The important role of fungi in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is a life-threatening and chronic inflammatory disease of gastrointestinal tissue, with complex pathogenesis. Current research on IBD has mainly focused on bacteria; however, the role of fungi in IBD is largely unknown due to the incomplete annotation of fungi in current genomic databases. With the development of molecular techniques, the gut mycobiome has been found to have great diversity. In addition, increasing evidence has shown intestinal mycobiome plays an important role in the physiological and pathological processes of IBD. In this review, we will systemically introduce the recent knowledge about multi-dimensional fungal dysbiosis associated with IBD, the interactions between fungus and bacteria, the role of fungi in inflammation in IBD, and highlight recent advances in the potential therapeutic role of fungus in IBD, which may hold the keys to develop new predictive, therapeutic or prognostic approaches in IBD.

In vivo real-time diagnosis of endoscopic ultrasound-guided needle-based confocal laser endomicroscopy in gastric subepithelial lesions.

BACKGROUND AND AIM: The effect of real-time analysis of needle-based confocal laser endomicroscopy (nCLE) for gastric subepithelial lesions (SELs) on the diagnostic value is unclear. The study aimed to investigate the diagnostic efficacy of real-time nCLE for gastric SELs and to assess the technical aspects and safety of real-time nCLE. METHODS: Consecutive patients with gastric SELs ≥ 1 cm were prospectively investigated by endoscopic ultrasound (EUS), followed by nCLE. During EUS-nCLE, real-time nCLE diagnosis was made by an expert endoscopist. The procedure-relative adverse events were assessed and recorded. One-month washout period later, nCLE videos were reviewed off-line by the same endoscopist. The nCLE diagnoses were compared with corresponding pathological results. Additionally, image quality and interobserver agreements for the criteria were evaluated by three experienced endomicroscopists. RESULTS: Except for one failing to be punctured, 60 patients completed EUS-nCLE procedures successfully. Real-time nCLE had high diagnostic accuracies of ≥ 88.3% for gastric SELs. There were no significant differences between real-time and off-line nCLE diagnoses for gastric SELs (P > 0.05). The overall accuracy of real-time nCLE for diagnosis of gastric SELs was 86.7%. There were no procedure-relative adverse events occurred. In addition, the mean image quality score was 3.6 (1 = poor and 5 = excellent). The interobserver agreement was "almost perfect" for ectopic pancreas and "substantial" for gastrointestinal stromal tumor, leiomyoma, and carcinoma. CONCLUSIONS: Endoscopic ultrasound-nCLE could provide in vivo real-time diagnostic imaging with a high diagnostic accuracy. Meanwhile, real-time nCLE was feasible and had a satisfactory safety profile.

Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy for diagnosis of gastric subepithelial tumors: a pilot study.

BACKGROUND: The diagnostic yield of current techniques for gastric subepithelial tumors (SETs) is suboptimal. This prospective study aimed to develop diagnostic criteria for needle-based confocal laser endomicroscopy (nCLE) of gastric SETs, and to evaluate the diagnostic efficacy, feasibility, and safety of endoscopic ultrasound-guided nCLE (EUS-nCLE). METHODS: Eligible patients were prospectively recruited to undergo EUS-nCLE. Four unblinded investigators evaluated nCLE videos and corresponding histopathology to develop the nCLE criteria. The recorded nCLE videos were reviewed off-line by one endoscopist 3 months later. Image quality (five-point scale, 1 = poor and 5 = very good) and the interobserver agreements were assessed. RESULTS: All 33 patients underwent successful EUS-nCLE procedures. The nCLE criteria for gastric SETs were established. Overall accuracy of off-line nCLE was significantly higher than that of EUS alone (87.9 % vs. 63.6 %; P = 0.02). The mean image quality score was 3.9. The kappa values of the interobserver agreements were 0.66 for gastrointestinal stromal tumor, 0.89 for ectopic pancreas, 0.58 for leiomyoma, and 0.72 for carcinoma. CONCLUSIONS: EUS-nCLE was feasible and safe to accurately diagnose gastric SETs.

Synthesis of α,α-difluoromethylene alkynes by palladium-catalyzed gem-difluoropropargylation of aryl and alkenyl boron reagents.

gem-Difluoropropargyl bromides are versatile intermediates in organic synthesis, but have rarely been employed in transition-metal-catalyzed cross-coupling reactions. The first palladium-catalyzed gem-difluoropropargylation of organoboron reagents with gem-difluoropropargyl bromides is now reported. The reaction proceeds under mild reaction conditions with high regioselectivity; it features a broad substrate scope and excellent functional-group compatibility and thus provides an attractive approach for the synthesis of complex fluorinated molecules, in particular for drug discovery and development.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma.

In this editorial, we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. We focused on identifying risk factors for lymph node metastasis (LNM) in superficial esophageal squamous cell carcinoma (SESCC) patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients, thereby helping to guide the selection of an appropriate treatment plan. The current standard treatment for SESCC is radical esophagectomy with lymph node dissection. However, esophagectomy is associated with considerable morbidity and mortality. Endoscopic resection (ER) offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome. However, since ER is a localized treatment that does not allow for lymph node dissection, the risk of LNM in SESCC limits the effectiveness of ER. Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy. Previous studies have shown that tumor size, macroscopic type of tumor, degree of differentiation, depth of tumor invasion, and lymphovascular invasion are factors associated with LNM in patients with SESCC. In addition, tumor budding is commonly associated with LNM, recurrence, and distant metastasis, but this topic has been less covered in previous studies. By comprehensively evaluating the above risk factors for LNM, useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Altered mucosal bacteria and metabolomics in patients with Peutz-Jeghers syndrome.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS. AIM: This study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS. METHODS: The bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples. RESULTS: High-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors. CONCLUSION: This is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. METHODS: Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF(+/-) mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF(+/+) mice following different doses of BDNF administration. RESULTS: Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF(+/-) than in BDNF(+/+) mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF(+/-) mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF(+/+) mice. CONCLUSIONS: The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.

[Retracted] Role of microRNA­210 in human intervertebral disc degeneration.

[This retracts the article DOI: 10.3892/etm.2016.3176.].

Clinical and endoscopic features of primary small bowel lymphoma: a single-center experience from mainland China.

Objective: The worldwide incidence of primary small intestinal lymphoma (PSIL) is increasing. However, little is known about the clinical and endoscopic characteristics of this disease. The aim of this study was to investigate the clinical and endoscopic data of patients with PSIL, with the goal of enhancing our understanding of the disease, improving diagnostic accuracy, and facilitating more accurate prognosis estimation. Methods: Ninety-four patients diagnosed with PSIL were retrospectively studied at Qilu Hospital of Shandong University between 2012 and 2021. The clinical data, enteroscopy findings, treatment modalities, and survival times were collected and analyzed. Results: Ninety-four patients (52 males) with PSIL were included in this study. The median age of onset was 58.5 years (range: 19-80 years). Diffuse large B-cell lymphoma (n=37) was the most common pathological type. Abdominal pain (n=59) was the most frequent clinical presentation. The ileocecal region (n=32) was the most commonly affected site, and 11.7% of patients had multiple lesions. At the time of diagnosis, the majority of patients (n=68) were in stages I-II. A new endoscopic classification of PSIL was developed, including hypertrophic type, exophytic type, follicular/polypoid type, ulcerative type, and diffusion type. Surgery did not show a significant increase in overall survival; chemotherapy was the most commonly administered treatment. T-cell lymphoma, stages III-IV, "B" symptoms, and ulcerative type were associated with poor prognosis. Conclusion: This study provides a comprehensive analysis of the clinical and endoscopic features of PSIL in 94 patients. This highlights the importance of considering clinical and endoscopic characteristics for accurate diagnosis and prognosis estimation during small bowel enteroscopy. Early detection and treatment of PSIL is associated with a favorable prognosis. Our findings also suggest that certain risk factors, such as pathological type, "B" symptoms, and endoscopic type, may affect the survival of PSIL patients. These results underscore the need for careful consideration of these factors in the diagnosis and treatment of PSIL.

Milk fat globule-epidermal growth factor 8 is decreased in intestinal epithelium of ulcerative colitis patients and thereby causes increased apoptosis and impaired wound healing.

Milk fat globule-epidermal growth factor 8 (MFG-E8) plays an important role in maintaining intestinal barrier homeostasis and accelerating intestinal restitution. However, studies of MFG-E8 expression in humans with ulcerative colitis are lacking. We examined MFG-E8 expression in colonic mucosal biopsies from ulcerative colitis patients and healthy controls (n = 26 each) by real-time quantitative polymerase chain reaction (PCR), Western blot analysis and immunohistochemistry. MFG-E8 mRNA and protein expression was lower in ulcerative colitis patients than in controls. MFG-E8 expression was inversely correlated with mucosal inflammatory activity and clinical disease activity in patients. MFG-E8 was present in human intestinal epithelial cells both in vivo and in vitro. Apoptosis induction was also detected in the intestinal epithelium of ulcerative colitis patients by terminal-deoxynucleoitidyl transferase mediated nick-end labeling assay. We used lentiviral vectors encoding human MFG-E8 targeting short hairpin RNA to obtain MFG-E8 knockdown intestinal epithelia cell clones. MFG-E8 knockdown could promote apoptosis in intestinal epithelial cell lines, accompanied by a decrease in level of the antiapoptotic protein B-cell lymphoma 2 (BCL-2) and induction of the proapoptotic protein BCL2-associated protein X (BAX). The addition of recombinant human MFG-E8 led to decreased BAX and cleaved caspase-3 levels and induction of BCL-2 level in intestinal epithelia cells. MFG-E8 knockdown also attenuated wound healing on scratch assay of intestinal epithelial cells. The mRNA level of intestinal trefoid factor 3, a pivotal factor in intestinal epithelial cell migration and restitution, was downregulated with MFG-E8 knockdown. In conclusion, we demonstrated that decreased colonic MFG-E8 expression in patients with ulcerative colitis may be associated with mucosal inflammatory activity and clinical disease activity through basal cell apoptosis and preventing tissue healing in the pathogenesis of ulcerative colitis.

Copper- and phosphine-ligand-free palladium-catalyzed direct allylation of electron-deficient polyfluoroarenes with allylic chlorides.

Simply id(all)ylic: a copper- and phosphine-ligand-free Pd-catalyzed direct allylation of electron-deficient polyfluoroarenes with allylic chlorides and the reaction mechanism are described. The simple catalytic system, broad substrate scope, and excellent functional-group compatibility of this protocol provides a useful and facile access to allylated polyfluoroarenes.

Effects of antithrombotic therapy on bleeding after endoscopic sphincterotomy: A systematic review and meta-analysis.

Background and study aims Bleeding is a common complication of following endoscopy sphincterotomy (EST), and antithrombotic therapy use during the procedure often increases risk of it. Although several guidelines have been released regarding the use of antithrombotic agents during EST, many issues about it remain controversial. We carried out a systematic review and meta-analysis to evaluate the effect of antithrombotic medication on the risk of EST bleeding. Methods A structured literature search was carried out in Web of Science, EMBASE, PubMed, and Cochrane Library databases. RevMan 5.2 was used for meta-analysis to investigate the rate of post-EST bleeding. Results Seven retrospective articles were included. Compared with patients who had never taken antithrombotic drugs, patients who discontinued antithrombotic drugs 1 day before the procedure had a significantly increased risk of post-EST bleeding (OR, 1.95; 95 %CI, 1.57-2.43), particularly for severe bleeding (OR, 1.83; 95 %CI, 1.44-2.34). In addition, compared with patients who discontinued antithrombotic therapy for at least 1 day, patients who continued taking antithrombotic drugs did have an increased risk of post-EST bleeding (OR, 0.70; 95 %CI, 0.40-1.23). Conclusions The use of antithrombotic drugs may increase the bleeding rate of EST, but discontinuing therapy 1 day before endoscopy does not significantly reduce the bleeding rate.

Altered Gut Microbiota in Patients With Peutz-Jeghers Syndrome.

Background: Peutz-Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots and gastrointestinal polyps and increased susceptibility to cancers. It remains unknown whether gut microbiota dysbiosis is linked to PJS. Aim: This study aimed to assess the structure and composition of the gut microbiota, including both bacteria and fungi, in patients with PJS and investigate the relationship between gut microbiota dysbiosis and PJS pathogenesis. Methods: The bacterial and fungal composition of the fecal microbiota was analyzed in 23 patients with PJS (cases), 17 first-degree asymptomatic relatives (ARs), and 24 healthy controls (HCs) using 16S (MiSeq) and ITS2 (pyrosequencing) sequencing for bacteria and fungi, respectively. Differential analyses of the intestinal flora were performed from the phylum to species level. Results: Alpha-diversity distributions of bacteria and fungi indicated that the abundance of both taxa differed between PJS cases and controls. However, while the diversity and composition of fecal bacteria in PJS cases were significantly different from those in ARs and HCs, fungal flora was more stable. High-throughput sequencing confirmed the special characteristics and biodiversity of the fecal bacterial and fungal microflora in patients with PJS. They had lower bacterial biodiversity than controls, with a higher frequency of the Proteobacteria phylum, Enterobacteriaceae family, and Escherichia-Shigella genus, and a lower frequency of the Firmicutes phylum and the Lachnospiraceae and Ruminococcaceae families. Of fungi, Candida was significantly higher in PJS cases than in controls. Conclusion: The findings reported here confirm gut microbiota dysbiosis in patients with PJS. This is the first report on the bacterial and fungal microbiota profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) participate in visceral hyperalgesia in chronic water avoidance stress rat model.

Stressfull life events have powerful influences on visceral perception of certain IBS patients. In the present study, we aimed to examine the involvement of TRPV1 and TRPA1 in the stress-induced visceral hyperalgesia. Rats were exposed to 1-h water avoidance stress (WAS) daily for 10 consecutive days. The abdominal withdrawal reflex (AWR) to colorectal distension was assessed at the end of the 10-day period. Western-blotting analysis was applied to investigate the alterations of TRPV1 and TRPA1 in the colonic afferent dorsal root ganglia (DRG). Compared with control rats, the WAS-treated rats demonstrated a significant increase in the AWR with the pressure > or = 40 mm Hg (P < 0.05). Meanwhile, in the WAS-treated rats, western-blotting analysis showed significant upregulation of TRPV1 and TRPA1 in the colonic afferent DRG. The results indicate that WAS could induce the upregulation of TRPV1 and TRPA1 in the colonic afferent DRG, and both receptors may be candidate molecules involved in the stress-induced visceral hyperalgesia in rats.

[Effect of Qishen Huoxue Granule for auxiliary treatment of critical cases of acute kidney injury].

OBJECTIVE: To explore the efficacy of Qishen Huoxue Granules (QHG) for auxiliary treatment of critical patients with acute kidney injury (AKI). METHODS: Fifty-two AKI patients came from critical care medical department of Beijing Friendship Hospital were randomly assigned to two groups: Group A (25 patients) was treated with QHG (consisted of Radix Astragali, Radix Salviae miltiorrhizae, Radix Paeoniae rubra, Flos Carthami, and Radix Angelicae sinensis, etc., 10 g/bag, administered via gastric perfusion, 3 times per day, 10 g in each time) and continuous renal replacement therapy (CRRT); Group B (27 cases) was treated only by CRRT, all for 14 days. Besides, mechanical ventilation and vasoactive drugs were applied in case of necessary. The time of renal function recovery, days in ICU, 28-day mortality, changes of serum Cystatin C concentration as well as the time of mechanical ventilation (T-V) and vasoactive drugs application (T-D) in patients, who received corresponding treatment were observed. RESULTS: The renal function recovery time in Group A was markedly earlier than that in Group B (P < 0.05), with concentration of serum Cystatin C began to decrease from day 10. T-V and T-D in Group A were markedly shorter than those in Group B, respectively (P < 0.05). No significantly statistical difference between the two groups for days in ICU and 28-day mortality was found (P > 0.05). CONCLUSION: QHG shows favorable prospect in treating critical AKI patients, it can significantly accelerate the renal function recovery time, shorten the duration of mechanical ventilation and vasoactive drugs application.

[Analysis method of the fingerprint of LiuWei DiHuang pills by near infrared spectroscopy].

The purpose of the present paper is to establish a method of the fingerprint of LiuWei DiHuang pills by the near infrared spectroscopy. First, the authors established the fingerprint of LiuWei DiHuang pills by high performance capillary electrophoresis (HPCE), and calculated its similarity. At the same time, the authors scanned its near infrared spectrogram. Then the authors established the mathematical model between the similarity of fingerprint and the near infrared spectrogram. Through the optimization of the model, the correlation(r), calibration standard deviation and the average relative error of the modeling set were 0.9046, 0.058 and 6.12%, respectively. It proved that the linearity between calculated and forecast of fingerprint was clear. The results showed that the method of the fingerprint of LiuWei DiHuang pills by the near infrared spectroscopy was feasible.

A facile synthesis of 2,4-disubstituted thiazoles using MnO2.

Structurally diverse thiazoles with electron-donating and electron-withdrawing groups were conveniently synthesized through manganese dioxide (MnO(2)) oxidation of the corresponding thiazolines. The effect of substitution at the 2- and 4-positions was investigated. The desired thiazoles with aryl or vinyl substitutions at the 2- or 4-position can be obtained in good to excellent yields.

Simulated manned Mars exploration: effects of dietary and diurnal cycle variations on the gut microbiome of crew members in a controlled ecological life support system.

BACKGROUND: Changes in gut microbiome are closely related to dietary and environment variations, and diurnal circle interventions impact on human metabolism and the microbiome. Changes in human gut microbiome and serum biochemical parameters during long-term isolation in a controlled ecological life support system (CELSS) are of great significance for maintaining the health of crewmembers. The Green Star 180 project performed an integrated study involving a four-person, 180-day duration assessment in a CELSS, during which variations in gut microbiome and the concentration of serum 25-hydroxyvitamin D, α-tocopherol, retinol and folic acid from the crewmembers were determined. RESULTS: Energy intake and body mass index decreased during the experiment. A trade-off between Firmicutes and Bacteroidetes during the study period was observed. Dynamic variations in the two dominant genus Bacteroides and Prevotella indicated a variation of enterotypes. Both the evenness and richness of the fecal microbiome decreased during the isolation in the CELSS. Transition of diurnal circle from Earth to Mars increased the abundance of Fusobacteria phylum and decreased alpha diversity of the fecal microbiome. The levels of serum 25-hydroxyvitamin D in the CELSS were significantly lower than those outside the CELSS. CONCLUSIONS: The unique isolation process in the CELSS led to a loss of alpha diversity and a transition of enterotypes between Bacteroides and Prevotella. Attention should therefore be paid to the transition of the diurnal circle and its effects on the gut microbiome during manned Mars explorations. In particular, serum 25-hydroxyvitamin D levels require monitoring under artificial light environments and during long-term space flight. Large-scale studies are required to further consolidate our findings.

[The rapid analysis of fatty acids in vegetable oils by near infrared spectrum].

In this research, The functional components of vegetable oils were analyzed by near infrared (NIR) spectral technology. The optimum conditions of mathematics model of four components (C16 : 0, C18 : 0, C18 : 1, C18 : 2) were studied, including the sample set selection, chemical value analysis, the detection methods and condition. Chemical value was analyzed by HPLC. 52 samples were selected, 41 for modeling set and 11 for testing set. All samples were placed in 5mm thick sample pools and swept by near infrared (NIR) with discrimination factor 8 cm(-1) without any other disposal. Using PLS methods sated model. Data were processed by first derivative method and centering method. 5 000-9 000 cm(-1) spectral region was analyzed. Correlating index (r), RMSECV and RMSEP were chose as evaluation index. The result demonstrated that the correlation between the reference value of the modeling sample set and the near infrared predictive value were r(C16 : 0) = 0.891, r(C18 : 0) = 0.837, r(C18 : 1) = 0.982, r(C18 : 2) = 0.971, respectively. And the correlation between the reference value of the testing sample set and the near infrared predictive value were 0.921, 0.891, 0.946 and 0.949, respectively. It proved that the near infrared predictive value was linear with chemical value and the mathematical model established for components of vegetable oils was feasible. For validation, 8 unknown samples were selected to be analysis by infrared (NIR). The result demonstrated that error between predict value and chemical value was less than 10%. That was to say infrared (NIR) had a good veracity in analysis components of vegetable oil. Because infrared (NIR) spectral technology is convenient, rapid than HPLC in oil components analysis, moreover, infrared (NIR) can analyze many components at the same time. It must have great application prospect in vegetable oil components analysis.