Ultra-broadband multi-tone frequency measurement based on the recirculating frequency shift of a frequency modulated continuous wave.

We proposed an ultra-broadband multi-tone frequency measurement (FM) approach based on frequency modulated continuous wave (FMCW). This work aims to achieve wide-range multi-tone FM without image interference, using electrical components with narrow bandwidth and low sampling rate, while maintaining high FM accuracy. The FM range is largely increased by extending the bandwidth of the optical FMCW through a recirculating frequency shift (RFS) loop, from 0.001 GHz-16 GHz to 0.001 GHz-437.5 GHz. The bandwidth-extended optical FMCW coherently beats with a continuous wave (CW) light modulated by the signal under test (SUT) at the balanced photodetector (BPD). The following low-pass filter (LPF) outputs pulses at the time when the frequencies of FMCW and SUT are equal, constructing frequency-to-time mapping (FTTM). Owing to the zero-intermediate-frequency (zero-IF) architecture, image interference is avoided. In addition, the up- and down-chirps of FMCW are used to achieve self-reference, avoiding the utilizing of reference signals, which realizes high FM accuracy. In the experiment, a FM within 0.1 GHz-43.5 GHz is demonstrated using an available microwave generator (MG) with a maximum output frequency of 43.5 GHz. The FM errors are kept within ±10 MHz for all frequencies with a mean and standard deviation of -0.3 MHz and 3.17 MHz, respectively. The multi-tone resolution is about 60 MHz at the FMCW chirp rate of 3.1998 G H z/µ s, which is consistent with the theoretical result. According to the theoretical derivation, the multi-tone resolution can be improved to 1 MHz by lowering the FMCW chirp rate.

Photonic-assisted fast broadband microwave vector network analyzer based on FMCW.

In the paper, we propose a photonic-assisted fast broadband microwave vector network analyzer (FB-VNA) based on frequency modulated continuous wave (FMCW). A photonic recirculating frequency shift (RFS) loop is used to extend the bandwidth of optical FMCW. The bandwidth-extended optical FMCW beats with the continuous wave (CW) light to generate the broadband electrical FMCW, which serves as the incident signal of the device under test (DUT). The response signals of the DUT are modulated on the bandwidth-extended optical FMCW to perform de-chirping. After coherently beating the de-chirped light with the CW light, the broadband response signals of DUT are down-converted to a single-tone intermediate frequency (IF) signal carrying the frequency response of DUT, and the scattering parameters of DUT can be obtained. The single-tone IF signal relaxes the demand on the bandwidth and sampling rate of the electrical backend. Thanks to the RFS loop and the short period of FMCW, the measurement frequency range is highly extended and measurement speed is greatly accelerated at the same time, which can be applied in monitoring sudden changes of DUT features. A bandwidth multiplication of the FMCW from 6-18 GHz to 6-498 GHz is experimentally implemented. With available photodetectors (PDs) and Mach-Zehnder modulators (MZMs), a 6-54 GHz FB-VNA is demonstrated, and the S parameters of a 25-GHz low-pass filter (LPF) is measured within 6 µs. The sudden changes of S21 parameter of DUT simulated by fast adjusting the bias voltage of the MZM used for de-chirping are also characterized by the proposed FB-VNA. The sudden changes as short as 0.01 µs can be captured.

Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.

Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.

The effects of anticoagulant therapy re-initiation after gastrointestinal bleeding: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Long-term anticoagulant/antithrombotic therapy is widely used for the management of thromboembolic conditions. Gastrointestinal bleeding is a common collateral manifestation of anticoagulant/antithrombotic therapy that complicates its administration. The continuation or discontinuation of anticoagulant/antithrombotic therapy after an episode of gastrointestinal bleeding has been a matter of debate. Despite recent positive reports from retrospective cohort studies suggesting a reduction in morbidity- and mortality-related outcomes with continued administration of anticoagulant/antithrombotic agents (even after gastrointestinal bleeding), no consensus or comparisons about the efficacies of continued or discontinued antithrombotic administration exist. Therefore, we developed this current state-of-evidence analysis evaluating the comparative effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. METHODS: We performed a systematic academic literature search according to the PRISMA guidelines across five databases: Web of Science, Embase, CENTRAL, Scopus and MEDLINE. Moreover, we conducted a random effect meta-analysis to compare the effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after an event of gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. RESULTS: We found seven eligible studies (from 1397 candidates) with 2532 participants (mean age, 73.1 ± 4.1 years). Our meta-analysis revealed lower odds of thromboembolic events (OR, -0.21), mortality outcomes (OR, -0.39) and an increase in the incidence of gastrointestinal bleeding (OR, 2.4) in the group with continued anticoagulant/antithrombotic therapy than in the group discontinuing the therapy. WHAT IS NEW AND CONCLUSION: We provide an updated evidence on the comparative effects between continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding events based on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. This study reports confirm an overall lower incidence of thromboembolic events and mortality outcomes for the continuation group than for the discontinuation group.

A case report of endoscopic resection for the treatment of duodenal Brunner's gland adenoma with upper gastrointestinal bleeding.

RATIONALE: Gastrointestinal bleeding as the first sign of Brunner's gland adenoma (BGA) is an extremely rare, and its clinical features and treatment methods have not been well described. PATIENT CONCERNS: We described a 81-year-old female patient with coronary artery disease and chronic atrial fibrillation presenting with presenting with gastrointestinal bleeding requiring blood transfusion. DIAGNOSES: The diagnosis of our case mainly refered to radiologic imaging and endoscopic examination. Histological result was compatible with BGA. INTERVENTIONS: This mass lesion (6 × 7 cm diameter) was successfully totally removed by endoscopic submucosal dissection (ESD) for more than three hours. OUTCOMES: The patient was followed up for 6 months to date without recurrence. LESSONS: Endoscopic removal is considered as a safe and low-risk treatment for elderly patients with severe underlying diseases presenting with gastrointestinal bleeding.

Endoscopic submucosal dissection of coexisting early esophageal carcinoma and leiomyoma: a case report and review of the literature.

The occurrence of early esophageal cancer located within an area of leiomyoma is extremely rare, and its clinical features and treatment methods have not been well described. We herein report the clinical characteristics, diagnosis, and treatment methods of early esophageal cancer that developed on top of a leiomyoma in the upper third of the esophagus in a 78-year-old woman. All tumor marker concentrations were normal. The leiomyoma was correctly diagnosed as a submucosal tumor by endoscopy and endoscopic ultrasonography. Endoscopic biopsy revealed esophageal squamous cell carcinoma. Both lesions were successfully treated by endoscopic submucosal dissection. The patient was followed up for 6 months without recurrence. Endoscopic submucosal dissection was a successful initial treatment method for esophageal carcinoma coexisting with esophageal leiomyoma in this case.

Dysregulated TFR and TFH cells correlate with B-cell differentiation and antibody production in autoimmune hepatitis.

Follicular helper T (TFH) cell provides germinal centre (GC) B cell with critical signals for autoantibody production in the immunopathogenesis and progression of autoimmune hepatitis (AIH). However, the immunoregulatory functions of follicular regulatory T (TFR) cell in AIH are still unclear. The numbers of circulating TFR/TFH cells were measured in AIH patients. Moreover, we established experimental autoimmune hepatitis (EAH) model to examine the function of TFR cells on B-cell differentiation and autoantibody production in vivo and vitro. AIH patients had significantly increased numbers of TFH cells and decreased numbers of TFR cells as well as imbalanced TFR/TFH-type cytokines (IL-10, TGF-ß1 and IL-21) compared with healthy controls (HCs). In addition, TFR cell numbers negatively correlated with TFH cell numbers. Also, serum hypergammaglobulinaemia (IgG and IgM) concentration negatively correlated the levels of serum IL-21, but positively correlated with the levels of serum IL-10 in AIH patients. Furthermore, in comparison with control group, significantly higher frequencies of spleen TFR cells but lower frequencies of spleen TFH cells were detected in the EAH group. Further analysis found that TFR cells simultaneously express the phenotypic characteristics of Treg and TFH cells, but exercise as negative regulators of autoantibody production in vitro culture. Our findings demonstrated that dysregulated between TFR and TFH cells might cause excessive production of autoantibodies and destruction of the immune homeostasis, leading to the immunopathological process in AIH.

A rare case report of fungal esophagitis combined with giant gastric ulcer in an immunocompetent patient.

RATIONALE: Fungal infection of gastrointestinal (GI) tract is usually seen in immunocompromised patients, but can rarely occur in immunocompetent people in whom no permissive factor is present. PATIENT CONCERNS: We describe a 68-year-old male immunocompetent patient presenting with simultaneous fungal esophagitis and giant gastric ulcer. DIAGNOSES: Repeated endoscopic biopsies were taken from the giant gastric ulcer edge and base and histology demonstrated granulation tissue and pseudohyphal fungal forms. INTERVENTIONS: The patient was treated with fluconazole and omeprazole for 8 weeks. OUTCOMES: After antifungal treatment with fluconazole, the patient's clinical symptoms gradually disappeared with the healing of gastric ulcer, which never recurred in this patient until 3 months after follow-up. LESSONS: Nonhealing gastroesophageal ulcers highlights the importance of repeated endoscopies and biopsies.

A case report of endoscopic therapy for radiation-induced hemorrhagic gastritis in patient with recurrent hepatocellular carcinoma.

RATIONALE: Radiation-induced hemorrhagic gastritis is an infrequent cause of upper gastrointestinal bleeding and difficult to manage. The current standard treatment has not been well established. PATIENT CONCERNS: We described a 32-year-old male patient with hemorrhagic gastritis induced by external radiotherapy for hepatocellular carcinoma recurrence. DIAGNOSES: The endoscopic examination showed a diffuse area of bleeding in the gastric antrum. INTERVENTIONS: After failure of conventional hemostasis treatment, we successfully stopped the hemorrhage with repeated endoscopic argon plasma coagulation (APC) combined with low-dose polyglycerol sclerotherapy. OUTCOMES: The patient was followed up for 6 months to date without recurrence. LESSONS: Based on this case, we think that endoscopic APC combined with low-dose polidocanol sclerotherapy can be tried as a treatment for potentially life-threatening radiation-induced hemorrhagic gastritis.

The Imbalance between Foxp3+Tregs and Th1/Th17/Th22 Cells in Patients with Newly Diagnosed Autoimmune Hepatitis.

This study is aimed at examining the potential role of regulatory T- (Treg-) Th1-Th17-Th22 cells in the pathogenic process of autoimmune hepatitis (AIH). The numbers of Foxp3+Tregs and Th1, Th17, and Th22 cells were measured in 32 AIH patients using flow cytometry. Moreover, a murine model of experimental autoimmune hepatitis (EAH) was also established and used to investigate the function of Treg-Th1-Th17-Th22 cells in disease progression. AIH patients undergoing an active state had significantly decreased numbers of CD3+CD4+CD25+Foxp3+Tregs and increased numbers of CD3+CD4+CD25-Foxp3+T, CD3+CD4+IFN-γ+Th1, CD3+CD4+IL-17+Th17, and CD3+CD4+IL-2+Th22 cells as well as higher levels of Th1/Th17/Th22-type cytokines compared to AIH patients in remission and HC. Additionally, the numbers of CD3+CD4+CD25+Foxp3+Tregs were negatively correlated with the numbers of Th1-Th17-Th22 cells. Also, the serum levels of IL-17A and IL-22 were correlated positively with liver injury (ALT/AST), whereas the serum levels of IL-10 were correlated negatively with hypergammaglobulinaemia (IgG, IgM) in AIH patients. Interestingly, the percentages of spleen Tregs, expression of Foxp3 mRNA, and liver IL-10 levels decreased, whereas the percentages of spleen Th1-Th17-Th22 cells, expression of T-bet/AHR/RORγt mRNA, and liver IFN-γ, IL-17, and IL-22 levels increased in the murine model of EAH. Our findings demonstrated that an imbalance between Tregs and Th1-Th17-Th22 cells might contribute to the pathogenic process of AIH.

Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis.

This study investigated the role of IL-33 in the pathogenesis of autoimmune hepatitis (AIH). The levels of IL-33/sST2 and Th1/Th2/Th17-type cytokines were determined by enzyme-linked immunosorbent assay in serum samples obtained from 30 AIH patients and 20 healthy controls (HCs). In addition, a murine model of experimental AIH (EAIH) was established to investigate the role of IL-33 in disease progression. The serum levels of IL-33, sST2, Th17 cytokines (IL-17A), Th1 cytokines (IFN-γ, TNF-α), and Th2 cytokines (IL-4) were significantly elevated in AIH patients compared to HCs. Following immunosuppression therapy, serum levels of IL-33 and sST2 were significantly decreased. Additionally, the serum levels of IL-33 in AIH patients were correlated positively with markers of hypergammaglobulinemia (IgG, IgM, and IgA) and liver injury (γ-GT/ALP). Also, the serum levels of IL-33 in AIH patients were correlated positively with proinflammatory cytokine levels (IL-17A and IL-4). Interestingly, treatment of EAIH mice with a specific IL-33 neutralizing antibody significantly reversed the increasing trend in serum ALT/AST and inhibited the production of the type 2 (IL-4) and type 17 cytokines (IL-17) but not the type 1 cytokine (IFN-γ). Our findings highlight the possible role of the IL-33/sST2 axis in the progression of AIH, opening a new door for developing a novel therapeutic strategy for AIH.

Ocular Toxoplasmosis in Tropical Areas: Analysis and Outcome of 190 Patients from a Multicenter Collaborative Study.

PURPOSE: To describe clinical findings and outcomes for ocular toxoplasmosis in an international multicenter collaborative study. METHODS: Retrospective analysis of 190 patients diagnosed with ocular toxoplasmosis from three study sites (Brazil, India, and Singapore). RESULTS: There were 93 (48.9%) females with a mean age of 32.8 years. The most common symptoms were isolated blurring of vision (36.8%), followed by blurring of vision with floaters (21.1%). Treatment regimens varied largely from monotherapy to multiple combination therapies. Final visual acuity of ≥20/40 was achieved in 106 (74.2%) patients. In a median follow-up period of 31 weeks (range 12-749 weeks), 83/190 (43.7%) patients suffered a relapse. CONCLUSIONS: There appears to be geographical variation in the presentation of ocular toxoplasmosis. Compared to previous studies, we did not observe the '"dual peak" phenomenon of chronic and active disease based on age at presentation, and there was less bilateral and macular involvement (but more peripheral involvement).

Cognitive variations among vascular dementia subtypes caused by small-, large-, or mixed-vessel disease.

INTRODUCTION: Vascular dementia (VaD) is a heterogeneous disease that can vary in clinical presentation and cognitive profile. The cognitive profiles of different VaD subtypes depend on the anatomical distribution of the vascular insults that have been documented. MATERIAL AND METHODS: We reviewed demographic, cognitive, and imaging data in 402 patients who were clinically diagnosed with VaD between January 2002 and June 2012 at the First Affiliated Hospital of Gan Nan Medical College in Ganzhou, China. RESULTS: Based on magnetic resonance imaging (MRI) results, patients were classified as having large- (24.1%), small- (70.4%), or mixed-vessel VaD (5.5%). Hypertension was the most prevalent risk factor (81%), followed by smoking (37%), hyperlipidemia (35%), and diabetes (27%). Hyperlipidemia, cardiac risk factors (history of cardiovascular disease, heart valve disorder) and carotid stenosis were more frequent in patients with large-vessel disease compared to those with small-vessel or mixed-vessel disease (p < 0.001). A median of 4 (maximum 11) cognitive domains were impaired in each VaD patient. After memory dysfunction, executive defects were the most prevalent (68.9%), and neurobehavioral dysfunction was the most rare (13.2%). Patients with small-vessel VaD showed more executive dysfunction than patients with large-vessel and mixed-vessel VaD (p < 0.05), whereas patients with large-vessel VaD had a higher prevalence of visuospatial or language dysfunction (p < 0.05). CONCLUSIONS: The results indicate that specific subtypes and underlying vascular mechanisms will help predict clinical courses and produce more focused treatment and prevention of VaD.