ulcerative colitis characterized by ferroptosis and neutrophil infiltration.

Clinical ulcerative colitis (UC) is a heterogeneous condition. Moreover, medical interventions are nonspecific, and thus, treatment responses are inconsistent. The aim of this study was to explore the molecular subtypes and biological characteristics of UC based on ferroptosis and neutrophil gene sets. Multiple intestinal mucosa gene expression profiles of UC patients in the Gene Expression Omnibus (GEO) database were downloaded. Unsupervised clustering methods were used to identify potential molecular subtypes based on ferroptosis and neutrophil gene sets. Multiple immune infiltration algorithms were used to evaluate the biological characteristics of the molecular subtypes. Machine learning identifies hub genes for molecular subtypes and analyses their diagnostic efficacy for UC and predictive performance for drug therapy. The relevant conclusions were verified by clinical samples and animal experiments. Four molecular subtypes were identified according to the ferroptosis and neutrophil gene sets: neutrophil, ferroptosis, mixed and quiescent. The subtypes have different biological characteristics and immune infiltration levels. Multiple machine learning methods jointly identified four hub genes (FTH1, AQP9, STEAP3 and STEAP4). Receiver operating characteristic (ROC) curve analysis revealed that the four hub genes could be used as diagnostic markers for UC. The clinical response profile data of infliximab treatment patients showed that AQP9 and STEPA4 were reliable predictors of infliximab treatment response. In human samples the AQP9 and STEAP4 protein were shown to be increased in UC intestinal samples. In animal experiments, the ferroptosis and neutrophil phenotype were confirmed. Dual analysis of ferroptosis and neutrophil gene expression revealed four subgroups of UC patients. The molecular subtype-associated hub genes can be used as diagnostic markers for UC and predict infliximab treatment response.

The potential mechanism of Bletilla striata in the treatment of ulcerative colitis determined through network pharmacology, molecular docking, and in vivo experimental verification.

Ulcerative colitis (UC) is a chronic nonspecific intestinal inflammatory disease, which belongs to a subtype of inflammatory bowel disease, but still lacks effective drug treatment. Bletilla striata (B. striata) is one of the most valuable traditional Chinese medicines (TCMs) in China, can stop bleeding, can promote wound healing, and can regulate immunity. Based on data mining, B. striata was found to be a common TCM for the treatment of UC, but the exact therapeutic mechanism is not yet known. This study aims to explore the potential mechanisms of B. striata in the treatment of UC using network pharmacology, molecular docking techniques, and in vivo experimental research. We extracted the active ingredients and targets of B. striata from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. We retrieved and screened the corresponding UC-related target genes in multiple databases. Subsequently, we constructed an herb-ingredient-target-disease-network, generated a protein-protein interaction network, performed Gene Ontology enrichment analysis, and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to identify potential treatment mechanisms. After screening for key active ingredients and target genes, we performed molecular docking using AutoDock Vina software to select the best binding target for molecular docking and validate the binding activity. The UC model was established in mice, and the results of network pharmacology and molecular docking were verified by in vivo experiments. In all, 5 compounds were obtained from the TCMSP database, and 74 UC-related pathogenic genes were obtained from GeneCards, DisGeNET, OMIM, TTD, and DrugBank. After KEGG enrichment analysis, pathways in cancer, the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway, and metabolic pathways were identified as the top three signalling pathways associated with UC treatment. The results of molecular docking showed that the active components of B. striata have good binding activities to the pivotal targets epidermal growth factor receptor (EGFR) and PIK3CA. In a dextran sulphate sodium-induced colitis model, we found that B. striata can alleviate the symptoms of UC, decrease the secretion of the inflammatory cytokines interleukin-6 and tumour necrosis factor-α, and downregulate the expression levels of EGFR, PIK3CA, and p-AKT. In conclusion, the treatment of UC with B. striata may alleviate the inflammatory response of the colon, and B. striata mainly inhibits the EGFR/PI3K/AKT signalling pathways.

Robust negative longitudinal magnetoresistance and spin-orbit torque in sputtered Pt3Sn and Pt3SnxFe1-x topological semimetal.

Contrary to topological insulators, topological semimetals possess a nontrivial chiral anomaly that leads to negative magnetoresistance and are hosts to both conductive bulk states and topological surface states with intriguing transport properties for spintronics. Here, we fabricate highly-ordered metallic Pt3Sn and Pt3SnxFe1-x thin films via sputtering technology. Systematic angular dependence (both in-plane and out-of-plane) study of magnetoresistance presents surprisingly robust quadratic and linear negative longitudinal magnetoresistance features for Pt3Sn and Pt3SnxFe1-x, respectively. We attribute the anomalous negative longitudinal magnetoresistance to the type-II Dirac semimetal phase (pristine Pt3Sn) and/or the formation of tunable Weyl semimetal phases through symmetry breaking processes, such as magnetic-atom doping, as confirmed by first-principles calculations. Furthermore, Pt3Sn and Pt3SnxFe1-x show the promising performance for facilitating the development of advanced spin-orbit torque devices. These results extend our understanding of chiral anomaly of topological semimetals and can pave the way for exploring novel topological materials for spintronic devices.

Room Temperature Spin-to-Charge Conversion in Amorphous Topological Insulating Gd-Alloyed BixSe1-x/CoFeB Bilayers.

Disordered topological insulator (TI) films have gained intense interest by benefiting from both the TI's exotic transport properties and the advantage of mass production by sputtering. Here, we report on the clear evidence of spin-charge conversion (SCC) in amorphous Gd-alloyed BixSe1-x (BSG)/CoFeB bilayers fabricated by sputtering, which could be related to the amorphous TI surface states. Two methods have been employed to study SCC in BSG (tBSG = 6-16 nm)/CoFeB(5 nm) bilayers with different BSG thicknesses. First, spin pumping is used to generate a spin current in CoFeB and detect SCC by the inverse Edelstein effect (IEE). The maximum SCC efficiency (SCE) is measured to be as large as 0.035 nm (IEE length λIEE) in a 6 nm thick BSG sample, which shows a strong decay when tBSG increases due to the increase of BSG surface roughness. The second method is THz time-domain spectroscopy, which reveals a small tBSG dependence of SCE, validating the occurrence of a pure interface state-related SCC. Furthermore, our angle-resolved photoemission spectroscopy data show dispersive two-dimensional surface states that cross the bulk gap until the Fermi level, strengthening the possibility of SCC due to the amorphous TI states. Our studies provide a new experimental direction toward the search for topological systems in amorphous solids.

Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB2 receptor agonists for pain management.

SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.

[Treatment of functional dyspepsia by Chinese medical syndrome typing: a randomized control research].

OBJECTIVE: To assess the short- and long-term efficacy and safety of treating functional dyspepsia (FD) by Chinese medical syndrome typing (CMST). METHODS: A randomized, positive-drug parallel controlled study was conducted. Recruited were 170 FD patients who were randomly assigned to the test group (13 cases, treated by Chinese herbs) and the control group (34 cases, treated by Western medicine) in the ratio of 4:1. Different recipes were administered to patients in the test group according to CMST at the 1st, 2nd, and 4th week, respectively, while those in the control group took Domperidone or Esomeprazole Magnesium Enteric-coated Tablet according to Roma III Criteria. The therapeutic efficacy was observed at the 1st, 2nd, and 4th week of the treatment, including (1) clinical symptom score; (2) the score of SF-36 quality of life scale; (3) safety (4) compliance; (5) satisfaction; (6) the relapse rate; (7) cost-effectiveness ratio (C/E). The follow-up were performed at the 1st, 3rd, and 6th month. RESULTS: Sixteen patients fell off in the test group and 4 fell off i the control group, and the expulsion rate being 11.76% in the two groups, showing no statistical difference ( P > 0.05). The clinical symptom scores in the test group decreased from 5.62 +/- 2.30 before treatment to 1.41 +/- 1.22 after 4-week treatment, showing statistical difference (P < 0.01), but with no statistical difference when compared with the control group at the same time point (P>0.05). The healing rate and the total effective rate at week 4 were 38.24% and 86.76% respectively in the test group, and they were 60.00% and 65.00% at 6-month withdrawal. They were 41.18%, 79.41%, 46.67%, and 50.00%, respectively, in the control group. There was no statistical difference between the two groups (P>0.05). The scores of physical component-summary (PCS) and mental component-summary (MCS) both increased after 4-week treatment in the two groups, showing no statistical difference when compared with before treatment (P>0.05). There was statistical difference in the scores of PCS and MCS between at 6-month withdrawal and before treatment (P<0.05), but there was no statistical difference between the two groups (P>0.05). No obvious adverse reaction occurred in the two groups. The compliance and satisfaction after 4-week treatment were 95.59% and 91.91% in the test group, and 94.12% and 91.18% in the control group, showing no statistical difference between the two groups (P>0.05). The relapse rate in the test group was 10.29%, 19.12%, and 29.41%, respectively, after 1, 3, 6-month withdrawal, lower than that of the control group (17.65%, 23.53%, and 35.29%, respectively) at the same time point, but with no statistical difference. The C/E ratio of the test group/the control group was 15.59: 16. 53 at 4-week treatment and 22.27:28.28 after 6-month withdrawal respectively. The further analysis of incremental cost/incremental effectiveness showed that the ratio in the long-term decreased from 5.44 to 2.35 in the test group. CONCLUSIONS: The 4-week treatment of CMST had definite short- and long-term efficacy on FD patients, and improved their quality of life. It had better safety, compliance, and satisfaction. It was dominant in lower relapse rate and the cost/effectiveness. Therefore, it was worth spreading.

[Effects of zhizhu tongbian decoction on the colon ink propelling rate, GDNF, and NOS mRNA expression in rats with slow transit constipation].

OBJECTIVE: To observe the effects of Zhizhu Tongbian Decoction (ZTD) on the enteric nervous system, mRNA expressions of glial cell line derived neurotrophic factor (GDNF) and nitric oxide synthase (NOS) in the slow transit constipation (STC) rats. METHODS: Thirty STC rat model was established by gastric irrigation of rhubarb. After the model building, they were randomly divided into three groups, i. e., the model group, the high dose ZTD group, and the low dose ZTD group, 10 in each. Another 10 rats were selected as the blank control group. Rats in the high dose ZTD group and the low dose ZTD group were administered with ZTD (at the daily dose of crude drug 4.8 g/kg and 2.4 g/kg respectively) by gastrogavage. Normal saline was given to rats in the blank control group and the model group. The ink propelling rate was determined using ink propelling test. Meantime, mRNA expressions of GDNF and NOS in the rat colon were measured using reverse transcriptional polymerase chain reaction (RT-PCR). RESULTS: Compared with the blank control group, the ink propelling rate and GDNF mRNA expression decreased, and NOS mRNA increased in the model group, showing statistical difference (P<0.01, P<0.05). Compared with the model group, the ink propelling rate increased in the high and low dose ZTD groups (P<0.01, P<0.05). The mRNA expressions of GDNF increased and the mRNA expressions of NOS decreased in the high dose ZTD group with statistical difference (P<0.01, P<0.05). But there was no difference in any index between the high and low dose ZTD groups. CONCLUSION: High dose ZTD could obviously improve the intestinal transmission function possibly through up-regulating the mRNA expressions of GDNF and down-regulating the mRNA expressions of NOS in STC rats.

CD8-positive indolent T-Cell lymphoproliferative disorder of the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract (ITLPD-GI), a primary tumor forming in the gastrointestinal (GI) tract, represents a rarely diagnosed clonal T-cell disease with a protracted clinical course. CASE SUMMARY: This report presented a 45-year-old male patient with a 6-year history of anal fistula and a more than 10-year history of recurrent diarrhea who was not correctly diagnosed until the occurrence of complications such as intestinal perforation. Postsurgical histopathological analysis, combined with hematoxylin-eosin staining, immunohistochemistry and TCRß/γ clonal gene rearrangement test, confirmed the diagnosis of CD8+ ITLPD-GI. CONCLUSION: Individuals with this scarce lymphoma frequently show non-specific symptoms that are hard to recognize. So far, indolent CD8+ ITLPD-GI has not been comprehensively examined. The current mini-review focused on evaluating indolent CD8+ ITLPD-GI cases based on existing literature and discussing future directions for improved differential diagnosis, detection of genetic and epigenetic alterations, and therapeutic target identification.

Neurophysiological Effects of the Anterior Cingulate Cortex on the Exacerbation of Crohn's Disease: A Combined fMRI-MRS Study.

Background: Crohn's disease (CD) is characterized by repetitive phases of remission and exacerbation, the quality of life of patients with CD is strongly influenced by disease activity, as patients in the active phase experience significantly worse symptoms. To investigate the underlying mechanism of how the course of CD is exacerbated based on the bi-directionality of the brain-gut axis (BGA), we conducted a multi-modality neuroimaging study that combined resting-state functional magnetic resonance imaging (rs-fMRI) with proton magnetic resonance spectroscopy (MRS) to detect abnormalities in the anterior cingulate cortex (ACC). Materials and Methods: Clinical scales including Visual Analog Scale (VAS) and Hospital Anxiety and Depression Scale (HADS) were used to evaluate the degree of abdominal pain and mood state of participants. We made a comparison between CD patients in the active phase, the remission phase and healthy controls (HCs), not only employed the innovative wavelet-transform to analyze the amplitude of low frequency fluctuation (ALFF) but also compared the sensitivity of wavelet-transform and the traditional fast Fourier transform (FFT). Brain metabolites such as glutamate (Glu), myo-inositol (mIns) and gamma-aminobutyric acid (GABA) were also detected. Then correlation analysis was made to see whether changes in the ACC correlated with CD's clinical symptoms. Results: CD patients in the active phase showed higher VAS scores (p = 0.025), the scores of anxiety and depression were also higher (all p < 0.05). Wavelet-transform is slightly more sensitive in the current research. Patients in the active phase exhibited higher ALFF in the left ACC and the left superior frontal gyrus, medial (SFGmed). Patients in the active phase showed increased Glu levels in the ACC than patients in the remission phase or HCs (p = 0.039 and 0.034 respectively) and lower levels of mIns than HCs (p = 0.036). There was a positive correlation between mWavelet-ALFF values of the ACC and HADS-depression scores in CD patients (r = 0.462, p = 0.006). Besides, concentrations of Glu positively correlated with mWavelet-ALFF in the ACC in all participants (r = 0.367, p = 0.006). Conclusion: Abnormal spontaneous activity and metabolic levels in the ACC were detected in CD patients in the active phase along with severer abdominal pain and worse mood state, these may contribute to the exacerbation of CD. Therefore, the ACC might be a potential neural alternative for managing the exacerbation of CD.

Infliximab trough level combined with inflammatory biomarkers predict long-term endoscopic outcomes in Crohn's disease under infliximab therapy.

BACKGROUND: Infliximab trough level (ITL) severely affects therapeutic outcomes of Crohn's disease (CD) patients under infliximab (IFX). Recently, frontier research has focused on identifying ITL based on different therapeutic targets. Although previous studies have elaborated clinical value of ITL monitoring on short-term outcomes in CD patients during therapy, studies contraposing the predictive value of ITL on long-term endoscopic outcomes in CD patients are still scarce domestically and overseas. AIM: To explore the predictive value of ITL in combination with inflammatory biomarkers on long-term endoscopic outcomes in CD with clinical remission during IFX maintenance therapy. METHODS: CD patients with endoscopic remission under long-term IFX maintenance therapy in the First Affiliated Hospital of Zhejiang Chinese Medicine University from January 2012 to December 2020 were collected. ITL and inflammatory biomarkers were continuously monitored during the therapy. The Step I study was conducted from weeks 14 to 54 of IFX treatment. The Step II study was conducted from weeks 54 to 108 of IFX treatment. Endoscopic outcomes were defined as endoscopic activity (Crohn's disease endoscopic index of severity score > 2 points or Rutgeerts score > i1) and endoscopic remission (Crohn's disease endoscopic index of severity score ≤ 2 points or Rutgeerts ≤ i1). Endoscopic relapse free survival was defined as endoscopic remission at the beginning of the study stage and maintaining endoscopic remission during the study stage. RESULTS: At week 14, low ITL [odds ratio (OR) = 0.666, 95% confidence interval (CI): 0.514-0.862, P < 0.01] and high fecal calprotectin (FCP) level (OR = 1.002, 95%CI: 1.001-1.004, P < 0.01) increased the risk of endoscopic activity at week 54. At week 54, low ITL (OR = 0.466, 95%CI: 0.247-0.877, P < 0.01) and high C-reactive protein (CRP) level (OR = 1.590, 95%CI: 1.007-2.510, P < 0.01) increased the risk of endoscopic activity at week 108. At week 14, ITL ≤ 5.60 µg/mL [area under the curve (AUC) = 0.83, 95%CI: 0.73-0.90, P < 0.001] and FCP > 238 µg/g (AUC = 0.82, 95%CI: 0.72-0.89, P < 0.001) moderately predicted endoscopic activity at week 54. ITL ≤ 5.60 µg/mL in combination with FCP > 238 µg/g indicated 82.0% possibility of endoscopic activity. At week 54, ITL ≤ 2.10 µg/mL (AUC = 0.85, 95%CI: 0.72-0.93, P < 0.001) and CRP > 3.00 mg/L (AUC = 0.73, 95%CI: 0.60-0.84, P = 0.012) moderately predicted moderate endoscopic activity at week 108. ITL ≤ 2.10 µg/mL in combination with CRP > 3.00 mg/L indicated 100.0% possibility of endoscopic activity. From weeks 14 to 54 of IFX treatment, patients with ITL > 5.60 µg/mL had higher rate of endoscopic relapse free survival than those with ITL ≤ 5.60 µg/mL (95.83% vs 46.67%). From weeks 54 to 108 of IFX treatment, patients with ITL > 2.10 µg/mL had higher rate of endoscopic survival free relapsed rate than those with ITL ≤ 2.10 µg/mL (92.68% vs 30.77%). CONCLUSION: Combination of ITL, CRP, and FCP contribute to long-term endoscopic prognosis monitoring. During IFX maintenance treatment, low ITL, high CRP level, and high FCP level were independent risk factors of CD patients with clinical remission in adverse endoscopy outcomes within 1-year follow-up.

Efficacy and safety of vibrating capsule for functional constipation (VICONS): A randomised, double-blind, placebo-controlled, multicenter trial.

Background: Functional constipation (FC) is an intractable disease that carries large financial burden as well as emotional and physical stress. We aimed to assess the efficacy and safety of the newly developed smartphone-controlled vibrating capsule (VC) in patients with FC. Methods: From December 2018 to February 2020, we did a multicenter, blinded, placebo-controlled randomised trial in six top general hospitals in China focusing on patients aged 18 to 80 with FC. Patients were randomly assigned in a 1:1 ratio to receive VCs or placebo treatment for six weeks (two capsules per week) after a two-week baseline period. The primary outcome was the responder rate, defined as the proportion of patients with an increase of at least one complete spontaneous bowel movement (CSBM) per week during treatment compared to baseline in the full analysis set. This trial is registered with ClinicalTrials.gov, number NCT04671264, and is completed. Findings: 107 patients aged from 18 to 74 were randomly assigned to receive VC (n = 53) or placebo treatment (n = 54). The responder rate in the VC group was significantly higher than that in the placebo group (64·2% vs. 35·8%; difference, 27·7% [95% CI, 10·4-45·1]; P = 0·005). More patients in the VC group reported weekly CSBMs ≥ 1 for at least four weeks during treatment (difference, 22·7% [95% CI, 8-46]; P = 0·022) and follow-up period (difference, 17.3% [95% CI, 0-35]; P = 0·048). The mean Patient Assessment of Constipation-Symptoms score and Patient Assessment of Constipation-Quality of Life score differed significantly from the baseline in both groups (all P < 0·0001). The most common adverse event associated with VC was abdominal discomfort (3·7%). Interpretation: VCs can promote defecation, as well as ameliorating symptoms and improving the quality of life in patients with FC with sustained efficacy. VC appears to be a potential alternative physical treatment for FC with the exact mechanism and parameters warranting further investigation. Funding: The study was supported by "One hundred leading scientists for 21st century" of Health Department of Shanghai Municipal Government (to ZL, No.2017BR005).

[The effect of exogenous glial cell line-derived neurotrophic factor on expression of gastric and colonic Akt, MAPK in slow transit constipation rats].

OBJECTIVE: To study the expression of Akt and MAPK in the stomach and colon of slow transit constipation (STC) in rats, as well as the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) on it. METHODS: Forty-four SD rats were divided into control group and model group randomly. The STC model group was established by gastric irrigation of rhubarb for 3.5 months. The control group was received normal saline. After model building, each group was equally divided into 2 subgroup randomly, administrated with exogenous GDNF and normal saline by vein injection for one week respectively. The expression of Akt and MAPK in stomach and colon was detected by immunohistochemistry. RESULTS: (1) The expression of Akt in the stomach tended to weaker in STC rats comparing with the normal rats (P > 0.05), but it was stronger in STC plus GDNF group than in STC group (P < 0.05). (2) The expression of Akt and MAPK in the colon was weaker in STC group than in the normal group (all P < 0.05), and was stronger in STC plus GDNF group than in STC group (all P < 0.05). (3) The expression of MAPK in the stomach in STC group was weaker than in normal group (P < 0.05), and was stronger in STC plus GDNF group than in STC group (P < 0.01). There was no significant difference among STC plus GDNF group, normal group and GDNF group (P > 0.05). CONCLUSIONS: Long term consumption of rhubarb could induce STC by down-regulating the expression of Akt and MAPK in digestive tract. Exogenous GDNF may have a potential role on the etiology of STC.