ARRDC3 inhibits liver fibrosis and epithelial-to-mesenchymal transition via the ITGB4/PI3K/Akt signaling pathway.

OBJECTIVE: The effect of ARRDC3 has not been reported in liver fibrosis. Our study aimed to explore the molecular mechanisms by which ARRDC3 attenuates liver fibrosis. METHODS: The vectors pcDNA-ARRDC3 (which promotes ARRDC3 expression) and si-ITGB4 (which blocks IGTB4 expression) and their negative controls were constructed. The rat liver fibrosis model was established by intraperitoneal injection of CCl4 with or without intraperitoneal injection of pcDNA-ARRDC3. ELISA was used to detect the concentrations of γ-GGT, ALT, AST, and ALP in serum. HE, Masson's trichome, and Sirius red staining were used to observe the pathological changes in liver tissue. LX-2 cells were treated with TGF-ß, and pcDNA-ARRDC3 or si-ITGB4RNA was transfected to promote ARRDC3 expression or knock down ITGB4 expression. Western blotting was used to detect the expression levels of proteins. RESULTS: ARRDC3 effectively reduced liver injury, improved liver function, and decreased collagen production and deposition in the CCl4-induced rat fibrosis model. The studies showed that overexpressed ARRDC3 remarkably reduced the expression of E-cadherin and collagen-related protein and increased the expression of mesenchymal markers and EMT-related transcription factors, consequently inhibiting the activity of the ITGB4/PI3K/Akt signaling pathway. CONCLUSION: Our study shows that ARRDC3 could ameliorate CCl4-induced liver fibrosis and EMT progression via the ITGB4/PI3K/Akt signaling pathway, which provides a meaningful reference for the clinical targeted treatment of liver fibrosis.

Characteristics and prognosis of isolated small-bowel Crohn's disease.

BACKGROUND: Previous studies suggest that Crohn's disease (CD) with both small bowel and colon involvement is more serious than colonic CD. However, clinical features of isolated small-bowel CD have not been fully investigated. METHODS: In this retrospective case-control study, 89 patients were divided into two groups according to capsule endoscopy, ileocolonoscopy, and enhanced computed tomography results. The case group was isolated small-bowel CD (n = 50) and the control group was CD with both small bowel and colon involvement (n = 39). We collected data of the patients and analyze it. RESULTS: In univariate analysis, isolated small-bowel CD group had higher percentage of stricture, Lewis score, platelet, plateletcrit and lower Harvey-Bradshaw index, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate. In multivariable analysis, it had lower Harvey-Bradshaw index (p = 0.000), which meaned relatively mild symptoms. However, it had higher Lewis score (p = 0.007), which meaned more serious small-bowel inflammation. The Kaplan-Meier survival curve also suggested that isolated small-bowel CD patients were more likely to accept partial small intestinal resection surgery (p = 0.029). CONCLUSIONS: Isolated small-bowel CD is easily overlooked for milder clinical symptoms and relatively limited lessions, but severe small-bowel histological injury results in owing worse clinical outcomes. Clinicians should pay more attention to the isolated small-bowel CD and take aggressive intervention during therapy.

Automated detection of small bowel lesions based on capsule endoscopy using deep learning algorithm.

BACKGROUND: In order to overcome the challenges of lesion detection in capsule endoscopy (CE), we improved the YOLOv5-based deep learning algorithm and established the CE-YOLOv5 algorithm to identify small bowel lesions captured by CE. METHODS: A total of 124,678 typical abnormal images from 1,452 patients were enrolled to train the CE-YOLOv5 model. Then 298 patients with suspected small bowel lesions detected by CE were prospectively enrolled in the testing phase of the study. Small bowel images and videos from the above 298 patients were interpreted by the experts, non-experts and CE-YOLOv5, respectively. RESULTS: The sensitivity of CE-YOLOv5 in diagnosing vascular lesions, ulcerated/erosive lesions, protruding lesions, parasite, diverticulum, active bleeding and villous lesions based on CE videos was 91.9 %, 92.2 %, 91.4 %, 93.1 %, 93.3 %, 95.1 %, and 100 % respectively. Furthermore, CE-YOLOv5 achieved specificity and accuracy of more than 90 % for all lesions. Compared with experts, the CE-YOLOv5 showed comparable overall sensitivity, specificity and accuracy (all P > 0.05). Compared with non-experts, the CE-YOLOv5 showed significantly higher overall sensitivity (P < 0.0001) and overall accuracy (P < 0.0001), and a moderately higher overall specificity (P = 0.0351). Furthermore, the time for AI-reading (5.62 ± 2.81 min) was significantly shorter than that for the other two groups (both P < 0.0001). CONCLUSIONS: CE-YOLOv5 diagnosed small bowel lesions in CE videos with high sensitivity, specificity and accuracy, providing a reliable approach for automated lesion detection in real-world clinical practice.

Acceptance and willingness to pay for DTaP-HBV-IPV-Hib hexavalent vaccine among parents: A cross-sectional survey in China.

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.

[Double balloon endoscopy in diagnosis of patients with obscure gastrointestinal bleeding].

OBJECTIVE: To assess the diagnostic value of double balloon endoscopy (DBE) for obscure gastrointestinal bleeding (OGIB) METHODS: The data of 103 OGIB patients who underwent DBE from January 2007 to September 2010 in the First Affiliated Hospital, Zhejiang University School of Medicine were retrospectively analyzed. RESULTS: DBE was successfully performed in all 103 patients without complications. Of 103 patients, 66(64.1 %) had positive DBE findings and 28 had surgery procedures(27.2 %). Ninety-four patients finally acquired positive diagnosis, including small intestine tumor(31.1 %), angiodysplasia(22.3 %), exulceratio simplex(9.7 %), Crohn's disease(6.8 %), diverticulum(4.9 %), abdominal purpure(4.9 %), etc. Lesions occurred more frequently in proximal small intestine than in distal small intestine (56.3 % Compared with 30.1 %, P<0.001). CONCLUSION: DBE is a safe, effective and reliable procedure for the diagnosis of OGIB.

A ratiometric fluorescence probe for selective and sensitive detection of leucine aminopeptidase in lysosome.

We designed a novel ratiometric fluorescent probe P1-Leu with a donor-acceptor-donor fluorophore for the detection of leucine aminopeptidase in lysosomes. P1-Leu exhibits a lower detection limit than the ratiometric donor-π-acceptor probe, due to the low ratiometric background. Besides, P1-Leu has good lysosome-targeting ability and realizes the distinction of LAP levels in different cells.

Bacterial diversity and competitors for degradation of hazardous oil refining waste under selective pressures of temperature and oxygen.

Oil refining waste (ORW) contains complex, hazardous, and refractory components, causing more severe long-term environmental pollution than petroleum. Here, ORW was used to simulate the accelerated domestication of bacteria from oily sludges and polymer-flooding wastewater, and the effects of key factors, oxygen and temperature, on the ORW degradation were evaluated. Bacterial communities acclimated respectively in 30/60 °C, aerobic/anaerobic conditions showed differentiated degradation rates of ORW, ranging from 5% to 34%. High-throughput amplicon sequencing and ORW component analysis revealed significant correlation between bacterial diversity/biomass and degradation efficiency/substrate preference. Under mesophilic and oxygen-rich condition, the high biomass and abundant biodiversity with diverse genes and pathways for petroleum hydrocarbons degradation, effectively promoted the rapid and multi-component degradation of ORW. While under harsh conditions, a few dominant genera still contributed to ORW degradation, although the biodiversity was severely restricted. The typical dominant facultative anaerobes Bacillus (up to 99.8% abundance anaerobically) and Geobacillus (up to 99.9% abundance aerobically and anaerobically) showed oxygen-independent sustainable degradation ability and broad-spectrum of temperature adaptability, making them promising and competitive bioremediation candidates for future application. Our findings provide important strategies for practical bioremediation of varied environments polluted by hazardous ORW.

Diagnosis of Suspected Small Bowel Bleeding by Capsule Endoscopy in Patients with COVID-19.

The current study evaluated the application of small-bowel capsule endoscopy (SBCE) in SARS-CoV-2-infected patients with suspected small bowel bleeding. We analyzed the clinical characteristics, SBCE procedures, examination results, and treatment for cases of suspected small bowel bleeding in two patients with critical COVID-19. SBCE showed active spotting bleeding in the jejunum and ileum with no identifiable lesions in case 1, while multiple small bowel ulcers were detected in case 2. Two patients had relevant changes in their management plans and received specific treatment based on SBCE findings. In summary, SBCE proved to be a non-invasive diagnostic tool for critical COVID-19 patients with suspected small bowel bleeding.

Genetically engineered thermotolerant facultative anaerobes for high-efficient degradation of multiple hazardous nitroalkanes.

Nitroalkanes are important industrial raw materials but also toxic pollutants, which are difficult to degrade once released into the environment. In this study, to significantly improve the degradation-efficiency of multiple nitroalkanes, a facultative anaerobe was genetically engineered, possible influencing factors and simulated application experiments of bioreactor were tested and evaluated. Among all engineered recombinants, the most effective strains NG-S1 (anaerobic) and NG-S2 (aerobic) displayed 2-fold and 2.8-fold final degradation rates higher than the wild type, respectively. Exogenous components, particularly those that enhance coenzyme synthesis, helped to increase the degradation rate, as the level of coenzymes affected full function of overexpressed nitroalkane oxidase. Importantly, simulated mixed-nitroalkane-wastewater bioreactor experiments proved excellent and sustainable degradation performance of the engineered strains for potential industrial applications. Collectively, these findings provide a promising thermophilic biological engineering platform and a new perspective for high-efficient and continuous environmental bioremediation of hazardous pollutants under aerobic and anaerobic conditions.

Diagnosis of obscure gastrointestinal hemorrhage with capsule endoscopy in combination with multiple-detector computed tomography.

AIM: To demonstrate the clinical efficacy of combination capsule endoscopy (CE) and multiple-detector computed tomography (MDCT) diagnostic imaging in the identification of gastrointestinal hemorrhages. METHODS: In the present study, 123 patients with gastrointestinal hemorrhages of obscure origin (GHOO) were examined with CE in combination with MDCT. The results were compared with findings of surgical pathology. RESULTS: Of the 123 patients, 57.72% (71/123) of the patients exhibited positive CE findings compared with 30.08% (37/123) on MDCT alone (P < 0.01). When used in combination, 65.85% (81/123) of patients scored positively. The detection rate due to the combination of diagnostic imaging was significantly higher than that of MDCT alone (P < 0.01), but was not significantly higher than that of CE alone (P > 0.05). Integrating the two diagnostic platforms improved the diagnosis of stromal tumors, hemangioma, Crohn's disease, vascular anomaly, Meckel's diverticulum, and ancylostomiasis. There was no significant difference in the positive detection rate between CE and MDCT when confirmed by surgical pathology. CONCLUSION: The contribution of CE is critical in the diagnosis of GHOO, given the fact that there is a significant difference in the detection rate between CE and MDCT, but there is no significant difference in the rate between CE plus MDCT and CE alone.

Effect of small bowel preparation with simethicone on capsule endoscopy.

BACKGROUND: Capsule endoscopy is a novel non-invasive method for visualization of the entire small bowel. The diagnostic yield of capsule endoscopy depends on the quality of visualization of the small bowel mucosa and its complete passage through the small bowel. To date, there is no standardized protocol for bowel preparation before capsule endoscopy. The addition of simethicone in the bowel preparation for the purpose of reducing air bubbles in the intestinal lumen had only been studied by a few investigators. METHODS: Sixty-four participants were randomly divided into two groups to receive a bowel preparation of polyethylene glycol (PEG) solution (Group 1) and both PEG solution and simethicone (Group 2). The PEG solution and simethicone were taken the night before and 20 min prior to capsule endoscopy, respectively. Frames taken in the small intestine were examined and scored for luminal bubbles by two professional capsule endoscopists. Gastric emptying time and small bowel transit time were also recorded. RESULTS: Simethicone significantly reduced luminal bubbles both in the proximal and distal small intestines. The mean time proportions with slight bubbles in the proximal and distal intestines in Group 2 were 97.1% and 99.0%, respectively, compared with 67.2% (P<0.001) and 68.8% (P<0.001) in Group 1. Simethicone had no effect on mean gastric emptying time, 32.08 min in Group 2 compared with 30.88 min in Group 1 (P=0.868), but it did increase mean small intestinal transit time from 227.28 to 281.84 min (P=0.003). CONCLUSION: Bowel preparation with both PEG and simethicone significantly reduced bubbles in the intestinal lumen and improved the visualization of the small bowel by capsule endoscopy without any side effects observed.

Is adult celiac disease really uncommon in Chinese?

Celiac disease (CD) is a type of intestinal malabsorption syndrome, in which the patients are intolerant to the gliadin in dietary gluten, resulting in chronic diarrhea and secondary malnutrition. The disease is common in Europe and the United States, but only sporadic reports are found in East Asia including China. Is CD really rare in China? We examined 62 patients by capsule endoscopy for chronic diarrhea from June 2003 to March 2008. Four patients with chronic diarrhea and weight loss were diagnosed to have CD. Under the capsule endoscopy, we observed that the villi of the proximal small bowel became short, and that the mucous membrane became atrophied in these four patients. Duodenal biopsies were performed during gastroscopy and the pathological changes of mucosa were confirmed to be Marsh 3 stage of CD. A gluten free diet significantly improved the conditions of the four patients. We suspect that in China, especially in the northern area where wheat is the main food, CD might not be uncommon, and its under-diagnosis could be caused by its clinical manifestations that could be easily covered by the symptoms from other clinical situations, particularly when it came to subclinical patients without obvious symptom or to patients with extraintestinal symptoms as the initial manifestations.

Genome Sequence of Aeribacillus pallidus W-12, a Thermophilic Bacterium Containing Possible Biodesulfurization and Biodenitrification Pathways.

Aeribacillus pallidus W-12 is a thermophilic bacterium isolated from Dagang oil reservoir sewage in northern China. The genome sequence of this strain reported here may provide insights into genomic characteristics regarding the biodegradation of organosulfur and organic nitrogen compounds under elevated temperature.

Comparative transcriptomic analysis revealed the key pathways responsible for organic sulfur removal by thermophilic bacterium Geobacillus thermoglucosidasius W-2.

Biodesulfurization is a promising method to desulfurize sulfur-containing compounds in oil with its unique advantages, such as environment-friendly treatments and moderate reaction conditions. In this study, a thermophilic bacterium Geobacillus thermoglucosidasius W-2 was reported to show nearly 40% and 55% desulfurization rates on heavy oil with 2.81% and 0.46% initial total sulfur content, respectively. Subsequently, comparative transcriptome analysis indicated that several possible key desulfurization-related genes of this strain were found to be differentially up-regulated induced by benzothiophene and dibenzothiophene, respectively. These desulfurization-related genes were considered to conduct key step to convert organic sulfur to inorganic sulfur. Moreover, the characterization of thermophilic alkanesulfonate monooxygenase systems SsuD1/SsuE1 and SsuD2/SsuE2 revealed that the enzymes exhibit considerable thermal and pH stability and wide substrates applicability. These enzymes probably endowed the strain W-2 with the ability to desulfurize oil and eliminate the sulfur-containing surfactants. Thus, this study provides novel alkanesulfonate monooxygenase systems that have the application potential for heavy oil biodesulfurization, oil demulsification and other biocatalytic processes.

Novel thermostable enzymes from Geobacillus thermoglucosidasius W-2 for high-efficient nitroalkane removal under aerobic and anaerobic conditions.

In this study, a thermophilic facultative anaerobic strain Geobacillus thermoglucosidasius W-2 was found to degrade nitroalkane under both aerobic and anaerobic conditions. Bioinformatical analysis revealed three putative nitroalkane-oxidizing enzymes (Gt-NOEs) genes from the W-2 genome. The three identified proteins Gt2929, Gt1378, and Gt1208 displayed optimal activities at high temperatures (70, 70, and 80 °C, respectively). Among these, Gt2929 exhibited excellent degradation capability, pH stability, and metal ion tolerance for nitronates under aerobic condition. Interestingly, under anaerobic condition, only Gt1378 still maintained high activity for 2-nitropropane and nitroethane, indicating that the W-2 strain utilized various pathways to degrade nitronates under aerobic and anaerobic conditions, respectively. Taken together, the first revelation of thermophilic nitroalkane-degrading mechanism under both aerobic and anaerobic conditions provides guidance and platform for biotechnological and industrial applications.

OMOM capsule endoscopy in diagnosis of small bowel disease.

OBJECTIVE: To assess the diagnostic efficiency of OMOM capsule endoscopy (CE) in a group of patients with different indications. METHODS: Data from 89 consecutive patients (49 males, 40 females) with suspected small bowel disease who underwent OMOM CE (Jinshan Science and Technology Company, Chongqing, China) examination were obtained by retrospective review. The patients' indications of the disease consisted of the following: obscure gastrointestinal bleeding (OGIB), abdominal pain or diarrhea, partial intestinal obstruction, suspected inflammatory bowel disease, tumor of unknown origin, hypoproteinemia, constipation, weight loss, and elevated tumor markers. RESULTS: CE failed in one patient. Visualization of the entire small bowel was achieved in 75.0%. Capsules were naturally excreted by all patients. The detection rate of abnormalities was 70.5% for patients with suspected small bowel disease, and the diagnostic yield for patients with OGIB was higher than that for patients with abdominal pain or diarrhea (85.7% vs 53.3%, P<0.005). Angiodysplasia was the most common small bowel finding. Active bleeding sites were noted in the small intestine in 11 cases. CONCLUSION: OMOM CE is a useful diagnostic tool for the diagnosis of variably suspected small bowel disease, whose diagnostic efficiency is similar to that of the Pillcam SB (small bowel) CE (Given Imaging, Yoqneam, Israel).

The value of endoscopic ultrasonography on diagnosis and treatment of esophageal hamartoma.

OBJECTIVE: To examine the values of endoscopic ultrasonography (EUS) on diagnosis and treatment of esophageal hamartoma. METHODS: We compared and analyzed various kinds of imaging examinations such as barium esophagram, contrast-enhanced computed tomography (CT) and conventional gastroscopy in retrospectively reviewing the clinical data of an esophageal hamartoma patient seen in our clinic in the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. Having received various imaging examinations, this patient was finally diagnosed with esophageal hamartoma and underwent gastroscopic resection of hamartoma with the diagnostic information obtained from EUS. The patient had been regularly followed up for 13 months after treatment. RESULTS: Barium esophagram, CT and conventional gastroscopy detected the lesion, but were unable to distinguish it from common esophagopolypus and other submucosal lesions, and unable to determine etiopathogenisis. EUS detected the hamartoma and identified its internal structure, echo, exact size, depth of invasion, origin and the relationship between adjacent tissues and organs, differentiating the lesion from other submucosal tumors and clearly defining the diagnosis. EUS-guided fine needle aspiration (FNA) also helped to identify the etiological diagnosis. CONCLUSION: EUS was superior to other imaging means in diagnosis and treatment of hamartoma.

[Diagnostic values of double-balloon enteroscopy and abdominal computed tomography in small bowel disease].

OBJECTIVE: To evaluate the diagnostic values of double-balloon enteroscopy (DBE) and abdominal computed tomography (CT) in small bowel disease. METHODS: Seventy eight DBE procedures were carried out in 70 patients, 40 males and 30 females; aged 47.7 (16 - 83) with suspected small bowel disease, all of whom received gastroscopy, colonoscopy, and abdominal CT examination at the same time. The diagnostic value of DBE was compared with that of CT. RESULTS: Seventeen kinds of small bowel lesions were detected, mainly including Crohn's disease, adenocarcinoma, gastrointestinal stroma tumor, vascular deformity, lymphoma, diverticulum, and polyp. There were no complications and all procedures were tolerated well. The mean duration of procedure was 110 min (30 - 240 min). Nineteen patients received surgical intervention. The diagnostic yield rate of DBE was 57.1% (40/70), significantly higher than that of CT (31.4%, 22/70, P < 0.01). The positive diagnosis rate of DBE combined with CT was 62.9% (44/70), not significant different from that of the DBE alone (P > 0.05). CONCLUSION: DBE shows a significantly higher diagnostic yield than CT in patients with suspected small bowel disease, and thus should be selected for the initial diagnosis. DBE Combined with CT did not increase the diagnostic yield. However, CT not only provides direction of intubation for DBE, but also clearly depicts the small bowel wall and extraenteric alterations. DBE and CT compliment each other in examining the patients with suspected small bowel disease.

A primary intestinal lymphangiectasia patient diagnosed by capsule endoscopy and confirmed at surgery: a case report.

Intestinal lymphangiectasia (IL) is a rare disease characterized by dilated lymphatic vessles in the intestinal wall and small bowel mesentery which induce loss of protein and lymphocytes into bowel lumen. Because it most often occurs in the intestine and cannot be detected by upper gastroendoscopy or colonoscopy, and the value of common image examinations such as X-ray and computerized tomography (CT) are limited, the diagnosis of IL is difficult, usually needing the help of surgery. Capsule endoscopy is useful in diagnosing intestinal diseases, such as IL. We here report a case of IL in a female patient who was admitted for the complaint of recurrent edema accompanied with diarrhea and abdominal pain over the last twenty years, and aggravated ten days ago. She was diagnosed by M2A capsule endoscopy as a primary IL and confirmed by surgical and pathological examination.