Inhibition of ASGR1 decreases lipid levels by promoting cholesterol excretion.

High cholesterol is a major risk factor for cardiovascular disease1. Currently, no drug lowers cholesterol through directly promoting cholesterol excretion. Human genetic studies have identified that the loss-of-function Asialoglycoprotein receptor 1 (ASGR1) variants associate with low cholesterol and a reduced risk of cardiovascular disease2. ASGR1 is exclusively expressed in liver and mediates internalization and lysosomal degradation of blood asialoglycoproteins3. The mechanism by which ASGR1 affects cholesterol metabolism is unknown. Here, we find that Asgr1 deficiency decreases lipid levels in serum and liver by stabilizing LXRα. LXRα upregulates ABCA1 and ABCG5/G8, which promotes cholesterol transport to high-density lipoprotein and excretion to bile and faeces4, respectively. ASGR1 deficiency blocks endocytosis and lysosomal degradation of glycoproteins, reduces amino-acid levels in lysosomes, and thereby inhibits mTORC1 and activates AMPK. On one hand, AMPK increases LXRα by decreasing its ubiquitin ligases BRCA1/BARD1. On the other hand, AMPK suppresses SREBP1 that controls lipogenesis. Anti-ASGR1 neutralizing antibody lowers lipid levels by increasing cholesterol excretion, and shows synergistic beneficial effects with atorvastatin or ezetimibe, two widely used hypocholesterolaemic drugs. In summary, this study demonstrates that targeting ASGR1 upregulates LXRα, ABCA1 and ABCG5/G8, inhibits SREBP1 and lipogenesis, and therefore promotes cholesterol excretion and decreases lipid levels.

Diverse mode operation fiber laser mode-locked by nonlinear multimode interference.

We present an all-fiber passively mode-locked (ML) laser with a nonlinear multimode interference (NLMI)-based saturable absorber (SA) capable of generating five pulse modes. The SA consists of two centrally aligned graded index multimode fiber (GIMF) with different diameters (105-50 µm) and features a widely adjustable transmission with saturable/reverse-saturable absorption. Based on this, dissipative soliton (DS), Q-switched rectangular pulse (QRP), dissipative soliton resonance (DSR), noise-like pulse (NLP) and bright-dark pulse pairs (BDP) are observed at three dispersions without additional filter. The DS has a pulse energy, bandwidth and duration of up to 1.15 nJ, 17.98 nm and ∼2.78 ps. The achievable pulse duration and energy of DSR and NLP are 5.21, 48.06 ns and 4.53, 5.12 nJ, respectively. Furthermore, it is demonstrated that the BDP is superimposed by a chair-case pulse (CP) and a rectangular pulse (RP) belonging to orthogonal polarization states. The versatility, flexibility, simplicity and energy scalability of the large-core hybrid GIMF-SA, make it interesting and highly attractive in ultrafast photonics.

Impact on cytokine accumulation in 35-day preserved whole blood due to resin adsorption.

Blood transfusion in critically ill individuals such as sepsis was associated with higher morbidity and mortality. During storage, various bioactive substances accumulated, may exacerbate the initial immunosuppressive reaction in severely ill patients. The objective of this study is to explore how resin adsorption impacts the accumulation of cytokines and the presence of extracellular microvesicles (EVs) in whole blood. Through comparative analysis and screening, amberchrom CG 300 C was chosen to assess the adsorption efficiency and evaluate the quality of whole blood after adsorption. Subsequently, the supernatants from both the unadsorpted (UA) and adsorpted (A) groups were co-cultured with peripheral blood mononuclear cells (PBMCs) to assess their effects on cellular growth and cytokine concentrations. The findings of our study revealed that resin adsorption effectively eradicated most bioactive components in conserved blood, including IL-8, TGF-ß, sCD40L, sFasL, without affecting the quality of the blood. Furthermore, scanning electron microscopy (SEM) revealed a reduction in extracellular microvesicles following adsorption. Compared to UA, A 's supernatant markedly enhanced PBMC growth (p < 0.01). Additionally, the A's supernatant markedly diminished the emission of pro-inflammatory cytokines, like IL-6. The research revealed that adsorbing resin effectively reduced bioactive substances from preserved whole blood, and did not impact red blood cell quality, proving to be a reliable method for extracting bioactive substances from storage blood. The results could pave the way for creating innovative blood bags and hold clinical significance in lowering the frequency of TRIM among patients who have undergone transfusions.

Endovascular Denervation for the Improvement of Limb Ischemia in Patients with Peripheral Artery Disease: A Randomized Clinical Trial.

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.

Two-dimensional electronic-vibrational sum frequency spectroscopy for interactions of electronic and nuclear motions at interfaces.

Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic-vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic-vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active (E)-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air-water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S2, is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm-1 Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S2 state to the lower excited state S1 We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces.

TMEM241 is a UDP-N-acetylglucosamine transporter required for M6P modification of NPC2 and cholesterol transport.

Accurate intracellular cholesterol traffic plays crucial roles. Niemann Pick type C (NPC) proteins NPC1 and NPC2, are two lysosomal cholesterol transporters that mediate the cholesterol exit from lysosomes. However, other proteins involved in this process remain poorly defined. Here, we find that the previously unannotated protein TMEM241 is required for cholesterol egressing from lysosomes through amphotericin B-based genome-wide CRISPR-Cas9 KO screening. Ablation of TMEM241 caused impaired sorting of NPC2, a protein utilizes the mannose-6-phosphate (M6P) modification for lysosomal targeting, resulting in cholesterol accumulation in the lysosomes. TMEM241 is a member of solute transporters 35 nucleotide sugar transporters family and localizes on the cis-Golgi network. Our data indicate that TMEM241 transports UDP-N-acetylglucosamine (UDP-GlcNAc) into Golgi lumen and UDP-GlcNAc is used for the M6P modification of proteins including NPC2. Furthermore, Tmem241-deficient mice display cholesterol accumulation in pulmonary cells and behave pulmonary injury and hypokinesia. Taken together, we demonstrate that TMEM241 is a Golgi-localized UDP-GlcNAc transporter and loss of TMEM241 causes cholesterol accumulation in lysosomes because of the impaired M6P-dependent lysosomal targeting of NPC2.

Deep learning-assisted identification and quantification of aneurysmal subarachnoid hemorrhage in non-contrast CT scans: Development and external validation of Hybrid 2D/3D UNet.

Accurate stroke assessment and consequent favorable clinical outcomes rely on the early identification and quantification of aneurysmal subarachnoid hemorrhage (aSAH) in non-contrast computed tomography (NCCT) images. However, hemorrhagic lesions can be complex and difficult to distinguish manually. To solve these problems, here we propose a novel Hybrid 2D/3D UNet deep-learning framework for automatic aSAH identification and quantification in NCCT images. We evaluated 1824 consecutive patients admitted with aSAH to four hospitals in China between June 2018 and May 2022. Accuracy and precision, Dice scores and intersection over union (IoU), and interclass correlation coefficients (ICC) were calculated to assess model performance, segmentation performance, and correlations between automatic and manual segmentation, respectively. A total of 1355 patients with aSAH were enrolled: 931, 101, 179, and 144 in four datasets, of whom 326 were scanned with Siemens, 640 with Philips, and 389 with GE Medical Systems scanners. Our proposed deep-learning method accurately identified (accuracies 0.993-0.999) and segmented (Dice scores 0.550-0.897) hemorrhage in both the internal and external datasets, even combinations of hemorrhage subtypes. We further developed a convenient AI-assisted platform based on our algorithm to assist clinical workflows, whose performance was comparable to manual measurements by experienced neurosurgeons (ICCs 0.815-0.957) but with greater efficiency and reduced cost. While this tool has not yet been prospectively tested in clinical practice, our innovative hybrid network algorithm and platform can accurately identify and quantify aSAH, paving the way for fast and cheap NCCT interpretation and a reliable AI-based approach to expedite clinical decision-making for aSAH patients.

Trem2 deficiency attenuates microglial phagocytosis and autophagic-lysosomal activation in white matter hypoperfusion.

Chronic cerebral hypoperfusion leads to sustained demyelination and a unique response of microglia. Triggering receptor expressed on myeloid cells 2 (Trem2), which is expressed exclusively on microglia in the central nervous system (CNS), plays an essential role in microglial response in various CNS disorders. However, the specific role of Trem2 in chronic cerebral hypoperfusion has not been elucidated. In this study, we investigated the specific role of Trem2 in a mouse model of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis (BCAS). Our results showed that chronic hypoperfusion induced white matter demyelination, microglial phagocytosis, and activation of the microglial autophagic-lysosomal pathway, accompanied by an increase in Trem2 expression. After Trem2 knockout, we observed attenuation of white matter lesions and microglial response. Trem2 deficiency also suppressed microglial phagocytosis and relieved activation of the autophagic-lysosomal pathway, leading to microglial polarization towards anti-inflammatory and homeostatic phenotypes. Furthermore, Trem2 knockout inhibited lipid droplet accumulation in microglia in vitro. Collectively, these findings suggest that Trem2 deficiency ameliorated microglial phagocytosis and autophagic-lysosomal activation in hypoperfusion-induced white matter injury, and could be a promising target for the treatment of chronic cerebral hypoperfusion.

TREM2 deficiency inhibits microglial activation and aggravates demyelinating injury in neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination.

Stem Cell Therapies for Restorative Treatments of Central Nervous System Ischemia-Reperfusion Injury.

Ischemic damage to the central nervous system (CNS) is a catastrophic postoperative complication of aortic occlusion subsequent to cardiovascular surgery that can cause brain impairment and sometimes even paraplegia. Over recent years, numerous studies have investigated techniques for protecting and revascularizing the nervous system during intraoperative ischemia; however, owing to a lack of knowledge of the physiological distinctions between the brain and spinal cord, as well as the limited availability of testing techniques and treatments for ischemia-reperfusion injury, the cause of brain and spinal cord ischemia-reperfusion injury remains poorly understood, and no adequate response steps are currently available in the clinic. Given the limited ability of the CNS to repair itself, it is of great clinical value to make full use of the proliferative and differentiation potential of stem cells to repair nerves in degenerated and necrotic regions by stem cell transplantation or mobilization, thereby introducing a novel concept for the treatment of severe CNS ischemia-reperfusion injury. This review summarizes the most recent advances in stem cell therapy for ischemia-reperfusion injury in the brain and spinal cord, aiming to advance basic research and the clinical use of stem cell therapy as a promising treatment for this condition.

Protective Effect of Hydrogen Sulfide on Cerebral Ischemia-Reperfusion Injury.

The brain is the most sensitive organ to hypoxia in the human body. Hypoxia in the brain will lead to damage to local brain tissue. When the blood supply of ischemic brain tissue is restored, the damage will worsen, that is, cerebral ischemia-reperfusion injury. Hydrogen sulfide (H2S) is a gaseous signal molecule and a novel endogenous neuroregulator. Indeed, different concentrations of H2S have different effects on neurons. Low concentration of H2S can play an important protective role in cerebral ischemia-reperfusion injury by inducing anti-oxidative stress injury, inhibition of inflammatory response, inhibition of cell apoptosis, reduction of cerebrovascular endothelial cell injury, regulation of autophagy, and other ways, which provides a new idea for clinical diagnosis and treatment of related diseases. This review aims to report the recent research progress on the dual effect of H2S on brain tissue during cerebral ischemia/reperfusion injury.

YAP1 inhibits RSL3-induced castration-resistant prostate cancer cell ferroptosis by driving glutamine uptake and metabolism to GSH.

High levels of YAP1 and ferroptosis activation in castration-resistant prostate cancer (CRPC) can inhibit CRPC progression and improve its sensitivity toward chemotherapeutics drugs. However, whether YAP1 regulates ferroptosis in CRPC cells and the underlying mechanisms are unknown. The protein levels of YAP1, SLC1A5, and GLS1 in benign prostatic hyperplasia (BPH), prostate cancer (PCa) that did not progress to CRPC, and CRPC tissue samples were evaluated using western blotting. In PC-3 and DU-145 cells, YAP1 overexpression vector, small-interfering RNA, specific inhibitor verteporfin, ferroptosis-inducer RSL3, SLC1A5-inhibitor V-9302, and GLS1-inhibitor CB-839 were used. Immunofluorescence, flow cytometry, dual-luciferase reporter gene, and related kits were used to investigate the effect of YAP1 on the ferroptosis activity in CRPC cells and its underlying mechanisms. YAP1 promoted extracellular glutamine uptake and subsequent production of glutamate and glutathione (GSH), and increases the GPX4 activity. For the activation of ferroptosis by RSL3, YAP1 decreased the levels of reactive oxygen species, malondialdehyde, and lipid peroxidation, and the proportion of dead cells. Mechanistically, YAP1 promoted the expression of SCL1A5 and GLS1 and further increased the GSH levels and GPX4 activity. Thus, inhibiting SLC1A5 or GLS1 activity could alleviate the antagonistic effect of YAP1 on the ferroptosis of RSL3-induced CRPC cells. In CRPC, the YAP1 level is high, which enters the nucleus and promotes the expressions of SLC1A5 and GLS1, thereby promoting cellular glutamine uptake and metabolism to generate glutamate and further synthesizing GSH, increasing GPX4 activity, improving cellular antioxidant capacity, and inhibiting cell death.

Characterization and molecular evolution analysis of Periploca forrestii inferred from its complete chloroplast genome sequence.

Periploca forrestii, a medicinal plant of the family Apocynaceae, is known as an effective and widely used clinical prescription for the treatment of rheumatoid diseases. In this study, we de novo sequenced and assembled the completement chloroplast (cp) genome of P. forrestii based on combined Oxford Nanopore PromethION and Illumina data. The cp genome was 153 724 bp in length and had four subregions. Moreover, an 84 433 bp large single-copy and a 17 731 bp small single-copy were separated by 25 780 bp inverted repeats (IRs). The cp genome included 132 genes with 18 duplicates in the IRs. A total of 45 repeat structures and 183 simple sequence repeats were detected. Codon usage showed a bias toward A/T-ending codons. A comparative study of Apocynaceae revealed that an IR expansion occurred on P. forrestii. The Ka/Ks values of eight species of Apocynaceae suggested that positive selection was exerted on the psaI and ycf2 genes, which might reflect specific adaptions to the P. forrestii particular growth environment. Phylogenetic analysis indicated that Periplocoideae was a sister to Asclepiadoideae, forming a monophyletic group in the family Apocynaceae. This study provided an important P. forrestii genomic resource for future evolutionary studies and the phylogenetic reconstruction of the family Apocynaceae.

Pneumonia-Plus: a deep learning model for the classification of bacterial, fungal, and viral pneumonia based on CT tomography.

OBJECTIVES: This study aims to develop a deep learning algorithm, Pneumonia-Plus, based on computed tomography (CT) images for accurate classification of bacterial, fungal, and viral pneumonia. METHODS: A total of 2763 participants with chest CT images and definite pathogen diagnosis were included to train and validate an algorithm. Pneumonia-Plus was prospectively tested on a nonoverlapping dataset of 173 patients. The algorithm's performance in classifying three types of pneumonia was compared to that of three radiologists using the McNemar test to verify its clinical usefulness. RESULTS: Among the 173 patients, area under the curve (AUC) values for viral, fungal, and bacterial pneumonia were 0.816, 0.715, and 0.934, respectively. Viral pneumonia was accurately classified with sensitivity, specificity, and accuracy of 0.847, 0.919, and 0.873. Three radiologists also showed good consistency with Pneumonia-Plus. The AUC values of bacterial, fungal, and viral pneumonia were 0.480, 0.541, and 0.580 (radiologist 1: 3-year experience); 0.637, 0.693, and 0.730 (radiologist 2: 7-year experience); and 0.734, 0.757, and 0.847 (radiologist 3: 12-year experience), respectively. The McNemar test results for sensitivity showed that the diagnostic performance of the algorithm was significantly better than that of radiologist 1 and radiologist 2 (p < 0.05) in differentiating bacterial and viral pneumonia. Radiologist 3 had a higher diagnostic accuracy than the algorithm. CONCLUSIONS: The Pneumonia-Plus algorithm is used to differentiate between bacterial, fungal, and viral pneumonia, which has reached the level of an attending radiologist and reduce the risk of misdiagnosis. The Pneumonia-Plus is important for appropriate treatment and avoiding the use of unnecessary antibiotics, and provide timely information to guide clinical decision-making and improve patient outcomes. CLINICAL RELEVANCE STATEMENT: Pneumonia-Plus algorithm could assist in the accurate classification of pneumonia based on CT images, which has great clinical value in avoiding the use of unnecessary antibiotics, and providing timely information to guide clinical decision-making and improve patient outcomes. KEY POINTS: • The Pneumonia-Plus algorithm trained from data collected from multiple centers can accurately identify bacterial, fungal, and viral pneumonia. • The Pneumonia-Plus algorithm was found to have better sensitivity in classifying viral and bacterial pneumonia in comparison to radiologist 1 (5-year experience) and radiologist 2 (7-year experience). • The Pneumonia-Plus algorithm is used to differentiate between bacterial, fungal, and viral pneumonia, which has reached the level of an attending radiologist.

Risk Factors for Access-Related Adverse Events Related to the Preclose Technique in Thoracic Endovascular Aortic Repair.

PURPOSE: To analyze the risk factors for access-related adverse events (AEs) of the preclose technique in thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Ninety-one patients with Stanford type B aortic dissection who underwent the preclose technique in TEVAR between January 2013 and December 2021 were included. According to the occurrence of access-related AEs, the patients were divided into 2 groups: those with AE and those without AE. Age, sex, combined diseases, body mass index, skin depth, femoral artery diameter, access calcification, iliofemoral artery tortuosity, and sheath size were recorded for risk factor analysis. The sheath-to-femoral artery ratio (SFAR), the ratio of the femoral artery inner diameter (in millimeters) to the sheath's outer diameter (in millimeters), was also included in the analysis. RESULTS: SFAR was identified as an independent risk factor for AEs using multivariable logistic analysis (odds ratio, 251.748; 95% CI, 7.004-9,048.534; P = .002). The cutoff value of SFAR was 0.85 and was related to a higher incidence of access-related AEs (5.2% vs 33.3%, P = .001), especially to a higher stenosis rate (0.0% vs 21.2%, P = .001). CONCLUSIONS: SFAR is an independent risk factor for access-related AEs of preclose in TEVAR with a cutoff value of 0.85. SFAR could be a new criterion for preoperative access evaluation in high-risk patients that may allow the detection and treatment of access-related AEs at the early stage.

The spin caloritronic transport properties of newly designed devices consisting of a sawtooth graphene nanoribbon and its derived five-member ring structure.

Achieving high spin polarization transport and a pure spin current is particularly desired in spintronics. We use a sawtooth graphene nanoribbon (STGNR) and its derived five-member ring structure (5-STGNR) to design new spin caloritronic devices, since they have been successfully prepared experimentally and have an interface with no lattice distortion. By using first-principle calculations combined with the non-equilibrium Green's function approach, we have studied the spin caloritronic transport properties of several STGNR-based devices, including the structures with symmetrical and asymmetrical edges, and found some excellent spin caloritronic properties, such as spin polarization, magnetoresistance and the spin Seebeck effect. By introducing a temperature difference, giant magnetoresistance and spin Seebeck effects are achieved in a heterojunction with a symmetrical edge, whereas spin polarization is more effective in a heterojunction with an asymmetrical edge. Meanwhile, the metal-semiconductor-metal junction, which is composed of STGNRs with a symmetrical edge, exhibits approximately 100% spin polarization and produces a perfect thermally induced pure spin current at room temperature. Our results indicate that the devices consisting of a sawtooth graphene nanoribbon and its derived five-member ring structure are promising novel spin caloritronic devices.

ADAM metallopeptidase with thrombospondin type 1 motif 16 is a potential marker for prognosis in clear cell renal cell carcinoma.

The mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. Immunohistochemical staining, Western blotting and real-time quantitative polymerase chain reaction were employed to evaluate ADAM (a disintegrin and metalloproteinase) metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) levels in ccRCC tissues and paired normal tissues, and all tissues were obtained from clinical samples of 46 cases of ccRCC patients. Moreover, we analyzed the role ADAMTS16 in the progression of ccRCC using Cell Counting Kit-8 assay and flow cytometry. ADAMTS16 levels in ccRCC tissues were markedly low, relative to normal tissues, and ADAMTS16 level closely correlated with tumor stage, lymph node metastasis as well as pathological grade. Patients with elevated ADAMTS16 expressions have a more favorable survival outcome, relative to patients with low expression of ADAMTS16. In vitro study showed ADAMTS16 expression markedly decreased in ccRCC cells and acted as a tumor suppressor compared with the normal cells. The expression of ADAMTS16 is down-regulated in ccRCC tissues, relative to normal tissues, and it may inhibit the malignancies of ccRCC. Such inhibitory effect may be ascribed to the involvement of AKT/mammalian target of rapamycin signaling. Hence, the present study of ADAMTS16 will provide new insight into the underlying biological mechanisms of ccRCC.

Placement of Bare Self-Expanding Metal Stent for Isolated Superior Mesenteric Artery Dissection.

BACKGROUND: To evaluate the safety and efficacy of placing bare self-expanding metal stent (SEMS) for treating isolated superior mesenteric artery dissection (ISMAD). METHOD: Patients with ISMAD who received bare SEMS from January 2014 to December 2021 at the authors' center were included. Baseline characteristics, clinical manifestation, radiological findings, and treatment outcomes, including symptom relief and SMA remodeling, were analyzed. RESULT: A total of 26 patients were included in this study. Among the patients, 25 were admitted due to persistent abdominal pain, and 1 was admitted based on computed tomography angiography (CTA) during physical examination. According to CTA scan, the percentage of stenosis was 91% (53.8-100%), and the length of dissection was 100.2 ± 8.4 mm. All patients received bare SEMS placement. The median time to symptom relief was 1 day (interquartile range, 1 3 days). The the median follow-up time of CTA was 6.8 months (range, 2-85 months), with an average of 16.2 months. Complete remodeling of the superior mesenteric artery (SMA) was recorded in 24 patients. The median time to remodeling was 3 months with an average of 4.7 months. Survival analysis indicated no significance difference in remodeling time between different ISMAD types based on Yun classification (P = 0.888) or between acute and nonacute disease (P = 0.423). Incomplete remodeling was noted in 2 patients. Distal stent occlusion without SMA-related symptoms was seen in 1 patient. Proximal stent stenosis occurred in 1 patient, and restenting was performed. The median follow-up time by telephone was 20.8 (4-91.5) months, and no intestinal ischemic symptoms were observed in any patient. CONCLUSIONS: Bare SEMS placement can effectively relieve SMA-related symptoms in a short time and promote dissection remodeling in ISMAD. Time from symptom onset and classification of ISMAD seem not to have effects on SMA remodeling after bare SEMS placement.

Ursolic acid nanoparticles for glioblastoma therapy.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and fatal primary tumor in the central nervous system (CNS). The effect of chemotherapy of GBM is limited due to the existence of blood-brain barrier (BBB). The aim of this study is to develop self-assembled nanoparticles (NPs) of ursolic acid (UA) for GBM treatment. METHODS: UA NPs were synthesized by solvent volatilization method. Western blot analysis fluorescent staining and flow cytometry were launched to explore the anti-glioblastoma mechanism of UA NPs. The antitumor effects of UA NPs were further confirmed in vivo using intracranial xenograft models. RESULTS: UA were successfully prepared. In vitro, UA NPs could significantly increase the protein levels of cleaved-caspase 3 and LC3-II to strongly eliminate glioblastoma cells through autophagy and apoptosis. In the intracranial xenograft models, UA NPs could further effectively enter the BBB, and greatly improve the survival time of the mice. CONCLUSIONS: We successfully synthesized UA NPs which could effectively enter the BBB and show strong anti-tumor effect which may have great potential in the treatment of human glioblastoma.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.