Extramammary Paget's Disease of the Scrotal and Penile: A Case Report and Review of the Literature.

INTRODUCTION: Extramammary Paget's disease of the scrotum and penis is a relatively rare cutaneous malignant tumor. At present, its pathogenesis, and clinical and pathological characteristics are not very clear. This is controversial regarding surgical margin width to decrease the high recurrence rate. This paper aimed to report the case and review the literature of extramammary Paget's disease of scrotum and penis. CASE PRESENTATION: We presented the case of a 74-year-old male patient with the patchy erythema and pruritus in the perineum who was admitted to our department. Biopsy of the large plaque revealed Paget disease. Under the condition of ensuring negative surgical margins by rapid frozen pathology, a wide local excision of the lesion, bilateral orchiectomy, and adnexectomy were performed on the patient. Pathology revealed that many scattered vacuolated Paget cells were observed in the epidermal layer, and the diagnosis was Paget's disease of the scrotum and penis. The 2 cm outside the skin lesion was used as the initial surgical margin, and free skin flap transplantation was used to repair the surgical wound. The patient recovered well and was discharged 1 week after surgery. CONCLUSION: Currently, histopathologic biopsy is the most important diagnostic method for EMPD. Once confirmed, for patients eligible for surgical intervention, wide local excision of the lesion and rapid intraoperative frozen pathological examination should be performed as soon as possible. The skin flap transplantation is the first choice for the repair of large-scale wound after surgery.

[Automatic epilepsy detection with an attention-based multiscale residual network].

The deep learning-based automatic detection of epilepsy electroencephalogram (EEG), which can avoid the artificial influence, has attracted much attention, and its effectiveness mainly depends on the deep neural network model. In this paper, an attention-based multi-scale residual network (AMSRN) was proposed in consideration of the multiscale, spatio-temporal characteristics of epilepsy EEG and the information flow among channels, and it was combined with multiscale principal component analysis (MSPCA) to realize the automatic epilepsy detection. Firstly, MSPCA was used for noise reduction and feature enhancement of original epilepsy EEG. Then, we designed the structure and parameters of AMSRN. Among them, the attention module (AM), multiscale convolutional module (MCM), spatio-temporal feature extraction module (STFEM) and classification module (CM) were applied successively to signal reexpression with attention weighted mechanism as well as extraction, fusion and classification for multiscale and spatio-temporal features. Based on the Children's Hospital Boston-Massachusetts Institute of Technology (CHB-MIT) public dataset, the AMSRN model achieved good results in sensitivity (98.56%), F1 score (98.35%), accuracy (98.41%) and precision (98.43%). The results show that AMSRN can make good use of brain network information flow caused by seizures to enhance the difference among channels, and effectively capture the multiscale and spatio-temporal features of EEG to improve the performance of epilepsy detection.

Biomass-Derived Bifunctional Cathode Electrocatalyst and Multiadaptive Gel Electrolyte for High-Performance Flexible Zn-Air Batteries in Wide Temperature Range.

High-efficiency and low-cost bifunctional electrocatalysts for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), as well as gel electrolytes with high thermal and mechanical adaptability are required for the development of flexible batteries. Herein, abundant Setaria Viridis (SV) biomass is selected as the precursor to prepare porous N-doped carbon tubes with high specific surface area and the 900 °C calcination product of SV (SV-900) shows the optimum ORR/OER activities with a small EOER -EORR of 0.734 V. Meanwhile, a new multifunctional gel electrolyte named C20E2G5 is prepared using cellulose extracted from another widely distributed biomass named flax as the skeleton, epichlorohydrin as the cross-linker and glycerol as the antifreezing agent. C20E2G5 possesses high ionic conductivity from -40 to + 60 °C, excellent tensile and compressive resistance, high adhesion, strong freezing and heat resistance. Moreover, the symmetrical cell assembled with C20E2G5 can significantly inhibit Zn dendrite growth. Finally, flexible solid-state Zn-air batteries assembled with SV-900 and C20E2G5 show high open circuit voltage, large energy density, and long-term operation stability between -40 and + 60 °C. This biomass-based approach is generic and can be used for the development of diverse next-generation electrochemical energy conversion and storage devices.

Clinical efficacy of flap transfer coverage in the treatment of vesicovaginal fistula.

INTRODUCTION AND HYPOTHESIS: Vesicovaginal fistula (VVF) brings severe psychological, physiological, and social stress to patients, which seriously affects the quality of their sexual life. Traditional transvaginal repair surgery can cause vaginal shortening. Transferring the lateral free flap can maintain vaginal length. This study was carried out to investigate the clinical efficacy of the surgery of flap transfer coverage for treating VVF. METHODS: A retrospective analysis was performed on 37 patients diagnosed with VVF and repaired by flap transfer coverage in the Urogynecology department of the First Affiliated Hospital of Kunming Medical University from January 2018 to June 2021. All patients took a prone split leg position to repair VVF with the flap transfer covering method and a chart review was performed. RESULTS: Among the 37 patients, there were 34 cases of primary complete healing, and the success rate reached 91.89% without recurrence and complications. Three cases recurred with leakage of urine; cystoscopy showed that the fistula was significantly reduced, and all patients were cured after secondary repair by the same surgical method without complications. CONCLUSIONS: Flap transfer coverage is a safe and effective surgical method for repairing VVF. The prone split leg position can better increase exposure. The fistula being away from the incision suture is the key to the success of the operation. Transferring the fistula can effectively improve the cure rate of VVF. Transferring the lateral free flap can maintain vaginal length.

Transcription Factor ERF194 Modulates the Stress-Related Physiology to Enhance Drought Tolerance of Poplar.

Drought is one of the main environmental factors limiting plant growth and development. The AP2/ERF transcription factor (TF) ERF194 play key roles in poplar growth and drought-stress tolerance. However, the physiological mechanism remains to be explored. In this study, the ERF194-overexpression (OX), suppressed-expression (RNA interference, RNAi), and non-transgenic (WT) poplar clone 717 were used to study the physiology role of ERF194 transcription factor in poplar growth and drought tolerance. Morphological and physiological methods were used to systematically analyze the growth status, antioxidant enzyme activity, malondialdehyde (MDA), soluble sugars, starch, and non-structural carbohydrate (NSC) contents of poplar. Results showed that, compared with WT, OX plants had decrease in plant height, internode length, and leaf area and increased number of fine roots under drought stress. In addition, OX had higher water potential, activities of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), contents of chlorophyll, soluble sugar, starch, and NSC, implying that ERF194 positively regulates drought tolerance in poplar. The growth status of RNAi was similar to those of WT, but the relative water content and CAT activity of RNAi were lower than those of WT under drought treatment. Based on the transcriptome data, functional annotation and expression pattern analysis of differentially expressed genes were performed and further confirmed by RT-qPCR analysis. Gene ontology (GO) enrichment and gene expression pattern analysis indicated that overexpression of ERF194 upregulated the expression of oxidoreductases and metabolism-related genes such as POD and SOD. Detection of cis-acting elements in the promoters suggested that ERF194 may bind to these genes through MeJA-responsive elements, ABA-responsive elements, or elements involved in defense and stress responses. The above results show that ERF194 improved tolerance to drought stress in poplar by regulating its growth and physiological factors. This study provides a new idea for the role of ERF194 transcription factor in plant growth and drought-stress response.

A Comparative Study on the Clinical Efficacy of Simple Transobturator Midurethal Sling and Posterior Pelvic Floor Reconstruction.

Background and Objectives: The purpose of this study was to compare the complications, success rate and satisfaction of pelvic floor reconstruction after transobturator midurethral sling (TOT) and TOT combined with pelvic floor reconstruction in the treatment of female stress urinary incontinence. To explore the pathogenesis of stress urinary incontinence after pelvic floor stress injury and improve the surgical treatment strategy. Materials and Methods: From 15 August 2018 to 24 February 2022, patients diagnosed with stress urinary incontinence (SUI) and secondary prolapse of the anterior pelvis were selected to receive surgically. Participants were followed up and evaluated at 2 months, 6 months and 1 year after treatment. According to the patient's chief complaint, the patient can urinate automatically without incontinence. The number of urinary incontinence and urine leakage was significantly reduced compared with those before operation. Urinary incontinence symptoms did not improve or worsen as ineffective, observing the efficacy and complications. Results: We included 191 patients in the TOT group and 151 patients in the pelvic floor reconstruction group after TOT was combined. The operation time and hospital stay in the TOT group were short, but the TOT group needed a second operation to treat recurrent SUI. Perioperative complications were mostly dysuria, and the incidence of postoperative complications in the group of TOT combined with pelvic floor reconstruction was low. The complete success rate and effective rate of pelvic floor reconstruction after TOT in the merger group were significantly higher than those in the TOT group, and the patient satisfaction and complete success rate were also higher. Conclusions: TOT combined with posterior pelvic floor reconstruction has a definite short-term effect on patients with SUI and anterior pelvic secondary prolapse. The operation design should pay attention to the support of the posterior wall of the perineum to the bladder neck and the middle and proximal end of the urethra.

Effect of exercise training on arterial stiffness in obese and overweight children: a meta-analysis.

The aim of this study was to investigate the effect of exercise training on arterial stiffness in obese and overweight children. Three databases were searched up to July 2021 for papers about exercise training and arterial stiffness in obese and overweight children. The quality of each identified study was evaluated. Effect sizes were estimated in terms of the standardized mean difference. Egger's test and sensitivity analysis were used to assess publication bias. In total, 26 studies by 19 researchers were included in the meta-analysis. Flow-mediated dilatation (FMD), pulse wave velocity (PWV), and intima-media thickness (IMT) were improved after exercise training in obese and overweight children. Subgroup analysis showed that exercise only reduced the PWV and IMT in individuals with a BMI < 30. FMD, PWV, and IMT were improved by exercise training in participants aged below 14 years, but only FMD was increased by exercise in participants aged 14 years and above. All types of training significantly improved FMD. Aerobic exercise (AE) and high-intensity intermittent training (HIIT) reduced the PWV of the participants, but were less effective than resistance training (RT) and aerobic plus resistance training. Only HIIT significantly reduced the IMT.   Conclusions: Exercise training improved vascular endothelial function and vascular sclerosis in overweight and obese children, especially in those with a BMI < 30 and younger than 14 years. AE had a more favorable effect on arterial stiffness. What is Known: • Exercise training was a good way to lose weight and subsequently promoted vascular function in overweight and obese children. What is New: • Exercise training was more effective on the vascular endothelial function and vascular sclerosis in overweight and obese children with a BMI<30. • Aerobic exercise had a more favorable effect on arterial stiffness, while the improvement was not effective after resistance training and combined training mode.

Dose-response association between the daily step count and all-cause mortality: A systematic review and meta-analysis.

This review aims to investigate the dose-response relationship between the daily step count and all-cause mortality. PubMed, the Cochrane Library, Embase, and Web of Science were searched for all articles of cohort studies investigating the association between the daily step count and all-cause mortality. Cohort research articles were included if they reported mortality with no less than 3 categories of the daily step count, and hazard ratio (HR) with a 95% Confidence Interval (CI) was reported. Dose-response association meta-analysis and subsequent sex subgroup analysis were performed. The final analysis included a total of nine studies. Compared with the low-step count population, the high-step count population had a 62% lower risk of all-cause death (HR = 0.38, 95% CI 0.27-0.49). There was a non-linear dose-response relationship between the daily step count and all-cause mortality. Compared with the least (1895 steps), the first quartile (4000 steps/day) had a 37% lower risk for all causes of death (HR = 0.63, 0.57-0.71), the second quartile (6388 steps/day) had a 60% lower risk for all causes of death (HR = 0.40, 0.32-0.49), the third quartile (9994.3 steps/day) had a 75% lower risk of all-cause death than the first quartile (HR = 0.25, 0.19-0.33).

Levels, distribution characteristics, and sources of heavy metals in indoor dust in Shijiazhuang, China.

Heavy metals in indoor dust are associated with health risks in humans. However, in Shijiazhuang, a city in northern China with severe haze, no research has been published on this topic. To determine the content, distribution characteristics, and sources of heavy metals in indoor dust in the city of Shijiazhuang, indoor dust samples from 33 sampling points in the main urban area of Shijiazhuang were collected and tested. Concentrations of Cu, Ni, Cr, Zn, Cd, and Pb were 87.0, 35.1, 104.4, 568.0, 1.980, and 187.6 mg·kg-1, respectively; their levels have been discussed statistically in comparison with the reported values in other cities in China. The sources of heavy metals were analyzed using enrichment factor, correlation coefficient, and principal component analysis. The results showed that the levels of all six elements in indoor dust in Shijiazhuang exceeded the background values of soil in Hebei Province. Among these, Cd, Pb, and Zn were significantly enriched. The enrichment factors of Cu, Ni, and Cr were below 10, and their levels at different sampling points were similar, indicating their geogenic source. The corresponding pollution levels of Cd, Pb, and Zn were relatively high, and their levels at different points were significantly different and correlated, indicating that they were derived mainly from transportation. Additionally, the level of Zn was significantly affected by the indoor environment. Our findings provide a basis for conducting health risk assessments in the future.

Surgical Effect Observation and Treatment Strategy Analysis of Pseudo Urgency Syndrome.

Background and Objectives: pseudo urgency syndrome among patients with mixed incontinence (MUI) causes and the corresponding treatment strategies is explored. Materials and Methods: A total of 40 patients with MUI are treated with transobturator tape (TOT) and/or solifenacin succinate. Further, 30 patients with simple stress urinary incontinence (SUI) that were treated with transobturator tape (TOT) from the period of December 2018 to August 2020 are retrospectively analyzed; then, their clinical characteristics and therapeutic effects were summarized and analyzed. Results: The effective rates of SUI symptoms in MUI and simple SUI groups were 85% and 90%, respectively; further, the difference was noted as not statistically significant (P > 0.05). Among the 40 patients with MUI, 12 patients had unstable bladder contraction, and the other 28 patients showed normal bladder compliance. The treatment effectiveness rates of SUI symptoms in patients with unstable bladder contraction and normal bladder compliance were 83.3% and 85.7%, respectively; further, no significant difference was noted (P > 0.05). However, the effective rates of urge urinary incontinence (UUI) were 50% and 85.7%, respectively, however the difference was noted as statistically significant (P < 0.05). Conclusions: Most of the UUI symptoms in MUI patients may be "pseudo urgency syndrome" caused by the worry about the leakage of urine, rather than a real sense of UUI that is caused by excessive bladder excitement. Direct surgical treatment in patients with MUI can improve the symptoms of urinary incontinence, and the effect is more obvious in patients with urinary frequency who have normal bladder compliance according to urodynamics.

The Anatomical Pathogenesis of Stress Urinary Incontinence in Women.

Stress urinary incontinence is a common disease in middle-aged and elderly women, which seriously affects the physical and mental health of the patients. For this reason, researchers have carried out a large number of studies on stress urinary incontinence. At present, it is believed that the pathogenesis of the disease is mainly due to changes related to age, childbirth, obesity, constipation and other risk factors that induce changes in the urinary control anatomy, including the anatomical factors of the urethra itself, the anatomical factors around the urethra and the anatomical factors of the pelvic nerve. The combined actions of a variety of factors lead to the occurrence of stress urinary incontinence. This review aims to summarize the anatomical pathogenesis of stress urinary incontinence from the above three perspectives.

Zoom lens with high zoom ratio design based on Gaussian bracket and particle swarm optimization.

In this paper, we use Gaussian brackets and a particle swarm optimization (PSO) algorithm to design a 20× four-group zoom lens with a focus tunable lens and two moving groups. This method uses Gaussian brackets to derive the paraxial design equations of the zoom lens and determine the lens parameters. In the optimization stage, we define an objective function as a performance indicator to optimize its first-order design and implement the PSO algorithm in MATLAB to find its global optimal first-order design. The optimized 20× zoom lens has a focal length of 4.5-90 mm and a total length of 145 mm. This method solves the difficulty of solving the initial structure of the zoom. Compared with traditional trial and error, the calculation speed is faster, the accuracy is higher, and it does not rely on the initial value. The results show that this method is suitable for the first-order design of complex optical systems.

50X five-group inner-focus zoom lens design with focus tunable lens using Gaussian brackets and lens modules.

This study presents a 50X five-group zoom lens design with two moving groups and one focus tunable lens (FTL) by applying Gaussian brackets and lens modules. After qualitative analysis of the paraxial properties, the initial structure is obtained by solving the power equations consisting of five groups by numerical analysis method. The optimized nearly 60X lens has a focal length of 5.1-300mm and f-number of 1.8-5.0 in wide and tele positions, with a total length of 160mm. The lens achieves a maximum FOV of 63° at short focal length. The tolerance analysis indicates that the design is suitable for mass production. The method eases the difficulty in initial structure design of the zoom lens with high zoom ratio, improves its optical design efficiency, and can be applied to the fields such as customs security cameras, military detecting devices, machine vision and industrial inspection, etc.

Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence.

Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high-glucose-induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy-dependent. Autophagy receptor microtubule-associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence-related cardiovascular diseases.

TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation during experimental autoimmune encephalomyelitis development.

BACKGROUND: Toll-like receptor 4 (TLR4) is well known for activating the innate immune system; however, it is also highly expressed in adaptive immune cells, such as CD4+ T-helper 17 (Th17) cells, which play a key role in multiple sclerosis (MS) pathology. However, the function and governing mechanism of TLR4 in Th17 remain unclear. METHODS: The changes of TLR4 in CD4+ T cells from MS patients and experimental autoimmune encephalomyelitis (EAE) mice were tested. TLR4-deficient (TLR4-/-) naïve T cells were induced in vitro and transferred into Rag1-/- mice to measure Th17 differentiation and EAE pathology. DNA sequence analyses combining with deletion fragments and mutation analyses, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA) were used to explore the mechanism of TLR4 signaling pathway in regulating Th17 differentiation. RESULTS: The levels of TLR4 were increased in CD4+ Th17 cells both from MS patients and EAE mice, as well as during Th17 differentiation in vitro. TLR4-/- CD4+ naïve T cells inhibited their differentiation into Th17, and transfer of TLR4-/- CD4+ naïve T cells into Rag1-/- mice was defective in promoting EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. TLR4 signal enhanced Th17 differentiation by activating RelA, downregulating the expression of miR-30a, a negative regulator of Th17 differentiation. Inhibition of RelA activity increased miR-30a level, but decreased Th17 differentiation rate. Furthermore, RelA directly regulated the expression of miR-30a via specific binding to a conserved element of miR-30a gene. CONCLUSIONS: TLR4-/- CD4+ naïve T cells are inadequate in differentiating to Th17 cells both in vitro and in vivo. TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation via direct binding of RelA to the regulatory element of miR-30a gene. Our results indicate modulating TLR4-RelA-miR-30a signal in Th17 may be a therapeutic target for Th17-mediated neurodegeneration in neuroinflammatory diseases.

Dual drug-loaded cubic liquid crystal gels for transdermal delivery: inner structure and percutaneous mechanism evaluations.

The goal of this paper was to develop and evaluate dual component-loaded with the hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) cubic liquid crystal gels for transdermal delivery. The gels was prepared with a vortex method using phytantriol/water (70:30, w/w) and characterized by polarized light microscopy, small-angle X-ray scattering and rheology. The inner structure of the gels were Pn3m cubic phase and exhibited a pseudoplastic fluid behavior. Furthermore, the in vitro release profile showed that the release behavior of the two drugs from cubic liquid crystal gels conformed to Higuchi equation and were dominated by Fick's diffusion (n < 0.45). The ex vivo penetration experiment indicated that dual components-loaded liquid crystal gels can enhance and extend the skin permeation of these two drugs, especially the ratio of SH to CA is 1: 0.5. Finally, transdermal mechanisms were evaluated using laser scanning confocal microscopy and attenuated total reflectance-fourier transform infrared, hinting that hydrophilic and lipophilic drugs weaken each other's transdermal velocity at the initial stage of penetration. In short, the dual drug-loaded liquid crystal gels was a promising strategy for transdermal applications in treatment of chronic disease.

A Novel Phytantriol-Based Lyotropic Liquid Crystalline Gel for Efficient Ophthalmic Delivery of Pilocarpine Nitrate.

The purpose of this paper was to investigate the potential of liquid crystalline (LC) gels for ophthalmic delivery, so as to enhance the bioavailability of pilocarpine nitrate (PN). The gels were prepared by a vortex method using phytantriol and water (in the ratio of 73:27 w/w). Their inner structures were confirmed by crossed polarized light microscopy, small-angle X-ray scattering, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. The in vitro release studies revealed that PN could keep sustained release from the gels over a period of 12 h. The ex vivo apparent permeability coefficient of the gels demonstrated a 3.83-folds (P < 0.05) increase compared with that of eye drops. The corneal hydration levels of the gel maintained in the normal range of 79.46 ± 2.82%, hinting that the gel could be considered non-damaging and safe to the eyes. Furthermore, in vivo residence time evaluation suggested that a better retention performance of LC gel was observed in rabbit's eyes compared to eye drops. In vivo ocular irritation study indicated that LC gel was nonirritant and might be suitable for various eye applications. In conclusion, LC gels might represent a potential ophthalmic delivery strategy to overcome the limitations of eye drops.

Characterization of Lipid-Based Lyotropic Liquid Crystal and Effects of Guest Molecules on Its Microstructure: a Systematic Review.

Liquid crystals (LCs) are conventionally divided into thermotropic or lyotropic, based on the organization and sequence of the controlled molecular system. Lipid-based lyotropic liquid crystal (LLC), such as lamellar (Lα), bicontinuous cubic (QII), or hexagonal (HII) phases, have attracted wide interest in the last few decades due to their practical potential in diverse applications and notable structural complexity. Various guest molecules, such as biopharmaceuticals, chemicals, and additives, can be solubilized in either aqueous or oily phase. And the LLC microstructure can be altered to affect the rate of drug release eventually. To utilize these microstructural variations to adjust the drug release in drug delivery system (DDS), it is crucial to understand the structure variations of the LLC caused by different types of guest molecules. Therefore, in this article, we review the effect of guest molecules on lipid-based LLC microstructures. In particular, we focus on the different characterization methods to evaluate this change caused by guest substances, such as polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), self-diffusion nuclear magnetic resonance (SD-NMR), and so on.

[Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent].

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the in vitro evaluation and practical application of the product.

Suppression of adenosine monophosphate-activated protein kinase selectively triggers apoptosis in activated T cells and ameliorates immune diseases.

Deficient apoptosis of activated T cells can result in immunological disorders. Molecules associated with energy and metabolisms are suggested to be involved in pathogenesis of immune diseases, but remain uninvestigated. In the present study we reported that glibenclamide exerted a new pharmacological effect on inflammatory responses by selectively triggering apoptosis of activated T cells. Glibenclamide demonstrated an inhibition on activated T lymphocytes, whereas showed no toxicity in the naive cells. This effect was mainly related with its ability to facilitate apoptosis in activated T cells with an up-regulation of cleaved-caspases and cleaved-PARP. Glibenclamide enhanced Fas expression and suppressed the expression of antiapoptotic cellular FLICE-inhibitory protein. The underlying mechanism of glibenclamide was not associated with its classical inhibitory effect on ATP-sensitive potassium channels, but due to a unique suppression on the phosphorylation of 5' adenosine monophosphate-activated protein kinase, which was augmented during T cell activation. An in vivo experiment further demonstrated that glibenclamide ameliorated T-cell-mediated contact hypersensitivity in mice. Altogether, these results suggest that AMPK inhibition by glibenclamide can regulate the survival and death of T lymphocytes and be beneficial for the treatment of autoimmune diseases.