The application of artificial intelligence in EUS.

Artificial intelligence (AI) is an epoch-making technology, among which the 2 most advanced parts are machine learning and deep learning algorithms that have been further developed by machine learning, and it has been partially applied to assist EUS diagnosis. AI-assisted EUS diagnosis has been reported to have great value in the diagnosis of pancreatic tumors and chronic pancreatitis, gastrointestinal stromal tumors, esophageal early cancer, biliary tract, and liver lesions. The application of AI in EUS diagnosis still has some urgent problems to be solved. First, the development of sensitive AI diagnostic tools requires a large amount of high-quality training data. Second, there is overfitting and bias in the current AI algorithms, leading to poor diagnostic reliability. Third, the value of AI still needs to be determined in prospective studies. Fourth, the ethical risks of AI need to be considered and avoided.

Efficacy and Safety of Enhanced Recovery After Surgery (ERAS) Protocols for Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of enhanced recovery after surgery (ERAS) in minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative disease (LDD). METHODS: Electronic databases including PubMed, Embase, the Cochrane Library, Web of Science, Clinical Trials.gov, etc. were searched from inception to October 2023. Randomized controlled trials (RCTs) and cohort studies (CSs) comparing ERAS program with traditional protocol of MIS-TLIF for LDD were included. RESULTS: A total of 11 studies were included for final analysis. The pooled results of RCTs showed that compared with MIS-TLIF, the ERAS program used in MIS-TLIF could reduce the length of hospital stay, operation time, intraoperative blood loss and incidence of postoperative complications, decrease visual analog scale and Oswestry Disability Index (ODI) score, and improve patient satisfaction (P < 0.05). However, the pooled results of CSs revealed no statistical difference in the ODI score, fusion rate, operation time, and incidence of complications between the two groups (P > 0.05). CONCLUSIONS: Compared with MIS-TLIF, the ERAS program used in MIS-TLIF could effectively shorten the length of hospital stay, operation time, decrease intraoperative blood loss, and incidence of postoperative complications, promote postoperative pain relief, functional recovery, and patient satisfaction. This study confirmed the value of ERAS in MIS-TLIF surgery and provided evidence for the standardization of ERAS in the future. Considering that the pooled results of RCTs and CSs are not completely consistent, more high-quality studies are needed to confirm these conclusions.

Direct transmission of severe fever with thrombocytopenia syndrome virus from farm-raised fur animals to workers in Weihai, China.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. METHOD: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. RESULTS: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. CONCLUSION: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.

Single-cell RNA sequencing reveals the process of CA19-9 production and dynamics of the immune microenvironment between CA19-9 (+) and CA19-9 (-) PDAC.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated. METHODS: We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (three each from CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. RESULTS: Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. CONCLUSIONS: Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Impact of glucocorticoids and rapamycin on autophagy in Candida glabrata-infected macrophages from BALB/c mice.

Objective: In the defense against microorganisms like Candida albicans, macrophages recruit LC3(Microtubule-associated protein 1A/1B-light chain 3) to the periplasm, engaging in the elimination process through the formation of a single-membrane phagosome known as LC3-associated phagocytosis (LAP). Building on this, we propose the hypothesis that glucocorticoids may hinder macrophage phagocytosis of Candida glabrata by suppressing LAP, and rapamycin could potentially reverse this inhibitory effect. Methods: RAW264.7 cells were employed for investigating the immune response to Candida glabrata infection. Various reagents, including dexamethasone, rapamycin, and specific antibodies, were utilized in experimental setups. Assays, such as fluorescence microscopy, flow cytometry, ELISA (Enzyme-Linked Immunosorbent Assay), Western blot, and confocal microscopy, were conducted to assess phagocytosis, cytokine levels, protein expression, viability, and autophagy dynamics. Results: Glucocorticoids significantly inhibited macrophage autophagy, impairing the cells' ability to combat Candida glabrata. Conversely, rapamycin exhibited a dual role, initially inhibiting and subsequently promoting phagocytosis of Candida glabrata by macrophages. Glucocorticoids hinder macrophage autophagy in Candida glabrata infection by suppressing the MTOR pathway(mammalian target of rapamycin pathway), while the activation of MTOR pathway by Candida glabrata diminishes over time. Conclusion: Our study elucidates the intricate interplay between glucocorticoids, rapamycin, and macrophage autophagy during Candida glabrata infection. Understanding the implications of these interactions not only sheds light on the host immune response dynamics but also unveils potential therapeutic avenues for managing fungal infections.

Quality of life, sleep and anxiety status among patients with rosacea in the Yunnan plateau region: A 2-year retrospective study.

OBJECTIVE: To investigate the life, sleep quality and anxiety of rosacea patients in Yunnan and the improvement of these aspects after treatment. METHODS: A total of 141 patients with rosacea and 123 healthy controls were included in our study. The quality of life, sleep quality and anxiety of patients with rosacea and healthy controls were investigated by the Rosacea Severity Scores (RSSs), the Medical Outcomes Study 36-item short-form health survey (SF-36), the Pittsburgh Sleep Quality Index (PSQI) and Self-rating Anxiety Scale (SAS). The quality of life, sleep quality and anxiety of patients with rosacea were assessed again after treatment. RESULTS: Compared with healthy controls, patients with rosacea had significantly lower physical component scores (PCS) and mental component scores (MCS) but higher PSQI and SAS scores. After treatment, rosacea patients showed significantly higher MCS but lower PSQI and SAS scores. Correlation analysis showed a significant correlation between PCS, MCS, PSQI, SAS and RSSs. CONCLUSIONS: Patients with rosacea have a lower quality of life and sleep quality and tend to be more anxious than healthy controls. In addition, the mental quality of life, sleep quality and anxiety of rosacea patients can be significantly improved after treatment. Therefore, it is important to pay attention to the psychological status of rosacea patients. Psychological counseling and intervention are necessary to better prevent and treat rosacea.

Decoding the tumor microenvironment and molecular mechanism: unraveling cervical cancer subpopulations and prognostic signatures through scRNA-Seq and bulk RNA-seq analyses.

Background: Cervical carcinoma (CC) represents a prevalent gynecological neoplasm, with a discernible rise in prevalence among younger cohorts observed in recent years. Nonetheless, the intrinsic cellular heterogeneity of CC remains inadequately investigated. Methods: We utilized single-cell RNA sequencing (scRNA-seq) transcriptomic analysis to scrutinize the tumor epithelial cells derived from four specimens of cervical carcinoma (CC) patients. This method enabled the identification of pivotal subpopulations of tumor epithelial cells and elucidation of their contributions to CC progression. Subsequently, we assessed the influence of associated molecules in bulk RNA sequencing (Bulk RNA-seq) cohorts and performed cellular experiments for validation purposes. Results: Through our analysis, we have discerned C3 PLP2+ Tumor Epithelial Progenitor Cells as a noteworthy subpopulation in cervical carcinoma (CC), exerting a pivotal influence on the differentiation and progression of CC. We have established an independent prognostic indicator-the PLP2+ Tumor EPCs score. By stratifying patients into high and low score groups based on the median score, we have observed that the high-score group exhibits diminished survival rates compared to the low-score group. The correlations observed between these groups and immune infiltration, enriched pathways, single-nucleotide polymorphisms (SNPs), drug sensitivity, among other factors, further underscore their impact on CC prognosis. Cellular experiments have validated the significant impact of ATF6 on the proliferation and migration of CC cell lines. Conclusion: This study enriches our comprehension of the determinants shaping the progression of CC, elevates cognizance of the tumor microenvironment in CC, and offers valuable insights for prospective CC therapies. These discoveries contribute to the refinement of CC diagnostics and the formulation of optimal therapeutic approaches.

Properties of Gangue Powder Modified Fly Ash-Based Geopolymer.

The environmental and economic problems caused by gangue accumulation continue to worsen. Therefore, the implementation of a cost-effective method for utilizing gangue resources is urgent. In this study, different gangue powder (GP) contents (0%, 10%, 20%, 30%, 40%, and 50%) for mechanical-thermal activation were used to modify a fly ash-based geopolymer (FAG). Further, the effect of GP was revealed by investigating the setting time, fluidity, porosity, water absorption rate, mechanical properties, drying shrinkage, and microstructure. Results showed that the addition of GP reduced the fluidity and setting time of gangue powder-fly ash-base geopolymer (GPFAG), improved density, and decreased the water absorption rate of GPFAG. Moreover, its mechanical properties gradually improved. Compared with GPFAG0 (FAG with 0% GP), the 28-d compressive and flexural strengths of GPFAG50 (FAG with 50% GP) increased by 246.4% and 136.8%, respectively. The incorporation of GP increased the drying shrinkage. The results of XRD and FTIR analyses showed that the addition of GP increased the production of amorphous silica-aluminate gels, such as N-S-A-H and C-S-A-H. Moreover, strong Si-O-T vibrational peaks appeared in the range 743-1470 cm-1, characterizing the GPFAG strength and reaction degree.

Role of interleukin-36γ induced by ultraviolet radiation in chronic actinic dermatitis.

BACKGROUND: Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterized by a high eosinophil count and total immunoglobulin E (IgE) in the peripheral blood of patients. At present, however, the reasons for their elevation remain unclear. OBJECTIVE: The current study aimed to detect changes in inflammatory cytokines in CAD and explore their role in this disease. METHODS: Enzyme-linked immunosorbent assay and Luminex assay were conducted to measure inflammatory factor levels. Immunohistochemical analysis and quantitative real-time polymerase chain reaction were performed to evaluate the expression levels of interleukin-36γ (IL-36γ), IL-8, chemokine (C-C motif) ligand 17 (CCL17), and CCL18. CCK8 kits were used to assess cell proliferation. Immunofluorescence was used to detect nuclear factor κB (NF-κB) p65 nuclear translocation. Western blot analysis was performed to detect the protein expression level of phosphorylated NF-κB (p-NF-κB) p65. Hematoxylin and eosin and Masson trichrome staining were applied to observe histological changes in a chronic photo-damaged mouse model. RESULTS: Eosinophils, total IgE, IL-36γ, IL-8, tumor necrosis factor α, CCL17, and CCL18 were elevated in CAD. Of note, IL-36γ promoted the proliferation of eosinophilic cells (EOL-1) and the production of IgE in peripheral blood mononuclear cells. IL-36γ also promoted the production of IL-8 and CCL18 in immortalized human keratinocytes (HaCaT cells), while ultraviolet radiation (UVR)-induced IL-36γ via activation of the NF-κB signaling pathway. CONCLUSIONS: IL-36γ was involved in the pathogenesis of CAD and UVR contributed to the production of IL-36γ, which may provide a novel therapeutic target for CAD.

High-Transparency and Colorless Polyimide Film Prepared by Inhibiting the Formation of Chromophores.

Colorless polyimides (CPIs) with outstanding mechanical properties are essential materials in the production of flexible display panels, foldable windows, and even spacecraft cockpits. This paper specifically elaborates that the Morkit unit, and azo and nitro chromophores are important factors contributing to yellow PI, together with the well-known charge transfer complex (CTC) theory. Three diamine monomers, two anhydrides monomers, and three blockers were used to inhibit chromophores formation and, thus, obtain CPI films. The cut-off wavelength was blue-shifts to 334 nm and the transmittance is improved to 98.9% in the UV-vis range. Mechanical and thermal properties of the CPI films are not reduced through coupling effects of the blockers. Therefore, the inhibition method of the Morkit units and chromophore groups is a promising process for preparing CPIs to be used as flexible display materials.

Deep Fungal Infections Among General Hospital Inpatients in Southwestern China: A 5-Year Retrospective Study.

Background: Deep fungal infection is a type of life-threatening opportunistic infection. Its incidence has been increasing in recent years. This infection can affect the prognosis of patients, prolong hospital stays and raise costs for patients and their families. Objective: We aimed to understand the current situation of deep fungal infections in the First Affiliated Hospital of Kunming Medical University and to provide a basis for the clinical diagnosis and treatment of deep fungal infections. Methods: This was a retrospective analysis of 528,743 cases in the hospital from 2015 to 2019, including the epidemiological characteristics, treatment and prognosis of deep fungal infections. Results: A total of 274 cases (0.05%) with deep fungal infections were identified, accounting for 0.05% of the total number of hospitalizations. The incidence of deep fungal infections in the hospital showed an increasing trend from 2015 to 2019. The most commonly infected site was the respiratory tract (93.07%). Among patients with deep fungal infections, 266 specimens were positive for fungal culture, by which 161 cultured Candida albicans (C. albicans), accounting for 60.53%, the main pathogen causing deep fungal infection. From 2015 to 2019, the percentage of C. albicans cases showed a downward trend, while that of non-C. albicans showed an opposite trend. Antibiotics were the most common predisposing factor for deep fungal infections (97.45%). Among the underlying diseases of patients with deep fungal infections, infectious diseases (59.49%) were the most common. Those with underlying diseases such as renal insufficiency and neurological diseases had a worse prognosis. Indwelling catheters, nervous system disease and tumors were risk factors for a poor prognosis. Conclusions: We report for the first time the epidemiological data of deep fungal infections in a general hospital in southwestern China from 2015 to 2019. In the past 5 years, the number of patients with deep fungal infections in the First Affiliated Hospital of Kunming Medical University has been increasing. Although the clinical data are limited, these results can provide references for the diagnosis and treatment of deep fungal infections.

Metabolic Profiling Reveals That the Olfactory Cues in the Duck Uropygial Gland Potentially Act as Sex Pheromones.

The exchange of information between animals is crucial for maintaining social relations, individual survival, and reproduction, etc. The uropygial gland is a particular secretion gland found in birds. We speculated that uropygial gland secretions might act as a chemical signal responsible for sexual communication. We employed non-targeted metabolomic technology through liquid chromatography and mass spectrometry (LC-MS) to identifying duck uropygial gland secretions. We observed 11,311 and 14,321 chemical substances in the uropygial gland secretion for positive and negative ion modes, respectively. Based on their relative contents, principal component analysis (PCA) showed that gender significantly affects the metabolite composition of the duck uropygial gland. A total of 3831 and 4510 differential metabolites were further identified between the two sexes at the positive and negative ion modes, respectively. Of them, 139 differential metabolites were finally annotated. Among the 80 differential metabolites that reached an extremely significant difference (p < 0.01), we identified 24 volatile substances. Moreover, we further demonstrated that five kinds of volatile substances are highly repeatable in all testing ducks, including picolinic acid, 3-Hydroxypicolinic acid, indoleacetaldehyde, 3-hydroxymethylglutaric acid, and 3-methyl-2-oxovaleric acid. All these substances are significantly higher in males than in females, and their functions are involved in the reproduction processes of birds. Our data implied that these volatile substances act as sex pheromones and may be crucial olfactory clues for mate selection between birds. Our findings laid the foundation for future research on whether uropygial gland secretion can affect ducks' reproduction and production.

An AIE triggered fluorescence probe with three-photon absorption and its biological applications.

Three-photon absorption (3 PA) in the near IR region is among the most prominent nonlinear optical (NLO) effects and has attractive applications in chemical/biological sensing and imaging. Yet, rationally constructed molecules with small molecular weight and reasonable 3 PA cross-section has been rarely reported. Herein, we designed a novel three-photon absorption photostable luminogen (namely X1) with enhanced aggregation induced emission (AIE) and the ability to achieve multi-photon imaging with femtosecond laser excitation. X1 was constructed from diaminobenzene and diethylamino salicylaldehyde forming a novel di-Schiff base. It possesses a large conjugated delocalization which exhibits large three-photon absorption (3 PA) cross-section values. We also showed that by using a suitable delivery vector, X1 compound could applied as a live cell imaging probe thus providing a valuable tool to study lipid droplets/lysosome interaction in depth tissues.

Effect of Antifungal-Treated Host Macrophages on Candida glabrata.

OBJECTIVE: Candida glabrata (C. glabrata) causes infections associated with severe sepsis and high mortality. This study describes the effects of micafungin (MCF), itraconazole (ICZ), and amphotericin B (AmB) on the function of macrophages during C. glabrata infection. METHODS: RAW264.1 macrophages were treated with MCF, ICZ, or AmB and then challenged with C. glabrata. Cytokines from infected macrophage supernatants and the levels of superoxide dismutase (SOD) in macrophages were measured at different time points after phagocytosis. RESULTS: The activity of SOD was significantly increased in RAW264.1 cells that phagocytized C. glabrata and reached a peak level at 6 hours (P < 0.05). ICZ and AmB did not affect the SOD activity in cells that phagocytized C. glabrata versus that in untreated macrophage. C. glabrata stimulated macrophages to secrete cytokines. Neither ICZ nor AmB affected the secretion of interleukin-6 (IL-6), interleukin-8 (IL-8), or tumor necrosis factor-α (TNF-α) by C. glabrata-infected macrophages. However, MCF downregulated the secretion of TNF-α by infected macrophages and reduced the SOD activity of C. glabrata compared with those in untreated controls. CONCLUSION: Echinocandins may increase their antifungal efficacy by altering the innate immune response of macrophages and attenuating antioxidants of this organism.

Live cell mitochondrial 3-dimensional dynamic ultrastructures under oxidative phosphorylation revealed by a Pyridine-BODIPY probe.

Recent advancements in super-resolution nanoscopy allowed the study of mitochondrial biology at nanoscale and boosted the understanding its correlated cellular processes those were previously poorly understood. Nevertheless, studying mitochondrial ultrastructure remains a challenge due to the lack of probes that could target specific mitochondrial substances (e.g. cristae or mtDNA) and survive under harsh super-resolution optical conditions. Herein, in this work, we have rationally constructed a pyridine-BODIPY (Py-BODIPY) derivative that could target mitochondrial membrane in living cells without interfering its physiological microenvironments. Furthermore, we found Py-BODIPY is a membrane potential independent probe, hence it is not limit to live-cell staining but also showed a strong internalization into pre-fixed and stimulus disrupted sample. Importantly, its cristae specificity and superb photostability allow the observation of mitochondrial dynamic nano-structures with an unprecedented resolution, allow demonstrating how mitochondrial 3D ultrastructure evolved under oxidative phosphorylation condition.

A multi-photon fluorescent probe based on quinoline groups for the highly selective and sensitive detection of lipid droplets.

Compared to general fluorescent probes, multi-photon fluorescent probes exhibit deeper tissue penetration, lower auto-fluorescence and lower photo-toxicity in the bio-imaging field. Herein, we synthesized a series multi-photon fluorescent probe (L1-L3) based on quinolone groups. Of notably, the three-photon fluorescence of L3 significantly enhanced when L3 interacted with liposome; moreover, L3 exhibited high selectivity towards lipid droplets in living cells. Due to its large Stokes shift, high selectivity and photon-stability, L3 was successfully used in lipid droplet imaging via multi-photon fluorescence bio-imaging.

Yes-Associated Protein Promotes the Development of Condyloma Acuminatum through EGFR Pathway Activation.

OBJECTIVE: Investigate the role of Yes-associated protein (YAP1) in the development of condyloma acuminatum (CA). METHODS: We enrolled 30 male patients with CA and 20 healthy individuals as a control group, to compare the YAP1 expression in their tissue samples. Following this, we overexpressed and downregulated YAP1 expression in HaCaT cells to examine the migratory, proliferative, and apoptotic potential of HaCaT cells expressing different levels of YAP1. RESULTS: In the CA patient tissue samples, an increase in YAP1 expression can be observed. In vitro,the overexpression of YAP1 was shown to promote the growth and migration of HaCaT cells and to activate epidermal growth factor receptor (EGFR) pathway-associated proteins, while the downregulation of YAP1 inhibited cell growth and migration of these cells. CONCLUSIONS: YAP1 promotes the growth of keratinocytes in CA through the activation of the EGFR pathway, and it may mediate the development of human papilloma virus-associated diseases.

Autoimmune Thyroid Disease in Patients with Systemic Lupus Erythematosus: A 7-year Retrospective Study in China.

BACKGROUND: The study was a retrospective case-controlled study. We aimed to determine the clinical and laboratory features of systemic lupus erythematosus (SLE) and compared the features of autoimmune thyroid disease (AITD) with those of SLE. MATERIALS AND METHODS: The study included 38 patients with SLE with AITD (SLE-AITD) and 190 age- and gender-matched SLE patients. The distribution of sociodemographic and clinical factors was compared between the SLE-AITD and SLE groups using Chi-square tests for gender and t tests for others. Univariate and multivariate logistic regression models were used to identify factors associated with the prevalence of AITD among SLE patients. RESULTS: In univariate analysis, malar rash, oral ulcers, serositis, anti-double-stranded DNA antibody positivity (anti-dsDNA+), anti-Sjögren's syndrome type A antibodies (SSA), anti-Sjögren's syndrome type B antibodies (SSB), low complement 3 (C3), and low complement 4 (C4) were significantly different between the SLE-AITD and SLE groups. There were no significant differences among other clinical or laboratory features. In multivariate analysis, serositis (adjusted odds ratio [AOR], 3.64; P = 0.00), anti-dsDNA+ (AOR, 0.30; P = 0.01) and low C3 (AOR, 0.30; P = 0.02) were all associated with SLE-AITD. CONCLUSIONS: In our study, serositis was a risk factor for AITD, so we propose that AITD should be considered in lupus patients with serositis.

[Distribution of podophyllotoxin-loaded nanostructured lipid carriers after topical application on cervical mucosa in Tibet minipigs].

OBJECTIVE: To assess the distribution and systemic toxicity of podophyllotoxin-loaded nanostructured lipid carriers (POD-NLC) after topical application on the cervical mucosa in Tibet minipigs. METHODS: Twelve Tibet mini-pigs were randomized into test group and control group to receive topical application of 0.5% POD-NLC and 0.5% POD tincture, respectively, on the cervical mucosa. Cervical mucosal irritation, targeted distribution and systemic absorption of POD were observed at different time points within 24 h after the drug application. RESULTS: No local inflammation reaction was observed in the test group, while serious local irritations (swelling, blisters, blood blisters, erosion and ulceration) occurred in the control group. The fluorescence intensity of POD in the mucosal tissue reached the peak level at 4 h after drug application in the control group, while the POD fluorescence intensity increased slowly and reached the peak level at 16 h in the test group. The peak blood POD concentration occurred at 6 h after POD-NLC application in the test group (14.28∓0.33 ng/mL), as compared to 4 h in the control group (42.46∓0.32 ng/mL). At all the time points within 24 h, blood POD concentration remained significantly lower in the test group than in the control group (P<0.05), and the area under curve of blood POD concentration in the control group was 1.38-fold greater than that in the test group. CONCLUSION: POD-NLC allows sustained release of POD and achieves a higher POD concentration in the mucosal tissue without causing local irritation or obvious systemic toxicity in Tibet minipigs.

Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms.

Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case- control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16-1.57; Ptrend = 1.18 × 10-4). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02-1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24-2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P < 0.01). Our data suggests that the deletion genotypes of CNV-67048 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese.