Altered Function and Structure of the Cerebellum Associated with Gut-Brain Regulation in Crohn's Disease: a Structural and Functional MRI Study.

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions.

A 3,5-dinitropyridin-2yl Substituted Flavonol-based Fluorescent Probe for Rapid Detection of H2S in Water, Foodstuff Samples and Living Cells.

A novel flavonol-based fluorescent probe, Fla-DNT, has been synthesized for the rapid and specific detection of H2S. Fla-DNT exhibits excellent selectivity and anti-interference properties, a short response time (4 min), large Stokes shift (138 nm), and low detection limit (1.357 µM). Upon exposure to H2S, Fla-DNT displays a remarkable increase in fluorescence intensity at 542 nm. Meanwhile, the recognizing site of H2S was predicted through Electrostatic potential and ADCH charges calculations, while the sensing mechanism of H2S was determined via HRMS analysis and DFT calculation. More importantly, the probe owes multiple applications, such as a recovery rate ranging from 92.00 to 102.10% for detecting H2S in water samples, and it can be fabricated into fluorescent strips to track H2S production during food spoilage by tracking color changes, thereby enabling real-time monitoring of food freshness. The bioimaging experiments demonstrate the capability of Fla-DNT to detect both endogenous and exogenous H2S in living cells. These results provide a reliable method and idea for H2S detection in complex environments.

Multiple Applications of a Novel Fluorescence Probe with Large Stokes Shift and Sensitivity for Rapid H2S Detection.

Herein, a novel fluorescence probe Fla-DNP based on flavonol has been designed and synthesized for rapid, specific detection of H2S. With the addition of H2S, Fla-DNP triggered thiolysis and released Fla displaying the "turn-on" fluorescence response at 566 nm, which is consistent with the reaction site predicted by calculating Electrostatic potential and ADCH charges. As an easily available H2S probe, Fla-DNP has the advantages of high selectivity, anti-interference, low detection limit (0.834 µM), short response time (6 min), and large Stokes shift (124 nm). The sensing mechanism of H2S was determined by HRMS analysis and DFT calculation. Moreover, Fla-DNP processes a wide range of multiple applications, including the detection of H2S in environmental water samples with good recovery rates ranging from 89.6% to 102.0%, as well as tracking the production of H2S during food spoilage. Meanwhile, the probe exhibits superior biocompatibility and can not only be available used for H2S detection in living cells but be further designed as an H2S-activated CO photoreleaser, based on which it can be developed as a targeted anti-cancer drug. A novel fluorescence probe Fla-DNP was synthesized utilizing 4-dimethylaminobenzoxanthone fluorescent dye (Fla) as the fluorophore, 2, 4-dinitrobenzenether group (DNP) as the recognition group, which can rapidly respond to H2S with high selectivity, anti-interference, low detection limit (0.834 µM), short response time (6 min), and large Stokes shift (124 nm) characteristics. The practical applications of Fla-DNP were further explored in water, foodstuffs samples and living cells. It is reflected that Fla-DNP can not only track H2S in complex environment water, but also can detect H2S produced during foodstuffs spoilage to monitor food freshness. More importantly, Fla-DNP can be available used for H2S detection in living cells and utilize the properties of the photoinduced release of CO from flavonols to be designed as a bifunctional platform for H2S detection and CO release. It is demonstrated that H2S-activated CO photoreleaser Fla-DNP has promise for development as an anti-cancer drug.

Counterion-Controlled Formation of Layered Honeycomb and Polythreading Uranyl Networks and the Highly Sensitive and Selective Detection of Fe3+ in Aqueous Media.

Under hydrothermal conditions, six uranium coordination polymers were obtained by employing the ligand of tris(2-carboxyethyl) isocyanurate (H3tci) and different combinations of d-block metal ions (Mn2+, Co2+, Zn2+, Ni2+) or N-donors (triethylamine (Et3N), 2,2'-bipyridine (2,2'-bipy)). Three uranium polymers [(UO2)2(tci)2]1/2-·[Mn2(µ2-O)(H2O)8]1/2+·2H2O (1), [(UO2)2(tci)2]1/2-·[Co2(µ2-O)(H2O)8]1/2+ (2), and [(UO2)2(tci)2]1/2-·[Zn2(µ2-O)(H2O)8]1/2+·2H2O (3) containing transition metal hydrated ions, crystallized as two-dimensional coordination polymers with the common (6, 3) net topology. X-ray crystal structures of 1-3 display that they have similar honeycomb-like frameworks with all ligands bis-chelating. [UO2(tci)]-3·[Ni(H2O)6]2+(H3O)+·2H2O (4) and [UO2(tci)]-·[NH(CH2CH3)3]1/3+·(2H3O+)1/3 (5) are made up of four interlocked sets and exhibit the 4-fold-interpenetrated frameworks. [UO2(tci)]-·(C10H9N2)+·H2O (6) comprises the 2,2'-bipy cation as counterion and represents a 2D grid layered structure. Additional metals and the N-donors are all free in the complexes, acting as the templates and compensation of the charge equilibrium. The solid-state emission spectra indicate that all of the synthesized compounds own fluorescence emissions. Furthermore, the results of the quenching ability of Fe3+ for complexes 5 and 6 exhibit their highly sensitive and selective detection for Fe3+ ions. Moreover, the uranium complexes can be used as a potential probe for Fe3+ in aqueous solutions.

Chronic active Epstein-Barr virus infection involving gastrointestinal tract mimicking inflammatory bowel disease.

BACKGROUND: Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease, which is difficult to be differentiated from inflammatory bowel disease (IBD). To cause the attention, we present twelve cases of CAEBV in immunocompetent patients with gastrointestinal tract involvement. METHODS: Twelve patients who fulfilled the diagnostic criteria of CAEBV were enrolled in this retrospective study. The control group was consisted of twenty-four IBD patients with EBV-DNA value increased in peripheral blood. The clinicopathologic and endoscopic characteristics were reviewed and analyzed. RESULTS: The major clinical presentations of CAEBV patients were intermittent fever (100%), hepatomegaly/splenomegaly (58%), lymphadenopathy (50%), diarrhea (50%) and hematochezia (50%). Compared with IBD patients, the incidence of intermittent fever and increased level of ferritin were significantly higher among CAEBV patients. The median values for EBV detected in peripheral blood were significantly higher in CAEBV group (1.42*10^6 copies/µg) than in IBD group (3.2*10^3 copies/µg, p<0.05). The main endoscopic findings of CAEBV included multifocal or isolated, irregular, multiform ulcers and diffuse inflammation, lacking of typical cobblestone appearance. Ten patients died within 5 years of disease onset. The average survival time is 21 months. CONCLUSIONS: Symptoms such as intermittent fever, increased level of ferritin and atypical endoscopic findings could be a sign for CAEBV. Early detections of EBV-DNA in serum and EBV-encoded small nuclear RNA (EBER) by in situ hybridization in intestinal tissue are essential for differential diagnosis between CAEBV and IBD.

The clinicopathologic features of chronic active Epstein-Barr virus infective enteritis.

Chronic active Epstein-Barr virus infective enteritis (CAEBV enteritis) is rare and has not been well described yet. Therefore, we reported the clinicopathologic features of 11 patients with chronic active Epstein-Barr virus infective enteritis and their differences from inflammatory bowel disease. The major clinical presentations of chronic active Epstein-Barr virus infective enteritis were intermittent fever over 39 °C (100%), diarrhea (73%), abdominal pain (64%), lymphadenopathy (64%), splenomegaly (64%), and hepatomegaly (27%). The main endoscopic findings included numerous shallow, small, and irregular ulcers, mainly involving colon and small intestine together, no cobble-like appearance, and longitudinal ulcers. Compared to inflammatory bowel disease patients, the frequency of intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, the value of C-reactive protein, and serum Epstein-Barr virus DNA (EBV DNA) were significantly higher in chronic active Epstein-Barr virus infective enteritis patients (p < 0.01). The histologic findings show transmural inflammation with extended lymphoid infiltration, fissuring ulcers, and intraepithelial lymphocytosis. But chronic active Epstein-Barr virus infective enteritis lacked granulomas and connective tissue changes such as neural hypertrophy and thickened muscularis mucosae. Three chronic active Epstein-Barr virus infective enteritis patients died within 5 years of disease onset, and those three patients have received total colectomy, two of them died within 1 month after surgery. In this study, clinicopathologic features have been summarized to better recognize chronic active Epstein-Barr virus infective enteritis. There are resemblances between chronic active Epstein-Barr virus infective enteritis and inflammatory bowel disease, but some symptoms, signs, and indexes like intermittent fever, hepatomegaly, splenomegaly, lymphadenopathy, and elevated C-reactive protein, Epstein-Barr virus DNA are characteristics to differentiate chronic active Epstein-Barr virus infective enteritis and inflammation. Histopathological features also help the discrimination. Serum Epstein-Barr virus DNA and intestinal tissue in situ hybridization for Epstein-Barr virus-encoded RNA are recommended to exclude chronic active Epstein-Barr virus infective enteritis.

Evaluation of Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging for Detection of Bowel Inflammation in Patients With Crohn Disease.

OBJECTIVES: This study aimed to evaluate the feasibility of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (DW-MRI) in detecting bowel inflammation in patients with Crohn disease (CD). METHODS: Sixteen patients who underwent intravoxel incoherent motion DW-MRI for CD and colonoscopy were recruited. Seventy-nine bowel segments were selected, and their mean D, D*, f, and apparent diffusion coefficient (ADC) values were measured. The receiver operating characteristic curve was performed to distinguish inflamed from normal bowel. RESULTS: The mean D, D*, f, and ADC values of inflamed bowel were significantly lower than those of normal bowel (P < 0.05). The area under the receiver operating characteristic curve for f (0.906) and ADC values (0.924) was greater than that for D (0.709) or D* values (0.686) for differentiating inflamed bowel from normal bowel (P < 0.05). CONCLUSIONS: Intravoxel incoherent motion DW-MRI is a feasible technique for detecting inflammation in CD patients. The ADC and f values have more potential than the D and D* values.

Targeted Metagenome Based Analyses Show Gut Microbial Diversity of Inflammatory Bowel Disease patients.

Inflammatory bowel disease (IBD) is a multifactorial disease including both genetic and environmental factors. We compared the diversity of intestinal microbesamong a cohort of IBD patients to study the microbial ecological effects on IBD. Fecal samples from patients were sequenced with next generation sequence technology at 16S rDNA region. With statistical tools, microbial community was investigated at different level. The gut microbial diversity of Crohn's disease (CD) patients and colonic polyp (CP) patients significantly different from each other. However, the character of ulcerative colitis (UC) patients has of both CD and CP features. The microbial community from IBD patients can be very different (CD patient) or somewhat similar (UC patients) to non-IBD patients. Microbial diversity can be an important etiological factor for IBD clinical phenotype.

MiR-133b Promotes neurite outgrowth by targeting RhoA expression.

BACKGROUND: MicroRNA-133b (miR-133b) has been shown to play a critical role in spinal cord regeneration. The aim of this study was to investigate the cellular role of miR-133b in neural cells. METHODS: PC12 cells and primary cortical neurons (PCNs) were transfected with lenti-miR-133b, lenti-miR-133b inhibitor, plasmid-shRNA-RhoA, plasmid-RhoA and their negative controls. After 48 hours of transfection, the levels of proteins and mRNA or miRNA were evaluated by Western blotting and qRT-PCR, respectively. Moreover, the neurite outgrowth was analyzed by Image J. For pharmacological experiments, inhibitors of MEK1/2 kinase (PD98059), phosphoinositide-3 kinase (PI3K) (LY294002) and ROCK (Y27632) were added into the culture medium. RESULTS: Overexpression of miR-133b in PC12 cells enhanced neurite outgrowth. Conversely, inhibition of miR-133b reduced neurite length. We further identified RhoA as a target and mediator of mir-133b for neurite extension by Western blot and knockdown experiment. Moreover, overexpression of RhoA could attenuate the neurite growth effects of miR-133b. Also, we observed that miR-133b activated MEK/ERK and PI3K/Akt signaling pathway by targeting RhoA. Finally, in PCNs, miR-133b also increased axon growth and attenuated axon growth restrictions from chondroitin sulfate proteoglycans (CSPG). CONCLUSIONS: In summary, our study suggested that miR-133b regulated neurite outgrowth via ERK1/2 and PI3K/Akt signaling pathway by RhoA suppression.

Cloning and identification of a novel thyroid hormone receptor ß isoform expressed in the pituitary gland.

We have previously identified a novel Trß isoform (TrßΔ) in the rat, in which a novel exon N (108 bps) was found between exon 3 and exon 4 of TrßΔ, which represents the only difference between TrßΔ and Trß1. In this study, we searched for an elongated Trß2-like subtype with one additional exon N. We successfully isolated the entire mRNA/cDNA of a novel elongated Trß2 isoform via PCR in the rat pituitary gland. The mRNA/cDNA was only 108 bps (exon N) longer than that Trß2, and the extension of the sequence was between exon 3 and 4 of Trß. The whole sequence of this novel Trß isoform has been published in NCBI GenBank (HM043807.1); it is named TRbeta2Delta (Trß2Δ). In adult rat pituitary tissue, quantitative real-time RT-PCR analysis showed that the mRNA levels of Trß2Δ and Trß2 were roughly equal (P > 0.05). We cloned, expressed, and purified the His-Trß2Δ protein [recombinant TRß2Δ (rTRß2Δ)]. SDS-PAGE and western blotting revealed that the molecular weight of rTRß2Δ was 58.2 kDa. Using a radioligand binding assay and an electrophoretic mobility shift assay, rTRß2Δ-bound T3 with high affinity and recognized thyroid hormone response element (TRE) binding sites. Finally, in vitro transfection experiments further confirmed that rTRß2Δ binding T3 significantly promotes the transcription of target genes via the TRE. Here, we have provided evidence suggesting that rTRß2Δ is a novel functional TR isoform.

"Platelet-coated bullets" biomimetic nanoparticles to ameliorate experimental colitis by targeting endothelial cells.

Intestinal vascular impairment is critical to the recovery of inflammatory bowel disease (IBD), and targeting vascular endothelial cells is a promising emerging therapeutic option. Considering the natural homing properties of platelets to activated vascular endothelium, platelet membrane-mimetic nanoparticles are expected to achieve precise treatment of IBD. Patchouli alcohol (PA) has proven efficacy in experimental colitis, yet its pharmacochemical properties require improvement to enhance efficacy. The rationale for targeting vascular lesions in IBD was analyzed by network pharmacology, and PA-affecting pathways were predicted. PA-encapsulated bio-nanoparticles (PNPs) were constructed to investigate the efficacy of agents on mouse intestinal microvascular endothelial cells (MIMVEC) inflammation model and dextran sulfate sodium (DSS)-induced acute mouse colitis model. PNPs were endocytosed by MIMVEC in vitro and efficiently enriched in inflamed colon. PNPs significantly alleviated the symptoms of experimental colitis and improved neutrophil infiltration. PNPs down-regulated LPS-induced aberrant elevation of il1ß, tnfα and il6 mRNAs and reduced p65 phosphorylation in MIMVEC. Intracellular calcium expression, mitochondrial respiration and reactive oxygen species expression were also downregulated by PNPs. PNPs amplified the potency of PA as a calcium antagonist, restrained intracellular Ca2+ perturbations to prevent endothelial activation, which may block leukocyte recruitment in vivo to improve colitis.

Characteristics and in-hospital outcomes of elderly patients with cancer in a top-ranked hospital in China, 2016-2020: Real-world study.

BACKGROUND: Cancer is mostly a disease of aging, and older patients with cancer are generally frailer. This study aimed to describe the characteristics and in-hospital outcomes and explore factors associated with duration, cost, and mortality during first hospitalization, in older patients with cancer admitted to a top-ranked hospital in China. METHODS: Data on patients with solid cancer ≥65 years consecutively hospitalized in 2016-2020 were retrieved from the electronic medical records of Ruijin Hospital in Shanghai, China. Baseline characteristics, duration, cost, and mortality during hospitalization were described. Factors associated with duration, cost, and mortality during first hospitalization were explored using multivariable-adjusted logistic regression. RESULTS: 20,650 eligible patients with male proportion of 59% and median age of 70 years were analyzed. 45% of the patients underwent resection in our hospital. Upon first admission, 49% of patients had hypertension, 19% diabetes, 22% weight loss, and 28% risks of malnutrition. The median duration and cost of first hospitalization were 9 days and 32,000 RMB, respectively. 118 (0.6%) and 228 (1.1%) deaths occurred during first and any hospitalization, respectively. For first hospitalization, longer duration and higher cost were positively associated with older ages, male gender, emergency admission, certain tumor locations and histology, histories of diabetes, cirrhosis, and anticoagulant intake, higher body mass index, weight loss, reduced food intake, risk of falling, and worse self-care ability; in-hospital mortality was positively associated with age ≥85 years, emergency admission, certain cancer types, histories of hypertension and psychotropic intake, reduced food intake, and worse self-care ability. CONCLUSIONS: This study identified certain baseline patient and tumor characteristics, medical and medication histories, changes of weight and food intake, diet, and self-care ability which were independently associated with in-hospital outcomes among older patients with cancer admitted to our hospital and which should be paid special attention to. While the factors might not be easily modifiable, our study can help identify patients at higher risks of inferior in-hospital outcomes.

Selection of suitable reference genes for normalization of quantitative real-time PCR in cartilage tissue injury and repair in rabbits.

When studying the altered expression of genes associated with cartilage regeneration by quantitative real-time RT-PCR (RT-qPCR), reference genes with highly stable expression during different stages of chondrocyte developmental are necessary to normalize gene expression accurately. Until now, no reports evaluating expression changes of commonly used reference genes in rabbit articular cartilage have been published. In this study, defects were made in rabbit articular cartilage, with or without insulin-like growth factor 1 (IGF-1) treatment, to create different chondrocyte living environments. The stability and intensity of the expressions of the candidate reference genes glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 18S Ribosomal RNA (18S rRNA), cyclophilin (CYP), hypoxanthine phosphoribosyl transferase (HPRT1), and beta-2-microglobulin (B2M) were evaluated. The data were analyzed by geNorm and NormFinder. B2M and 18S rRNA were identified to be suitable reference genes for rabbit cartilage tissues.

Machine Learning Model in Predicting Sarcopenia in Crohn's Disease Based on Simple Clinical and Anthropometric Measures.

Sarcopenia is associated with increased morbidity and mortality in Crohn's disease. The present study is aimed at investigating the different diagnostic performance of different machine learning models in identifying sarcopenia in Crohn's disease. Patients diagnosed with Crohn's disease at our center provided clinical, anthropometric, and radiological data. The cross-sectional CT slice at L3 was used for segmentation and the calculation of body composition. The prevalence of sarcopenia was calculated, and the clinical parameters were compared. A total of 167 patients were included in the present study, of which 127 (76.0%) were male and 40 (24.0%) were female, with an average age of 36.1 ± 14.3 years old. Based on the previously defined cut-off value of sarcopenia, 118 (70.7%) patients had sarcopenia. Seven machine learning models were trained with the randomly allocated training cohort (80%) then evaluated on the validation cohort (20%). A comprehensive comparison showed that LightGBM was the most ideal diagnostic model, with an AUC of 0.933, AUCPR of 0.970, sensitivity of 72.7%, and specificity of 87.0%. The LightGBM model may facilitate a population management strategy with early identification of sarcopenia in Crohn's disease, while providing guidance for nutritional support and an alternative surveillance modality for long-term patient follow-up.

[Values of serum copper and serum free copper in the diagnosis and monitoring of Wilson's disease and its carriers].

OBJECTIVE: To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD. METHODS: A total of 80 WD patients (hepatic type, n = 60; encephalic type, n = 20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed. RESULTS: The free serum copper increased in the patients with WD (0.17 mg/L ± 0.04 mg/L), carriers (0.13 mg/L ± 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period. CONCLUSION: There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease.

Biological functions of NLRP3 inflammasome: A therapeutic target in inflammatory bowel disease.

Cases of inflammatory bowel disease (IBD), a debilitating intestinal disorder with complex pathological mechanisms, have been increasing in recent years, straining the capacity of healthcare systems. Thus, novel therapeutic targets and innovative agents must be developed. Notably, the NLRP3 inflammasome is upregulated in patients with IBD and/or in animal experimental models. As an innate immune supramolecular assembly, the NLRP3 inflammasome is persistently activated during the pathogenesis of IBD by multiple stimuli. Moreover, this protein complex regulates pro-inflammatory cytokines. Thus, targeting this multiprotein oligomer may offer a feasible way to relieve IBD symptoms and improve clinical outcomes. The mechanisms by which the NLRP3 inflammasome is activated, its role in IBD pathogenesis, and the drugs administered to target this protein complex are reviewed herein. This review establishes that the use of inflammasome-targeting drugs are effective for IBD treatment. Moreover, this review suggests that the value and potential of naturally sourced or derived medicines for IBD treatment must be recognized and appreciated.

Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease.

Introduction: Inflammatory bowel disease (IBD) is a systemic disease with immune abnormalities that can affect the entire digestive tract. A high percentage of patients with IBD are unresponsive to current pharmacological agents, hence the need exists for novel therapeutic approaches. There is compelling evidence that macrophage polarization plays a key role in the remission of IBD patients and that it could open up future treatment options for patients.Areas covered: This paper highlights the crucial role of macrophage polarization in IBD. The authors shed light on the phenotype and function of macrophages and potential drug targets for polarization regulation. Existing approaches for regulating macrophage polarization are discussed and potential solutions for safety concerns are considered. We performed a literature search on the IBD and macrophage polarization mainly published in PubMed January 2010-July 2020.Expert opinion: Evidence indicates that there are fewer M2 macrophages and a high proportion of M1 macrophages in the intestinal tissues of individuals who are non- responsive to treatment. Regulating macrophage polarization is a potential novel targeted option for IBD treatment. Improved mechanistic insights are required to uncover more precise and effective targets for skewing macrophages into a proper phenotype.

Brain functional changes in patients with Crohn's disease: A resting-state fMRI study.

BACKGROUND: Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in-depth. OBJECTIVE: To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices. METHODS: A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed. RESULTS: Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point. CONCLUSION: CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive-related functions, which provides more information to further understand the neural mechanisms of the disease.

Safety and efficacy of thalidomide in patients with transfusion-dependent ß-thalassemia: a randomized clinical trial.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent ß-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non ß0/ß0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Iron deficiency anaemia can be improved after eradication of Helicobacter pylori.

BACKGROUND: Recent guidelines on iron deficiency anaemia (IDA) have confirmed the aetiological role of Helicobacter pylori (H pylori), but the relationship still remains controversial. METHODS: Starting in May 2009, searches of the following databases were undertaken: Medline (1966 to April 2009), Embase (1980 to April 2009), the Cochrane library (1800 to June 2008), Cochrane Central Register of Controlled Trials, Premedline, Healthstar, CBMdisc and the Chinese National Knowledge Infrastructure Database (January 1970 to April 2009). Changes in haemoglobin (Hb) concentrations and serum ferritin (SF) concentrations were recorded for intervention and control groups. The meta-analysis used random effect models and subgroup analyses were performed to explain heterogeneity. RESULTS: Eight studies met the inclusion criteria. All studies were performed in Asia, an area with a high incidence of IDA and H pylori. The pooled analysis of eight studies showed that H pylori eradication therapy can improve IDA, since changes in Hb and SF concentrations in the intervention groups were higher than in controls. The weighted mean difference (WMD) of Hb was 12.88 g/l (95% CI 6.03 to 19.74 g/l, p<0.00001); the WMD of SF was 10.05 mug/l (95% CI 5.48 to 14.63 mug/l, p<0.00001). CONCLUSIONS: H pylori eradication therapy combined with iron administration is more effective than iron administration alone for the treatment of IDA. Eradication therapy has different effects on adults and children. Bismuth based triple therapy has a better response in terms of increased Hb and SF concentrations than proton pump inhibitor (PPI) based triple therapy.