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1.
ACS Omega ; 7(17): 14591-14610, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35557656

RESUMO

Recently, deep shale reservoirs are emerging as time requires and commence occupying a significant position in the further development of shale gas. However, the understanding of pore characteristics in deep shale remains poor, prohibiting accurate estimation of the hydrocarbon content and insights into fluid mobility. This study focuses on the Longmaxi Formation from the Luzhou (LZ) region, southern Sichuan. Scanning electron microscopy (SEM), low-temperature N2/CO2 adsorption, X-ray diffraction, and geochemical analysis were performed to investigate the micro-nanopore size distribution, main controlling factors, and unique pore features distinct from other regions. Results showed that the pores can be classified into four categories, organic matter (OM) pores, intergranular pores, intragranular pores, and microfractures, according to SEM images. The total pore volume is overwhelmingly dominated by mesopores and contributed by pores in the range of 0.5-0.6, 2-4, and 10-30 nm. The specific surface area is primarily contributed by micropores and mesopores in the range of 0.5-0.7 and 2-4 nm. By analyzing the influencing factors extensively, it is concluded that the buried depth, geochemical factors, and mineral composition can impact the pore structure in the overmature deep shales. Specifically, the total organic carbon content plays a more effective and positive role in the development of micropores, mesopores, total pores, and the porosity when compared with vitreous reflectance (Ro). The micropores are inferred to be OM-related. On the contrary, clay mineral is detrimental to the development of micropores and mesopores and the petrophysical properties (porosity and permeability), which may be attributed to the occurrence of chlorite and kaolinite instead of illite. The plagioclase conforms to the same law as clay due to their coexistence. Quartz, carbonate minerals, and pyrite can barely contribute to the pores. Eventually, the compared results suggest that the Longmaxi Formation of the LZ region are qualified with a superior pore size distribution, complicated structure, and diverse morphology, implying a potential to generate and store hydrocarbons. Overall, this study improves the understanding of complex pore structures in deep shale and provides significant insights into the development and exploration of unconventional resources in the future.

2.
J Steroid Biochem Mol Biol ; 221: 106117, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35504423

RESUMO

Accumulation of androgens mediate alterations in prostate growth and has emerged as an essential factor in benign prostate hyperplasia (BPH). Dihydrotestosterone (DHT), the most potent natural androgen, binds to androgen receptors (AR) and regulates the prostate growth. Many inhibitors of DHT synthesis have been developed to reduce DHT levels and used in the treatment of prostate diseases. However, therapies targeting the elimination of the DHT remain limited. The DHT in prostate is metabolized by UDP-glucuronosyltransferase 2B (UGT2B) and transforms into inactive products. In this study, we analyzed and demonstrated that two enantiomers of naftopidil (NAF), an α1D/1A-adrenoceptor blocker, induced expression and activity of UGT2B in BPH rat prostate models as well as UGT2B15 in human prostate cells, BPH-1. The NAF enantiomers reduced intraprostatic and intracellular DHT levels, thus promoting cell apoptosis. Besides, assays with siRNA UGT2B15 transfection showed that UGT2B15 played an essential role in mediating the effects of the NAF enantiomers. The UGT2B15 mediated the inhibition of AR and PSA expression by NAF enantiomers. The data showed that the mechanism of upregulating UGT2B15 by the NAF enantiomers might differ from that of AR antagonists and 5α-reductase inhibitors. Together, our results demonstrated that NAF enantiomers could be potential and novel UGT2B15 regulators, which accelerated the DHT elimination and promoted apoptosis of BPH-1 cells. This study could help expand the clinical application of NAF and support the development of new therapeutic strategies targeting the elimination of androgens for the treatment of BPH and other androgen-sensitive diseases.

3.
ACS Nano ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506539

RESUMO

Quantum efficiencies remain a critical issue for general applications of semiconducting polymers in optoelectronics and others. In this work, we demonstrate that nearly 100% quantum efficiencies (η's) in thin solid films can be reached when the polymer molecules are mechanically stretched into molecular confinement. We selected three conjugated polymers of varied backbone stiffness and interchain coupling, prepared in both diluted and pristine states. All of the polymers when highly diluted (c = 0.1 wt %) exhibited massive η increases after stretching to very large strains (∼300-500%) via micronecking, with the rigid polyfluorene (PFO) and semirigid MEH-PPV both manifesting η ≈ 90%, while the most flexible yet regioregular polythiophene (P3HT-rr) exhibited a 10-fold increase to ∼21%. In the pristine state, molecular aggregation and interchain coupling curtail development of the molecular confinement, but the large-strain deformation still enhances η's significantly, to ∼90% (PFO) and ∼55% (MEH-PPV) despite no increases for the crystalline P3HT-rr. Moreover, upon substitution by a bulkier side-group to reduce interchain coupling, the pristine films of polythiophene (P3EHT) exhibited a ∼3-fold increase of η after the stretching. The nearly 100% of η's in fully stretched molecules indicates that the in situ self-trapping occurring via sub-picosecond backbone interactions can be mostly responsible for energy dissipations and quite suppressible by segmental stress control. The mechanical confinement effects also indicate the fundamental role of molecular mechanics during stabilization and migration of photoexcited charges.

4.
Sci Rep ; 12(1): 7785, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546349

RESUMO

Microbial enhanced oil recovery (MEOR) technology is an environmental-friendly EOR method that utilizes the microorganisms and their metabolites to recover the crude oil from reservoirs. This study aims to research the potential application of strain SL in low permeability reservoirs. Strain SL is identified as Bacillus subtilis by molecular methods. Based on the mass spectrometry, the biosurfactant produced by strain SL is characterized as lipopeptide, and the molecular weight of surfactin is 1044, 1058, 1072, 1084 Da. Strain SL produces 1320 mg/L of biosurfactant with sucrose as the sole carbon source after 72 h. With the production of biosurfactant, the surface tension of cell-free broth considerably decreases to 25.65 ± 0.64 mN/m and the interfacial tension against crude oil reaches 0.95 ± 0.22 mN/m. The biosurfactant exhibits excellent emulsification with crude oil, kerosene, octane and hexadecane. In addition, the biosurfactant possesses splendid surface activity at pH 5.0-12.0 and NaCl concentration of 10.0% (w/v), even at high temperature of 120 °C. The fermentation solution of strain SL is applied in core flooding experiments under reservoir conditions and obtains additional 5.66% of crude oil. Hence, the presented strain has tremendous potential for enhancing the oil recovery from low-permeability reservoirs.

5.
Front Nutr ; 9: 851972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548580

RESUMO

Epigallocatechin-3-gallate (EGCG), a frequently studied catechin in green tea, has been shown involved in the anti-proliferation and apoptosis of human nasopharyngeal carcinoma (NPC) cells. However, the underlying molecular mechanism of the apoptotic effects of EGCG has not been fully investigated. Recent literature emphasized the importance of Sirtuin 1 (SIRT1), an NAD+-dependent protein deacetylase, in regulating cellular stress responses, survival, and organismal lifespan. Herein, the study showed that EGCG could significantly inhibit cell proliferation and promote apoptosis of 2 NPC (CNE-2 and 5-8F) cell lines. Moreover, it was also found that SIRT1 is down-regulated by EGCG, and the SIRT1-p53 signaling pathway participates in the effects of EGCG on CNE-2 and 5-8 F cells. Taken together, the findings of this study provided evidence that EGCG could inhibit the growth of NPC cell lines and is linked with the inhibition of the SIRT1-p53 signaling pathway, suggesting the therapeutic potential of EGCG in human NPC.

6.
J Thorac Dis ; 14(4): 1120-1129, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35572910

RESUMO

Background: This study aimed to explore the effect of early extubation combined with physical training on pulmonary rehabilitation of patients after lung transplantation. Methods: This is an open parallel randomized controlled trial. A total of 96 lung transplant patients admitted to Wuxi People's Hospital (July 2018 to June 2019) were included. Inclusion criteria: (I) aged 18-75; (II) lung transplantation; (III) communicate normally; (IV) voluntary participation. According to the random number method, they were divided into the control group (routine nursing intervention) and the observation group (early extubation combined with a physical training program). The indwelling tracheal intubation time, discharge time, intensive care unit (ICU) stay time, lung function, 6 Minutes Walk Distance (6MWD), Modified Barthel Index (MBI) and satisfaction rate were recorded and analyzed. Results: The observation group's first-time postoperative ambulation (t=2.10, P=0.039), indwelling tracheal intubation time (Z=2.864, P=0.004), and discharge time (t=3.111, P<0.001) were shorter than the control group, while the difference of ICU stay time was not statistically significant (Z=-1.658, P=0.097). Before treatment, there was no significant difference in the lung function, 6MWD, and MBI of the two groups (P>0.05). After treatment, the Forced Expiratory Volume In 1 s (FEV1)% (t=-2.707, P<0.001), forced vital capacity (FVC)% (t=-3.716, P<0.001), FEV1/FVC (t=-3.539, P<0.001), 6MWD (t=-5.567, P<0.001), and MBI indexes (t=-4.073, P<0.001) were better than in observation group. The satisfaction rate of the observation group was better than the control group (P<0.05). Conclusions: For lung transplant recipients, early extubation combined with a physical training program is scientific, safe, and feasible. This approach is helpful to promote the postoperative recovery of lung transplant patients, reduce the length of hospitalization, help patients improve their lung function and ability to engage in activities of daily living, and increase the satisfaction rate of postoperative recovery. Results show that the combination of early extubation and a physical training program is worthy of clinical promotion for lung transplant recipients. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100051954.

7.
Cerebrovasc Dis ; : 1-9, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35490673

RESUMO

BACKGROUND: Limited data exist on the significance of acute cerebral microinfarcts (A-CMIs) in the context of acute ischemic stroke (AIS). We aimed to determine the profile and prognostic significance of A-CMIs on magnetic resonance imaging (MRI) in patients presenting with AIS. METHODS: A prospective single-center series of patients with AIS who had 3T MRIs between March 2013 and December 2019. The presence, number, and location of A-CMIs on diffusion-weighted imaging, and markers of cerebral small vessel disease (CSVD), macroinfarcts features, and etiology were classified as cardioembolism (CE) or large artery atherosclerosis (LAA) or none. RESULTS: Among 273 patients, A-CMIs were detected in 130 patients (47.6%), of whom cortical A-CMIs were found in 95 (73.0%) patients. Patients with A-CMIs were significantly older, less likely to have diabetes mellitus, and more likely to have atrial fibrillation and an embolic source (CE or LAA) compared to other patients. Patients with A-CMI had a higher frequency of macroinfarcts (diameter >20 mm), more often multiple and distributed in single or multiple vessel territories than other patients. An embolic source (LAA or CE) was independently associated with cortical A-CMIs (LAA adjusted odds ratio [aOR] 4.0 95% confidence interval [CI] 1.6-9.5; CE aOR 2.5, 95% CI 1.1-5.6), whereas lacunes were independently related to subcortical A-CMIs (aOR 2.6, 95% CI 1.2-5.8). CONCLUSIONS: We have shown A-CMIs occur in cortical and subcortical regions in nearly half of AIS patients, where microembolism and CSVD are, respectively, the key presumed etiological mechanism.

8.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35552974

RESUMO

The γ-aminobutyric acid type A receptors (GABA(A)Rs) are the main inhibitory neurotransmitter receptors in the CNS. They control the synaptic and extrasynaptic GABA-mediated inhibitory signals in the brain. They are the target of general anesthetics, sedatives and anticonvulsants. Our overall goal is to design and develop site specific Null Allosteric Ligands (NALs) for GABA(A)Rs as reversal agents of these actions. For example, faster recovery from general anesthesia is associated with less postoperative anesthesia-related complications such as memory loss and confusion. Whereas flumazenil is a NAL that binds to the benzodiazepine site in the extracellular domain's (ECD) α+/γ- interface, there are no known NALs that bind to the transmembrane domain (TMD) sites. We adopted a strategy based on the structures of etomidate, flavanols and barbiturates as starting points, while utilizing computational docking, SAR studies and radioligand binding assays to assist in the design and development of the new agents. Here, we report the first NAL that binds to the TMD of GABA(A)Rs and that antagonizes the action of R-mTFD-MPAB (it binds to the TMD at the α+/ß- and γ+/ß- interfaces), while having a marginal effect on the binding of the agonist, [3 H]muscimol. The development of the first NAL(s) targeting the TMD of GABA(A)Rs will aid in understanding GABAergic actions in the CNS, support the mechanistic studies on GABA(A)Rs and potentially lead to reversal agents for general anesthesia and sedation.

10.
ChemSusChem ; : e202200548, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35502630

RESUMO

Highly selective conversion of methane to oxygenates with O2 as a green oxidant remains a great challenge. It is still difficult to suppress the generation of COx (x=1, 2) as undesired by-products due to unavoidable overoxidation reaction. Hence, tungsten-doped (W-doped) TiO2 photocatalysts were designed with a tunable band structure for photocatalytic oxidation of methane to C1 oxygenates using O2 at low temperature (30 °C). The W-doping effectively modified the electronic and band structure of pristine TiO2 to enhance photocatalytic performance. Liquid oxygenates productivity could reach as high as 12.2 mmol g-1 with high selectivity of 99.4 %. Moreover, COx selectivity was effectively decreased from 21.2 % over TiO2 to 0.6 % for W-doped catalyst. Detailed characterizations further disclosed that W-doping not only enhanced light absorption, but also promoted the separation of photo-generated carriers to improve methane conversion. This work provides new insights into the design of highly efficient photocatalysts for methane oxidation.

11.
Bioengineered ; 13(5): 12003-12020, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35603567

RESUMO

Despite great progress, the current cancer treatments often have obvious toxicity and side effects. and a poor prognosis (some patients). One of the reasons for the poor prognosis is that certain enzymes prevent anticancer drugs from killing tumor cells. AKT1 is involved in regulating PI3K/AKT/mTOR, a tumor-generating pathway. Ipatasertib, a highly selective inhibitor of AKT1, is widely used in the treatment of tumors. In this study, many structural and biochemical methodswere used to find better AKT1(Threonine Kinase 1) inhibitors, which laid a foundation for the further development of AKT1 inhibitors and provided new drugs for the treatment of tumors. ZINC15 database and Discovery Studio 4.5, a computer-aided drug screening software with many modules (LibDock for virtual screening, ADME (Absorption, Distribution, Metabolism, Excretion) and TOPKAT (toxicity prediction module) for the toxicity and properties analysis, and MD simulation for stability prediction), were employed. CCK8 assay, ELISA assay genicity and higher tolerance to cytochrome P4502D6. MD simulations indicated they could bind with AKT1 stably in the natural environment. The cell experiment and specific assay for AKT1 inhibition showed they could inhibit the proliferation and AKT1 expression of MG63 cells (Osteosarcoma cells). Moreover, these novel compounds with structural modifications can be potential contributors that lead to further rational drug design for targeting AKT1.AbbreviationAKT1, AKT Serine/Threonine Kinase 1; ADME, absorption, distribution, metabolism, excretion; TOPKAT, toxicity prediction by Computer assisted technology; CCK8, Cell Counting Kit 8; ELISA, Enzyme-linked immunosorbent assay; CYP2D6, cytochrome P4502D6 inhibition; GBM, Glioblastoma; AGC kinase, protein kinase A, G, and C families (PKA, PKC, PKG); PKB, protein kinase B; PAM pathway, PI3K/AKT/mTOR pathway; OS, overall survival; PFS, progression-free survival; LD50, lethal dose half in rats; LOAEL, lowest observed adverse effect level; NPT, normal pressure and temperature; PME, particle mesh Ewald; LINCS, linear constraint solver; RMSD, root-mean-square deviation; BBB, blood-brain barrier; DS, Discovery Studio; DTP, Developmental toxicity potential; PPB, Plasma protein binding; MTD, Maximum Tolerated Dosage; AB, Aerobic Biodegradability; NTP, US. National Toxicology Program; DTP, developmental toxicity potential.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Citocromos , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/química , Ratos , Serina , Serina-Treonina Quinases TOR
12.
J Ethnopharmacol ; 293: 115282, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35405254

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The prescription of Wei-Tong-Xin (WTX) is improved based on the prescription "Wanyingyuan", a famous decoction documented in the book of Huatuozhongzangjing in the Han dynasty. Many years of clinical verification have demonstrated that WTX can be used to treat gastrointestinal diseases, especially gastric ulcer (GU). However, the potential pharmacological mechanism is undefined. AIM OF THE STUDY: This research was conducted to explore the pharmacological mechanisms under the consideration of the therapeutical effect of WTX against GU by combining the network pharmacology strategy and in-vivo verified experiments. MATERIALS AND METHODS: A prediction network describing the relationship between WTX and GU was established based on information collected from multiple databases. Then, the intersecting protein-protein interaction (PPI) network of the drug-disease overlapping gene targets was constructed, and several key targets related to both WTX and GU were obtained. Besides, the Gene Ontology (GO) biological enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the key target genes and pathways of WTX against GU. Then, the candidate targets and signaling pathways of network pharmacology were validated in a rat model of GU induced by indomethacin following the results and available proof. RESULTS: There are 243 targets obtained from the 65 active ingredients in WTX, and 1362 disease targets related to GU were identified. Then, 6 key targets were determined with the PPI interaction network, which was structured from 126 overlapping gene targets. GO and KEGG analyses revealed that the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway might play a crucial role in the therapeutic mechanism of GU. In vivo verified experiments, WTX significantly reduced the ulcer area and improved the histopathological appearance of gastric tissues. Moreover, down-regulated the protein levels of IL6, TNF-α, and Caspase 3 in the gastric tissues while up-regulating the expression of p-PI3K, p-AKT, p-P53, and VEGFA compared to the model group. CONCLUSION: WTX, an ancient traditional Chinese medicine (TCM) compound prescription, may affect the inflammatory response and apoptosis process by regulating PI3K/AKT signaling pathway and related gene targets. Therefore, it is an effective drug candidate for the modern treatment of GU.

13.
Front Surg ; 9: 856293, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35433806

RESUMO

Background: Whether the utilization of preoperative three-dimensional (3D) lung simulation can improve the outcomes of segmentectomy for lung cancer (LC) is still controversial. Our meta-analysis was performed to compare preoperative 3D lung simulation with non-3D procedures in terms of perioperative outcomes. Methods: Seven databases (Embase, Ovid Medline, ScienceDirect, PubMed, Web of Science, Cochrane Library, and Scopus) were searched for eligible articles. Intraoperative outcomes (conversion, operative time, etc.), postoperative indicators (postoperative hospital stay, total number of complications, etc.) and postoperative complications were endpoints. Results: After applying predefined inclusion criteria, we included 8 studies and 989 patients (3D group: 552 patients; non-3D group: 437 patients) in our meta-analysis. The results of the meta-analysis showed that preoperative 3D lung simulation could significantly decrease the blood loss (mean difference [MD]: -16.21 [-24.95 to -7.47]ml, p = 0.0003), operative time (MD: -13.03 [-25.56 to -0.50]ml, p = 0.04), conversion rate (conversion from segmentectomy to thoracotomy or lobectomy) (MD: 0.12 [0.03-0.48], p = 0.003), postoperative hospital stay (MD: -0.25 [-0.46 to 0.04]days, p = 0.02) and total number of complications (MD: 0.59 [0.43-0.82], p = 0.001) compared with non-3D procedures. The number of resected lymph nodes (LNs), postoperative drainage time, postoperative forced expiratory volume in the first second (postoperative FEV1) and postoperative drainage volume were similar in the two groups. Arrhythmia (5.30%), pulmonary air leakage (2.72%), atrial fibrillation (2.20%), pulmonary infection (2.04%), and pneumonia (1.73%) were the top 5 postoperative complications in the 3D group. Conclusions: Preoperative 3D lung simulation was better than non-3D procedures in segmentectomy for LC, with better intraoperative and postoperative outcomes. However, our results should be confirmed in larger prospective randomized controlled trials. Systematic Review Registration: PROSPERO, identifier: CRD42021275020.

14.
Angew Chem Int Ed Engl ; : e202204116, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35362182

RESUMO

Selective oxidation of methane to oxygenates with O2 under mild conditions remains a great challenge. Here we report a ZSM-5 (Z-5) supported PdCu bimetallic catalyst (PdCu/Z-5) for methane conversion to oxygenates by reacting with O2 in the presence of H2 at low temperature (120 °C). Benefiting from the co-existence of PdO nanoparticles and Cu single atoms via tandem catalysis, the PdCu/Z-5 catalyst exhibited a high oxygenates yield of 1178 mmol g-1 Pd h-1 (mmol of oxygenates per gram Pd per hour) and at the same time high oxygenates selectivity of up to 95 %. Control experiments and mechanistic studies revealed that PdO nanoparticles promoted the in situ generation of H2 O2 from O2 and H2 , while Cu single atoms not only accelerated the activation of H2 O2 for the generation of abundant hydroxyl radicals (⋅OH) from H2 O2 decomposition, but also enabled the homolytic cleavage of CH4 by ⋅OH to methyl radicals (⋅CH3 ). Subsequently, the ⋅OH reacted quickly with the ⋅CH3 to form CH3 OH with high selectivity.

15.
Front Aging Neurosci ; 14: 847648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462687

RESUMO

Objective: To investigate the current management of thrombolysis related hemorrhagic transformation (HT) in real-world practice, and whether these treatments would reduce the risk of 3-month death and hematoma expansion after HT. Methods: A multicenter retrospective study was performed in three comprehensive stroke centers in China (West China Hospital, The First People's Hospital of Ziyang, and Mianyang Central Hospital) between January 1st 2012 and December 31th 2020. Participants were patients diagnosed with HT after intravenous thrombolytics on brain computed tomography (CT) within 36 h after stroke onset. The treatment after thrombolysis related HT included aggressive therapy (procoagulant, neurosurgical treatment) and dehydration therapy (mannitol or glycerin and fructose). The primary clinical outcome was 3-month death. The primary radiographic outcome was hematoma expansion, defined as a 33% increase in the hematoma volume using the (A × B × C)/2 method on follow-up imaging. Results: Of 538 patients with ischemic stroke receiving thrombolysis included during the study period, 94 patients (17.4%) were diagnosed with HT, 50% (47/94) of whom were symptomatic HT. The 3-month death was 31.5% (29/92), with two patients having been lost to follow up. A total of 68 patients (72.3%) had follow-up brain CT scans after HT detection for evaluating hematoma expansion, of whom 14.7% (10/68) had hematoma expansion. Among the 10 patients with hematoma expansion, 7 patients were from symptomatic HT group, and 3 patients were from the asymptomatic hematoma group. In regard to escalation in therapy, six patients received neurosurgical treatment and three patients had a fresh frozen plasma infusion. In addition, dehydration therapy was the most common management after HT diagnosis [87.2% (82 of 94)]. In the multivariable models, refusing any treatment after HT diagnosis was the sole factor associated with increased 3-month death (odds ratio, 13.6; 95% CI, 3.98-56.9) and hematoma expansion risk (odds ratio, 8.54; 95% CI, 1.33-70.1). In regard to the effects of aggressive therapy, a non-significant association of receiving hemostatic/neurosurgery therapy with a lower 3-month death and hematoma expansion risk was observed (all P > 0.05). Conclusion: Refusing any treatment after HT detection had a significant trend of increasing 3-month death and hematoma expansion risk after HT. Our finding of hematoma expansion among patients with asymptomatic HT in non-western populations suggests an opportunity for intervention. Very few patients after thrombolysis related HT diagnosis received procoagulant or neurosurgical therapies. Large multicenter studies enrolling diverse populations are needed to examine the efficacy of these therapies on different HT subtypes.

16.
Front Oncol ; 12: 812358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463321

RESUMO

Objective: To develop and validate a bone metastasis prediction model based on skull base invasion (SBI) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort study enrolled 290 patients with LA-NPC who received intensity-modulated radiation therapy in two hospitals from 2010 to 2020. Patient characteristics were grouped by SBI and hospital. Both unadjusted and multivariate-adjusted models were used to determine bone metastasis risk based on SBI status. Subgroup analysis was performed to investigate heterogeneity using a forest graph. Cox proportional hazard regression analysis was used to screen for risk factors of bone metastasis-free survival (BMFS). A nomogram of BMFS based on SBI was developed and validated using C-index, receiver operating characteristic curve, calibration curves, and decision curve analysis after Cox proportional hazard regression analysis. Results: The incidence of bone metastasis was 14.83% (43/290), 20.69% (24/116), and 10.92% (19/174) in the overall population, SBI-positive group, and SBI-negative group, respectively. In the unadjusted model, SBI was associated with reduced BMFS [HR 2.43 (1.32-4.47), P = 0.004], and the results remained stable after three continuous adjustments (P <0.05). No significant interaction was found in the subgroup analyses (P for interaction >0.05). According to Cox proportional hazard regression analysis and clinical value results, potential risk factors included SBI, Karnofsky performance status, TNM stage, induction chemotherapy, concurrent chemoradiotherapy, and adjuvant chemotherapy. Using a training C-index of 0.80 and a validation C-index of 0.79, the nomogram predicted BMFS and demonstrated satisfactory prognostic capability in 2, 3, and 5 years (area under curve: 83.7% vs. 79.6%, 81.7% vs. 88.2%, and 79.0% vs. 93.8%, respectively). Conclusion: Skull base invasion is a risk factor for bone metastasis in patients with LA-NPC. The SBI-based nomogram model can be used to predict bone metastasis and may assist in identifying LA-NPC patients at the highest risk of bone metastasis.

17.
Front Endocrinol (Lausanne) ; 13: 873820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464058

RESUMO

Background: As an endocrine organ, the thyroid acts on the entire body by secreting a series of hormones, and bone is one of the main target organs of the thyroid. Summary: This review highlights the roles of thyroid hormones and thyroid diseases in bone homeostasis. Conclusion: Thyroid hormones play significant roles in the growth and development of bone, and imbalance of thyroid hormones can impair bone homeostasis.


Assuntos
Sistema Endócrino , Glândula Tireoide , Osso e Ossos , Sistema Endócrino/fisiologia , Hormônios , Hormônios Tireóideos/fisiologia
18.
Front Genet ; 13: 810157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401684

RESUMO

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality, and so far patients have failed to benefit from therapeutics clinically available. Max interacting protein 1-0 (Mxi1-0) is one of the functional isoforms of Mxi1. Although it also binds to Max, Mxi1-0, unlike other Mxi1 isoforms, cannot antagonize the oncoprotein c-Myc because of its unique proline rich domain (PRD). While Mxi1-0 was reported to promote cell proliferation via largely uncharacterized mechanisms, it is unknown whether and how it plays a role in the pathogenesis of HPH. Methods: GEO database was used to screen for genes involved in HPH development, and the candidate players were validated through examination of gene expression in clinical HPH specimens. The effect of candidate gene knockdown or overexpression on cultured pulmonary arterial cells, e.g., pulmonary arterial smooth muscle cells (PASMCs), was then investigated. The signal pathway(s) underlying the regulatory role of the candidate gene in HPH pathogenesis was probed, and the outcome of targeting the aforementioned signaling was evaluated using an HPH rat model. Results: Mxi1 was significantly upregulated in the PASMCs of HPH patients. As the main effector isoform responding to hypoxia, Mxi1-0 functions in HPH to promote PASMCs proliferation. Mechanistically, Mxi1-0 improved the expression of the proto-oncogene c-Myc via activation of the MEK/ERK pathway. Consistently, both a MEK inhibitor, PD98059, and a c-Myc inhibitor, 10058F4, could counteract Mxi1-0-induced PASMCs proliferation. In addition, targeting the MEK/ERK signaling significantly suppressed the development of HPH in rats. Conclusion: Mxi1-0 potentiates HPH pathogenesis through MEK/ERK/c-Myc-mediated proliferation of PASMCs, suggesting its applicability in targeted treatment and prognostic assessment of clinical HPH.

19.
Curr Neurovasc Res ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388755

RESUMO

BACKGROUND/OBJECTIVE: Systemic immune-inflammation index (SII) is a novel inflammatory factor, which may be involved in the destruction of the blood-brain barrier (BBB) after acute ischemic stroke (AIS); however, the association between SII and symptomatic intracranial hemorrhage (sICH) in AIS patients undergoing endovascular treatment (EVT) remains unclear. METHODS: Patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO) who underwent EVT were consecutively enrolled. Blood samples were collected in the emergency room and SII was calculated by neutrophils × platelets/lymphocytes. Participants were categorized into tertiles according to admission SII. The main outcome was defined as the occurrence of sICH, following the European Cooperative Acute Stroke Study III (ECASS-III) criteria. RESULTS: A total of 379 AIS-LVO patients with EVT were enrolled (median age = 71 years, 52.5% males). The median baseline National Institutes of Health Stroke Scale (NIHSS) score was 15 (IQR, 12-18). The median of SII was 820.9 × 109/L (IQR, 473.1-1345.2). Forty-three (11.3%) patients who developed sICH. SII was found to be independently associated with sICH after EVT (adjusted odd ratio (OR) = 1.005 (per 10 units increase); 95% confidence interval (CI): 1.002-1.008; p = 0.002). Compared to patients in the lowest SII tertile, patients in the highest tertile had a higher risk of sICH (adj-OR 3.379; 95% CI 1.302-8.768; p = 0.012). The risk of sICH increased with the increase of SII in a dose-dependent manner (p for trend = 0.004). There was no interaction between potential modifiers and SII on sICH. CONCLUSIONS: Admission SII positively associated with sICH in AIS-LVO patients treated with EVT. These results need to be confirmed in future studies.

20.
Curr Neurovasc Res ; 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388758

RESUMO

BACKGROUND: Carotid artery stenosis (CAS) patients show reduced blood flow in the ophthalmic artery. This study aimed to assess the changes in the choriocapillaris and choroidal thickness in patients with unilateral carotid artery stenosis after carotid stenting using swept-source optical coherence tomography (SS-OCT)/swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Fifty-three mild to moderate CAS patients and 40 controls were enrolled in this study. All participants underwent digital subtraction angiography (DSA) and SS-OCT/SS-OCTAA imaging before and 4 days after carotid artery stenting. SS-OCTA was used to image and measure the perfusion of the choriocapillaris (mm2) while SS-OCT was used to image and measure the choroidal thickness (µm). The stenosed side was described as the ipsilateral eye while the other side was the contralateral eye. RESULTS: Choroidal thickness was significantly thinner (P = 0.024) in CAS when compared with controls. Ipsilateral eyes of CAS patients showed significantly thinner (P = 0.008) choroidal thickness when compared with contralateral eyes. Ipsilateral eyes of CAS patients showed thicker (P = 0.027) choroidal thickness after carotid artery stenting while contralateral eyes showed thinner choroidal thickness (P = 0.039). CONCLUSIONS: Our report suggests that in vivo quantification of the choroid with the SS-OCT/SS-OCTA may allow monitoring of CAS and enable the assessment of purported treatments.

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