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1.
Risk Manag Healthc Policy ; 17: 763-773, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562250

RESUMO

Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.

3.
J Chem Phys ; 160(13)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38557844

RESUMO

The moisture with salt ions adsorbed on the mineral soil surface is crucial to the cohesion process when the media is exposed to marine or coastal environments. However, the impact of salinity on the cohesion of soils is not well studied at the nanoscale. In this study, the salinity effect was investigated by studying the wettability and capillary force of NaCl solutions on quartz substrates via a molecular dynamics-based approach. Besides, a new visualization method was proposed to measure the contact angle of liquid droplets from the aspect of nanoscale. The results indicated that salt ions can weaken the wettability of the liquid on the quartz surface and inhibit the capillary force. Compared with water, the liquid with a 10% NaCl solution can achieve a capillary force reduction of around 70%, resulting in a detrimental effect on the cohesion of soils. Overall, this study enhanced the understanding of the nanoscale salinity effect on the cohesion process and provided insights into the modification of the mechanical properties of soils from the aspect of nanoscale.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38577956

RESUMO

BACKGROUND: The behavioral manifestations and neurophysiological responses to sedation can assist in understanding brain function after neurological damage, and can be described by cortical functional connectivity. Glioma patients may experience neurological deficits that are not clinically detectable before sedation. We hypothesized that patients with gliomas exhibit distinct cortical connectivity patterns compared to non-neurosurgical patients during sedation. METHODS: This is a secondary analysis of a previously published prospective observational study. Patients scheduled for resection of supratentorial glioma (n=21) or a non-neurosurgical procedure (n=21) under general anesthesia were included in this study. Frontal electroencephalography (EEG) signals were recorded at different sedation levels as assessed by the Observer Assessment of Alertness/Sedation (OAA/S) score. Kernel principal component analysis and k-means clustering were used to determine possible temporal dynamics from the weighted phase lag index characteristics. RESULTS: Ten EEG connectivity states were identified by clustering (76% consistency), each with unique properties. At OAA/S 3, the median (Q1, Q3) occurrence rates of state 6 (glioma group, 0.110 [0.083, 0.155] vs. control group, 0.070 [0.030, 0.110]; P=0.008) and state 7 (glioma group, 0.105 [0.083, 0.148] vs. control group: 0.065 [0.038, 0.090]; P=0.001), which are dominated by beta connectivity, were significantly different between the 2 groups, reflecting differential conversion of the beta band between the left and right brain regions. In addition, the temporal dynamics of the brain's functional connectivity was also reflected in the transition relationships between metastable states. CONCLUSIONS: There were differences in EEG functional connectivity, which is dynamic, between the glioma and nonglioma groups during sedation.

5.
Sci Bull (Beijing) ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38599957

RESUMO

There is a pressing demand for the development of novel birefringent crystals tailored for compact optical components, especially for crystals exhibiting large birefringence across a range of temperatures. This has commonly been achieved by introducing various deformable groups with high polarizability anisotropy. In this study, we combined both rigid and deformable groups to synthesise a new birefringent crystal, Al2Te2MoO10, which demonstrates an exceptional birefringence value of 0.29@550 nm at room temperature. Not only is this higher birefringence than that of commercial crystals, but Al2Te2MoO10 exhibits excellent birefringence stability over a wide temperature range, from 123 to 503 K. In addition, the first-principles theory calculations and structural analyses suggest that although the rigid AlO6 groups do not make much contribution to the prominent birefringence, they nonetheless played a role in maintaining the structural anisotropy at elevated temperatures. Based on these findings, this paper proposes a novel structural design strategy to complement conventional approaches for developing optimal birefringent crystals under various environmental conditions.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38602101

RESUMO

BACKGROUND: Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism by which myocyte AKAP150 (A-kinase anchoring protein 150) inhibition induced by exercise training alleviates voltage-dependent L-type Ca2+ channel (CaV1.2) activity and restores cerebral arterial function in hypertension. METHODS: Spontaneously hypertensive rats and newly generated smooth muscle-specific AKAP150 knockin mice were used to assess the role of myocyte AKAP150/CaV1.2 channel in regulating cerebral artery function after exercise intervention. RESULTS: Activation of the AKAP150/PKCα (protein kinase Cα) signaling increased CaV1.2 activity and Ca2+ influx of cerebral arterial myocyte, thus enhancing vascular tone in spontaneously hypertensive rats. Smooth muscle-specific AKAP150 knockin mice were hypertensive with higher CaV1.2 channel activity and increased vascular tone. Furthermore, treatment of Ang II (angiotensin II) resulted in a more pronounced increase in blood pressure in smooth muscle-specific AKAP150 knockin mice. Exercise training significantly reduced arterial myocyte AKAP150 expression and alleviated CaV1.2 channel activity, thus restoring cerebral arterial function in spontaneously hypertensive rats and smooth muscle-specific AKAP150 knockin mice. AT1R (AT1 receptor) and AKAP150 were interacted closely in arterial myocytes. Exercise decreased the circulating Ang II and Ang II-involved AT1R-AKAP150 association in myocytes of hypertension. CONCLUSIONS: The current study demonstrates that aerobic exercise ameliorates CaV1.2 channel function via inhibiting myocyte AKAP150, which contributes to reduced cerebral arterial tone in hypertension.

7.
J Med Chem ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630077

RESUMO

Multitarget medications represent an appealing therapy against the disease with multifactorial abnormalities─cancer. Therefore, simultaneously targeting son of sevenless 1 (SOS1) and epidermal growth factor receptor (EGFR), two aberrantly expressed proteins crucial for the oncogenesis and progression of prostate cancer, may achieve active antitumor effects. Here, we discovered dual SOS1/EGFR-targeting compounds via pharmacophore-based docking screening. The most prominent compound SE-9 exhibited nanomolar inhibition activity against both SOS1 and EGFR and efficiently suppressed the phosphorylation of ERK and AKT in prostate cancer cells PC-3. Cellular assays also revealed that SE-9 displayed strong antiproliferative activities through diverse mechanisms, such as induction of cell apoptosis and G1 phase cell cycle arrest, as well as reduction of angiogenesis and migration. Further in vivo findings showed that SE-9 potently inhibited tumor growth in PC-3 xenografts without obvious toxicity. Overall, SE-9 is a novel dual-targeting SOS1/EGFR inhibitor that represents a promising treatment strategy for prostate cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38622933

RESUMO

Bubble-enhanced shock waves induce the transient opening of the blood-brain barrier (BBB) providing unique advantages for targeted drug delivery of brain tumor therapy, but little is known about the molecular details of this process. Based on our BBB model including 28 000 lipids and 280 tight junction proteins and coarse-grained dynamics simulations, we provided the molecular-level delivery mechanism of three typical drugs for the first time, including the lipophilic paclitaxel, hydrophilic gemcitabine, and siRNA encapsulated in liposome, across the BBB. The results show that the BBB is more difficult to be perforated by shock-induced jets than the human brain plasma membrane (PM), requiring higher shock wave speeds. For the pores formed, the BBB exhibits a greater ability to self-heal than PM. Hydrophobic paclitaxel can cross the BBB and be successfully absorbed, but the amount is only one-third of that of PM; however, the absorption of hydrophilic gemcitabine was almost negligible. Liposome-loaded siRNAs only stayed in the first layer of the BBB. The mechanism analysis shows that increasing the bubble size can promote drug absorption while reducing the risk of higher shock wave overpressure. An exponential function was proposed to describe the relation between bubble and overpressure, which can be extended to the experimental microbubble scale. The calculated overpressure is consistent with the experimental result. These molecular-scale details on shock-assisted BBB opening for targeted drug delivery would guide and assist experimental attempts to promote the application of this strategy in the clinical treatment of brain tumors.

9.
Bull Entomol Res ; : 1-10, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623047

RESUMO

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

10.
Langmuir ; 40(15): 8180-8193, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38581394

RESUMO

Ni-rich layered materials Li[NixCoyMnzAl1-x-y-z]O2 (x > 0.8) are regarded as the competitive cathode for practical applications in lithium-ion batteries owing to the large discharging capacity. Nevertheless, the strong oxidation activity, the poor structure, and the thermal stability at the electrode-electrolyte interface would lead to much trouble, for example, inferior electrochemical properties and acute safety issues. To ameliorate the above problems, this work reports a strategy for the double modification of F- doping and LiNbO3 covering in LiNi0.88Co0.06Mn0.03Al0.03O2 cathode via using high-temperature calcining and ball-milling technology. As a result, the cathodes after F- doping and LiNbO3 covering not only demonstrate a more stabilized crystal structure and particle interface but also reduce the release of high-activity oxygen species to ameliorate the thermal runaway. The electrochemical tests show that the LiNbO3-F--modified cathode displays a superior rate capability of 159.3 mAh g-1 at 10.0 C and has the predominant capability retention of 92.1% in the 200th cycle at 25 °C, much superior than those (125.4 mAh g-1 and 84.0%) of bare cathode. Thus, the F- doped and LiNbO3-coated Ni-rich oxides could be a promising cathode to realize the high capacity and a stabilized interface.

11.
Zhongguo Zhong Yao Za Zhi ; 49(3): 809-818, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621885

RESUMO

Scutellariae Radix extract is one of the important components in Shuganning Injection. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for simultaneously determining five components in Shuganning Injection and Scutellariae Radix extract in bile, urine, and feces of rats, so as to reveal the difference in the excretion process of Shuganning Injection and Scutellariae Radix extract in rats and explore the law of the excretion process of the five components in vivo before and after the compatibility of Scutellariae Radix. Rats were injected with Shuganning Injection and Scutellariae Radix extract(4.2 mL·kg~(-1)), respectively, and the excretion of baicalin, baicalein, oroxylin A, oroxylin A-7-O-ß-D-glucuronide, and scutellarin in bile, urine, and feces of rats in 24 h was observed. The results showed that except for baicalin, the other four index components were excreted as prototype components in a high proportion after intravenous injection of Shuganning Injection and Scutellariae Radix extract in rats, respectively. The excretion of each component was relatively high in urine and less in feces and bile. After the compatibility of Scutellariae Radix extract, the accumulative excretion of five index components in rats all decreased. Among them, the cumulative excretion of baicalein in bile, urine, and feces significantly decreased by 26.67%, 48.11%, and 31.01%. The cumulative excretion of baicalin in bile, urine, and feces decreased significantly by 70.69%, 19.43%, and 31.22%. The result showed that the five index components in Scutellariae Radix extract were mainly excreted by the kidneys, and other components in Shuganning Injection delayed the excretion process and prolonged the residence time. This study is of great significance for elucidating the compatibility rationality of Shuganning Injection.


Assuntos
Bile , Scutellaria baicalensis , Ratos , Animais , Cromatografia Líquida , Espectrometria de Massas em Tandem , Flavonoides , Fezes , Cromatografia Líquida de Alta Pressão
12.
Nat Commun ; 15(1): 2810, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561347

RESUMO

Osteosarcoma is the most common primary malignant bone tumor with a strong tendency to metastasize, limiting the prognosis of affected patients. Genomic, epigenomic and transcriptomic analyses have demonstrated the exquisite molecular complexity of this tumor, but have not sufficiently defined the underlying mechanisms or identified promising therapeutic targets. To systematically explore RNA-protein interactions relevant to OS, we define the RNA interactomes together with the full proteome and the transcriptome of cells from five malignant bone tumors (four osteosarcomata and one malignant giant cell tumor of the bone) and from normal mesenchymal stem cells and osteoblasts. These analyses uncover both systematic changes of the RNA-binding activities of defined RNA-binding proteins common to all osteosarcomata and individual alterations that are observed in only a subset of tumors. Functional analyses reveal a particular vulnerability of these tumors to translation inhibition and a positive feedback loop involving the RBP IGF2BP3 and the transcription factor Myc which affects cellular translation and OS cell viability. Our results thus provide insight into potentially clinically relevant RNA-binding protein-dependent mechanisms of osteosarcoma.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Proliferação de Células/genética , Linhagem Celular Tumoral , Osteossarcoma/metabolismo , Neoplasias Ósseas/metabolismo , RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Regulação Neoplásica da Expressão Gênica
13.
Ren Fail ; 46(1): 2327494, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38566467

RESUMO

BACKGROUND: Renal dysfunction leads to poor prognosis of patients with coronary artery disease (CAD). Current studies have reported the prognosis or mortality of various diseases using different estimated glomerular filtrate rate (eGFR) formulas, while the performance of these equations is unclear in CAD patients. We aim to evaluate the predict effect of creatinine-based eGFR (eGFRcr), cystatin C-based eGFR (eGFRcys), and both creatinine and cystatin C-based eGFR (eGFRcr-cys) in CAD patients. METHODS: A total of 23,178 patients with CAD were included from CIN-II cohort study. The association of eGFRcr, eGFRcys and eGFRcr-cys with cardiovascular and all-cause mortality was detected by Cox regression analysis. The predictive effect of eGFRcr, eGFRcys and eGFRcr-cys on mortality was assessed. RESULTS: During a median follow up of 4.3 years, totally 2051 patients (8.8%) experience all-cause mortality, of which 1427 patients (6.2%) died of cardiovascular disease. For the detection of cardiovascular mortality among CAD patients, eGFRcr-cys had high discriminatory capacity with area under the curve (AUC) in receiver operator characteristic analysis of 0.730, which was significantly better than eGFRcr (AUC = 0.707, p < 0.001) and eGFRcys (AUC = 0.719, p < 0.001). Similar results were observed in all-cause mortality. Restricted cubic spline showed a U-shaped association between eGFRcr and all outcomes in patients with both reduced and supranormal eGFR levels, while a L-shaped association in eGFRcys and eGFRcr-cys. CONCLUSIONS: Estimated GFR based on both creatinine and cystatin C has highest predictive effect for cardiovascular and all-cause mortality among CAD patients. Meanwhile, supranormal eGFRcr may indicate a higher risk of mortality.


Assuntos
Doença da Artéria Coronariana , Nefropatias , Insuficiência Renal Crônica , Humanos , Creatinina , Estudos de Coortes , Taxa de Filtração Glomerular , Cistatina C , Nefropatias/diagnóstico
14.
Onco Targets Ther ; 17: 327-338, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617088

RESUMO

Gastrointestinal angiosarcoma is an extremely rare malignant tumor of the digestive tract, characterized by a very poor prognosis, with few patients surviving more than 1 year after diagnosis. This case report describes a 71-year-old female patient with a 3-year history of intermittent abdominal pain and significant exacerbation of abdominal pain and bloating 2 weeks prior to treatment. After surgical treatment, the pathological and immunohistochemical diagnosis was primary epithelioid angiosarcoma of the jejunal mesentery. The patient refused postoperative adjuvant chemotherapy and died 4 months after diagnosis due to widespread systemic metastasis. In addition, this article reviews 38 previously reported cases of primary gastrointestinal angiosarcoma, aiming to further understand angiosarcoma and thus guide clinical practitioners in providing more comprehensive treatment approaches.

15.
Hum Vaccin Immunother ; 20(1): 2333098, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38619056

RESUMO

DTaP-HBV-IPV-Hib hexavalent vaccine has been used in high-income countries for many years to prevent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and invasive Haemophilus influenzae type b disease. Currently, no hexavalent vaccines have been approved for use in China. Evidence of parental acceptance and interest in hexavalent vaccines can help policy makers and manufacturers make decisions about entering the vaccine market and the immunization program in China. We measured parental acceptance and willingness-to-pay (WTP) for a hexavalent vaccine to provide such evidence. We conducted a cross-sectional survey of children's caregivers in 16 vaccination clinics in seven cities in China and obtained information on socio-demographics, knowledge of disease, confidence in vaccines, previous vaccination experience, and acceptance of and WTP for hexavalent vaccine. Multivariate logistic regression was used to determine factors influencing acceptance, and multivariate tobit regression was used to identify factors impacting WTP. Between April 28 and June 30, 2023, a total of 581 parents of children aged 0-6 years participated in the survey; 435 (74.87%, 95% CI:71.3%-78.4%) parents indicated acceptance of hexavalent vaccine. Residence location, parents' education level, experience paying for vaccination, and disease knowledge scores were key factors affecting parents' choices for vaccination. Mean (SD) and median (IQR) willingness to pay for full 4-dose course vaccination were 2266.66 (1177.1) CNY and 2400 (1600-2800) CNY. Children's age (p < .001), parents' education level (p = .024), and perceived price barriers (p < .001) were significantly associated with WTP. Parents have high acceptance and willingness to pay for hexavalent vaccine. The less money parents have to pay out of pocket, the more willing they can be to accept the vaccine. Therefore, acceptance may increase even further if the vaccine is covered by medical insurance, provided free of charge by the government, or if its price is reduced. Our results provide reference for optimizing and adjusting immunization strategies in China.


Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Vacinas contra Hepatite B , Criança , Humanos , Vacinas Combinadas , Estudos Transversais , China
16.
J Hazard Mater ; 470: 134111, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38581870

RESUMO

Microplastics (MPs) pose a significant global concern, requiring a multifaceted approach to their risk assessment procedures, especially concerning their characteristics in the environment. The Horqin Left Middle Banner in Northeast China was chosen for the research region to investigate the abundance, composition, distribution, and ecological impact of MPs in surface agricultural soils. The concentrations of MPs ranged from 300 to 12800 items/kg, with a median concentration of 1550 items/kg (average = 1994 items/kg). The normal-sized MPs (500-5000 µm) had a higher relative abundance than small MPs (<500 µm). MPs were mainly derived from textiles and packaging and were affected by atmospheric transportation. Rayon and PET fibers were the main polymers identified. Furthermore, the potential environmental risks posed by the fundamental characteristics (abundance, chemical composition, and size) of MPs were quantified using multiple risk assessment models. The conditional fragmentation model indicated a propensity for MPs to degrade into smaller particles. Ecological risk assessments using pollution load index, pollution hazard index, and potential ecological risk index models revealed varying levels of risk. This study conducted a comprehensive assessment of the ecological risks of MPs based on their environmental characteristics, emphasizing the importance of considering multiple factors in the risk assessment process. ENVIRONMENT IMPLICATION: This study investigates the occurrence, distribution, and ecological risk of microplastics (MPs) in agricultural soils of the Northeast Plain of China, a major food production area. MPs are persistent organic pollutants that can pose threats to soil health, crop quality, and food security. By analyzing the composition, size, and source of MPs, as well as their fragmentation and stability in soil, this study provides valuable data for assessing the environmental risk of MPs in agricultural regions. The study also suggests strategies for mitigating MPs pollution and protecting soil ecosystems.

17.
J Pharm Biomed Anal ; 245: 116156, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636190

RESUMO

Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata extracts (PCE) have been used in combination with levofloxacin (LVFX) to treat urinary tract infections (UTIs) for a long time. However, little is known about the absorption of LVFX and transporter expression in the intestine after combined treatment with PCE, restricting the development and utilization of PCE. In view of this, a UPLC-MS/MS method was established for the determination of LVFX in intestinal sac fluid samples and in situ intestinal circulation perfusate samples to explore the effect of PCE on the intestinal absorption characteristics of LVFX ex vivo and in vivo. To further evaluate the interaction between LVFX and PCE, western blotting, immunohistochemistry, and RT-qPCR were utilized to determine the expression levels of drug transporters (OATP1A2, P-gp, BCRP, and MRP2) involved in the intestinal absorption of LVFX after combined treatment with PCE. Using the everted intestinal sac model, the absorption rate constant (Ka) and cumulative drug absorption (Q) of LVFX in each intestinal segment were significantly lower in groups treated with PCE than in the control group. Ka at 2 h decreased most in the colon segment (from 0.088 to 0.016 µg/h·cm2), and Q at 2 h decreased most in the duodenum (from 213.29 to 33.92 µg). Using the intestinal circulation perfusion model, the Ka value and percentage absorption rate (A) of LVFX in the small intestine decreased significantly when PCE and LVFX were used in combination. These results showed that PCE had a strong inhibitory effect on the absorption of LVFX in the rat small intestine (ex vivo and in vivo intestinal segments). In addition, PCE increased the protein and mRNA expression levels of efflux transporters (P-gp, BCRP, and MRP2) and decreased the expression of the uptake transporter OATP1A2 significantly. The effects increased as the PCE concentration increased. These findings indicated that PCE changed the absorption characteristics of levofloxacin, possibly by affecting the expression of transporters in the small intestine. In addition to revealing a herb-drug interaction (HDI) between PCE and LVFX, these results provide a basis for further studies of their clinical efficacy and mechanism of action.

18.
Br J Haematol ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639167

RESUMO

The dysregulation of the Janus family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) is closely related to acute lymphoblastic leukaemia (ALL), whereas the clinical value of phosphorylated STAT5 (pSTAT5) remains elusive. Herein we performed a prospective study on clinical significance of flow cytometry-based pSTAT5 in adult B-ALL patients. A total of 184 patients were enrolled in the Precision-Classification-Directed-Target-Total-Therapy (PDT)-ALL-2016 cohort between January 2018 and December 2021, and STAT5 phosphorylation was detected by flow cytometry at diagnosis. Based on flow-pSTAT5, the population was classified into pSTAT5low (113/184, 61.1%) and pSTAT5high (71/184, 38.9%). Overall survival (OS) and event-free survival (EFS) were inferior in pSTAT5high patients than in those with pSTAT5low (OS, 44.8% vs. 65.2%, p = 0.004; EFS, 23.5% vs. 52.1%, p < 0.001), which was further confirmed in an external validation cohort. Furthermore, pSTAT5 plus flow-based minimal residual disease (MRD) postinduction defines a novel risk classification as being high risk (HR, pSTAT5high + MRD+), standard risk (SR, pSTAT5low + MRD-) and others as moderate-risk group. Three identified patient subgroups are distinguishable with disparate survival curves (3-year OS rates, 36.5%, 56.7% and 76.3%, p < 0.001), which was confirmed on multivariate analysis (hazard ratio 3.53, p = 0.003). Collectively, our study proposed a novel, simple and flow-based risk classification by integrating pSTAT5 and MRD in favour of risk-guided treatment for B-ALL.

19.
Analyst ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639445

RESUMO

Anisotropic growth of nanomaterials enables advances in building diverse and complex architectures, which exhibit unique properties and enrich the choice of nano-building modules for electrochemical sensor devices. Herein, an anisotropic growth method was proposed to anchor gold nanoparticles (AuNPs) onto both ends of quasi-two-dimensional CdSe semiconductor quantum nanoplatelets (NPLs), appearing with a monodisperse and uniform nano-dumbbell shape. Then, these AuNPs were exploited as natural anchor points and further initiated self-assembly to create complex architectures via dithiol bridges. Detailed studies illustrated that the covalent Se-Au bonds facilitate effective charge transfer in the internal metal-semiconductor (M-S) electric field. The narrowed energy gap and up-shifted highest occupied molecular orbital were favored for electron removal during the electro-oxidation process. The ultrathin CdSe NPLs supplied a large specific surface area, carrying remaining holes and abundant active sites for target electro-catalysis. As a result, using the assembled complex as the electrode matrix with well-connected electronic circuits, a reliable electrochemical sensor was achieved for enrofloxacin detection. Under the optimal conditions, the current response exhibits two linear dynamic ranges, 0.01-10.0 µM and 10.0-250 µM, and the detection limit was calculated as 0.0026 µM. This work not only opens up broad application prospects for heterogeneous M-S combinations as effective electrochemical matrixes but also develops reliable antibiotic assays for food and environmental safety.

20.
Regen Biomater ; 11: rbae029, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638701

RESUMO

Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.

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