Differences in glucose homeostasis and islet injury among diverse mice strains post acute pancreatitis.

Diverse animal models have been used to study postpancreatitis diabetes mellitus (PPDM) development; however, no study has yet conducted a comparative analysis of the specific differences in glucose homeostasis and islet injury between these models. Therefore, we investigated the differences in pancreatic islet injury and glucose homeostasis among diverse strains in a cerulein-induced acute pancreatitis (AP) model to determine the appropriate animal model for PPDM. BALB/cJ, C57BL/6J, C57BL/6 N, and FVB/NJ mice were administered cerulein to induce AP. Serum amylase levels, pancreatic acinar injury, blood glucose homeostasis, islet function, and islet injury were measured and analyzed. All strains exhibited elevated amylase secretion post pancreatitis, and BALB/cJ, C57BL/6J, and C57BL/6 N mice exhibited sex-related differences. All strains exhibited pancreatic acinar injury post pancreatitis but mostly recovered within 15 days. Overall, glucose homeostasis remained balanced post pancreatitis in all strains compared to that in the control groups, except in FVB/NJ male and female mice, which exhibited an imbalance in glucose homeostasis on day 7 post pancreatitis. All the strains, except BALB/cJ mice, exhibited a decline in Homeostasis model assessment-ß(HOMA-ß) values post pancreatitis, with significant decrease in C57BL/6J females and FVB/NJ males. Islet size decreased post pancreatitis in all strains, except BALB/cJ mice. Pancreatic islet insulin secretion levels significantly decreased in male FVB/NJ mice post pancreatitis onset and did not recover within 15 days. Therefore, FVB/NJ male mice are a useful model for studying PPDM.

Efficacy and safety of dabigatran and rivaroxaban in atrial fibrillation patients with impaired liver function: a multicenter retrospective cohort study.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with impaired liver function (ILF) have not been sufficiently studied. The aim of this study was to evaluate the efficacy and safety of DOACs for stroke prevention in patients with AF and ILF. METHOD: This study was based on data from 15 centers in China, including 4,982 AF patients. The patients were divided into 2 subgroups based on their liver function status: patients with normal liver function (NLF)(n = 4213) and patients with ILF (n = 769). Logistic regression analysis was used to investigate the risk of total bleeding, major bleeding, thromboembolism, and all-cause deaths in AF patients with NLF and ILF after taking dabigatran or rivaroxaban, respectively. RESULTS: Among AF patients treated with dabigatran or rivaroxaban, patients with ILF were associated with significantly higher major bleeding, compared with NLF patients (aOR: 4.797; 95% CI: 2.224-10.256; P < 0.001). In patients with NLF, dabigatran (n = 2011) had considerably lower risk of total bleeding than rivaroxaban (n = 2202) (aOR: 1.23; 95% CI: 1.002-1.513; P = 0.049). In patients with ILF, dabigatran (n = 321) significantly favored lower risks of major bleeding compared with rivaroxaban(n = 448) (aOR: 5.484; 95% CI: 1.508-35.269; P = 0.026). CONCLUSION: After using dabigatran or rivaroxaban, patients with ILF had remarkably increased risk of major bleeding compared with patients with NLF. In AF patients with NLF, dabigatran had the distinct strength of significantly reduced risk of total bleeding compared with rivaroxaban. In patients with AF and ILF, dabigatran use was associated with lower risk for major bleeding compared with rivaroxaban.

Effectiveness of a Full Course Health Education in the Care of Patients with Chronic Kidney Disease Receiving Peritoneal Dialysis.

Background: Chronic kidney disease (CKD) patients undergoing peritoneal dialysis face numerous challenges that can impact their health behaviors, treatment adherence, and overall quality of life. A comprehensive health education program tailored for CKD patients on peritoneal dialysis is imperative to enhance the effectiveness of treatment and address these issues. Objective: The primary objective was to evaluate the impact of a full course health education program on health behaviors, treatment adherence, quality of life, and the occurrence of adverse events in CKD patients receiving peritoneal dialysis. Methods: A total of 98 CKD patients on peritoneal dialysis at our hospital between October 2019 and October 2022 were selected. The patients were randomly assigned to receive either routine care (n=52) or participate in a full-course health education program (n=46). The comparative assessments included health behavior scores, treatment adherence, Kidney Disease Targeted Area (KDTA) scores, monitoring adverse events, and tracking readmissions. Results: Patients in the observation group who underwent the full course health education program exhibited significant improvements in health behavior scores and treatment adherence (P < .05). Notably, the observation group demonstrated higher levels of medication compliance, timely reviews, and catheter maintenance. Moreover, full-course health education contributed to an enhanced quality of life, reflected in higher KATA scores, and led to a reduction in adverse events and readmission rates compared to routine care (P < .05). Conclusions: This study concludes that a full-course health education program is effective in improving health behaviors, treatment adherence, and quality of life while reducing adverse events among CKD patients undergoing peritoneal dialysis.

Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration.

Wet age-related macular degeneration (wet AMD) is a primary contributor to visual impairment and severe vision loss globally, but the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells (ECs) is mainly dictated by angiogenic growth factors. Even though treatments targeting vascular endothelial growth factor (VEGF), like ranibizumab, are widely administered, more than half of patients still exhibit inadequate or null responses, suggesting the involvement of other pathogenic mechanisms. With advances in research in recent years, it has become well recognized that EC metabolic regulation plays an active rather than merely passive responsive role in angiogenesis. Disturbances of these metabolic pathways may lead to excessive neovascularization in angiogenic diseases such as wet AMD, therefore targeted modulation of EC metabolism represents a promising therapeutic strategy for wet AMD. In this review, we comprehensively discuss the potential applications of EC metabolic regulation in wet AMD treatment from multiple perspectives, including the involvement of ECs in wet AMD pathogenesis, the major endothelial metabolic pathways, and novel therapeutic approaches targeting metabolism for wet AMD.

Correction: Lattice engineering of noble metal-based nanomaterials via metal-nonmetal interactions for catalytic applications.

Correction for 'Lattice engineering of noble metal-based nanomaterials via metal-nonmetal interactions for catalytic applications' by Long Zheng et al., Nanoscale, 2024, https://doi.org/10.1039/d4nr00561a.

Lattice engineering of noble metal-based nanomaterials via metal-nonmetal interactions for catalytic applications.

Noble metal-based nanomaterials possess outstanding catalytic properties in various chemical reactions. However, the increasing cost of noble metals severely hinders their large-scale applications. A cost-effective strategy is incorporating noble metals with light nonmetal elements (e.g., H, B, C, N, P and S) to form noble metal-based nanocompounds, which can not only reduce the noble metal content, but also promote their catalytic performances by tuning their crystal lattices and introducing additional active sites. In this review, we present a concise overview of the recent advancements in the preparation and application of various kinds of noble metal-light nonmetal binary nanocompounds. Besides introducing synthetic strategies, we focus on the effects of introducing light nonmetal elements on the lattice structures of noble metals and highlight notable progress in the lattice strain engineering of representative core-shell nanostructures derived from these nanocompounds. In the meantime, the catalytic applications of the light element-incorporated noble metal-based nanomaterials are discussed. Finally, we discuss current challenges and future perspectives in the development of noble metal-nonmetal based nanomaterials.

Advances in Extracellular-Vesicles-Based Diagnostic and Therapeutic Approaches for Ocular Diseases.

Extracellular vesicles (EVs) are nanoscale membrane vesicles of various sizes that can be secreted by most cells. EVs contain a diverse array of cargo, including RNAs, lipids, proteins, and other molecules with functions of intercellular communication, immune modulation, and regulation of physiological and pathological processes. The biofluids in the eye, including tears, aqueous humor, and vitreous humor, are important sources for EV-based diagnosis of ocular disease. Because the molecular cargos may reflect the biology of their parental cells, EVs in these biofluids, as well as in the blood, have been recognized as promising candidates as biomarkers for early diagnosis of ocular disease. Moreover, EVs have also been used as therapeutics and targeted drug delivery nanocarriers in many ocular disorders because of their low immunogenicity and superior biocompatibility in nature. In this review, we provide an overview of the recent advances in the field of EV-based studies on the diagnosis and therapeutics of ocular disease. We summarized the origins of EVs applied in ocular disease, assessed different methods for EV isolation from ocular biofluid samples, highlighted bioengineering strategies of EVs as drug delivery systems, introduced the latest applications in the diagnosis and treatment of ocular disease, and presented their potential in the current clinical trials. Finally, we briefly discussed the challenges of EV-based studies in ocular disease and some issues of concern for better focusing on clinical translational studies of EVs in the future.

Mg-Cross-Linked Alginate Hydrogel Induces BMSC/Macrophage Crosstalk to Enhance Bone Tissue Regeneration via Dual Promotion of the Ligand-Receptor Pairing of the OSM/miR-370-3p-gp130 Signaling Pathway.

Macrophages play a pivotal role in the crosstalk between the immune and skeletal systems, while Mg-based biomaterials demonstrate immunomodulatory capabilities in this procedure. However, the mechanism of how Mg2+ promotes osteogenesis through the interplay of bone marrow-derived mesenchymal stem cells (BMSCs) and macrophages remains undescribed. Here, we demonstrated that a Mg-cross-linked alginate hydrogel exerted a dual enhancement of BMSCs osteogenic differentiation through the ligand-receptor pairing of the OSM/miR-370-3p-gp130 axis. On the one hand, Mg2+, released from the Mg-cross-linked hydrogel, stimulates bone marrow-derived macrophages to produce and secrete more OSM. On the other hand, Mg2+ lowers the miR-370-3p level in BMSCs and in turn, reverses its suppression on gp130. Then, the OSM binds to the gp130 heterodimer receptor and activates intracellular osteogenic programs in BMSCs. Taken together, this study reveals a novel cross-talk pattern between the skeletal and immune systems under Mg2+ stimulation. This study not only brings new insights into the immunomodulatory properties of Mg-based biomaterials for orthopedic applications but also enriches the miRNA regulatory network and provides a promising target to facilitate bone regeneration in large bone defects.

Transcranial direct current stimulation over the right parietal cortex improves the depressive disorder: A preliminary study.

OBJECTIVE: The right posterior parietal cortex is the core brain region of emotional processing and executive control network in the human brain, and the function of the right posterior parietal cortex is decreased in patients with major depressive disorder. This study aims to preliminarily investigate whether the excitation of the right posterior parietal cortex by transcranial direct current stimulation (tDCS) could improve their clinical symptoms. METHODS: In this study, 12 patients with major depressive disorder were given tDCS treatment at Xuanwu Hospital of Capital Medical University and the First Hospital of Hebei Medical University. The stimulating electrode (anode) was placed on the patients' right parietal cortex, whereas the reference electrode (cathode) was placed on the patients' left mastoid. The stimulation intensity was set as 2.0 mA. The patients with depressive disorder were treated for 20 min at a time twice a day for 14 consecutive days. The severity of the clinical symptoms was evaluated using the Hamilton Depression Rating Scale-17 (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS) at before and right after treatment. RESULTS: The HDRS-17 scores of patients with depressive disorder decreased significantly following the tDCS treatment compared with those before treatment (p < .001). Further analysis revealed that the patients' anxiety/somatization, cognitive deficit, retardation, and sleep disorder scores all decreased significantly after the tDCS treatment (p < .05), although there was no significant change in their weight. Moreover, the patients' HARS scores decreased significantly after the tDCS treatment when compared with those before treatment (p < .01). CONCLUSION: The right parietal cortex may be another key stimulation targets to improving the efficacy of tDCS treatment to the patients with major depressive disorder.

Analysis of etiology and clinical features of spontaneous downbeat nystagmus: a retrospective study.

Objective: To investigate the topical diagnosis, possible etiology and mechanism of spontaneous downbeat nystagmus (sDBN) patients with dizziness/vertigo. Methods: The clinical features of dizziness/vertigo patients accompanied with DBN were retrospectively reviewed in the Vertigo Center of our hospital from January 2018 to March 2021. The clinical features of dizziness/vertigo patients accompanied with DBN were reviewed. Comprehensive VNG, bithermal caloric testing, video-head-impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP), head magnetic resonance imaging (MRI), three-dimensional fluid-attenuated incersion recovery magnetic resonance imaging (3D-FLAIR MRI) in the inner ear, serum immunology and other examinations were to determine the lesion site, and analyze its possible etiology and mechanism. Results: A total of 54 patients were included. Among them, 70.4% (n = 38) of DBN patients were diagnosed with episodic vestibular syndrome (EVS), 22.2% (n = 12) with chronic vestibular syndrome (CVS), and 7.4% (n = 4) with acute vestibular syndrome (AVS). Among all the patients, 51.9% of DBN patients had clear etiology, with central lesions of 29.6% and peripheral diseases of 22.2%. The most common diseases in DBN patients were cerebellar lesions (13.0%, n = 7) and vestibular migraine (13.0%, n = 7), followed by benign positional paroxysmal vertigo (7.4%, n = 4) and drug-related dizziness/vertigo (5.6%, n = 3). The other 48.1% of the patients had unknown etiology. 53.8% (14/26) of patients with idiopathic DBN had decreased semicircular canal function, with 42.9% (6/14) decreased posterior semicircular canal function. The posterior semicircular canal gain in DBN patients decreased compared to the anterior semicircular canal in the same conjugate plane. Patients with peripheral DBN were more prone to horizontal/torsional nystagmus during positional testing. Conclusion: In our study, DBN patients have a relative decrease in posterior semicircular canal gain, which is possibly a particular result found in a subset of downbeat nystagmus patients. The changes in nystagmus during positional testing may be helpful in distinguishing between peripheral and central causes.

A universal solvent-replacement strategy to convert alginate hydrogels into mechanically strong and transparent alginate eutectogels for sensitive strain sensors.

Eutectogels based on natural polymers have attracted significant attention as an alternative to easily dehydrated hydrogels and expensive ionogels in the development of flexible strain sensors. The feasibility of employing eutectogels derived from pure natural polymers could be greatly enhanced if their mechanical properties satisfy the requirements of applications. Herein, alginate eutectogels (AEs) with high mechanical properties (tensile strain 217 % and strength 2.26 MPa at fracture), and excellent transparency (over 90 %) are acquired via CaCl2 inducing ionic crosslinking and subsequent deep eutectic solvents (DESs, composed of glycerol and choline chloride) initiating physical crosslinking with a universal solvent- replacement strategy. Among them, sodium alginate, a natural polysaccharide polymer, is selected as representative supporting scaffolds and forms water-insoluble alginate hydrogels (AHs) in CaCl2 coagulation bath. The exchange of DESs with water of AHs not only restrengthens the polymer network by physical crosslinking, but also endows the obtained AEs with long-term solvent retention and high temperature resistance. In addition, the AEs not only have high reliability but also exhibit better linear sensitivity in a wide strain range (0-200 %). In particular, the AEs display multiple sensitivity to stretching, bending, and human motions, demonstrating feasibility as sensitive strain sensors.

Barthel Index, SPAN-100, and NIHSS Studies on the Predictive Value of Prognosis in Patients With Thrombolysis.

OBJECTIVE: We mainly explore the predictive value of Barthel Index (BI), SPAN-100, and National Institute of Health stroke scale (NIHSS) scores on clinical prognosis and functional outcomes in thrombolytic patients and compare the differences in the predictive values of the above 3 scales so as to provide an effective basis to evaluate the prognosis of thrombolytic patients. METHODS: Data were collected from 212 patients with the first-onset AIS (acute ischemic stroke). The enrolled patients were treated with recombinant tissue plasminogen activator thrombolytic therapy and were divided into 2 groups according to the modified Rankin Scale (mRS) score at discharge: the prognosis group (mRS≤2 points) and the poor prognosis group (mRS≥3 points). Logistic multivariate analysis was used to analyze the predictors of poor prognosis in patients with thrombolysis. MedCalc software was used to plot receiver operating characteristic (ROC) curves, calculate the area under the ROC curve (AUC), and compare the prediction performance of the 3 scales by the Delong and colleagues' method, and the difference of P <0.05 was statistically significant. RESULTS: Logistic binary regression multivariate analysis suggested that BI was a predictor of poor prognosis for thrombolytic therapy in patients with AIS. The lower the BI score, the poorer the prognosis. The AUC for BI score was 0.862, 95% CI (0.808-0.906), NIHSS score AUC was 0.665, 95% CI (0.597-0.728), and SPAN-100 score AUC was 0.640, 95% CI (0.572-0.705). AUC comparison of 3 scoring ROC curves suggested statistically significant differences between BI and NIHSS ( PC =0.0000), BI and SPAN-100 ( PC =0.0000); no significant difference was observed between SPAN-100 and NIHSS ( PC =1.7997). CONCLUSIONS: Simple BI scores have a high prognostic value for thrombolytic therapy in AIS.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases.

BACKGROUND: Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality, with the liver being the primary organ of metastasis. Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases (CRLMs). Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy. However, the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy. Body mass index (BMI) is one of the factors affecting the tumorigenesis and progression of colorectal cancer as well as prognosis after various antitumour therapies. Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight, particularly when receiving first-line chemotherapy regimens in combination with bevacizumab. AIM: To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs. METHODS: A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023. Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response. The Kaplan-Meier method with log rank test was used to compare progression-free survival (PFS) between patients with high and low BMI. BMI < 24.0 kg/m2 was defined as low BMI, and tumour regression grade 1-2 was defined as complete tumour response. RESULTS: Low BMI was observed in 74 (58.7%) patients and complete tumour response was found in 27 (21.4%) patients. The rate of complete tumour response was significantly higher in patients with low BMI (29.7% vs 9.6%, P = 0.007). Multivariate analysis revealed that low BMI [odds ratio (OR) = 4.56, 95% confidence interval (CI): 1.42-14.63, P = 0.011], targeted therapy with bevacizumab (OR = 3.02, 95%CI: 1.10-8.33, P = 0.033), preoperative carcinoembryonic antigen level < 10 ng/mL (OR = 3.84, 95%CI: 1.19-12.44, P = 0.025) and severe sinusoidal dilatation (OR = 0.17, 95%CI: 0.03-0.90, P = 0.037) were independent predictive factors for complete tumour response. The low BMI group exhibited a significantly longer median PFS than the high BMI group (10.7 mo vs 4.7 mo, P = 0.011). CONCLUSION: In CRLM patients receiving preoperative chemotherapy, a low BMI may be associated with better tumour response and longer PFS.

Novel therapeutic perspectives for wet age-related macular degeneration: RGD-modified liposomes loaded with 2-deoxy-D-glucose as a promising nanomedicine.

Choroidal neovascularization (CNV), characterized as a prominent feature of wet age-related macular degeneration (AMD), is a primary contributor to visual impairment and severe vision loss globally, while the prevailing treatments are often unsatisfactory. The development of conventional treatment strategies has largely been based on the understanding that the angiogenic switch of endothelial cells is dictated by angiogenic growth factors alone. Even though treatments targeting vascular endothelial growth factor (VEGF), like Ranibizumab, are widely administered, more than half of the patients still exhibit inadequate or null responses, emphasizing the imperative need for solutions to this problem. Here, aiming to explore therapeutic strategies from a novel perspective of endothelial cell metabolism, a biocompatible nanomedicine delivery system is constructed by loading RGD peptide-modified liposomes with 2-deoxy-D-glucose (RGD@LP-2-DG). RGD@LP-2-DG displayed good targeting performance towards endothelial cells and excellent in vitro and in vivo inhibitory effects on neovascularization were demonstrated. Moreover, our mechanistic studies revealed that 2-DG interfered with N-glycosylation, leading to the inhibition of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream signaling. Notably, the remarkable inhibitory effect on neovascularization and biocompatibility of RGD@LP-2-DG render it a highly promising and clinically translatable therapeutic candidate for the treatment of wet AMD and other angiogenic diseases, particularly in patients who are unresponsive to currently available treatments.

18F-BMS-986229 PET to Assess Programmed-Death Ligand 1 Status in Gastroesophageal Cancer.

Anti-programmed death 1 (PD-1) inhibitors are the standard of care for advanced gastroesophageal cancer. Although recommendations and approval by regulatory agencies are often based on programmed death ligand 1 (PD-L1) expression, pathologic assessments of PD-L1 status have several limitations. Single-site biopsies do not adequately capture disease heterogeneity within individual tumor lesions or among several lesions within the same patient, the PD-L1 combined positive score is a dynamic biomarker subject to evolution throughout a patient's disease course, and repeated biopsies are invasive and not always feasible. Methods: This was a prospective pilot study of the PD-L1-targeting radiotracer, 18F-BMS-986229, with PET imaging (PD-L1 PET) in patients with gastroesophageal cancer. Patients were administered the 18F-BMS-986229 radiotracer intravenously at a dose of 370 MBq over 1-2 min and underwent whole-body PET/CT imaging 60 min later. The primary objective of this study was to evaluate the safety and feasibility of 18F-BMS-986229. The trial is registered with ClinicalTrials.gov (NCT04161781). Results: Between February 3, 2020, and February 2, 2022, 10 patients with gastroesophageal adenocarcinoma underwent PD-L1 PET. There were no adverse events associated with the 18F-BMS-986229 tracer, and imaging did not result in treatment delays; the primary endpoint was achieved. Radiographic evaluation of PD-L1 expression was concordant with pathologic assessment in 88% of biopsied lesions, and 18F-BMS-986229 uptake on PET imaging correlated with pathologic evaluation by the combined positive score (Spearman rank correlation coefficient, 0.64). Seventy-one percent of patients with 18F-BMS-986229 accumulation on PET imaging also had lesions without 18F-BMS-986229 uptake, highlighting the intrapatient heterogeneity of PD-L1 expression. Patients treated with frontline programmed death 1 inhibitors who had 18F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. Conclusion: PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.

Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Comparison of clinical characteristics and vestibular function test results in patients with vestibular migraine and Menière's disease

Abstract Objectives The differentiation between Vestibular Migraine (VM) and Meniere's Disease (MD) is difficult because of overlapping symptoms. The study aimed to compare the clinical characteristics and vestibular function test results between VM and MD patients. Methods Seventy-one patients with definite VM and 31 patients with definite unilateral MD were included. All patients received Caloric Test (CT), Video Head Impulse Test (vHIT) and Vestibular Evoked Myogenic Potential (VEMP) test within 7 days after visiting the hospital. Results of these tests were compared between groups. Results Most VM patients (64.0%) experienced spontaneous internal vertigo, while most MD patients (66.7%) experienced spontaneous external vertigo. MD patients had more severe vestibular symptoms and autonomic responses compared to VM patients during attacks (p= 0.03, p= 0.00, respectively). The nystagmus intensity of CT-induced was greater in VM patients than in MD patients (p= 0.003). More VM patients had CT intolerance and Central Positional Nystagmus (CPN) compared to MD patients (p= 0.002, p = 0.006, respectively). More MD patients had CT(+) and vHIT saccades wave compared to VM patients (p< 0.001, p= 0.002, respectively). The non-elicitation rate of cervical VEMP was higher, and the ocular VEMP amplitudes were lower in MD patients than in VM patients (p = 0.002, p= 0.018). Conclusions Vestibular symptoms during attacks combined with the results of vestibular function tests may be used to differentiate between VM and MD. The diverse nature of vestibular symptoms (especially internal vertigo), history of motion sickness and CT intolerance may provide clues to the diagnosis of VM, whereas spontaneous external vertigo, CT(+) with vHIT(-), and the presence of saccades may provide clues to the diagnosis of MD. Level of evidence: 4.

Therapeutic effects of benzoylaconitine and paeoniflorin in rats with collagen-induced arthritis

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1ß, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1ß, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination