The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review.

Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of ß-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.

Visualisation of the vomerovaginal canal during endonasal transpterygoid approaches and CT imaging diagnosis.

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.

Antifungal and Mucoadhesive Properties of an Orally Administered Chitosan-Coated Amphotericin B Nanostructured Lipid Carrier (NLC).

Surface-modified nanostructured lipid carriers (NLC) represent a promising mode of drug delivery used to enhance retention of drugs at absorption site. Formulated chitosan-coated amphotericin-B-loaded NLC (ChiAmp NLC) had a size of 394.4 ± 6.4 nm, encapsulation and loading efficiencies of 86.0 ± 3% and 11.0 ± 0.1% respectively. Amphotericin-B release from NLCs was biphasic with no changes in physical properties upon exposure to simulated gastrointestinal conditions. Antifungal properties of Amphotericin-B and ChiAmpB NLC were comparable but ChiAmpB NLC was twice less toxic to red blood cells and ten times safer on HT-29 cell lines. In vitro mucoadhesion data were observed ex vivo, where ChiAmpB NLC resulted in higher retention within the small intestine compared to the uncoated formulation. The data strongly offers the possibility of orally administering a non-toxic, yet effective Amphotericin-B nanoformulation for the treatment of systemic fungal infections.

Comprehensive analysis and establishment of a prognostic model based on non-genetic predictors in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a systemic hematological malignancy usually incurable. The value of some important prognostic factors may gradually decrease. OBJECTIVE: We aimed to explore the non-genetic indexes, prognostic models, and significance of clinical staging systems of MM. METHODS: A retrospective analysis was conducted on clinical data from 110 patients with MM who first visit the First Affiliated Hospital of Guangzhou Medical University between September 2005 to December 2018. RESULTS: Bone marrow plasma cell percentage (BMPC%), cystatin C (CysC), and ß2 microglobulin (ß2-MG) were positively correlated with Durie-Salmon (D-S) and international staging system (ISS) stages, while red blood cell count (RBC) and hemoglobin volume (HGB) were negatively correlated (P< 0.05). Univariate analysis showed that ISS stage, treatment protocol, immunofixation electrophoresis (IFE), ratio of red cell distribution width to platelet count (RPR), monocyte count (MONO), lactate dehydrogenase, and immunoglobulin G were significantly associated with the three-year overall survival (OS). IFE, treatment protocol, and ß2-MG significantly affected progression-free survival (P< 0.05). Multivariate analysis showed that the treatment protocol, ISS stage, RPR, MONO, and IFE were independent prognostic factors for three-year OS (P< 0.05). CONCLUSIONS: BMPC%, CysC, and ß2-MG were positively correlated with both clinical staging systems and RBC and HGB were negatively correlated. RPR and MONO affect MM prognosis and the established prognostic model can guide patient prognosis.

Propensity score matching analysis comparing the efficacy of Ruxolitinib to historical controls in second-line or beyond treatment for chronic GvHD after steroid failure.

Established first-line therapy for chronic graft-versus-host disease (cGvHD) comprises corticosteroids with/without calcineurin inhibitors, but about half of cGvHD patients are refractory to corticosteroid therapy. The present study retrospectively analyzed treatment outcomes in 426 patients and undertook a propensity-score matching (PSM) analysis between ruxolitinib (RUX) treated group and a historical group of cGvHD patients treated with best available treatment (BAT). PSM process adjusted unbalanced risk factors between the 2 groups, including GvHD severity, HCT-CI score, and treatment line, extracting 88 patients (44 in BAT/RUX groups each) for final analysis. In PSM subgroup, RUX group showed 74.7% 12 months' FFS rate vs 19.1% for BAT group (p < 0.001), whereas 12 months' OS rates were 89.2% and 77.7%, respectively. Multivariate analysis for FFS confirmed RUX superiority over BAT together with HCT-CI score 0-2 vs ≥3. For OS, RUX was superior to BAT, while age ≥60 years and severe grade cGvHD adversely impacted OS. In PSM subgroup, at months 0, 3, and 6, 4.5%, 12.2% and 22.2% more patients in RUX group could discontinue prednisone compared to BAT group, respectively. In conclusion, the current study showed that for FFS, RUX was superior to BAT as second-line therapy or beyond in cGvHD patients after therapy failure.

A Multicenter, Retrospective Study Evaluating Clinical Outcomes of Ruxolitinib Therapy In Heavily Pretreated Chronic GVHD Patients With Steroid Failure.

Although ruxolitinib is emerging as the treatment of choice for steroid-refractory or -dependent chronic graft versus host disease (cGVHD) based on randomized control trial data, there is relatively little real-world data published on ruxolitinib for this indication. We wanted to evaluate the real-world efficacy and safety of ruxolitinib in cGVHD patients who have failed any previous systemic therapy for cGVHD. We retrospectively evaluated the efficacy of ruxolitinib in 115 heavily pretreated patients with steroid-refractory or -dependent chronic GVHD across 5 transplantation centers. The majority of the study population had severe cGVHD (60%) and received ruxolitinib at the fourth treatment line or beyond (82%, n = 96). The median duration of follow-up in this study population was 13 months. The overall response rate (ORR) was 48.6%, 54.9%, and 48.5% at 3, 6, and 12 months, respectively. Clinical benefit (an outcome metric combining ORR with steroid reduction) was observed in 58.7%, 64.8%, and 60.6% of patients at 3, 6, and 12 months, respectively. Approximately one third of patients (37.9%) were able to discontinue prednisone at 12 months, and 63.8% were able to taper prednisone to a daily dose <0.1 mg/kg at 12 months. Failure-free survival at 12 months was 64.6% (54.1%-73.2%). Multivariate analysis identified that patients with severe cGVHD were at a higher risk of failure because of a therapy switch, whereas a pretransplantation hematopoietic stem cell transplantation-comorbidity index score ≥ 3 was associated with a high risk of failure because of increasing risk of non-relapse mortality. Overall, this study demonstrates the therapeutic efficacy of ruxolitinib for cGVHD in a heavily pretreated real-world population.

Improved Bioavailability of Poorly Soluble Drugs through Gastrointestinal Muco-Adhesion of Lipid Nanoparticles.

Gastrointestinal absorption remains indispensable in the systemic delivery of most drugs, even though it presents several challenges that, paradoxically, may also provide opportunities that can be exploited to achieve maximal bioavailability. Drug delivery systems made from nanoparticle carriers and especially, lipid carriers, have the potential to traverse gastrointestinal barriers and deploy in the lymphatic pathway, which aptly, is free from first pass via the liver. Several poorly soluble drugs have presented improved systemic bioavailability when couriered in lipid nanoparticle carriers. In this review, we propose an additional frontier to enhancing the bioavailability of poorly soluble drugs when encapsulated in lipid nano-carriers by imparting muco-adhesion to the particles through application of appropriate polymeric coating to the lipid carrier. The combined effect of gastrointestinal muco-adhesion followed by lymphatic absorption is a promising approach to improving systemic bioavailability of poorly soluble drugs following oral administration. Evidence to the potential of this approach is backed-up by recent studies within the review.

Compatibility Optimal Design of Axially Loaded Circular Concrete-Filled Steel Tube Stub Columns.

Numerous studies have been carried out on the axially loaded circular concrete-filled steel tube (CCFST) stub columns. However, to date, no clear evaluation criterion for the compatibility of its design parameters has been established. In the present study, the compatibility of the design parameters (concrete compressive strength fc, steel yield strength fy, diameter D and thickness of steel tube t) of axially loaded CCFST stub columns was quantitatively investigated in terms of the contribution of the composite actions to the axial bearing capacity of the columns. The composite ratio λ was proposed as an indicator to represent the effectiveness of the composite actions. A numerical framework of the determination of λ was established, making use of a series of existing widely recognized constitutive models of structural steel and concrete. Some modifications were carried out on these models to ensure the numerical stability of the presented analysis. Moreover, the rationality of the combined use of these models was verified. The analytical results show that excessive or very small D/t ratio should be avoided in design. Meanwhile, the combined use of low-strength steel and high-strength concrete should be avoided. A table of optimal D/t ratios corresponding to different material strength matches was provided for designers. Finally, an optimization of the design parameters using the proposed method and the existing design specification was performed.

Numerical Investigation of Composite Behavior and Strength of Rectangular Concrete-Filled Cold-Formed Steel Tubular Stub Columns.

The objective of this study was to investigate the composite behavior of rectangular concrete-filled cold-formed steel (CFS) tubular stub columns under axial compression. A fine finite 3D solid element model of rectangular concrete-filled cold-formed steel tubular stub column was established by ABAQUS, which utilized a constitutive model of cold-formed steel considering the cold-forming effect and a triaxial plastic-damage constitutive model of the infilled concrete. Good agreement was achieved and the average discrepancy between the experimental and FE results was less than 5%. Based on the verified models, a further parametric analysis was carried out to reveal the influence of various factors on the strength and behavior of the concrete-filled rectangular cold-formed steel tubular stub columns. The factors included constitutive models adopted for cold-formed steel, length over width ratio of the rectangular section, wall-thickness and width, and concrete strength and yield strength of the cold-formed steel. A total of 144 FE models were analyzed. The stress nephogram was reasonably simplified in accordance with the limit state and a theoretical formula considering confinement coefficient was proposed to estimate the ultimate bearing capacity of concrete-filled rectangular cold-formed steel tubular stub columns using the superposition method. The calculated results showed satisfactory agreement with both the experimental and FE results, which proved the validity and accuracy of the formula proposed in this paper. In the proposed formula, the confinement coefficient of square concrete-filled cold-formed steel tubular stub columns is larger than that of hot-rolled steel counterparts but smaller than that of the stainless steel counterparts.

Sanfu herbal patch applied at acupoints in patients with bronchial asthma: study protocol for a randomized controlled trial.

BACKGROUND: Bronchial asthma is one of the most common inflammatory airway disorders. As one of the main non-drug therapies, the Sanfu herbal patch (SHP) has been widely used to treat bronchial asthma, although the evidence for its efficacy and associated mechanism are inconclusive. The objective of this trial is to clarify the clinical efficacy and safety of the SHP in the treatment of bronchial asthma in the chronic persistent or clinical remission stage and to provide high-quality data for further research. METHODS: We propose a multicentre, double-blinded, parallel, randomized, placebo-controlled clinical trial involving 4 study hospitals in China. A total of 72 eligible participants will be randomized into an SHP group and a placebo group. They will receive an SHP for 3 treatment sessions. The primary outcome will be changes in forced expiratory volume in 1 s after 3 treatment sessions. Secondary outcomes will include the following: (1) the Asthma Quality of Life Questionnaire, Asthma Control Test, and Asthma Long-term Follow-up Scale; (2) levels of Metallothionein-2 and Transgelin-2 in blood and urine; and (3) levels of IL-5, IL-13, IL-23, IL-25, and thymic stromal lymphopoietin in blood. Analysis of the data will be performed at baseline, at the end of the 2nd and 3rd treatment sessions, and at the 24-week follow-up. The safety of the SHP will be evaluated at each treatment session. DISCUSSION: The aims of this trial are to determine whether the SHP is more effective than placebo in the treatment of patients with bronchial asthma, as well as whether the SHP works by reducing airway inflammation and reversing bronchoconstriction. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ), ChiCTR1900024616. Registered on 19 July 2019.

Traumatic transnasal penetrating injury with cerebral spinal fluid leak.

CSF leak in penetrating skull base injury is relatively rare compared to close head injury involving skull base fracture. We report a 5-year-old boy presented with epistaxis and impacted pencil into the left nostril. The child was hemodynamically stable without any neurological deficit. Intraoperatively, there was a nasal septal defect posteriorly with anterior skull base fracture associated with CSF leak. The pencil was removed from the left nostril and the CSF leak was repaired using harvested abdominal fat under the same setting. Computed Tomography (CT) of the brain showed right cribriform plate fracture with small pneumocranium. Postoperatively, a prophylactic antibiotic was given for seven days and he was discharged well. Subsequent clinic visits up to one-year postoperative period showed no recurrence of the CSF leak. History taking, physical examination and CT imaging give valuable diagnostic values in managing the penetrating skull base injury. Early intervention for removal of the foreign body and repair of the CSF leak is advocated to prevent catastrophic complication.

[Study on chemical components of the essential oil from Fructus Canarii by GC-MS].

OBJECTIVE: To study on the main chemical components of essential oil from Fructus Canarii. METHODS: The essential oil from Fructus Canarii was extracted by steam-stilling and analyzed by GC-MS. The relative content of each component was determined by normalization method. RESULTS: 121 compounds were separated and 65 compounds were identified, which weighed 91.25% of the total oil. The main chemical components of the oil were caryophilene (24.78%), (+/-)-2-methylene-6,6-dimethyl,-bicyclo [3.1.1]-heptane (13.51%), p-menth-1-en-8-ol (7.15%) and so on. CONCLUSION: This experiment has provided scientific foundation for further utilization of Fructus Canarii.

Chemical constituents from Canarium album Raeusch and their anti-influenza A virus activities.

Two new dyhydrophaseic acid glucoside isomers, (1'S, 3'R, 5'S, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-ß-D-glucopyranoside (2) and (1'R, 3'S, 5'R, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-ß-D-glucopyranoside (4), together with 10 known compounds [myo-inositol (1), 3,4-dihydroxybenzoic acid (3), 3-O-galloyl quinic acid (5), ellagic acid (6), gallic acid (7), ethyl gallate (8), scopoletin (9), ellagic acid-4-O-ß-D-glucopyranoside (10), ellagic acid-4-O-α-L-rhamnopyranoside (11), and isocorilagin (12)] were isolated from the chloroform extract of Canarium album Raeusch fruits by repeated chromatography on macroporous adsorption resin, silica gel, Sephadex LH-20, Toyopearl HW-40F, and reverse-phase C18 columns, etc. Their structures and absolute configurations were determined by comprehensive analysis of 1D- and 2D-nuclear magnetic resonance (NMR), high-resolution electron spray ionization mass spectrometry (HR-ESI-MS), ESI-MS, optical rotation, circular dichroism spectra, and comparison of NMR data with data of known compounds. Bioassay of their anti-influenza virus A activities showed that compounds 9 and 12 displayed a significant inhibitory effect with IC50 values of 22.9 ± 3.7 and 5.42 ± 0.97 µg/ml, respectively.

[Lactic acid inhibits the formation of semen-derived amyloid fibrils].

OBJECTIVE: To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation. METHODS: PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The ß sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining. RESULTS: Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of ß-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion. CONCLUSION: Lactic acid inhibits SEVI fibril formation in vitro.

Mantle Cell Lymphona Masquerading as Obstructive Sleep Apnoea

@#Tonsillar malignancy typically presents with asymmetrical tonsillar enlargement, lesion on the tonsils, sore throat or a neck mass. We report a case of unsuspected tonsillar malignancy in a 56-year-old gentleman who presented with symptoms of obstructive sleep apnoea. His tonsils were grade III bilaterally with normal mucosa. Tonsillectomy was performed to improve patient’s compliance with Continuous Positive Airway Pressure (CPAP) therapy. These tonsillar specimens were reported to be Mantle Cell Lymphoma (MCL) based on the histology and ancillary studies. This case highlights that benign-looking symmetrical tonsillar enlargement can harbour occult malignancy. It is important to note that OSA symptoms may be the presentation for haematological malignancies. Tonsillar specimens should be sent for histopathological examination regardless of the indication to avoid misdiagnosis and delay in treatment.

[Semen-derived enhancer of viral infection--a key factor in sexual transmission of HIV].

Semen-derived enhancer of viral infection(SEVI) is a peptide fragment (PAP248-286) from prostatic acid phosphatase(PAP), which can enhance human immunodeficiency virus infection. The mechanisms of SEVI include: (1) SEVI with several cationic amino acid residues reduced electrostatic repulsion between HIV virus and the target cells; (2) The disorder state of SEVI in the human body fluids was helpful to the interaction between virus and the target cell membranes; (3) SEVI could capture HIV particles directly and speed the velocity of virus on the surface of the target cells and improve adsorption and fusion. Currently, the substances of inhibiting SEVI activity include: EGCG from green tea, small molecule compound of aminoquinoline Surfen, ThT analogs BTA-EG6. Those compounds might block the combination of HIV and SEVI or prevent the formation of amyloid fibers, and then reduce the enhancement of SEVI. The studies on the biological characteristics and mechanisms of SEVI have a big benefit for the prevention and treatment of HIV infection.