EMR-HRNet: A Multi-Scale Feature Fusion Network for Landslide Segmentation from Remote Sensing Images.

Landslides constitute a significant hazard to human life, safety and natural resources. Traditional landslide investigation methods demand considerable human effort and expertise. To address this issue, this study introduces an innovative landslide segmentation framework, EMR-HRNet, aimed at enhancing accuracy. Initially, a novel data augmentation technique, CenterRep, is proposed, not only augmenting the training dataset but also enabling the model to more effectively capture the intricate features of landslides. Furthermore, this paper integrates a RefConv and Multi-Dconv Head Transposed Attention (RMA) feature pyramid structure into the HRNet model, augmenting the model's capacity for semantic recognition and expression at various levels. Last, the incorporation of the Dilated Efficient Multi-Scale Attention (DEMA) block substantially widens the model's receptive field, bolstering its capability to discern local features. Rigorous evaluations on the Bijie dataset and the Sichuan and surrounding area dataset demonstrate that EMR-HRNet outperforms other advanced semantic segmentation models, achieving mIoU scores of 81.70% and 71.68%, respectively. Additionally, ablation studies conducted across the comprehensive dataset further corroborate the enhancements' efficacy. The results indicate that EMR-HRNet excels in processing satellite and UAV remote sensing imagery, showcasing its significant potential in multi-source optical remote sensing for landslide segmentation.

Impaired glucose metabolism underlies articular cartilage degeneration in osteoarthritis.

Osteoarthritis (OA) is the leading joint disease characterized by cartilage destruction and loss of mobility. Accumulating evidence indicates that the incidence and severity of OA increases with diabetes, implicating systemic glucose metabolism in joint health. However, a definitive link between cellular metabolism in articular cartilage and OA pathogenesis is not yet established. Here, we report that in mice surgically induced to develop knee OA through destabilization of medial meniscus (DMM), expression of the main glucose transporter Glut1 is notably reduced in joint cartilage. Inducible deletion of Glut1 specifically in the Prg4-expressing articular cartilage accelerates cartilage loss in DMM-induced OA. Conversely, forced expression of Glut1 protects against cartilage destruction following DMM. Moreover, in mice with type I diabetes, both Glut1 expression and the rate of glycolysis are diminished in the articular cartilage, and the diabetic mice exhibit more severe cartilage destruction than their nondiabetic counterparts following DMM. The results provide proof of concept that boosting glucose metabolism in articular chondrocytes may ameliorate cartilage degeneration in OA.

Prediction of risk factors for scrub typhus from 2006 to 2019 based on random forest model in Guangzhou, China.

OBJECTIVES: Scrub typhus is an increasingly serious public health problem, which is becoming the most common vector-borne disease in Guangzhou. This study aimed to analyse the correlation between scrub typhus incidence and potential factors and rank the importance of influential factors. METHODS: We collected monthly scrub typhus cases, meteorological variables, rodent density (RD), Normalised Difference Vegetation Index (NDVI), and land use type in Guangzhou from 2006 to 2019. Correlation analysis and a random forest model were used to identify the risk factors for scrub typhus and predict the importance rank of influencing factors related to scrub typhus incidence. RESULTS: The epidemiological results of the scrub typhus cases in Guangzhou between 2006 and 2019 showed that the incidence rate was on the rise. The results of correlation analysis revealed that a positive relationship between scrub typhus incidence and meteorological factors of mean temperature (Tmean ), accumulative rainfall (RF), relative humidity (RH), sunshine hours (SH), and NDVI, RD, population density, and green land coverage area (all p < 0.001). Additionally, we tested the relationship between the incidence of scrub typhus and the lagging meteorological factors through cross-correlation function, and found that incidence was positively correlated with 1-month lag Tmean , 2-month lag RF, 2-month lag RH, and 6-month lag SH (all p < 0.001). Based on the random forest model, we found that the Tmean was the most important predictor among the influential factors, followed by NDVI. CONCLUSIONS: Meteorological factors, NDVI, RD, and land use type jointly affect the incidence of scrub typhus in Guangzhou. Our results provide a better understanding of the influential factors correlated with scrub typus, which can improve our capacity for biological monitoring and help public health authorities to formulate disease control strategies.

Complete mitochondrial genome of Penicillidia jenynsii (Diptera: Hippoboscoidea: Nycteribiidae) and phylogenetic relationship.

In recent years, bat-associated pathogens, such as 2019 novel coronavirus, have been ravaging the world, and ectoparasites of bats have received increasing attention. Penicillidia jenynsii is a member of the family Nycteribiidae which is a group of specialized ectoparasites of bats. In this study, the complete mitochondrial genome of P. jenynsii was sequenced for the first time and a comprehensive phylogenetic analysis of the superfamily Hippoboscoidea was conducted. The complete mitochondrial genome of P. jenynsii is 16 165 base pairs (bp) in size, including 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes and 1 control region. The phylogenetic analysis based on 13 PCGs of the superfamily Hippoboscoidea known from the NCBI supported the monophyly of the family Nycteribiidae, and the family Nycteribiidae was a sister group with the family Streblidae. This study not only provided molecular data for the identification of P. jenynsii, but also provided a reference for the phylogenetic analysis of the superfamily Hippoboscoidea.

Analysis of steroidal glycoalkaloids and their metabolites in Solanum nigrum fruits based on liquid chromatography-tandem mass spectrometry and molecular networking.

Solanum nigrum fruit is like a treasure house for anticancer drugs because of its steroidal alkaloids. However, the clinical treatment of cancer mainly uses immature fruits, which can cause a toxic reaction if eaten directly, while mature fruits are eaten as fruit. In order to clarify the reasons for the differences in pharmacodynamics and toxicity between them, we studied the composition and metabolism of steroidal alkaloids in fruits of different maturities based on liquid chromatography-tandem mass spectrometry and molecular networking. As a result, 114 steroidal glycoalkaloids were identified. During fruit ripening, the aglycones of steroidal alkaloids mainly undergo hydroxylation and carboxylation, and the sugar side chains mainly undergo acylation and glycosylation reactions. Furthermore, 219 steroidal alkaloids were identified in a metabolism experiment in rats. Metabolic processes include deglycosylation, redox, sulfuric acid binding, acetyl binding, and glucuronic acid-binding. Steroidal alkaloids in mature fruits have high molecular weight and polarity, which are difficult to absorb, and most of them are excreted through feces and urine, which may be the reason for their poor efficacy. This study lays a foundation for research on the biosynthesis of steroidal alkaloids and provides potential candidates for the discovery of new steroidal alkaloid anticancer drugs.

Gastrointestinal disease is an important influencing factor of osteoporosis fracture:a retrospective study in chinese postmenopausal women.

BACKGROUD: The influencing factors of osteoporosis are complex, the incidence of osteoporosis is higher in middle-aged and elderly women, and osteoporotic fractures (OF) can seriously affect quality of life. Currently, the correlation analysis between gastrointestinal diseases and OF focuses more on diseases such as gastric cancer and inflammatory bowel disease (IBD). This study analyzed the risk factors for osteoporosis and osteoporotic fractures in 1567 postmenopausal women in Fuzhou, China. The purpose is to explore the potential influence of gastrointestinal diseases on the occurrence of OF. METHODS: According to inclusion and exclusion criteria, a total of 1567 subjects were included in the analysis of OP risk factors, including 647 in the OP group and 920 in the NOP group. A total of 616 subjects were included in the analysis of correlation between OF and gastrointestinal diseases, including 132 in OF group and 484 in NF group. Statistical analysis shows that age (OR = 1.062, 95% CI = 1.045-1.080), height (OR = 0.089, 95% CI = 0.009-0.857), weight (OR = 0.981,95% CI = 0.967-0.995) and nature of work (P = 0.010) are the main risk factors for osteoporosis in postmenopausal women in southeast China, and gastrointestinal diseases (OR = 1.583, 95% CI = 1.070-2.343) and height (OR = 0.003, 95% CI = 0.000-0.104) are the main risk factors of OF. CONCLUSIONS: The main factors affecting the occurrence of OP in postmenopausal women in southeast China are individual characteristic. Gastrointestinal diseases that do not directly affect BMD increase the risk of OF in osteoporotic patients.

Environmental reservoir dynamics predict global infection patterns and population impacts for the fungal disease white-nose syndrome.

Disease outbreaks and pathogen introductions can have significant effects on host populations, and the ability of pathogens to persist in the environment can exacerbate disease impacts by fueling sustained transmission, seasonal epidemics, and repeated spillover events. While theory suggests that the presence of an environmental reservoir increases the risk of host declines and threat of extinction, the influence of reservoir dynamics on transmission and population impacts remains poorly described. Here we show that the extent of the environmental reservoir explains broad patterns of host infection and the severity of disease impacts of a virulent pathogen. We examined reservoir and host infection dynamics and the resulting impacts of Pseudogymnoascus destructans, the fungal pathogen that causes white-nose syndrome, in 39 species of bats at 101 sites across the globe. Lower levels of pathogen in the environment consistently corresponded to delayed infection of hosts, fewer and less severe infections, and reduced population impacts. In contrast, an extensive and persistent environmental reservoir led to early and widespread infections and severe population declines. These results suggest that continental differences in the persistence or decay of P. destructans in the environment altered infection patterns in bats and influenced whether host populations were stable or experienced severe declines from this disease. Quantifying the impact of the environmental reservoir on disease dynamics can provide specific targets for reducing pathogen levels in the environment to prevent or control future epidemics.

Gold Nanoparticle-Bridge Array to Improve DNA Hybridization Efficiency of SERS Sensors.

The interfacial mass transfer rate of a target has a significant impact on the sensing performance. The surface reaction forms a concentration gradient perpendicular to the surface, wherein a slow mass transfer process decreases the interfacial reaction rate. In this work, we self-assembled gold nanoparticles (AuNPs) in the gap of a SiO2 opal array to form a AuNP-bridge array. The diffusion paths of vertical permeability and a microvortex effect provided by the AuNP-bridge array synergistically improved the target mass transfer efficiency. As a proof of concept, we used DNA hybridization efficiency as a research model, and the surface-enhanced Raman spectroscopy (SERS) signal acted as a readout index. The experimental verification and theoretical simulation show that the AuNP-bridge array exhibited rapid mass transfer and high sensitivity. The DNA hybridization efficiency of the AuNP-bridge array was 15-fold higher than that of the AuNP-planar array. We believe that AuNP-bridge arrays can be potentially applied for screening drug candidates, genetic variations, and disease biomarkers.

Expression and role of miR-146a and SMAD4 in placental tissue of pregnant women with preeclampsia.

INTRODUCTION: To investigate the expression of miR-146a in severe preeclampsia (PE) and its effect on trophoblast cell proliferation, invasion and apoptosis, as well as its relationship with SMAD4. MATERIAL AND METHODS: Participants were divided into the severe PE group (n = 30) and the normal group (n = 30). The expression of miR-146a and SMAD4 in placenta tissue was detected by immunohistochemistry, qRT-PCR, and western blot. Trophoblast cell lines HTR-8/SVneo were cultured to detect the expression of miR-146a under the Cobalt chloride (CoCl2 )-simulated hypoxia. The effects of miR-146a transfection on cell proliferation, invasion, apoptosis, and SMAD4 expression were analyzed. RESULTS: Compared with the normal group, miR-146a expression was decreased and the protein and mRNA levels of SMAD4 were increased in placenta tissues of the severe PE group. Our in vitro experiments showed that the expression of miR-146a decreased after CoCl2 treatment. Silencing miR-146a caused increased expression of SMAD4 and decreased expression of VEGF. After transfection with miR-146a inhibitor, compared with the NC group, the invasion and proliferation of HTR-8/Svneo cells were decreased, while the apoptosis was enhanced. CONCLUSION: The expression of miR-146a decreased in severe PE and was negatively correlated with SMAD4 expression. The expression of miR-146a was inhibited under hypoxia, and the low expression of miR-146a affected the proliferation, invasion, and apoptosis of trophoblast cells.

Metabolic Reconfiguration Activates Stemness and Immunomodulation of PDLSCs.

Periodontal ligament derived stem cells (PDLSC) are adult multipotent mesenchymal-like stem cells (MSCs) that can induce a promising immunomodulation to interact with immune cells for disease treatment. Metabolic reconfiguration has been shown to be involved in the immunomodulatory activity of MSCs. However, the underlying mechanisms are largely unknown, and it remains a challenging to establish a therapeutic avenue to enhance immunomodulation of endogenous stem cells for disease management. In the present study, RNA-sequencing (RNA-seq) analysis explores that curcumin significantly promotes PDLSC function through activation of MSC-related markers and metabolic pathways. In vitro stem cell characterization further confirms that self-renewal and multipotent differentiation capabilities are largely elevated in curcumin treated PDLSCs. Mechanistically, RNA-seq reveals that curcumin activates ERK and mTOR cascades through upregulating growth factor pathways for metabolic reconfiguration toward glycolysis. Interestingly, PDLSCs immunomodulation is significantly increased after curcumin treatment through activation of prostaglandin E2-Indoleamine 2,3 dioxygenase (PGE2-IDO) signaling, whereas inhibition of glycolysis activity by 2-deoxyglucose (2-DG) largely blocked immunomodulatory capacity of PDLSCs. Taken together, this study provides a novel pharmacological approach to activate endogenous stem cells through metabolic reprogramming for immunomodulation and tissue regeneration.

Cerebral blood flow alterations in migraine patients with and without aura: An arterial spin labeling study.

BACKGROUND: Migraine aura is a transient, fully reversible visual, sensory, or other central nervous system symptom that classically precedes migraine headache. This study aimed to investigate cerebral blood flow (CBF) alterations of migraine with aura patients (MwA) and without aura patients (MwoA) during inter-ictal periods, using arterial spin labeling (ASL). METHODS: We evaluated 88 migraine patients (32 MwA) and 44 healthy control subjects (HC) who underwent a three-dimensional pseudo-continuous ASL MRI scanning. Voxel-based comparison of normalized CBF was conducted between MwA and MwoA. The relationship between CBF variation and clinical scale assessment was further analyzed. The mean CBF values in brain regions showed significant differences were calculated and considered as imaging features. Based on these features, different machine learning-based models were established to differentiate MwA and MwoA under five-fold cross validation. The predictive ability of the optimal model was further tested in an independent sample of 30 migraine patients (10 MwA). RESULTS: In comparison to MwoA and HC, MwA exhibited higher CBF levels in the bilateral superior frontal gyrus, bilateral postcentral gyrus and cerebellum, and lower CBF levels in the bilateral middle frontal gyrus, thalamus and medioventral occipital cortex (all p values < 0.05). These variations were also significantly correlated with multiple clinical rating scales about headache severity, quality of life and emotion. On basis of these CBF features, the accuracies and areas under curve of the final model in the training and testing samples were 84.3% and 0.872, 83.3% and 0.860 in discriminating patients with and without aura, respectively. CONCLUSION: In this study, CBF abnormalities of MwA were identified in multiple brain regions, which might help better understand migraine-stroke connection mechanisms and may guide patient-specific decision-making.

High Elongation and Transparent Nacre-Inspired PVA/MMT Nanocomposites.

Currently, high strength nacre-inspired PVA/MMT (polyvinyl alcohol/montmorillonite) nanocomposites with high MMT nanofiller content (50-70 wt%) have been constructed successfully. However, this seriously sacrifices the elongation and reduces the corresponding transparency. In this paper, high elongation and transparent PVA/MMT nanocomposites with high MMT content are prepared by the evaporation-induced assembly with the introduction of the micro-crosslinking. Results demonstrate that the micro-crosslinking can inhibit the formation of rod-shaped arrays, and contribute to a more ordered layered microstructure, where an elongation of 76.2% in 47.8 wt% MMT content nanocomposites is gained, nearly 19 times of that of non-crosslinked nanocomposites (ultimate strain is 4.1%). This provides a potential approach for compromise between high strength and excellent elongation at the same MMT content. Moreover, disappearance of rod-shaped arrays and resultant ordered layered microstructure make eventual films more transparent.

Low-Temperature Hypergolic Ignition of 1-Octene with Low Ignition Delay Time.

The attainment of the efficient ignition of traditional liquid hydrocarbons of scramjet combustors at low flight Mach numbers is a challenging task. In this study, a novel chemical strategy to improve the reliable ignition and efficient combustion of hydrocarbon fuels was proposed. A directional hydroboration reaction was used to convert hydrocarbon fuel into highly active alkylborane, thereby leading to changes in the combustion reaction pathway of hydrocarbon fuel. A directional reaction to achieve the hypergolic ignition of 1-octene was designed and developed by using Gaussian simulation. Borane dimethyl sulfide (BDMS), a high-energy additive, was allowed to react spontaneously with 1-octene to achieve the hypergolic ignition of liquid hydrocarbon fuel at -15 °C. Compared with the ignition delay time of pure 1-octene (565 °C), the ignition delay time of 1-octene/BDMS (9:1.2) decreased by 3850% at 50 °C. Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry confirmed the directional reaction of the hypergolic ignition reaction pathway of 1-octene and BDMS. Moreover, optical measurements showed the development trend of hydroxyl radicals (OH·) in the lower temperature hypergolic ignition and combustion of 1-octene. Finally, this study indicates that the enhancement of the low-temperature ignition performance of 1-octene by hydroboration in the presence of BDMS is feasible and promising for jet propellant design with tremendous future applications.

A Report of Chigger Mites on the Striped Field Mouse, Apodemus agrarius, in Southwest China.

Based on the field investigations in 91 investigation sites (counties) in southwest China between 2001 and 2019, the present paper reported the chigger mites on A. agrarius mice in southwest China for the first time by using a series of statistical methods. From 715 striped field mice captured in 28 of 91 investigated sites, only 255 chiggers were collected, and they were identified as 14 species, 6 genera in 3 subfamilies under 2 families. Of 715 A. agrarius mice, only 24 of them were infested with chigger mites with low overall prevalence (PM=3.4%), overall mean abundance (MA=0.36 mites/host) and overall mean intensity (MI=10.63 mites/host). The species diversity and infestation of chiggers on A. agrarius were much lower than those previously reported on some other rodents in southwest China. On a certain species of rodent, A. agrarius mouse in southwest China seems to have a very low susceptibility to chigger infestations than in other geographical regions. Of 14 chigger species, there were 3 dominant species, Leptotrombidium sialkotense, L. rupestre and Schoengastiella novoconfuciana, which were of aggregated distribution among different individuals of A. agrarius hosts. L. sialkotense, one of 6 main vectors of scrub typhus in China, was the first dominant on A. agrarius. The species similarity of chigger mites on male and female hosts was low with CSS=0.25, and this reflects the sex-bias of different genders of A. agrarius mice in harboring different chigger species.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling.

BACKGROUND: Migraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine. METHODS: This study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated. RESULTS: In comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R. CONCLUSIONS: Our results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Altered amygdala effective connectivity in migraine without aura: evidence from resting-state fMRI with Granger causality analysis.

BACKGROUND: Granger causality analysis (GCA) has been used to investigate the pathophysiology of migraine. Amygdala plays a key role in pain modulation of migraine attack. However, the detailed neuromechanism remained to be elucidated. We applied GCA to explore the amygdala-based directional effective connectivity in migraine without aura (MwoA) and to determine the relation with clinical characteristics. METHODS: Forty-five MwoA patients and forty age-, sex-, and years of education-matched healthy controls(HCs) underwent resting-state functional magnetic resonance imaging (fMRI). Bilateral amygdala were used as seed regions in GCA to investigate directional effective connectivity and relation with migraine duration or attack frequency. RESULTS: MwoA patients showed significantly decreased effective connectivity from right amygdala to right superior temporal gyrus, left superior temporal gyrus and right precentral gyrus compared with HCs. Furthermore, MwoA patients demonstrated significantly decreased effective connectivity from the left amygdala to the ipsilateral superior temporal gyrus. Also, MwoA patients showed enhanced effective connectivity from left inferior frontal gyrus to left amygdala. Effective connectivity outflow from right amygdala to right precentral gyrus was negatively correlated to disease duration. CONCLUSIONS: Altered directional effective connectivity of amygdala demonstrated that neurolimbic pain networks contribute to multisensory integration abnormalities and deficits in pain modulation of MwoA patients.

Altered lateral geniculate nucleus functional connectivity in migraine without aura: a resting-state functional MRI study.

OBJECTIVES: To investigate the structural and functional connectivity changes of lateral geniculate nucleus (LGN) and their relationships with clinical characteristics in patients without aura. METHODS: Conventional MRI, 3D structure images and resting state functional MRI were performed in 30 migraine patients without aura (MwoA) and 22 healthy controls (HC). The lateral geniculate nucleus volumes and the functional connectivity (FC) of bilateral lateral geniculate nucleus were computed and compared between groups. RESULTS: The lateral geniculate nucleus volumes in patient groups did not differ from the controls. The brain regions with increased FC of the left LGN mainly located in the left cerebellum and right lingual gyrus in MwoA compared with HC. The increased FC of right LGN located in left inferior frontal gyrus in MwoA compared with HC. The correlation analysis showed a positive correlation between VLSQ-8 score and the increased FC of left cerebellum and right lingual gyrus. CONCLUSIONS: Photophobia in MwoA could be mediated by abnormal resting state functional connectivity in visual processing regions, the pain perception regulatory network and emotion regulation network. This result is valuable to further understanding about the clinical manifestation and pathogenesis of migraine.

Gene expression vs. sequence divergence: comparative transcriptome sequencing among natural Rhinolophus ferrumequinum populations with different acoustic phenotypes.

BACKGROUND: Although the sensory drive hypothesis can explain the geographic variation in echolocation frequencies of some bat species, the molecular mechanisms underlying this phenomenon are still unclear. The three lineages of greater horseshoe bat (Rhinolophus ferrumequinum) in China (northeast, central-east, and southwest) have significant geographic variation in resting frequencies (RF) of echolocation calls. Because their cochleae have an acoustic fovea that is highly sensitive to a narrow range of frequencies, we reported the transcriptomes of cochleae collected from three genetic lineages of R. ferrumequinum, which is an ideal organism for studying geographic variation in echolocation signals, and tried to understand the mechanisms behind this bat phenomenon by analyzing gene expression and sequence variation. RESULTS: A total of 8190 differentially expressed genes (DEGs) were identified. We identified five modules from all DEGs that were significantly related to RF or forearm length (FL). DEGs in the RF-related modules were significantly enriched in the gene categories involved in neural activity, learning, and response to sound. DEGs in the FL-related modules were significantly enriched in the pathways related to muscle and actin functions. Using 21,945 single nucleotide polymorphisms, we identified 18 candidate unigenes associated with hearing, five of which were differentially expressed among the three populations. Additionally, the gene ERBB4, which regulates diverse cellular processes in the inner ear such as cell proliferation and differentiation, was in the largest module. We also found 49 unigenes that were under positive selection from 4105 one-to-one orthologous gene pairs between the three R. ferrumequinum lineages and three other Chiroptera species. CONCLUSIONS: The variability of gene expression and sequence divergence at the molecular level might provide evidence that can help elucidate the genetic basis of geographic variation in echolocation signals of greater horseshoe bats.

Paclitaxel, 5-fluorouracil, and leucovorin combination chemotherapy as first-line treatment in patients with advanced gastric cancer.

The aim of this retrospective analysis was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, 5-fluorouracil, and leucovorin (TFL) as first-line treatment in patients with advanced gastric cancer (AGC). One hundred and thirteen patients were enrolled in the study who were confirmed to have AGC by histopathology. These patients were treated with TFL: paclitaxel at a dose of 135 mg/m as a 3-h intravenous infusion on day 1, LV 400 mg/m as an intravenous infusion over 2 h on day 1, followed by 5-fluorouracil 2400 mg/m as an infusion over a 46-h period on 3 consecutive days. Cycles were repeated every 2 weeks. A total of 113 patients were assessed for their response to therapy. A total of three patients achieved complete responses and 46 patients achieved partial responses, yielding an overall objective response rate of 43.4% [95% confidence interval (CI): 34.3-52.5%]. Fifty-four cases of stable disease and 10 cases of progressive disease were observed in the remaining patients. The median time to progression and overall survival were 5.2 months (95% CI: 4.7-5.8 months) and 14.1 months (95% CI: 12.5-15.8 months), respectively. Toxicities were tolerable and moderate. The most common grade 3-4 toxicities included leukopenia (16.8%), neutropenia (17.7%), anemia (8.0%), thrombocytopenia (5.3%), and fatigue (6.2%). Combination chemotherapy with TFL offers an active and safe therapeutic approach for patients with AGC.

An accurate and reproducible method for simultaneous determination of four flavonoids in EtOAc extracts from Sophora flavescens Ait. in rat plasma based on UHPLC Q-Exactive Mass spectrometry: Application to a pharmacokinetics study.

In previous studies, it was revealed that ethyl acetate (EtOAc) extracts from Sophora flavescens Ait. improved glucose tolerance, reduced hyperglycemia, and restored insulin levels in diabetic patients. The aim of this study was to develop an accurate and sensitive UHPLC-MS method for simultaneous determination of flavonoids in EtOAc extracts of Kushen in rat plasma. Ethyl acetate-acetonitrile (2:1) was selected as the solvent to extract the four flavonoids from rat plasma. A BEH C18 column (2.1 mm × 100 mm, 1.7 µm) with a C18 guard cartridge was chosen as the separation plant using a gradient elution with acetonitrile (solvent A) and 0.1% formic acid (solvent B) in water. For all four analytes, the method showed good linearity (r2 > 0.991) in 1-500 ng/mL. The inter- and intra-day accuracy ranged from -13.78 to 7.19%, and the precision (RSD) was <8.75%. Recoveries of all four flavonoids ranged from 85.9 to 101.3%. According to the results of multitarget pharmacokinetic studies, four active flavonoids in EtOAc extracts from Kushen have similar absorption kinetics but very different metabolic kinetics, and a double peak phenomenon was observed in the concentration-time curve of norkurarinone, which is different from the previous study. In conclusion, detection and multitarget pharmacokinetic studies successfully determined active flavonoids after oral administration of EtOAc extracts from Kushen by an efficient, sensitive and selective UHPLC-MS method, and the results may provide a foundation for future studies of Kushen.