Assessment of Coronary Involvement with MDCT and Long-term Outcomes in Patients with Takayasu's Arteritis.

RATIONALE AND OBJECTIVES: Takayasu's arteritis (TA) mainly affects the aorta and its branches involving the coronary arteries. Coronary CT angiography can be used to detect coronary artery lesions. Outcome of TA patients with coronary involvement has not been well established. Our study aimed to systematically analyze coronary lesions in patients with TA and to access long-term outcome in TA patients with coronary involvement. MATERIALS AND METHODS: A retrospective cohort study of TA patients with coronary CT angiography was conducted between January 2009 and October 2021. Baseline clinical characteristics, laboratory parameters, imaging features and therapeutic features were collected and analyzed. Follow-up was scheduled since the onset of TA. Overall survival and major adverse cardiovascular events (MACE) were analyzed in patients with coronary lesions. RESULTS: 48 (59.3%) TA patients had coronary involvement. Coronary ostial stenosis was detected in 31 (64.6%) patients by MDCT. Prevalence of disease activity (p = 0.007) was higher in patients with ostial stenosis. The median follow-up was 10.0 years. Death was observed in nine patients including seven died from myocardial infarction. TA patients with ostial stenosis had higher rate of MACE (p = 0.013). Baseline activity(HR: 5.250, 95%CI 2.004-8.639), ostial involvement(HR:8.954, 95%CI 3.875-56.038), stenosis≥ 70% (HR: 10.822, 95%CI 2.764-61.230) and activity recurrence (HR:11.913, 95%CI 2.321-85.747) were independently associated with increased major cardiovascular events. CONCLUSION: MDCT should be performed in patients suspected with coronary involvement to make early diagnosis. Myocardial ischemia is the major cause of longterm death in TA patients with coronary lesions. Baseline disease activity, coronary ostial stenosis, stenosis ≥ 70% and activity recurrence were independent risk factors of cardiovascular events in TA patients.

Pityriasis Rosea-Like Eruption following anti-fatigue traditional herbs: Aconitum carmichaelii Debx and Panax Ginseng suspected.

Traditional herbs have a history of clinical use in anti-fatigue. However, several adverse effects of herbs have been identified. Pityriasis rosea-like eruption (PR-LE) is a rare cutaneous complication of herbs. To the best of our knowledge, there have been few reports of PR-LE following herbs. Here, we described a case of PR-LE that developed 6 days after taking anti-fatigue herbs. After the 17 days of stopping Aconitum carmichaelii Debx and Panax Ginseng, it notably faded. So, when anti-fatigue herbs being authorized for fatigue use, monitoring for potential adverse effects is necessary.

2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside promotes liver regeneration after partial hepatectomy in mice: The potential involvement of PPARα-mediated fatty acid metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: 2,3,5,4'-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) is the principal bioactive compound contained in Polygonum multiflorum Thunb. (PMT), which is traditionally recorded to possess tonic and anti-aging efficacy. AIM OF THE STUDY: To identify the TSG-provided promotion on liver regeneration (LR) following partial hepatectomy (PHx) in mice and to explicate its involved mechanism. MATERIALS AND METHODS: The promotion of TSG on LR was evaluated by hematoxylin and eosin (H&E), 5-bromodeoxyuridinc (BrdU) and Ki-67 staining, and measuring the level of proliferating cell nuclear antigen (PCNA) and Cyclin D1 in mice with PHx at different time points. Gene Expression Omnibus (GEO, GSE15239) database and the label-free quantitative proteomics from liver of mice at 24 h after PHx were integrated to identify potential involved critical proteins, which were verified by Western-blot, Real-time polymerase chain reaction (RT-PCR), molecular docking and luciferase activity assay. Primary hepatocytes isolated from mice were used to investigate the TSG-provided promotion on proliferation in vitro. RESULTS: TSG (20 mg/kg) promoted LR in mice after PHx. Results from RNA expression data from clinical samples and proteomic analysis from liver tissues indicated that peroxisome proliferator-activated receptor α (PPARα)-mediated fatty acid metabolism pathway were crucially associated with the TSG-provided promotion on LR. TSG enhanced the nuclear translocation of PPARα and the mRNA expression of a series of PPARα-regulated downstream genes. In addition, TSG lowered hepatic triglyceride (TG) and non-esterified fatty acid (NEFA) amounts and increased hepatic adenosine triphosphate (ATP) level in mice after PHx. TSG up-regulated the transcriptional activity of PPARα in vitro. Next results displayed that TSG promoted cell proliferation as well as ATP level in mice primary hepatocytes, which were abolished when PPARα was suppressed. Meanwhile, the cell viability was also elevated in mice primary hepatocytes treated with ATP. CONCLUSION: Activating PPARα-mediated fatty acid ß-oxidation (FAO) pathway led to the production of ATP, which contributed to the TSG-provided promotion on LR after PHx in mice.

Enhanced flexibility of high-yield bamboo pulp fibers via cellulase immobilization within guar gum/polyacrylamide/polydopamine interpenetrating network hydrogels.

Softness is a crucial criterion in assessing the comfort and usability of tissue paper. Flexible fibers contribute to the softness of the tissue paper by allowing the sheets to conform to the contours of the skin without feeling rough or abrasive. This study focuses on developing innovative CGG/APAM/PDA hydrogels with interpenetrating networks consisting of cationic guar gum, anionic polyacrylamide, and polydopamine for cellulase immobilization, aimed at improving bamboo fiber flexibility. Cellulase biomolecules are efficiently immobilized on CGG/APAM/PDA hydrogels through the Schiff base reaction. Immobilized cellulases have a wider pH applicability than free cellulases, good storage stability, and can maintain high relative activity at relatively high temperatures. The treatment of bamboo fibers with immobilized cellulase results in a significant increase in flexibility, reaching 6.90 × 1014 N·m2, which is 7.18 times higher than that of untreated fibers. The immobilization of cellulases using CGG/APAM/PDA hydrogels as carriers results in a substantial enhancement of storage stability, pH applicability, and inter-fiber bonding strength, as well as the capacity to sustain high relative enzymatic activity at elevated temperatures. The immobilization of cellulase within CGG/APAM/PDA interpenetrating network hydrogels presents a viable strategy for enhancing bamboo fiber flexibility, thereby expanding the accessibility of tissue products.

Isotoosendanin inhibits triple-negative breast cancer metastasis by reducing mitochondrial fission and lamellipodia formation regulated by the Smad2/3-GOT2-MYH9 signaling axis.

Triple-negative breast cancer (TNBC) is incurable and prone to widespread metastasis. Therefore, identification of key targets for TNBC progression is urgently needed. Our previous study revealed that isotoosendanin (ITSN) reduced TNBC metastasis by targeting TGFßR1. ITSN is currently used as an effective chemical probe to further discover the key molecules involved in TNBC metastasis downstream of TGFßR1. The results showed that GOT2 was the gene downstream of Smad2/3 and that ITSN decreased GOT2 expression by abrogating the activation of the TGF-ß-Smad2/3 signaling pathway through directly binding to TGFßR1. GOT2 was highly expressed in TNBC, and its knockdown decreased TNBC metastasis. However, GOT2 overexpression reversed the inhibitory effect of ITSN on TNBC metastasis both in vitro and in vivo. GOT2 interacted with MYH9 and hindered its binding to the E3 ubiquitin ligase STUB1, thereby reducing MYH9 ubiquitination and degradation. Moreover, GOT2 also enhanced the translocation of MYH9 to mitochondria and thus induced DRP1 phosphorylation, thereby promoting mitochondrial fission and lamellipodia formation in TNBC cells. ITSN-mediated inhibition of mitochondrial fission and lamellipodia formation was associated with reduced GOT2 expression. In conclusion, ITSN prevented MYH9-regulated mitochondrial fission and lamellipodia formation in TNBC cells by enhancing MYH9 protein degradation through a reduction in GOT2 expression, thus contributing to its inhibition of TNBC metastasis.

Coronary Atherosclerosis Progression Provides Incremental Prognostic Value and Optimizes Risk Reclassification by Computed Tomography Angiography.

PURPOSE: This study investigated the prognostic value and risk reclassification ability of coronary atherosclerosis progression through serial coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study enrolled patients with suspected or confirmed coronary artery disease who underwent serial CCTA. Coronary atherosclerosis progression was represented by coronary artery calcium score (CACS) and segment stenosis score (SSS) progression. The baseline and follow-up CCTA characteristics and coronary atherosclerosis progression were compared. Furthermore, the incremental prognostic value and reclassification ability of three models (model 1, baseline risk factors; model 2, model 1 + SSS; and model 3, model 2 + SSS progression) for major adverse cardiovascular events (MACEs) were compared. RESULTS: In total, 516 patients (aged 56.40 ± 9.56 y, 67.4% men) were enrolled. During a mean follow-up of 65.29 months, 114 MACE occurred. The MACE group exhibited higher CACS and SSS than the non-MACE group at baseline and follow-up CCTA (P < 0.001), and demonstrated higher coronary atherosclerosis progression than the non-MACE group (ΔSSS: 2.63 ± 2.50 vs 1.06 ± 1.78, P < 0.001; ΔCACS: 115.15 ± 186.66 vs 89.91 ± 173.08, P = 0.019). SSS progression provided additional prognostic information (C-index = 0.757 vs 0.715, P < 0.001; integrated discrimination index = 0.066, P < 0.001) and improved the reclassification ability of risk (categorical-net reclassification index = 0.149, P = 0.015) compared with model 2. CONCLUSIONS: Coronary atherosclerosis progression through CCTA significantly increased the prognostic value and risk stratification for MACE compared with baseline risk factor evaluation and CCTA only.

Application of Li6.4La3Zr1.45Ta0.5Mo0.05O12/PEO Composite Solid Electrolyte in High-Performance Lithium Batteries.

Replacing the flammable liquid electrolytes with solid ones has been considered to be the most effective way to improve the safety of the lithium batteries. However, the solid electrolytes often suffer from low ionic conductivity and poor rate capability due to their relatively stable molecular/atomic architectures. In this study, we report a composite solid electrolyte, in which polyethylene oxide (PEO) is the matrix and Li6.4La3Zr1.45Ta0.5Mo0.05O12 (LLZTMO) and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) are the fillers. Ta/Mo co-doping can further promote the ion transport capacity in the electrolyte. The synthesized composite electrolytes exhibit high thermal stability (up to 413 °C) and good ionic conductivity (LLZTMO-PEO 2.00 × 10-4 S·cm-1, LLZTO-PEO 1.53 × 10-4 S·cm-1) at 35 °C. Compared with a pure PEO electrolyte, whose ionic conductivity is in the range of 10-7~10-6 S·cm-1, the ionic conductivity of composite solid electrolytes is greatly improved. The full cell assembled with LiFePO4 as the positive electrode exhibits excellent rate performance and good cycling stability, indicating that prepared solid electrolytes have great potential applications in lithium batteries.

Flavor Variations in Precious Tricholoma matsutake under Different Drying Processes as Detected with HS-SPME-GC-MS.

By employing headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), this study displayed the compositional changes in volatile organic compounds (VOCs) in Tricholoma matsutake samples subjected to hot-air drying (HAD) and vacuum freeze-drying (VFD) processes from their fresh samples. A total of 99 VOCs were detected, including 2 acids, 10 aldehydes, 10 alcohols, 13 esters, 12 ketones, 24 alkanes, 14 olefins, 7 aromatic hydrocarbons, and 7 heterocyclic compounds. Notably, the drying process led to a decrease in most alcohols and aldehydes, but an increase in esters, ketones, acids, alkanes, olefins, aromatic, and heterocyclic compounds. Venn diagram (Venn), principal component analysis (PCA), and partial least squares-discriminant analysis (PLS-DA) analyses enabled an easy and rapid distinction between the VOC profiles of T. matsutake subjected to different drying methods. Among the identified VOCs, 30 were designated as marker VOCs indicative of the employed drying process. And the VFD method was more capable of preserving the VOCs of fresh T. matsutake samples than the HAD method. Benzaldehyde, 1-Octen-3-ol, 3-Octanol, and (E)-2-Octen-1-ol were identified as markers for FRESH T. matsutake. Conversely, (E)-3-Hexene, lavender lactone, and α-Pinene were associated with VFD T. matsutake. For HAD T. matsutake, olefins, pyrazine, and esters, particularly ocimene, 2,5-Dimethyl-pyrazine, and methyl cinnamate, significantly contributed to its particularities. The results from this present study can provide a practical guidance for the quality and flavor control of volatile organic compounds in preciously fungal fruiting bodies by using drying processes.

Mild Catalytic Degradation of Crystalline Polyethylene Units in a Solid State Assisted by Carboxylic Acid Groups.

Crystalline polyethylenes bearing carboxylic acid groups in the main chain were successfully degraded with a Ce catalyst and visible light. The reaction proceeds in a crystalline solid state without swelling in acetonitrile or water at a reaction temperature as low as 60 or 80 °C, employing dioxygen in air as the only stoichiometric reactant with nearly quantitative recovery of carbon atoms. Heterogeneous features of the reaction allowed us to reveal a dynamic morphological change of polymer crystals during the degradation.

Overexpression of zinc finger DHHC-type containing 1 is associated with poor prognosis and cancer cell growth and metastasis in uterine corpus endometrial carcinoma.

The zinc finger DHHC-type containing 1 (ZDHHC1) gene is implicated in the pathogenesis and progression of various malignant tumors, but its precise involvement in uterine corpus endometrial carcinoma (UCEC) remains unknown. Thus, this study investigated ZDHHC1 expression in UCEC using publicly available TCGA and Xena databases and elucidated the functions and mechanisms of the ZDHHC1 gene in UCEC progression using bioinformatics and in vitro experiments. The correlation between ZDHHC1 expression and prognosis, clinical features, immune cells, and RNA modifications of UCEC was evaluated using nomograms, correlation, ROC, and survival analyses. The impacts of ZDHHC1 overexpression on UCEC progression and mechanisms were explored with bioinformatics and in vitro experiments. Our study revealed that ZDHHC1 expression was significantly downregulated in UCEC and correlated with poor prognosis, cancer diagnosis, clinical stage, age, weight, body mass index, histological subtypes, residual tumor, tumor grade, and tumor invasion. Notably, Cox regression analysis and constructed nomograms showed that downregulated ZDHHC1 expression was a prognostic factor associated with poor prognosis in patients with UCEC. Conversely, above-normal ZDHHC1 expression inhibited the cell growth, cell cycle transition, migration, and invasion of UCEC cells, which may be related to the cell cycle, DNA replication, PI3K-AKT, and other pathways that promote tumor progression. Altered ZDHHC1 expression in UCEC was significantly associated with RNA modifications and the changes in cancer immune cell populations, such as CD56 bright NK cells, eosinophils, Th2 cells, and cell markers. In conclusion, considerably reduced ZDHHC1 expression in UCEC is associated with cancer cell growth, metastasis, poor prognosis, immune infiltration, and RNA modifications, revealing the promising potential of ZDHHC1 as a prognostic marker for UCEC.

Association between Hepatitis B virus infection and liver metastasis in colorectal cancer.

The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ (n = 1696) and HBV- (n = 4175) groups and further within HBV+ subgroups of chronic (CHB, n = 474) and occult (OHB, n = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.

Crystal structural effects on up/down-conversion luminescence properties of GdInO3:Tm,Yb perovskite phosphors for effective dual-mode anti-counterfeit applications.

Developing advanced luminescent materials that are recognizable under specified conditions provides better opportunity for reliable optical anti-counterfeiting techniques. In this work, to the best of our knowledge, novel GdInO3:Tm,Yb perovskite phosphors with ultrafine sizes and rounded morphologies were successfully synthesized by a facile chemical precipitation route. Two-type perovskites with orthorhombic and hexagonal structures could be obtained by calcining the precursor at 850 and 1100 °C, respectively. Under 980 nm excitation, the two phosphors exhibited cyan-bluish emission at ∼460-565 nm, red emission at 645-680 nm, and near-infrared emission at 770-825 nm arising from 1G4 + 1D2→3H5,6, 3F2,3→3H6, and 3H4→3H6 transitions of Tm3+, respectively, where the hexagonal perovskite phosphor had relatively strong and sharp red emission as well as red-shifted cyan-bluish emission via successive cross relaxations. The Yb3+ sensitizer enhanced the upconversion luminescence via effective Yb3+→Tm3+ energy transfer and the optimal Yb3+ concentrations were 10 at.% for orthorhombic perovskite and 5 at.% for hexagonal one. The upconversion mechanism mainly ascribed to two-photon processes while three-photon was also present. Upon excitation at 254 nm, their down-conversion spectra exhibited broad multibands in the wavelength range of 400-500 nm deriving from combined effects of the defect-induced emission of GdInO3 and the 1D2→3F4 + 4G4→3H6 emissions of Tm3+. The energy transfer from GdInO3 defect level to Tm3+ excitation state was observed for the first time. The unclonable security codes prepared by screen printing from those dual-mode emitting perovskite phosphors were almost invisible under natural light, which had promising potential for anti-counterfeiting application.

Finite element analysis of modified Slongo's external fixation in the treatment of supracondylar humeral fractures in older children.

Older children over 8 years old are at higher risk of elbow joint stiffness after treatment of supracondylar humeral fractures. The objective of this study was to improve the Slongo's external fixation system for treating supracondylar humeral fractures in older children. This would be achieved by increasing fixation strength and providing a theoretical basis through finite element analysis and mechanical testing. A 13-year-old female patient with a history of previous fracture was selected for CT data processing to create a three-dimensional model of the distal humerus fracture. Two internal fixation models were established, using the Slongo's external fixation method with Kirschner wire (Group A) and modifying the Slongo's external fixation (Kirschner wire tail fixation) (Group B). The fracture models were then subjected to mechanical loading analysis using Finite Element Analysis Abaqus 6.14 software to simulate separation, internal rotation, and torsion loads. A PVC humeral bone model was used to create a supracondylar fracture model, and the A and B internal fixation methods were applied separately. The anterior-posterior and torsional stresses were measured using the Bose Electroforce3510 testing system, followed by a comparative analysis. The finite element simulation results showed that under the same tensile, torsion, and inversion forces, the osteotomy model fixed with Kirschner wire at the distal end in Group B exhibited smaller tensile stress and deformation compared to the unfixed osteotomy model in Group A. This indicated that the fixation strength of Group B was superior to that of Group A. According to the test results of the Bose Electroforce3510 testing system, a simple linear regression analysis was conducted using SPSS software. The K values of rotation angle-torque tests and front and rear displacement-stress tests were calculated for Groups A and B, with Group B showing higher values than Group A. The results of this study supported the significantly enhanced biomechanical reliability and stability of fracture fixation in Group B, which utilized the modified Slongo's external fixation (Kirschner wire tail fixation). This optimized method provides a new choice for the clinical treatment of supracondylar humeral fractures in older children, backed by both clinical evidence and theoretical basis.

Performance of the 2019 ESC pre-test probability model in predicting obstructive coronary artery disease in a Chinese population using coronary computed tomography angiography outcomes.

BACKGROUND: The 2019 European Society of Cardiology (ESC) guidelines proposed a pre-test probability (PTP) model to determine the likelihood of coronary artery disease (CAD). However, the prediction accuracy of this model has not yet been evaluated in Chinese populations. This study aimed to validate the 2019 ESC-PTP model in predicting CAD using coronary computed tomography angiography (CCTA) outcomes in a Chinese population. METHODS: A total of 26,346 consecutive patients with suspected CAD who underwent CCTA were included. The 2019 ESC-PTP model and 2013 ESC-PTP model were calculated for each patient, considering age, sex, and the symptom of chest pain, and the patients were categorized into low-, intermediate-, and high-risk groups. The predictive performance of the 2019 ESC-PTP model was evaluated by comparing it with the 2013 ESC-PTP model and the observed prevalence of CAD from CCTA. RESULTS: Among the 11,234 patients analyzed in the study, 1896 (16.9%) patients were found to have obstructive CAD from CCTA. The 2019 ESC-PTP model had better calibration compared to the 2013 ESC-PTP model. After categorization, 80.9% of patients (67.9% in men and 94.4% in women) were in the same risk category as in the 2019 ESC-PTP model, but the risks of younger patients (7.5% versus 2.5%; P â€‹< â€‹0.001) and patients with non-anginal chest pain (13.7% versus 8.2%; P â€‹< â€‹0.001) were underestimated in the 2019 ESC-PTP model. CONCLUSION: The 2019 ESC-PTP model demonstrated a good calibration in predicting CAD in a Chinese population who underwent CCTA, but it exhibited an underestimation of CAD probability in younger patients and patients with non-anginal chest pain.

Forsythiaside-A improved bile-duct-ligation-induced liver fibrosis in mice: The involvement of alleviating mitochondrial damage and ferroptosis in hepatocytes via activating Nrf2.

Liver fibrosis is a key and reversible stage in the progression of many chronic liver diseases to cirrhosis or hepatocellular carcinoma. Forsythiaside-A (FTA), a main compound isolated from Forsythiae Fructus, has an excellent liver protective activity. This study aims to investigate the efficacy of FTA in improving cholestatic liver fibrosis. Bile-duct-ligation (BDL) was conducted to induce liver fibrosis in mice. Hepatic collagen deposition was evaluated by Masson and Sirus red staining. The bile acid spectrum in the liver and serum was analyzed by mass spectrometry. Liver oxidative stress injury and mitochondria damage were observed by using Mito-Tracker Red fluorescence staining, transmission electron microscopy, etc. The level of ferrous iron (Fe2+) and the expression of ferroptosis-associated molecules were detected. The binding between FTA and its target protein was confirmed by Co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR). Our results demonstrated that FTA alleviated BDL-induced liver fibrosis in mice. FTA did not decrease the elevated amount of bile acids in BDL-treated mice, but reduced the bile acid-induced mitochondrial damage, oxidative stress and ferroptosis in hepatocytes, and also induced nuclear factor erythroid 2-related factor-2 (Nrf2) activation. In Nrf2 knock-out mice, the FTA-provided protection against BDL-induced liver fibrosis was disappeared, and FTA's inhibition on mitochondrial damage, oxidative stress and ferroptosis were lowered. Further results displayed that FTA could directly bind to Kelch-like ECH-associated protein-1 (Keap1), thereby activating Nrf2. Moreover, the BDL-induced liver fibrosis was markedly weakened in liver-specific Keap1 knockout mice. Hence, this study suggests that FTA alleviated the BDL-induced liver fibrosis through attenuating mitochondrial damage and ferroptosis in hepatocytes by activating Nrf2 via directly binding to Keap1.

Development of CO2-switchable deep eutectic solvent-based liquid-liquid microextraction approach: Application in urinary excretion and tissue distribution studies.

BACKGROUND: Pharmacokinetic studies are pivotal in drug development, focusing on absorption, distribution, and excretion of active compounds. Effective sample preparation methods play a crucial role in these studies. Traditional techniques like protein precipitation and liquid-liquid extraction often involve toxic solvents and are time-consuming. Recently, deep eutectic solvent (DES) has emerged as an eco-friendly alternative due to its high efficiency, low cost, and low toxicity. This study introduces a novel sample pretreatment method using CO2-switchable DES in liquid-liquid microextraction (LLME) to enhance speed, accuracy, and sensitivity in complex biological samples analysis. RESULTS: A liquid-liquid microextraction sample pretreatment method based on switchable DES combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was established for the analysis of urine and tissue samples. The method was optimized through systematic investigation of key parameters, including DES type, volume, molar ratio, pH, vortex time, gas purge time, and salt addition. The resulting procedure exhibited satisfying linearity (r2 ≥ 0.9958), good precision (RSD ≤6.01 %), desirable recovery (52.44%-98.12 %) and matrix effect (86.22%-119.30 %), and the accuracy and precision of stability were within the ±15 % limit. The proven methods were further applied to urinary excretion study and tissue distribution study of Nelumbinis plumula (NP) extract. The results indicated that the total cumulative excretion of liensinine, isoliensinine and neferine in urine within 240 h was 4.96 %, 0.66 % and 0.44 %, respectively. The tissue distribution study showed that alkaloids mainly distribute in liver, kidney, and spleen. SIGNIFICANCE: This research introduces a groundbreaking technique distinguished by its simplicity, speed, cost-effectiveness, and environmental friendliness. This approach, utilizing CO2-switchable DES as an extraction solvent for LLME, integrates deproteinization and removal of interfering molecules into a single step. This integration showcases its efficiency and convenience, demonstrating significant promise for various applications in the analysis of biological samples. Additionally, this study provides the first report on urinary excretion and tissue distribution of alkaloids from NP using a DES-LLME method. These findings offer valuable insights into the in vivo behavior of herbal medicine, enhancing understanding of pharmacological actions and facilitating clinical rational administration.

Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial.

BACKGROUND: Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient. METHODS: Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment. RESULTS: Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment. CONCLUSIONS: We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.