Siderophore-harboring gut bacteria and fecal siderophore genes for predicting the responsiveness of fecal microbiota transplantation for active ulcerative colitis.

BACKGROUND: Predictive markers for fecal microbiota transplantation (FMT) outcomes in patients with active ulcerative colitis (UC) are poorly defined. We aimed to investigate changes in gut microbiota pre- and post-FMT and to assess the potential value in determining the total copy number of fecal bacterial siderophore genes in predicting FMT responsiveness. METHODS: Patients with active UC (Mayo score ≥ 3) who had undergone two FMT procedures were enrolled. Fecal samples were collected before and 8 weeks after each FMT session. Patients were classified into clinical response and non-response groups, based on their Mayo scores. The fecal microbiota profile was accessed using metagenomic sequencing, and the total siderophore genes copy number via quantitative real-time polymerase chain reaction. Additionally, we examined the association between the total siderophore genes copy number and FMT efficacy. RESULTS: Seventy patients with UC had undergone FMT. The clinical response and remission rates were 50% and 10% after the first FMT procedure, increasing to 72.41% and 27.59% after the second FMT. The cumulative clinical response and clinical remission rates were 72.86% and 25.71%. Compared with baseline, the response group showed a significant increase in Faecalibacterium, and decrease in Enterobacteriaceae, consisted with the changes of the total bacterial siderophore genes copy number after the second FMT (1889.14 vs. 98.73 copies/ng, P < 0.01). Virulence factor analysis showed an enriched iron uptake system, especially bacterial siderophores, in the pre-FMT response group, with a greater contribution from Escherichia coli. The total baseline copy number was significantly higher in the response group than non-response group (1889.14 vs. 94.86 copies/ng, P < 0.01). A total baseline copy number cutoff value of 755.88 copies/ng showed 94.7% specificity and 72.5% sensitivity in predicting FMT responsiveness. CONCLUSIONS: A significant increase in Faecalibacterium, and decrease in Enterobacteriaceae and the total fecal siderophore genes copy number were observed in responders after FMT. The siderophore genes and its encoding bacteria may be of predictive value for the clinical responsiveness of FMT to active ulcerative colitis.

Geometric Remodeling of Nitrilase Active Pocket Based on ALF-Scanning Strategy To Enhance Aromatic Nitrile Substrate Preference and Catalytic Efficiency.

Nitrilase can catalyze nitrile compounds to generate corresponding carboxylic acids. Nitrilases as promiscuous enzymes can catalyze a variety of nitrile substrates, such as aliphatic nitriles, aromatic nitriles, etc. However, researchers tend to prefer enzymes with high substrate specificity and high catalytic efficiency. In this study, we developed an active pocket remodeling (ALF-scanning) based on modulating the geometry of the nitrilase active pocket to alter substrate preference and improve catalytic efficiency. Using this strategy, combined with site-directed saturation mutagenesis, we successfully obtained 4 mutants with strong aromatic nitrile preference and high catalytic activity, W170G, V198L, M197F, and F202M, respectively. To explore the synergistic relationship of these 4 mutations, we constructed 6 double-combination mutants and 4 triple-combination mutants. By combining mutations, we obtained the synergistically enhanced mutant V198L/W170G, which has a significant preference for aromatic nitrile substrates. Compared with the wild type, its specific activities for 4 aromatic nitrile substrates are increased to 11.10-, 12.10-, 26.25-, and 2.55-fold, respectively. By mechanistic dissection, we found that V198L/W170G introduced a stronger substrate-residue π-alkyl interaction in the active pocket and obtained a larger substrate cavity (225.66 Å3 to 307.58 Å3), making aromatic nitrile substrates more accessible to be catalyzed by the active center. Finally, we conducted experiments to rationally design the substrate preference of 3 other nitrilases based on the substrate preference mechanism and also obtained the corresponding aromatic nitrile substrate preference mutants of these three nitrilases and these mutants with greatly improved catalytic efficiency. Notably, the substrate range of SmNit is widened. IMPORTANCE In this study, the active pocket was largely remodeled based on the ALF-scanning strategy we developed. It is believed that ALF-scanning not only could be employed for substrate preference modification but might also play a role in protein engineering of other enzymatic properties, such as substrate region selectivity and substrate spectrum. In addition, the mechanism of aromatic nitrile substrate adaptation we found is widely applicable to other nitrilases in nature. To a large extent, it could provide a theoretical basis for the rational design of other industrial enzymes.

Oxidation of Membrane Lipids Alters the Activity of the Human Serotonin 1A Receptor.

Lipid oxidation has significant effects on lipid bilayer properties; these effects can be expected to extend to interactions between the lipid bilayer and integral membrane proteins. Given that G protein-coupled receptor (GPCR) activity is known to depend on the properties of the surrounding lipid bilayer, these proteins represent an intriguing class of molecules in which the impact of lipid oxidation on protein behavior is studied. Here, we study the effects of lipid oxidation on the human serotonin 1A receptor (5-HT1AR). Giant unilamellar vesicles (GUVs) containing integral 5-HT1AR were fabricated by the hydrogel swelling method; these GUVs contained polyunsaturated 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine (PLinPC) and its oxidation product 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) at various ratios. 5-HT1AR-integrated GUVs were also fabricated from lipid mixtures that had been oxidized by extended exposure to the atmosphere. Both types of vesicles were used to evaluate 5-HT1AR activity using an assay to quantify GDP-GTP exchange by the coupled G protein α subunit. Results indicated that 5-HT1AR activity increases significantly in bilayers containing oxidized lipids. This work is an important step in understanding how hyperbaric oxidation can change plasma membrane properties and lead to physiological dysfunction.

Comparison of the Therapeutic Effects of Iodine-125 Seed Implantation and Conventional Radiochemotherapy for Advanced Esophageal Cancer.

BACKGROUND: The purpose of this study was to explore the feasibility, safety and efficacy of iodine-125 seed implantation in the treatment of dysphagia of advanced esophageal cancer. METHODS: We retrospectively analyzed patients with advanced esophageal cancer who underwent EUS-guided iodine-125 seed implantation or conventional chemoradiotherapy in our hospital. The propensity score match was used to reduce the baseline differences. RESULTS: A total of 127 patients were enrolled, 17 patients received EUS-guided iodine 125 seed implantation (Group A), 31 patients received radiotherapy (Group B), 38 patients received chemotherapy (Group C) and 41 patients received chemotherapy combined with radiotherapy (Group D). At half month postoperatively, the dysphagia remission rate in Group A (100%) was better than that in Groups B (39.3%), C (20%), D (15.8%), respectively, in the original cohort (P < 0.01); At 1 month postoperatively, the dysphagia remission rate in Group A (86.7%) was better than that in Group B (57.1%) (P > 0.05), Group C (25.7%) (P < 0.05) and Group D (34.2%) (P < 0.05), respectively, in the original cohort. There was no statistically significant difference in median overall survival (OS) between Group A (16 months) and Group B (37 months) (P = 0.149), and between Group A (16months) and Group C (16 months) (P = 0.918) in the original cohort. The mean OS of Group D (54 months) was better than that of Group A (20 months) in the original cohort (P = 0.031). The incidences of grade ≥2 myelosuppression in Groups B, C, and D were 12.9%, 28.9%, and 43.9%, respectively; the incidence of grade ≥2 gastrointestinal adverse events in Groups B, C, and D were 12.9%, 15.8%, 12.2%, respectively. No serious adverse events were found in Group A. The radiation dose around the patient was reduced to a safe range after the distance from the implantation site was more than 1 m (4.2 ± 2.6 µSv/h) or with lead clothing (0.1 ± 0.07 µSv/h). CONCLUSIONS: Compared with conventional radiotherapy or chemotherapy alone, iodine-125 seed implantation might improve dysphagia more quickly and safely, further clinical data is needed to verify whether it could effectively prolong the OS of patients.

Analysis of risk factors for post-endoscopic papillectomy bleeding.

BACKGROUND: Endoscopic papillectomy (EP) is an effective treatment for ampullary lesions but technically challenging because of anatomical specificities concerning the high rate of adverse events. Bleeding is one of the most feared complications and can be potentially life-threatening. AIM: To study the risk factors for bleeding after EP are presented with the goal of establishing preventive measures. METHODS: A total of 173 consecutive patients with ampullary lesions undergone EP from January 2006 to October 2020 were enrolled in this study. They were divided into a bleeding group and a non-bleeding group depending on whether postoperative bleeding occurred. Related factors were analyzed by univariate and multivariate logistics regression. RESULTS: Postoperative bleeding was experienced in 33 patients (19.07%). Multivariate analysis also identified intraoperative bleeding (OR: 4.38, 95% CI: 1.87-11.15, p = .001) and endoscopic closure (OR: 0.25, 95% CI: 0.10-0.58, p = .001) as independent factors significantly associated with bleeding after EP. Lesion size (≥3 cm) was shown as an independent factor significantly associated with intraoperative bleeding (OR: 4.25, 95% CI: 1.21-16.44, p = .028). CONCLUSIONS: This retrospective evaluation found that endoscopic closure was associated with reduced risk and intraoperative bleeding with increased risk of bleeding after EP. Lesion size may indirectly influence the risk of postoperative bleeding by increasing the risk of intraoperative bleeding.

Endoscopic follow-up of mucosal defect after hot versus cold snare polypectomy in animal model.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) has received increasing attention in recent years, but few studies have assessed defect repair after polypectomy. Therefore, we compared the repair of mucosal defect after CSP and hot snare polypectomy (HSP) in a rabbit model. METHODS: Resection of normal colonic mucosa using both HSP and CSP were performed in 40 male New Zealand white rabbits by an experienced endoscopist. Follow-up colonoscopy was performed after 7 and 15 days by another endoscopist. We assessed mucosal defect repair, status of healing, scar formation, and intraoperative or delayed complications (including perforation and bleeding). RESULTS: Eight animals died of intraoperative or delayed perforation; follow-up colonoscopy was performed in 32 animals. On follow-up colonoscopy at 7 days after operation, 78.1% cases in the CSP group showed healing of mucosal defect compared with none in the HSP group (P < 0.001); mucosal repair score in the CSP group was significantly higher than HSP group (P < 0.001). On follow-up colonoscopy at 15 days, mucosal defect after CSP had completely healed in all cases (100%) versus 96.9% after HSP (P = 0.313). Among these healed defects, scar formation was observed in 2 of 32 cases in the CSP group compared with 19 of 31 in the HSP group (P < 0.001). Intraoperative perforation rate was significantly higher in the HSP group (15% vs 2.5%; P = 0.048). CONCLUSIONS: Mucosal defect repair after CSP is quicker compared with HSP and is more likely to result in scarless healing. HSP is more likely to cause perforation in the thin colon walls.

2D Metal-Organic Frameworks (MOFs) for High-Performance BatCap Hybrid Devices.

Two identical layered metal-organic frameworks (MOFs) (CoFRS and NiFRS) are constructed by using flexible 1,10-bis(1,2,4-triazol-1-yl)decane as pillars and 1,4-benzenedicarboxylic acid as rigid linkers. The single-crystal structure analysis indicates that the as-synthesized MOFs possess fluctuant 2D networks with large interlayer lattices. Serving as active electrode elements in supercapacitors, both MOFs deliver excellent rate capabilities, high capacities, and longstanding endurances. Moreover, the new intermediates in two electrodes before and after long-lifespan cycling are also examined, which cannot be identified as metal hydroxides in the peer reports. After assembled into battery-supercapacitor (BatCap) hybrid devices, the NiFRS//activated carbon (AC) device displays better electrochemical results in terms of gravimetric capacitance and cycling performance than CoFRS//AC devices, and a higher energy-density value of 28.7 Wh kg-1 compared to other peer references with MOFs-based electrodes. Furthermore, the possible factors to support the distinct performances are discussed and analyzed.

Improving the biocatalytic performance of co-immobilized cells harboring nitrilase via addition of silica and calcium carbonate.

To improve nicotinic acid (NA) yield and meet industrial application requirements of sodium alginate-polyvinyl alcohol (SA-PVA) immobilized cells of Pseudomonas putida mut-D3 harboring nitrilase, inorganic materials were added to the SA-PVA immobilized cells to improve mechanical strength and mass transfer performance. The concentrations of inorganic materials were optimized to be 2.0% silica and 0.6% CaCO3. The optimal pH and temperature for SA-PVA immobilized cells and composite immobilized cells were both 8.0 and 45 °C, respectively. The half-lives of composite immobilized cells were 271.48, 150.92, 92.92 and 33.12 h, which were 1.40-, 1.35-, 1.22- and 1.63-fold compared to SA-PVA immobilized cells, respectively. The storage stability of the composite immobilized cells was slightly increased. The composite immobilized cells could convert 14 batches of 3-cyanopyridine with feeding concentration of 250 mM and accumulate 418 g ·L-1 nicotinic acid, while the SA-PVA immobilized cells accumulated 346 g L-1 nicotinic acid.

Transvaginal natural orifice transluminal endoscopic surgery in the diagnosis of ascites of unknown origin.

BACKGROUND AND AIMS: Natural orifice transluminal endoscopic surgery (NOTES) has been established in animal models and human studies, but few clinical studies have investigated transvaginal NOTES in the diagnosis of unexplained refractory ascites. We aimed to assess the feasibility, efficacy, and safety of transvaginal NOTES for the diagnosis of unexplained ascites in female patients. METHODS: A prospective study was done involving 3 female patients with unexplained ascites. After general anesthesia and disinfection, a 1.0-cm incision was made in the posterior fornix of the vagina. A gastroscope was inserted into the abdominal cavity through the transvaginal incision and an artificial pneumoperitoneum was created; NOTES peritoneoscopy was performed to scrutinize the pathologic changes. Endoscopic biopsy specimens were obtained for pathologic examination. The transvaginal incision was closed by direct suturing. RESULTS: Transvaginal NOTES for diagnostic peritoneoscopy was successfully performed in 3 patients. The mean operative time was 61 minutes. The estimated blood loss was 5 to 10 mL. The pathologic diagnoses were tuberculosis for all patients, and the symptoms and ascites disappeared after antituberculosis therapy. During the 4-year follow-up, no clinically significant adverse events occurred in any patient after NOTES. No patient experienced an annex inflammation, vaginitis, dyspareunia, or sexual dysfunction. All patients were comfortable and satisfied with the nonscarring surgical procedure. CONCLUSIONS: Transvaginal NOTES for the diagnosis of unexplained ascites is feasible, effective, and safe. This method had no long-term effect on female sexual function and is particularly suitable for women who have special aesthetic requirements. (Clinical trial registration number: ChiCTR-TRC-10001053.).

Gender, Age, and Concomitant Diseases of Colorectal Diverticulum in China: A Study of 7,964 Cases.

AIM: To analyze the epidemiological features of colorectal diverticulum (CRD) in China. METHODS: We retrospectively analyzed CRD patients in 8 tertiary hospitals located in 5 regions of China from 2000 to 2016. The detection rates, number and distribution, demographic information, concomitant disorders, and their associations were investigated. RESULTS: Of 3,446,118 cases, 7,964 (2.3%) were CRD with a mean age of 56 years (11-92 years). The detection rate increased yearly and with increasing age. Males had a higher detection rate than females (3.0 vs. 1.47%, p < 0.01) and 1.8-times higher increase rate. The detection rate increased with age; however, females of > 60 years had a 2.8-times increasing rate than males. CRD occurred most frequently in the right-side colon, followed by rectum. Multiple diverticula were common in males and increased with age, with a 3-times higher increase rate than single lesion. Single-segment CRD occurred more frequently in males than in females (80.1 vs. 76.4%, p < 0.01). Concurred colon polyps were seen in 51.05% cases. CONCLUSION: CRD detection rates increased annually and with age, particularly in senior females in China. Multiple diverticula were common in males and increased with age. CRD was predominant in the right-side colon. Polyps are the most common comorbidity associated with CRD.

New experience of endoscopic papillectomy for ampullary neoplasms.

AIM: To establish the clinical value of endoscopic papillectomy for duodenal papillary tumor based on endoscopic and clinical characteristics. PATIENTS AND METHODS: This single-center, retrospective study included 110 patients with duodenal papillary tumor who underwent endoscopic papillectomy between January 2006 and April 2017 at the gastrointestinal endoscopic center of the Chinese PLA General Hospital. Clinical data, postoperative pathology, procedure-related complications, and therapeutic outcomes were analyzed. RESULTS: Endoscopic papillectomy was technically feasible in all patients, and was mainly performed by four experienced endoscopists. The primary success rate of endoscopic papillectomy for ampullary neoplasms was 78.2%. A total of 13 patients experienced recurrence during a mean follow-up period of 16.28 months (range 6-132 months), the predictive factors that were related to recurrence were complete resection (53.8% vs. 94.2%; P = 0.001), and final pathology findings (P = 0.001). Delayed hemorrhage, the most common procedure-related complication, occurred in 20% (22/110) of patients and was significantly related to intraoperative bleeding (P = 0.042). Pancreatitis was the second most common complication, which was closely related to intraoperative bleeding requiring intervention (P = 0.040) and larger tumor size (P = 0.044). Histology, type of resection, stent placement, sphincterotomy, and duration of procedure were not related to post-procedure hemorrhage or pancreatitis. Older age (63.7 ± 13.5 vs. 57.4 ± 12.2; P = 0.033), jaundice (47.8% vs. 13.8%; P = 0.001), endoscopic forceps biopsy diagnosis of high-grade intraepithelial neoplasia (82.6% vs. 14.9%; P = 0.001), tumor size ≥ 2 cm (60.9% vs. 34.5%; P = 0.022), and dilation of the bile duct (34.8% vs. 9.2%; P = 0.006) were clinical features for ampullary carcinoma. The rate of complete resection (52.2% vs. 92.0%; P = 0.001) and recurrence (34.8% vs. 6.8%; P = 0.001) were also related to the diagnosis of ampullary carcinoma at final pathology. CONCLUSIONS: Endoscopic papillectomy is a feasible and reasonable option for both diagnosis and treatment of tumors of the duodenal papilla in properly selected patients.

[A pilot study of treating ulcerative colitis with fecal microbiota transplantation].

OBJECTIVE: To explore the procedure, effectiveness and safety of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). METHODS: Seven patients (6 men and 1 woman, aged 17-66 years) with active UC were treated with FMT through endoscopic duodenal infusion or combined endoscopic duodenal and colonic approaches. The clinical manifestations and laboratory results were recorded before and after FMT respectively. Disease response was evaluated with Mayo scores. Fresh fecal suspension prepared from healthy donors who were strictly screened, was infused into patients' intestinal tracts within 6 hours. RESULTS: The average disease duration of 7 patients with UC was (9.1 ± 8.5) years (range 0.5-24.0 years). One patient underwent FMT for three times and one for twice, while the other five were treated for once. The follow-up time was (98.6 ± 70.8) days (30-210 days). All patients achieved some extent of improvements with the reduction of Mayo scores 7, 4, 6, 5, 6, 9 and 9, respectively. Transient fever, diarrhea and abdominal distension were observed in some patients after FMT, while alleviated spontaneously 2-3 days after the procedure. One patient had high fever and mild ascites caused by secondary infections, which were controlled by the symptomatic treatment and antibiotics. Severe adverse reactions were not found. CONCLUSIONS: FMT is effective to active UC, the short-term side effects and complications are basically acceptable and controllable. The long-term efficacy and risks of FMT need to be verified further.

Anisotropic Scale-Invariant Ellipse Detection.

Detecting ellipses poses a challenging low-level task indispensable to many image analysis applications. Existing ellipse detection methods commonly encounter two fundamental issues. First, inferior detection accuracy could be incurred on a small ellipse than that on a large one; this introduces the scale issue. Second, inferior detection accuracy could be yielded along the minor axis than along the major one of the same ellipse; this leads to the anisotropy issue. To address these issues simultaneously, a novel anisotropic scale-invariant (ASI) ellipse detection methodology is proposed. Our basic idea is to perform ellipse detection in a transformed image space referred to as the ellipse normalization (EN) space, in which the desired ellipse from the original image is 'normalized' to the unit circle. With the establishment of the EN-space, an analytical ellipse fitting scheme and a set of distance measures are developed. Theoretical justifications are then derived to prove that both our ellipse fitting scheme and distance measures are invariant to anisotropic scaling, and thus each ellipse can be detected with the same accuracy regardless of its size and ellipticity. By incorporating these components into two recent state-of-the-art algorithms, two ASI ellipse detectors are finally developed and exploited to verify the effectiveness of our proposed methodology.

Microbiota treatment of functional constipation: Current status and future prospects.

Functional constipation (FC) is a common disorder that is characterized by difficult stool passage, infrequent bowel movement, or both. FC is highly prevalent, recurs often, accompanies severe diseases, and affects quality of life; therefore, safe and effective therapy with long-term benefits is urgently needed. Microbiota treatment has potential value for FC treatment. Microbiota treatments include modulators such as probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation (FMT). Some probiotics and prebiotics have been adopted, and the efficacy of other microbiota modulators is being explored. FMT is considered an emerging field because of its curative effects; nevertheless, substantial work must be performed before clinical implementation.

Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to respiratory failure, and eventually death. However, there is a lack of effective treatments for ALS. Here we report the results of fecal microbiota transplantation (FMT) in two patients with late-onset classic ALS with a Japan ALS severity classification of grade 5 who required tracheostomy and mechanical ventilation. In both patients, significant improvements in respiratory function were observed following two rounds of FMT, leading to weaning off mechanical ventilation. Their muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in beneficial Bacteroides species (Bacteroides stercoris, Bacteroides uniformis, Bacteroides vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated levels of metabolites involved in arginine biosynthesis and decreased levels of metabolites involved in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and provide new insights into ALS in general.

Characterization of biliary and duodenal microbiota in patients with primary and recurrent choledocholithiasis.

Purpose: To explore the biliary and duodenal microbiota features associated with the formation and recurrence of choledocholithiasis (CDL). Methods: We prospectively recruited patients with primary (P-CDL, n = 29) and recurrent CDL (R-CDL, n = 27) for endoscopic retrograde cholangiopancreatography (ERCP). Duodenal mucosa (DM), bile and bile duct stones (BDS) samples were collected in P- and R-CDL patients. DM samples were also collected in 8 healthy controls (HC). The microbiota profile analysis was performed with 16S rRNA gene sequencing. Results: Short-course antibiotic application before ERCP showed no significant effects in alpha and beta diversities of the biliary and duodenal microbiota in CDL. Alpha diversity showed no difference between DM and bile samples in CDL. The duodenal microbial richness and diversity was lower in both P- and R-CDL than HC. The biliary microbiota composition showed a high similarity between P- and R-CDL. Fusobacterium and Enterococcus were higher abundant in DM, bile, and BDS samples of R-CDL than P-CDL, as well as Escherichia and Klebsiella in bile samples of R-CDL. The enriched duodenal and biliary bacteria in CDL were closely associated with cholecystectomy, inflammation and liver dysfunction. The bile-associated microbiota of R-CDL expressed enhanced capacity of D-glucuronide and D-glucuronate degradation, implicating an elevated level of ß-glucuronidase probably produced by enriched Escherichia and Klebsiella in bile. Conclusions: The duodenal microbiota was in an imbalance in CDL. The duodenal microbiota was probably the main source of the biliary microbiota and was closely related to CDL formation and recurrence. Enterococcus, Fusobacterium, Escherichia and Klebsiella might contribute to CDL recurrence. Clinical trials: The study was registered at the Chinese Clinical Trial Registry (https://www.chictr.org.cn/index.html, ChiCTR2000033940). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00267-2.

The role of EUS-guided iodine-125 seed implantation in patients with unresectable ampullary cancer after relief of obstructive jaundice.

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer.

Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.

The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE: The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

Bile acid-induced expression of farnesoid X receptor as the basis for superiority of internal biliary drainage in experimental biliary obstruction.

AIMS AND OBJECTIVES: The aim is to determine the efficacy of internal and external biliary drainage (ED) with special reference to the effect of bile acid on intestinal epithelium during experimental biliary obstruction. Methods. A total of 59 male Sprague Dawley rats were randomly assigned to four groups: (I) sham operation (SH); (II) obstructive jaundice (OJ); (III) OJ and ED; and (IV) OJ and internal biliary drainage (ID). The animals underwent surgical ligation of the bile duct on day 1. They were reoperated on day 8 for biliary drainage procedure. Blood cultures were obtained from portal vein and inferior vena cava on day 15. Samples were also drawn for serum total bile acid (TBA) and white blood cell (WBC) counts. The terminal ileum was harvested to study the tight junction-associated protein ("occludin") and bile acid receptor ("farnesoid X receptor" [FXR]) using immunohistochemical method. RESULTS: Serum TBA (118.9 ± 39.0 µmol/L) and WBC (11.4 ± 2.7 × 10(9)/L) were significantly increased (p = 0.001) after bile duct ligation as compared with SH rats (38.0 ± 15.0 µmol/L and 5.5 ± 1.0 × 10(9)/L, respectively; p = 0.001). The resulting mucosal lesion was high grade and the expressions of FXR and Occludin were decreased. After ED, there was slight decrease in total WBCs, whereas TBA levels declined significantly. The expression of FXR was minimal and Occludin showed no change (ED vs. OJ: p = 0.533). However, both WBC and TBA decreased after ID. The ileal structure, grade of mucosal lesion, and expression of FXR/Occludin were comparable with SH group (p > 0.05). The rate of bacterial translocation was: 57.1% (OJ); 62.5% (ID); and 80% (ED) with identical strains in cultures from the portal vein and inferior vena cava. CONCLUSION: Downregulation of TBA/FXR expression during biliary obstruction results in damage to intestinal epithelium. Unlike ED, ID restores FXR/Occludin expression in the terminal ileum through reappearance of intestinal bile acid, which thus appears to be a key factor in maintaining integrity of the epithelial barrier.

Clinical features and comprehensive diagnosis of autoimmune pancreatitis in China.

AIM: To search for the key factors of autoimmune pancreatitis (AIP) in China and to improve the early identification of AIP in order to avoid misdiagnosing it as pancreatic carcinoma. METHODS: Clinical, imaging, laboratory, and pathological data about AIP were collected and analyzed from 1996 to 2011 in The Chinese People's Liberation Army General Hospital. RESULTS: A total of 33 patients (male 29, female 4) aged 35-76 years (52.3 ± 9.3 years) meeting the International Consensus Diagnostic Criteria for type 1 (n = 32) or type 2 (n = 1) AIP were included. With improved understanding of AIP, the misdiagnosis rate and unnecessary laparotomy rate was decreased from 95.7% (22/23) and 91.3% (21/23) before 2006, to 20.0% (2/10) (p = 0.001) and 0.0% (p = 0.001) respectively after 2006. The major symptoms were jaundice in (24/33, 72.7%) and abdominal pain (12/33, 36.4%). Half of the patients had other accompanied autoimmune disorders. Laboratory tests showed an elevated level of serum IgG in 9 out of 11 patients (81.8%) and an increased eosinophil count in 16 out of 33 patients (48.5%). The serum IgG4 levels were twice the upper limit of the normal value. CT scan showed a low-contrast margin characterized by a capsule-like rim in 24 of 32 patients (75.0%). Pathologic examinations showed fibrosis and infiltration of massive lymphocytes and plasma cells in the pancreas. Prednisone was given to the patients and proved to be quite effective for all of them (12/12, 100%). CONCLUSION: Type 1 AIP shows a sex predilection compared with type 2 AIP in China. In order to diagnose AIP exactly, a comprehensive strategy, especially including imaging and pathological examination, should be used. With growing awareness, fewer AIP patients with this diagnosis would be misdiagnosed and incorrectly treated.