Optimal concentration of Lugol's solution for detecting early esophageal carcinoma: A randomized controlled trial.

BACKGROUND AND AIM: Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. METHODS: This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. RESULTS: In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P < 0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P > 0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P < 0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W = 554.500, P = 0.005). CONCLUSIONS: The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).

Simplified robot-assisted endoscopic submucosal dissection for esophageal and gastric lesions: a randomized controlled porcine study (with videos).

BACKGROUND AND AIMS: Effective countertraction is a main challenging issue in endoscopic submucosal dissection (ESD). Several countertraction methods have been developed to address this issue. The aim of this study was to compare the efficacy of ESD using a novel simplified robot, the flexible auxiliary single-arm transluminal endoscopic robot (FASTER), with a traditional technique. METHODS: This was a prospective, randomized animal study. Forty-eight ESDs in 6 pigs were carried out at 8 different locations (gastric antrum, gastric body, lower esophagus, and middle esophagus) by the conventional method (n = 24) and by the FASTER-assisted method (n = 24). The primary outcomes were total procedure time, dissection time, and rate of direct-vision dissection. Secondary endpoints were completeness of en-bloc resection and adverse event rate. RESULTS: The total procedure time was significantly shorter in FASTER-assisted ESD than in conventional ESD (18.8 vs 32.8 minutes; P < .001). In contrast to the median direct-vision dissection rate of 73% with conventional ESD, the FASTER-assisted group had a significantly higher rate of 96% (P < .001). The number of sites of muscular damage was significantly lower using the FASTER-assisted method than the conventional method (6 vs 21, respectively; P = .018). This improvement was more apparent in esophageal lesions compared with gastric lesions. CONCLUSIONS: This study demonstrated that using a simplified robot during ESD is technically feasible and enables the endoscopist to dynamically use countertraction. This device could significantly reduce procedure time compared with conventional ESD techniques.

A novel flexible auxiliary single-arm transluminal endoscopic robot facilitates endoscopic submucosal dissection of gastric lesions (with video).

BACKGROUND: Using conventional endoscope to perform endoscopic submucosal dissection (ESD) is difficult because of the one-handed operation and blind dissection caused by gravity. Poor visualization of the submucosal plane causes ESD to be associated with a high risk of bleeding and perforation. This study aimed to develop a novel ESD-assistive robot system and to evaluate its efficacy. METHODS: A novel flexible auxiliary single-arm transluminal endoscopic robot (FASTER) was developed. A total of 36 artificial lesions in ex vivo porcine stomachs were removed using the FASTER-assisted ESD method (n = 18) and the conventional ESD method (n = 18). Lesions were 2 cm or 4 cm in diameter, located on the anterior and posterior walls of the antrum. Primary outcome measurements were dissection time and dissection speed. RESULTS: The dissection time in FASTER-assisted ESD was significantly shorter than that in conventional ESD (7 min vs 13 min, p = 0.012), mainly because of the faster dissection speed (148.6 vs 97.0 mm2/min, p = 0.002). The total procedure time in FASTER-assisted ESD was shorter than that in conventional ESD, but the difference was not significant (16 min vs 24 min, p = 0.252). Complete en bloc resection was achieved in all lesions. No perforations were detected. The FASTER exhibited the ability of regrasp, multidirectional traction, and proper tension control during ESD. CONCLUSION: FASTER significantly increased the dissection speed by providing proper traction and achieving good submucosal vision. This new device is expected to facilitate ESD in clinical practice.

Complete genome sequencing of Peyer's patches-derived Lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity.

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.

Real-time artificial intelligence for endoscopic diagnosis of early esophageal squamous cell cancer (with video).

BACKGROUND AND AIMS: Endoscopic diagnosis of early esophageal squamous cell cancer (ESCC) is complicated and dependent on operators' experience. This study aimed to develop an artificial intelligence (AI) model for automatic diagnosis of early ESCC. METHODS: Non-magnifying and magnifying endoscopic images of normal/noncancerous lesions, early ESCC, and advanced esophageal cancer (AEC) were retrospectively obtained from Qilu Hospital of Shandong University. A total of 10,988 images from 5075 cases were chosen for training and validation. Another 2309 images from 1055 cases were collected for testing. One hundred and four real-time videos were also collected to evaluate the diagnostic performance of the AI model. The diagnostic performance of the AI model was compared with endoscopists by magnifying images and the assistant efficiency of the AI model for novices was evaluated. RESULTS: The AI diagnosis for non-magnifying images showed a per-patient accuracy, sensitivity, and specificity of 99.5%, 100%, 99.5% for white light imaging, and 97.0%, 97.2%, 96.4% for optical enhancement/iodine straining images. Regarding diagnosis for magnifying images, the per-patient accuracy, sensitivity, and specificity were 88.1%, 90.9%, and 85.0%. The diagnostic accuracy of the AI model was similar to experts (84.5%, P = 0.205) and superior to novices (68.5%, P = 0.005). The diagnostic performance of novices was significantly improved by AI assistance. When it comes to the diagnosis for real-time videos, the AI model showed acceptable performance as well. CONCLUSIONS: The AI model could accurately recognize early ESCC among noncancerous mucosa and AEC. It could be a potential assistant for endoscopists, especially for novices.

Microbial and metabolomic profiles in correlation with depression and anxiety co-morbidities in diarrhoea-predominant IBS patients.

BACKGROUND: Psychological co-morbidities in irritable bowel syndrome (IBS) have been widely recognized, whereas less is known regarding the role of gut microbial and host metabolic changes in clinical and psychological symptoms in IBS. RESULTS: A total of 70 diarrhoea-predominant IBS (IBS-D) patients and 46 healthy controls were enrolled in this study. Stool and urine samples were collected from both groups for 16S rRNA gene sequencing and metabolomic analysis. The results showed that fecal microbiota in IBS-D featured depleted Faecalibacterium (adjusted P = 0.034), Eubacterium rectale group (adjusted P = 0.048), Subdoligranulum (adjusted P = 0.041) and increased Prevotella (adjusted P = 0.041). O-ureido-L-serine, 3,4-dihydroxybenzenesulfonic acid and (R)-2-Hydroxyglutarate demonstrated lower urinary concentrations in IBS-D patients. We further built correlation matrices between gut microbe abundance, differentiated metabolite quantities and clinical parameters. Dialister manifested negative association with IBS severity (r = - 0.285, P = 0.017), anxiety (r = - 0.347, P = 0.003) and depression level (r = - 0.308, P = 0.010). Roseburia was negatively associated with IBS severity (r = - 0.298, P = 0.012). Twenty metabolites correlated with anxiety or depression levels, including 3,4-dihydroxymandelaldehyde with SAS (r = - 0.383, P = 0.001), 1-methylxanthine with SDS (r = - 0.347, P = 0.004) and 1D-chiro-inositol with SAS (r = - 0.336, P = 0.005). In analysis of microbe-metabolite relationship, 3,4-dihydroxymandelaldehyde and 1-methylxanthine were negatively correlated with relative abundance of Clostridiumsensu stricto. CONCLUSIONS: Our findings demonstrated altered microbial and metabolomic profiles associated with clinically and psychological symptoms in IBS-D patients, which may provide insights for further investigations.

Endocuff-assisted colonoscopy versus cap-assisted colonoscopy for adenoma detection rate: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Add-on devices have been widely used in clinical practice. The aim of this meta-analysis was to compare the adenoma detection rate between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). METHODS: PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference. RESULTS: Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta-analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0% vs 45.1%; P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95). CONCLUSION: EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.

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.

Cresyl violet as a new contrast agent in probe-based confocal laser endomicroscopy for in vivo diagnosis of gastric intestinal metaplasia.

BACKGROUND AND AIM: Cresyl violet (CV) is a topical dye that allows simultaneous chromoendoscopy and in vivo confocal laser endomicroscopy in identification of neoplastic changes of the lower gastrointestinal tract without intravenous injection of fluorescein, but as yet no investigation has reported its application in the diagnosis of gastric intestinal metaplasia (GIM). This study aims to assess the feasibility as well as diagnosis accuracy of topical CV for in vivo diagnosis of GIM by using probe-based confocal laser endomicroscopy (pCLE). METHODS: In this prospective, open-label, feasibility study, 129 confocal videos from 22 patients with known GIM were analyzed and compared with corresponding histological images to establish the CV staining characteristics. In addition, 47 patients with known or suspected GIM were prospectively enrolled to evaluate the accuracy of this topical CV endomicroscopic imaging. RESULTS: Probe-based confocal laser endomicroscopy with topical CV enabled clear visualization of the goblet cells, absorptive cells, and intestinal villi of GIM. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pCLE diagnosis of GIM on a per-location analysis was 93.01%, 91.95%, 93.51%, 86.96%, and 96.11%, respectively. The intraclass correlation coefficient for inter-observer agreement and mean kappa value for intra-observer agreement for the diagnosis of GIM was 0.82 and 0.87, respectively. CONCLUSIONS: Topical CV enables real-time chromoendoscopy in conjunction with pCLE examination of the stomach and warrants accurate diagnosis of GIM. It may be an acceptable and potentially alternative dye for confocal imaging in the future.

[Prevalence of pediatric asthma in the rural areas of China: a Meta analysis].

OBJECTIVE: To systematically review the prevalence of pediatric asthma in the rural areas of China, and to provide data for the prevention and treatment of pediatric asthma. METHODS: PubMed, Cochrane, China National Knowledge Infrastructure, Wanfang Database, and Embase were searched for cross-sectional studies on the prevalence of pediatric asthma in the rural areas of China published up to August 31, 2019. Two researchers independently conducted preliminary screening and data extraction. Stata 14.0 and R software were used to perform a Meta analysis of prevalence rate. Subgroup analysis was also performed. RESULTS: A total of 24 articles were reviewed, with a sample size of 212 814 children, among whom there were 3 254 children with asthma, with an overall prevalence rate of 2.02% (95%CI: 1.67%-2.36%). Boys had a significantly higher prevalence rate than girls (3.64% vs 2.03%, P<0.001). The annual prevalence rate increased from 1.21% in 1990-1999 to 3.36% in 2011-2015. The prevalence rate of pediatric asthma was 3.15% in South China, which was higher than that in East China (2.31%), Southwest China (2.15%), North China (1.19%), and Central China (1.12%). Preschool children had the highest prevalence rate of 2.63%, followed by infants and young children (2.48%) and school-age children (1.41%). CONCLUSIONS: The prevalence rate of pediatric asthma is relatively low but tends to increase in the rural areas of China. Boys have a higher prevalence rate of asthma than girls, and the prevalence rate is higher in South China. Preschool children have the highest prevalence rate.

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.

[Characteristics and Risk Assessment of Antibiotic Contamination in Oujiang River Basin in Southern Zhejiang Province].

Antibiotic pollution in the environment has a negative impact on ecosystem security. Taking the Oujiang River Basin as an example,high-performance liquid chromatography mass spectrometry(LC-MS)was used to detect the concentration of six classes of 35 antibiotics in the surface water of the southern Zhejiang River Basin. The concentration level and spatial distribution of antibiotics were analyzed,the risk of antibiotics to ecology and human health were assessed using relevant models,and the sources of antibiotics were discussed. The results showed that in 20 sampling sites,a total of four classes of 12 antibiotics were detected,including sulfonamides,quinolones,tetracyclines,and lincosamides. The total concentration was ND-1 018 ng·L-1. The highest detection rate was that of Lincomycin(90.48%),followed by that of sulfapyridine(38.10%). The three antibiotics with the highest average concentrations were ofloxacin(12.49 ng·L-1),Lincomycin(11.08 ng·L-1),and difloxacin(7.38 ng·L-1). Antibiotics in the basin showed mainly spotty pollution,which had large spatial differentiation. The average concentration of antibiotics in the upstream(54.39 ng·L-1)was higher than that mid-downstream(46.64 ng·L-1). The degree of antibiotic pollution from upstream to downstream showed a characteristic of being "sparse in the upstream and dense in the downstream. " This indicated that the concentration of antibiotics in the upstream was significantly different,whereas the pollution degree of antibiotics in the downstream was uniform. The upstream was mainly polluted by health,livestock,and poultry breeding wastewater emissions,and downstream pollution was mainly caused by densely populated activities and the rapid development of economy,trade,and industry. The ecological risk assessment results showed that the upstream site H6 had the highest risk quotient,ofloxacin and enrofloxacin had high risk levels, and lincomycin had a moderate risk level. Health risk assessment results showed that the Oujiang River surface water antibiotics posed no risk to human health.

Excessive Mitochondrial Fission Suppresses Mucosal Repair by Impairing Butyrate Metabolism in Colonocytes.

BACKGROUND: Mucosal healing is one of the principal therapeutic targets for ulcerative colitis (UC). Mitochondria are dynamic organelles that undergo constant fusion and fission; however, the process that is most conducive to mucosal healing remains unclear. This study investigated the role of mitochondrial fission in mucosal healing in UC patients. METHODS: Quantitative polymerase chain reaction, Western blotting, and immunostaining were used to detect mitochondrial fission in UC patients and a dextran sulfate sodium-induced colitis model. Colonic organoids were used to investigate the role of mitochondrial fission in butyrate metabolism. Enzyme activity assays were performed to identify the key proteins involved in this mechanism. RESULTS: It was found that inhibition of mitochondrial fission promoted mucosal healing in mice and that there was an increase in mitochondrial fission in colonic epithelial cells of UC patients. Excessive fission inhibits stem cell proliferation by impairing butyrate metabolism in colonic organoids. The mitochondrial fission antagonist P110 failed to promote mucosal healing in antibiotic-treated mice, and the addition of exogenous butyrate reversed this effect. Increased butyrate exposure in the colonic stem cell niche has also been observed in UC patients. Mechanistically, enzyme activity assays on colonic organoids revealed that excessive fission inhibits mitochondrial acetoacetyl-CoA thiolase activity via reactive oxygen species. CONCLUSIONS: Collectively, these data indicate that excessive mitochondrial fission suppresses mucosal repair by inhibiting butyrate metabolism and provides a potential target for mucosal healing in patients with ulcerative colitis.

Squamous cell carcinoma associated with endometriosis in the uterus and ovaries: A case report.

BACKGROUND: Endometriosis is a common benign gynecological disease that causes dysmenorrhea in women of childbearing age. Malignant tumors derived from endometriosis are rarely reported and are found in only 1% of all patients with endometriosis. Here, we report a well-differentiated squamous cell carcinoma (SCC) caused by squamous metaplasia of endometriosis that co-occurred in the uterus and ovaries. CASE SUMMARY: A 57-year-old postmenopausal woman had a 6-month history of irregular uterine bleeding. The uterus and adnexa were examined by computed tomography, and there were two solid cystic masses in the pelvis and right adnexa. Histological findings of surgical specimens showed well-differentiated SCC arising from squamous metaplasia of ectopic endometrial glands in the uterus and ovaries. The patient received chemotherapy after surgery and was followed up for 3 mo without metastasis. CONCLUSION: The continuity between ectopic endometrial glands and SCC supports that SCC originates from ectopic endometrial glands with metaplasia towards squamous epithelium.

A new norisoprenoid and other compounds from Fuzhuan brick tea.

Fuzhuan brick tea, a kind of dark tea consumed mainly in the border regions of Southwestern and Northwestern China since the 1860s, is produced from the leaves of Camellia sinensis var. sinensis by microbial fermentation. From this special fermented tea, a new norisoprenoid, 3R,9R-oxido-5-megastigmene, was isolated, together with α-linolenic acid, strictin, isovitexin, astragalin, (+)-catechin, (-)-epicatechin, (-)-epicatechin gallate, (+)-gallocatechin, (-)-epigallocatechin, (-)-epigallocatechin gallate and gallic acid. The structures of the compounds were identified by spectroscopic means. The new compound didn't show any inhibition activity against the tested enteric pathogenic microorganisms at a concentration of 800 µg/mL by the hole plate diffusion method.

[Epithelioid sarcoma-like hemangioendothelioma: a clinicopathologic and immunohistochemical study of 3 cases].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of epithelioid sarcoma-like hemangioendothelioma (ES-H). METHODS: The clinical, radiologic and pathologic features of three cases of ES-H were analyzed. RESULTS: All the 3 cases occurred in male adults. The age ranged from 44 to 53 years. The presentations included left neck mass, iliac pain and bilateral shoulder masses. Histologically, ES-H was composed of a mixture of spindle and epithelioid tumor cells. Transition between the two cell types was demonstrated. The tumor cells were arranged in compact sheets, vague nodules or intersecting fascicles, amongst a collagenous stroma. Central coagulative necrosis was identified in one case, reminiscent the morphology that seen in epithelioid sarcoma. There was no evidence of angiogenesis, though focal presence of intracytoplasmic vacuoles was seen in one case, as in classic examples of epithelioid hemangioendothelioma. Immunohistochemical study showed that the tumor cells expressed both epithelial (AE1/AE3, CAM5.2 and epithelial membrane antigen) and endothelial (CD31, Fli-1 and factor VIII-related antigen) markers. Two of the cases were also positive for CD34. All of the patients were treated by surgical resection. Two patients remain well at 14-month and 9-month follow up, respectively. The remaining patient had repeated local recurrences during a 6-year period. CONCLUSIONS: ES-H represents a rare morphologic type of hemangioendothelioma. It has some overlapping histologic features with epithelioid sarcoma and epithelioid hemangioendothelioma. The endothelial nature of ES-H is difficult to be verified on the basis of morphologic examination alone. Confirmation of the diagnosis with immunohistochemistry is necessary. ES-H is likely related to epithelioid hemangioendothelioma and may represent a cellular spindle cell variant of epithelioid hemangioendothelioma.

Probiotic Interventions Alleviate Food Allergy Symptoms Correlated With Cesarean Section: A Murine Model.

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

Two Different 1-Week Quadruple Therapies Given Back-to-Back Consecutive Therapy for Difficult-to-Treat Helicobacter pylori Infection: A Pilot Study.

INTRODUCTION: We aim to evaluate the efficacy of 2 different 1-week quadruple therapies given back-to-back consecutive therapy in patients with difficult-to-treat Helicobacter pylori infection. METHODS: Patients with proven H. pylori infection were recruited after >3 failed standard quadruple eradication. They received consecutive therapy consisting of esomeprazole 40 mg or rabeprazole 20 mg twice daily, amoxicillin 1,000 mg twice daily, tetracycline 500 mg 4 times daily, and furazolidone 100 mg 3 times daily for the first 7 days, followed by colloidal bismuth pectin 200 mg twice daily in place of furazolidone 100 mg for another 7 days. Eradication rates, treatment-emergent adverse events (TEAEs), and compliance were assessed. RESULTS: Sixty-five patients were enrolled. The mean number of previous eradications was 3.6 (range: 3-7). The intention-to-treat and per-protocol eradication rates were 90.8% (59/65) and 95.1% (58/61). In total, 23.4% (15/64) of patients experienced drug-related TEAEs. No serious adverse events were observed. None of the patients required treatment for TEAEs, and 95.3% (61/64) showed good compliance. Overall, 51 patients (78.5%) were with the available antimicrobial susceptibility testing results. The resistance rates to clarithromycin, metronidazole, levofloxacin, and amoxicillin were 60.8% (31/51), 100% (51/51), 70.6% (36/51), and 2.0% (1/51), respectively. No resistance was detected to either furazolidone or tetracycline. However, in 54.9% of patients (28/51), H. pylori was resistant to 3 antibiotics (metronidazole, levofloxacin, and clarithromycin). DISCUSSION: Consecutive therapy, including amoxicillin, tetracycline, and furazolidone, achieved a good eradication rate (>90%), with desirable compliance and tolerability in difficult-to-treat H. pylori infection.

Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner.

Levels of type 2 cytokines are elevated in the blood and intestinal tissues of ulcerative colitis (UC) patients in the active phase; this phenomenon indicates the participation of type 2 immune response in UC progression. The beneficial effects of melatonin in dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) colitis models have been illustrated, but its role in the oxazolone (Oxa)-induced colitis model (driven by type 2 immune response) remains relatively unknown. We investigated the relationship between melatonin concentration and the severity of UC, revealing a significantly negative correlation. Subsequently, we investigated the effects of melatonin in Oxa-induced colitis mice and the potential underlying mechanisms. Administration of melatonin significantly counteracted body weight loss, colon shortening, and neutrophil infiltration in Oxa-induced colitis mice. Melatonin treatment mitigated Oxa-induced colitis by suppressing type 2 immune response. In addition, melatonin attenuated intestinal permeability by enhancing the expression of ZO-1 and occludin in colitis mice. Interestingly, the protective effect of melatonin was abolished when the mice were co-housed, indicating that the regulation of gut microbiota by melatonin was critical in alleviating Oxa-induced colitis. Subsequently, 16S rRNA sequencing was performed to explore the microbiota composition. Decreased richness and diversity of intestinal microbiota at the operational taxonomic unit (OTU) level resulted from melatonin treatment. Melatonin also elevated the abundance of Bifidobacterium, a well-known probiotic, and reduced proportions of several harmful bacterial genera, such as Desulfovibrio, Peptococcaceae, and Lachnospiraceae. Fecal microbiota transplantation (FMT) was used to explore the role of microbiota in the function of melatonin in Oxa-induced colitis. Microbiota transplantation from melatonin-treated mice alleviated Oxa-induced colitis, suggesting that the microbiome participates in the relief of Oxa-induced colitis by melatonin. Our findings demonstrate that melatonin ameliorates Oxa-induced colitis in a microbiota-dependent manner, suggesting the therapeutic potential of melatonin in treating type 2 immunity-associated UC.

Fusobacterium nucleatum Causes Microbial Dysbiosis and Exacerbates Visceral Hypersensitivity in a Colonization-Independent Manner.

Background: Microbial dysbiosis is closely associated with visceral hypersensitivity and is involved in the pathogenesis of irritable bowel syndrome (IBS), but the specific strains that play a key role have yet to be identified. Previous bioinformatic studies have demonstrated that Fusobacterium is a shared microbial feature between IBS patients and maternal separation (MS)-stressed rats. In this study, we assessed the potential role of Fusobacterium nucleatum (F. nucleatum) in the pathogenesis of IBS. Methods: Fecal samples of patients with diarrhea predominant-IBS (IBS-D) and healthy controls were obtained. An MS rat model was established to receive gavage of either F. nucleatum or normal saline. Visceral sensitivity was evaluated through colorectal distension test, and fecal microbiota was analyzed by 16S rRNA gene sequencing. F. nucleatum-specific IgA levels in fecal supernatants were assessed by western blotting. The antigen reacted with the specific IgA of F. nucleatum was identified by mass spectrometry and the construction of a recombinant Escherichia coli BL21 (DE3). Results: IBS-D patients showed a lower Shannon index and a higher abundance of Fusobacterium. The F. nucleatum-gavage was shown to exacerbate visceral hypersensitivity in MS rats, with both the F. nucleatum-gavage and MS causing a decreased Shannon index and a clear segregation of fecal microbiota. In addition, specific IgA against F. nucleatum was detected in fecal supernatants of both the F. nucleatum-gavaged rats and the IBS-D patients. The FomA protein, which is a major outer membrane protein of F. nucleatum, was confirmed to react with the specific IgA of F. nucleatum in fecal supernatants. Conclusion: Fusobacterium increased significantly in IBS-D patients, and F. nucleatum was involved in the pathogenesis of IBS by causing microbial dysbiosis and exacerbating visceral hypersensitivity in a colonization-independent manner. Meanwhile, F. nucleatum was found to induce an increase in specific secretory IgA through FomA.