Effects of prolonged fluoride exposure on innate immunity, intestinal mechanical, and immune barriers in mice.

The aim of this study is to explore the effects of fluoride on the innate immunity, intestinal mechanical barrier, and immune barrier of C57BL/6 mice, as well as to analyze the degree of structural and tissue damage, providing reference data for related research. Mice were randomly divided into four groups and then treated with 0 mg/L (control), 50 mg/L, 100 mg/L, 125 mg/L sodium fluoride solution, respectively, for 120 days. Histological technique, ELISA, MTT colorimetry methods were used to detect and analyze the effects of different concentrations of fluoride on the intestinal morphology, mechanical barrier and the immune functions and innate immunity of mice. The results showed that compared with the control group, the villi were injured in different degrees of the three fluoride groups, the number of goblet cells, the protein expression levels of connexin ZO-1, Claudin-1 and Occludin, the content of Diamine Oxidase (DAO), endotoxin (ET) and D-lactic acid (D-LA), the activity of natural killer cell (NK cells), the number and percentage of neutrophils and erythrocytes, the phagocytic rate of neutrophils, and the rate of C3bR rosette (which is formed by the adhesion of C3b receptors on the red blood cell membrane to complement sensitized yeast) and IC rosette (which is formed by the adhesion of C3b molecules in the immunecomplex adhered to the red blood cell membrane to non sensitized yeast) of red blood cells, the content of interlenkin 1 beta (IL-1ß) and interlenkin 8 (IL-8), the number and percentage of lymphocytes decreased with the increasing of fluoride concentration. In addition, the content of the Immunoglobulin A (sIgA) showed a trend of increase at first and then decrease in salivary gland and jejunum. It is concluded that excessive intake of fluoride for a long time has a certain damage effect on the intestinal tract, leading to an increase in the permeability of the intestinal tract, thereby destroying the mechanical and immune barrier function of the intestinal tract.

Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice.

Background: The widely accepted microbiome-gut-brain axis (MGBA) hypothesis may be essential for explaining the impact of high-altitude exposure on the human body, especially brain function. However, studies on this topic are limited, and the underlying mechanism remains unclear. Therefore, this study aimed to determine whether high-altitude-induced working memory dysfunction could be exacerbated with gut microbiota disruption. Methods and results: C57BL/6 mice were randomly divided into three groups: control, high-altitude exposed (HAE), and high-altitude exposed with antibiotic treatment (HAE-A). The HAE and HAE-A groups were exposed to a low-pressure oxygen chamber (60-65 kPa) simulating the altitude of 3,500-4,000 m for 14 days, The air pressure level for the control group was maintained at 94.5 kPa. Antibiotic water (mixed with 0.2 g/L of ciprofloxacin and 1 g/L of metronidazole) was provided to the HAE-A group. Based on the results of the novel object test and P300 in the oddball behavioral paradigm training test, working memory dysfunction was aggravated by antibiotic treatment. We determined the antioxidant capacity in the prefrontal cortex and found a significant negative influence (p < 0.05) of disturbed gut microbiota on the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The same trend was also observed in the apoptosis-related functional protein content and mRNA expression levels in the prefrontal cortex, especially the levels of bcl-2, Bax, and caspase-3. The high-altitude environment and antibiotic treatment substantially affected the richness and diversity of the colonic microbiota and reorganized the composition and structure of the microbial community. S24-7, Lachnospiraceae, and Lactobacillaceae were the three microbial taxa with the most pronounced differences under the stimulation by external factors in this study. In addition, correlation analysis between colonic microbiota and cognitive function in mice demonstrated that Helicobacteraceae may be closely related to behavioral results. Conclusion: Disrupted gut microbiota could aggravate working memory dysfunction induced by high-altitude exposure in mice, indicating the existence of a link between high-altitude exposure and MGBA.

In vivo animal study of the magnetic navigation system for capsule endoscope manipulation within the esophagus, stomach, and colorectum.

BACKGROUND/PURPOSES: Magnetic navigation capsule endoscopy (MNCE) is considered to be an important means to realize the controllable and precise examination of capsule endoscopy (CE) in the unstructured gastrointestinal (GI) tract. For the current magnetic navigation system (MNS), due to the limitation of workspace, driving force, and control method of the CE, only clinical application in the stomach has been realized, whereas the examination of other parts of the GI tract is still in the experimental stage. More preclinical studies are needed to achieve the multisite examination of the GI tract. METHODS: Based on the MNS (Supiee) developed in the laboratory, an X-ray imaging system with magnetic shielding and a commercial CE are integrated to form the MNCE system. Then, in vivo GI tract experiments with a porcine model are performed to verify the clinical feasibility and safety of this system. Moreover, the effects of different control modes on the efficiency and effect of GI tract examination are studied. RESULTS: Animal experiments demonstrate that with the MNCE system, it is convenient to achieve steering control in any direction and multiple reciprocating movements of CE in the GI tract. Benefiting from the flexibility of the three basic control modes, the achieved swing movement pattern of CE can effectively reduce the inspection time. It is demonstrated that the esophageal examination time can be reduced from 13.2 to 9.2 min with a maximum movement speed of 5 mm/s. CONCLUSION: In this paper, the feasibility, safety, and efficacy of the MNCE system for a one-stop examination of the in vivo GI tract (esophagus, stomach, and colorectum) is first demonstrated. In addition, complex movement patterns of CE such as the swinging are proved to effectively improve examination efficiency and disease detection rates. This study is crucial for the clinical application of the MNCE system.

Bronchobiliary fistula after ablation of hepatocellular carcinoma adjacent to the diaphragm: Case report and literature review.

BACKGROUND: Bronchobiliary fistula is a rare, but life-threatening complication after ablation of hepatocellular carcinoma. Few cases of bronchobiliary fistula have been reported and the treatment is controversial. METHODS: From 2006 to 2019, a total of 11 patients were diagnosed with bronchobiliary fistula after ablation and received nonsurgical treatment. RESULTS: All 11 patients presented with cough and bilioptysis. There were only two patients in which MRI revealed an obvious fistulous tract connecting the pleural effusion and biliary lesions. Pleural effusion, liver abscess and hepatic biloma were found in other patients. Three patients died of uncontrolled bronchobiliary fistula. CONCLUSIONS: Bronchobiliary fistula is a rare post-ablation complication but should be taken into consideration in clinical decisions. Minimally invasive interventional treatment is a relatively effective means of dealing with bronchobiliary fistula, but as for the more severe cases, greater clinical experience is required.

Computed tomography-guided radiofrequency ablation combined with transarterial embolization assisted by a three-dimensional visualization ablation planning system for hepatocellular carcinoma in challenging locations: a preliminary study.

OBJECTIVE: To assess the clinical efficacy and safety of computed tomography-guided radiofrequency ablation(CT-RFA) combined with transarterial embolization(TAE) assisted by a three-dimensional visualization ablation planning system(3DVAPS) for hepatocellular carcinoma(HCC) in challenging locations. METHODS: Data from 62 treatment-naive patients with hepatocellular carcinoma(HCC), with 83 lesions in challenging locations, and who met the Milan criteria and underwent CT-RFA between June 2013 and June 2016 were reviewed. Patients were divided into one of two groups according to different treatment modalities: study group (TAE combined with RFA assisted by 3DVAPS [n = 32]); and control (RFA only [n = 30]). Oncological outcomes included ablation-related complications, local tumor progression (LTP), and overall survival (OS). Univariate and multivariate Cox proportional hazards regression analyses were performed to assess risk factors associated with LTP and OS. RESULTS: HCC lesions (mean size, 1.9 ± 1.0 mm in diameter) abutting the gastrointestinal tract (n = 25), heart and diaphragm (n = 21), major vessels (n = 13), and gallbladder (n = 3) were treated. A significant difference was detected in LTP between the two groups (P = 0.034), with no significant difference in OS between the two groups (P = 0.193). There were no severe complications related to ablation. Univariate analysis revealed that sex (P = 0.046) and child-turcotte-pugh (CTP) grade (P<0.001) were risk factors for OS, whereas CTP grade and treatment method (P<0.001) were risk factors for LTP. Multivariate analysis revealed that CTP grade B (P = 0.005) was independently associated with poor OS, and RFA alone (P<0.001) was independently associated with poor LTP. CONCLUSION: CT-RFA combined with TAE assisted by a 3DVAPS provided ideal clinical efficiency for HCC in challenging locations and was a highly safe treatment modality.

Computed tomography-guided radiofrequency ablation of the retained iodized oil after simultaneous combination with transarterial embolization in small recurrent or residual hepatocellular carcinoma.

OBJECTIVE: To assess the clinical efficacy and safety of transarterial embolization (TAE) in simultaneous combination with computed tomography (CT)-guided radiofrequency ablation (RFA) for recurrent or residual hepatocellular carcinoma (HCC), and to determine the risk factors influencing local tumor progression following this procedure. METHODS: One hundred eighteen patients with recurrent or residual HCC (tumor size, 10-30 â€‹mm) underwent RFA. During the 19-month follow-up, 59 patients received RFA only (RFA group), and the remaining 59 received RFA immediately after TAE (TAE â€‹+ â€‹RFA group). All patients were followed up to observe the short-term therapeutic effects and complications. The cumulative local tumor progression rates in both groups were calculated using unpaired Student's t tests and the Kaplan-Meier method. RESULTS: The rate of major complications was 5.08% in the TAE â€‹+ â€‹RFA group and 3.39% in the RFA group. The overall response rate was 96.61% in the TAE â€‹+ â€‹RFA group and 79.66% in the RFA group (P â€‹= â€‹0.008). The disease control rate was significantly higher in the TAE â€‹+ â€‹RFA group than in the RFA group (94.92% vs. 79.66%, P â€‹= â€‹0.024). The median time to local tumor progression was 4.8 months in the RFA group and 9.6 months in the TAE â€‹+ â€‹RFA group. The cumulative local tumor progression rate at 1 year was 10.60% in the RFA group and 23.60% in the TAE â€‹+ â€‹RFA group (P â€‹= â€‹0.016). CONCLUSION: TAE in simultaneous combination with CT-guided RFA was effective and safe against recurrent or residual HCC. Local tumor progression can be minimized by the complete ablation of targeted iodized oil deposits after simultaneous TAE.

Adjuvant cytokine-induced killer cells with minimally invasive therapies augmented therapeutic efficacy of unresectable hepatocellular carcinoma.

OBJECTIVE: To investigate the safety and therapeutic efficacy of adjuvant cytokine-induced killer (CIK) cells to minimally invasive therapies in unresectable hepatocellular carcinoma (u-HCC). MATERIALS AND METHODS: Hundred patients diagnosed with having u-HCC in our department from January 1, 2001, to July 31, 2018, were recruited. Forty-three patients received microwave ablation (MWA) and transcatheter arterial chemoembolization (TACE) together with autologous CIK cell treatment (TACE + MWA + CIK group), whereas 57 patients received TACE and MWA only (TACE + MWA group). Postprocedural complications and cumulative therapeutic effects were assessed in all patients. The disease control rate, median survival time (MST), and cumulative survival rate were compared between the cohorts using the Kaplan-Meier method and unpaired Student's t-tests. RESULTS: The overall response (complete response [CR] + partial response [PR]) rate was 74.42% (32/43) and 77.19% (44/57) for TACE + MWA + CIK and TACE + MWA groups, respectively (P = 0.243). Those of the TACE + MWA + CIK group had better rates of disease control (CR + PR + stable disease) in contrast to the TACE + MWA group (87.72% vs. 79.07%, respectively) but this failed to achieve statistical significance (P = 0.748). Based on the Kaplan-Meier survival graphs, those of the TACE + MWA + CIK groups possessed markedly increased overall survival (41 months vs. 24 months, P = 0.002) and progression-free survival (17 months vs. 10 months, P = 0.023) rates in compared to the TACE + MWA group. Survival rates were raised also TACE + MWA + CIK group than in TACE + MWA group (P = 0.002), with a MST of 6.13 ± 0.83 months and 11.61 ± 1.59 months in the TACE + MWA + CIK and TACE + MWA groups, respectively. Patients in the TACE + MWA + CIK group were not reported to have any severe complications. CONCLUSION: CIK cell immunotherapy as an adjuvant to TACE and MWA enhanced long-term prognosis and improved quality of life in patients with u-HCC. This regimen may be recommended as a novel treatment regime in u-HCC patients.