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The quality requirements of Corydalis Rhizoma (CR) in different producing areas are uniform, resulting in uneven efficacy. As a genuine producing area, the effective quality control of CR in Zhejiang Province (ZJ) could provide a theoretical basis for the rational application of medicinal materials. The purpose of this study was to effectively distinguish the CR inside and outside ZJ, and provided a theoretical basis for the quality control and material basis research of ZJ CR. The core components of ZJ CR could be identified by HPLC combined with chemometrics screening, and the quality of CR from different producing areas was evaluated by a genetic algorithm-back propagation (GA-BP) neural network. Chromaticity and near-infrared (NIR) spectroscopy were used to identify CR inside and outside ZJ, and rapid content prediction was realized. The analgesic effect of CR in different regions was compared by a zebrafish analgesic experiment. Analgesic experiments in rats and analysis of the research status of quality components were used to screen the quality control components of ZJ CR. The contents of palmatine hydrochloride (YSBMT), dehydrocorydaline (TQZJJ), tetrahydropalmatine (YHSYS), tetrahydroberberine (SQXBJ), corydaline (YHSJS), stylopine (SQHLJ), and isoimperatorin (YOQHS) in ZJ CR were higher than those in CR from outside ZJ, but the content of protopine (YAPJ) and berberine hydrochloride (YSXBJ) was lower than that in CR from outside ZJ. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. The GA-BP neural network showed that the relative importance of ZJ CR was the strongest. Chroma-content correlation analysis and the NIR qualitative model could effectively distinguish CR from inside and outside of ZJ, and the NIR quantitative model could quickly predict the content of CR from inside and outside of ZJ. Zebrafish experiments showed that ZJ, Shaanxi (SX), Henan (HN), and Sichuan (SC) CR had significant analgesic effects, while Hebei (HB) CR had no significant analgesic effect. Overall comparison, the analgesic effect of ZJ CR was better than that of CR outside ZJ. The comprehensive score of the grey correlation degree between YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, YHSJS, SQXBJ, and SQHLJ were higher than 0.9, and the research frequency were extremely high. The relative importance of the content and origin of most components of ZJ CR was higher than that of CR outside ZJ. The holistic analgesic effect of ZJ CR was better than that of CR outside ZJ, but slightly lower than that of SX CR. YHSJS and SQHLJ could be used as the core components to identify ZJ CR. YAPJ, YSBMT, YSXBJ, TQZJJ, YHSYS, SQXBJ, YHSJS, and SQHLJ could be used as the quality control components of ZJ CR. The multidimensional evaluation method used in this study provided a reference for the quality control and material basis research of ZJ CR. [Display omitted] • The quality index components protopine, palmatine hydrochloride, berberine hydrochloride, dehydrocorydaline, tetrahydropalmatine, corydaline, tetrahydroberberine and stylopine of Corydalis Rhizoma from Zhejiang Province were screened out. • The core components corydaline and stylopine that can identify Corydalis Rhizoma inside and outside Zhejiang Province were screened out. • Through the multi-dimensional evaluation model, the comparative study of Corydalis Rhizoma from Zhejiang Province and other producing areas outside Zhejiang Province was carried out, and a number of quality control indicators and methods suitable for Corydalis Rhizoma from Zhejiang Province were summarized, which provided a reference for the quality research of Corydalis Rhizoma from Zhejiang Province. [ABSTRACT FROM AUTHOR]

The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. The three specifications of ZJ CR were CR (Diameter ≥1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard. [Display omitted] • The quality control methods of ZJ CR with different specifications were proposed. • The pharmacodynamic material basis of ZJ CR with different specifications was screened. • The evaluation method of character-quality-efficacy combination was adopted. [ABSTRACT FROM AUTHOR]

Background: Neurolytic splanchnic nerve block is used to manage pancreatic cancer pain. However, its impact on survival and quality of life remains controversial. The authors' primary hypothesis was that pain relief would be better with a nerve block. Secondarily, they hypothesized that analgesic use, survival, and quality of life might be affected.Methods: This randomized, double-blind, parallel-armed trial was conducted in five Chinese centers. Eligible patients suffering from moderate to severe pain conditions were randomly assigned to receive splanchnic nerve block with either absolute alcohol (neurolysis) or normal saline (control). The primary outcome was pain relief measured on a visual analogue scale. Opioid consumption, survival, quality of life, and adverse effects were also documented. Analgesics were managed using a protocol common to all centers. Patients were followed up for 8 months or until death.Results: Ninety-six patients (48 for each group) were included in the analysis. Pain relief with neurolysis was greater for the first 3 months (largest at the first month; mean difference, 0.7 [95% CI, 0.3 to 1.0]; adjusted P < 0.001) compared with placebo injection. Opioid consumption with neurolysis was lower for the first 5 months (largest at the first month; mean difference, 95.8 [95% CI, 67.4 to 124.1]; adjusted P < 0.001) compared with placebo injection. There was a significant difference in survival (hazard ratio, 1.56 [95% CI, 1.03 to 2.35]; P = 0.036) between groups. A significant reduction in survival in neurolysis was found for stage IV patients (hazard ratio, 1.94 [95% CI, 1.29 to 2.93]; P = 0.001), but not for stage III patients (hazard ratio, 1.08 [95% CI, 0.59 to 1.97]; P = 0.809). No differences in quality of life were observed.Conclusions: Neurolytic splanchnic nerve block appears to be an effective option for controlling pain and reducing opioid requirements in patients with unresectable pancreatic cancer.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Immune checkpoint therapy has achieved significant efficacy by blocking inhibitory pathways to release the function of T lymphocytes. In the clinic, anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) monoclonal antibodies (mAbs) have progressed to first-line monotherapies in certain tumor types. However, the efficacy of anti-PD-1/PD-L1 mAbs is still limited due to toxic side effects and de novo or adaptive resistance. Moreover, other immune checkpoint target and biomarkers for therapeutic response prediction are still lacking; as a biomarker, the PD-L1 (CD274, B7-H1) expression level is not as accurate as required. Hence, it is necessary to seek more representative predictive molecules and potential target molecules for immune checkpoint therapy. Fibrinogen-like protein 1 (FGL1) is a proliferation- and metabolism-related protein secreted by the liver. Multiple studies have confirmed that FGL1 is a newly emerging checkpoint ligand of lymphocyte activation gene 3 (LAG3), emphasizing the potential of targeting FGL1/LAG3 as the next generation of immune checkpoint therapy. In this review, we summarize the substantial regulation mechanisms of FGL1 in physiological and pathological conditions, especially tumor epithelial to mesenchymal transition, immune escape and immune checkpoint blockade resistance, to provide insights for targeting FGL1 in cancer treatment. [ABSTRACT FROM AUTHOR]

• Based on quaternion theory, Mittag-Leffler function and nabla h -Laplace transform, two new inequalities are obtained. • In order to realize synchronization more conveniently, we design a quaternion controller with time delay. • Under the direct quaternion framework, quasi-synchronization criteria of DTFQMNNs are obtained by utilizing our lemmas and some analysis techniques. Besides, the error bound for quasi-synchronization is evaluated. In this paper, quasi-synchronization of discrete-time fractional-order quaternion-valued memristive neural networks (DTFQMNNs) with time delays and uncertain parameters is investigated. Firstly, some related preliminaries are introduced and two new inequalities are obtained based on nabla fractional difference, quaternion theory and nabla h -Laplace transform. Then, a quaternion-valued controller with time delay is designed to realize quasi-synchronization goal, and some sufficient criteria are derived to guarantee quasi-synchronization of DTFQMNNs by using our created inequalities and some analysis techniques. Finally, a numerical example is provided to verify the correctness of our theoretical results. [ABSTRACT FROM AUTHOR]

Background: Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasmafibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC.Methods: In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed.Results: The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed thathigher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. Conclusions: This study showed that the reduction in plasma fibrinogen levels induced by chemotherapy might be as a promising biomarker as CEA and CA125 for evaluating the efficacy of chemotherapy in advanced NSCLC. In addition, basal plasma fibrinogen levels could be used as an independent prognostic parameter for the OS of patients with advanced NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: Recently ultrafast techniques enable 2D NMR spectra to be obtained in a single scan. They have been successfully applied for 2D COSY, TOCSY, DOSY, HMQC, and J-resolved spectra. In this paper, two alternative ultrafast 2D COSY methods (g-COSY and gDQF-COSY) based on continuous constant-time phase-modulated spatial encoding were proposed. Theoretical expressions of the resulting signals were deduced. Experiments were performed to verify our theoretical analysis and the feasibility of the methods. Comparisons between the experimental results of our methods and those of the previous real-time phase-modulated spatial encoding method demonstrate that the signal-to-noise ratio and resolution of the 2D COSY spectra are improved, and a good 2D COSY spectrum is easier to achieve by using our methods. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis, which is partly due to the presence of liver cancer stem cells (CSCs). CSCs participate in tumor recurrence, metastasis, and chemoresistance. However, the mechanisms underlying liver CSC regulation are unknown. In this study, we found that miR-3168 expression is increased in HCC and that it predicts poor prognosis. Functional assays showed that miR-3168 promotes HCC cells' proliferation and facilitates liver CSC self-renewal and tumorigenicity. Mechanistically, bioinformatics and the luciferase reporter assay demonstrated that miR-3168 targets the 3'UTR of the p53 mRNA. MiR-3168 expression was negatively correlated with p53 mRNA in HCC tissue samples. Rescue assays demonstrated that p53 knockdown abrogates the discrepancies in proliferation, self-renewal, and tumorigenicity between miR-3168 knockdown HCC cells and control HCC cells. Furthermore, miR-3168 expression was negatively correlated with p53 in HCC tissues. The combined HCC panels exhibited a worse prognostic value for HCC patients than any of these components alone. Moreover, miR-3168 expression was increased in cisplatin-resistant HCC cells and patient-derived xenografts. Clinical cohort analysis revealed that HCC patients with low miR-3168 levels have a superior survival rate when treated with postoperative transcatheter arterial chemoembolization compared with that of patients with high miR-3168 levels. In conclusion, our study uncovered a novel mechanism of liver CSC regulation and provided a potential therapeutic target for liver CSCs. [ABSTRACT FROM AUTHOR]

Purpose: Pulmonary ground‐glass opacity (GGO) nodules are more likely to be malignant compared with solid solitary nodules. Due to indistinct boundaries of GGO nodules, the detection and diagnosis are challenging for doctors. Therefore, designing an automatic GGO nodule detection and classification scheme is significantly essential. Methods: In this paper, we proposed a two‐stage 3D GGO nodule detection and classification framework. First, we used a pretrained 3D U‐Net to extract lung parenchyma. Second, we adapted the architecture of Mask region‐based convolutional neural networks (RCNN) to handle 3D medical images. The 3D model was then applied to detect the locations of GGO nodules and classify lesions (benign or malignant). The class‐balanced loss function was also used to balance the number of benign and malignant lesions. Finally, we employed a novel false positive elimination scheme called the feature‐based weighted clustering (FWC) to promote the detection accuracy further. Results: The experiments were conducted based on fivefold cross‐validation with the imbalanced data set. Experimental results showed that the mean average precision could keep a high level (0.5182) in the phase of detection. Meanwhile, the false positive rate was effectively controlled, and the competition performance metric (CPM) reached 0.817 benefited from the FWC algorithm. The comparative statistical analyses with other deep learning methods also proved the effectiveness of our proposed method. Conclusions: We put forward an automatic pulmonary GGO nodules detection and classification framework based on deep learning. The proposed method locate and classify nodules accurately, which could be an effective tool to help doctors in clinical diagnoses. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. Methods: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation–qPCR (MeRIP–qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. Results: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. Conclusion: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine. [ABSTRACT FROM AUTHOR]

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication. [ABSTRACT FROM AUTHOR]

Kidney-Yang deficiency syndrome (KYDS) is one of the common diseases of the elderly and closely related to the ageing of the body, it has a major impact on the quality of life of the patient. Eucommiae Cortex (EC) is the dried bark of Eucommia ulmoides Oliv. Which has the effect of tonifying the liver and kidneys, strengthening the muscles and bones. In Traditional Chinese Medicine clinics, EC is commonly used in the treatment of KYDS, but the material basis for the improvement of its efficacy in treating KYDS after salt processing remains unclear. This study aimed to find the main active ingredients that could improve the treatment of KYDS efficacy of EC after salt processing. Firstly, the fingerprints of raw and salt-processed EC were established to determine the common components by using HPLC, and then an experimental study on the treatment of KYDS efficacy was carried out to compare the difference in the efficacy between raw and salt-processed EC. Thirdly, the spectrum-effect relationship of chemical components and pharmacodynamic indexes was established by using Grey Relational Analysis and Entropy Method. Finally, the network pharmacology and molecular docking technique was used to verify the kidney tonifying effect of the active ingredients of EC. According to the results of the analysis of hormonal index levels on the hypothalamic-pituitary-target gland axis and the extent of renal lesions, the therapeutic effect of EC on KYDS was mainly reflected in the regulation of the Adrenocorticotropic hormone, Corticosterone in the hypothalamic-pituitary-adrenal axis and Tri-iodothyronine, Tetra-iodothyronine in the hypothalamic-pituitary-thyroid axis, moreover the therapeutic effect of salt-processed EC was stronger than that of raw EC. The pharmacologically active ingredients that improved its treatment of KYDS efficacy after salt processing were peak 1 (geniposidic acid), peak 2 (chlorogenic acid), peak 5 (geniposide), peak 6 (genipin), peak 7 (pinoresinol diglucoside) and peak 11 (hyperoside). Meanwhile, the results of network pharmacology and molecular docking showed that the 6 active ingredients could exert kidney tonic effects through multiple signaling pathways by acting on core targets such as AKT1 and PTGS2. As far as we known, this was the first time to establish and compare the spectrum-effect relationship between raw and salt-processed EC, which laid the foundation for the pharmacokinetics studies of EC and provided a reference for future EC studies. [Display omitted] • Salted Eucommiae Cortex can improve the treatment of Kidney-Yang deficiency syndrome. • Geniposidic acid and other five components may be the active ingredients. • GRA and Entropy Method were used to establish the spectrum-effect relationship. • First time use spectrum-effect relationship to compare raw and salted Eucommiae Cortex. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between CT imaging features and pathological subtypes of pulmonary nodules and construct a prediction model using deep learning. Methods: We collected information of patients with pulmonary nodules treated by surgery and the reference standard for diagnosis was post-operative pathology. After using elastic distortion for data augmentation, the CT images were divided into a training set, a validation set and a test set in a ratio of 6:2:2. We used PB-LNet to analyze the nodules in pre-operative CT and predict their pathological subtypes. Accuracy was used as the model evaluation index and Class Activation Map was applied to interpreting the results. Comparative experiments with other models were carried out to achieve the best results. Finally, images from the test set without data augmentation were analyzed to judge the clinical utility. Results: Four hundred seventy-seven patients were included and the nodules were divided into six groups: benign lesions, precursor glandular lesions, minimally invasive adenocarcinoma, invasive adenocarcinoma Grade 1, Grade 2 and Grade 3. The accuracy of the test set was 0.84. Class Activation Map confirmed that PB-LNet classified the nodules mainly based on the lungs in CT images, which is in line with the actual situation in clinical practice. In comparative experiments, PB-LNet obtained the highest accuracy. Finally, 96 images from the test set without data augmentation were analyzed and the accuracy was 0.89. Conclusions: In classifying CT images of lung nodules into six categories based on pathological subtypes, PB-LNet demonstrates satisfactory accuracy without the need of delineating nodules, while the results are interpretable. A high level of accuracy was also obtained when validating on real data, therefore demonstrates its usefulness in clinical practice. [ABSTRACT FROM AUTHOR]

Many sets of Paleozoic marine organic-rich shale strata are developed in southern China. However, the exploration and development degree of these strata are different. Cambrian shale and Ordovician-Silurian shale are two horizons with high degree of exploration, while Devonian shale and Carboniferous shale exploration is deficient. Based on XRD, FE-SEM, and gas adsorption experiment, pore development characteristics and controlling factors of Devonian and Carboniferous shale are investigated. There are mainly four lithofacies in Devonian and Carboniferous shale: mixed shale (M), carbonate/siliceous mixed shale (M-1), argillaceous/siliceous mixed shale (M-2), and argillaceous-rich siliceous shale (S-3). Reservoir characteristics of both two sets of shale strata are quite different. The averages of porosity, pore volume, and specific surface area of Devonian shale are 3.81 % , 9.7 × 10 − 3 cm3/g and 11.8 m2/g, while those of Carboniferous shale are 3.57%, 17.3 × 10 − 3 cm3/g and 19.8 m2/g. Thermal evolution (Ro) and tectonic preservation conditions are the main factors affecting the pore development. Carboniferous shale (Ro ≈ 2 %) is in the stage of producing a large number of organic pores. Devonian shale (Ro ≈ 3.5 %) is having difficulty preserving organic pores due to high thermal evolution. Meanwhile, Devonian shale (well GTD1) is strongly affected by tectonic movement; tectonic fractures and calcite veins are developed. Carboniferous shale (well GRY1) is in relatively stable area; tectonic fractures are not developed. Under the influence of compaction, the pore volume and specific surface area of Carboniferous shale are 78.3% and 67.8% higher than those of Devonian shale, respectively. This research can provide reference for clarifying shale pore development and evolution mechanism and similar shale gas exploration both in study area and around the world. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. Methods: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation–qPCR (MeRIP–qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. Results: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. Conclusion: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine. [ABSTRACT FROM AUTHOR]

• Different combinations of AM fungi has varying effects on tomato' growth promotion. • Different combinations of AM fungi has varying effects on disease resistance. • R. intraradices had more effects on promoting tomato growth and nutrient uptake. • C. etunicatum + R. intraradices was effective in growth promotion and disease-resistant. • Mycorrhization improved fruit quality in water-fertilizer integrated greenhouse. In this study, we investigated the effects of combinations of arbuscular mycorrhizal (AM) fungal species on tomato seedling growth and Fusarium wilt control. The study was conducted in greenhouse pot experiments using the tomato (Solanum lycopersicum) variety Fusan 88 and the fungi Funneliformis mosseae , Diversispora versiformis , Claroideoglomus etunicatum , and Rhizophagus intraradices as inoculants. The results showed higher mycorrhizal root colonization rates in all inoculation mixtures than in single-inoculum treatments, while growth-promotion effects differed significantly among AM fungal species and their combinations. Except for inoculation with F. mosseae alone, other inoculation treatments significantly promoted the growth of tomato seedlings. Of all fungal species, R. intraradices had the most significant effect on promoting seedling growth, as observed in all inoculum combinations containing this species. The greatest effect on seedling growth was observed for combined inoculation with D. versiformis + R. intraradices , which led to increases in above- and belowground biomass of 67.74 % and 100 %, respectively, compared to the control (CK), followed by C. etunicatum + R. intraradices , which led to increases in above- and belowground biomass of 61.29 % and 100 % compared to CK. Redundancy analyses showed that compared to the other three species, R. intraradices had more significant effects on promoting plant nitrogen, phosphorus, and potassium uptake and increasing above- and belowground dry weight. Mycorrhizalized seedlings were more resistant to Fusarium wilt and had lower malondialdehyde content and higher catalase, superoxide dismutase, and polyphenol oxidase activity in tomato plants. The lowest Fusarium wilt disease index value was 39.96 %, for mixed inoculation with F. mosseae + D. versiformis + C. etunicatum ; this was 34.28 % lower than that of CK, and the control effect was 34.27 %, followed by inoculation with C. etunicatum + R. intraradices , which had a disease index value of 41.48 %, 31.78 % lower than that of CK, with a control effect value of 31.76 %. Therefore, we transplanted tomato seedlings inoculated with C. etunicatum + R. intraradices , which had both good growth-promotion and disease-resistance effects, to a greenhouse for sand culture under conditions of high water and fertilization. The mycorrhizal relationships developed in these plants at the seedling stage remained stable throughout the tomato reproductive period. The mycorrhizal seedlings had a significantly lower incidence of Fusarium wilt and lower disease index values, indicating better disease control than observed in non-mycorrhizal seedlings. The mycorrhizal plants produced fruits with a significantly higher soluble-sugar content and sugar:acid ratio (30.8 % and 42.3 % higher, respectively, than CK) and a significantly lower organic acid content (11.5 % lower than CK). Thus, mycorrhization significantly improved tomato plants' growth, disease resistance, and fruit quality. These findings lay a foundation for the application of mycorrhizal fungi in tomato agriculture. [ABSTRACT FROM AUTHOR]

Surgery remains the first option for curing early stage lung cancer. However, many patients are diagnosed at an advanced stage, and thus miss the chance to undergo surgery. As such patients derive limited benefits from chemotherapy or radiotherapy, alternatives based on local control have emerged, including iodine-125 seed implantation. The Interstitial Brachytherapy Society, Committee of Minimally Invasive Therapy in Oncology, the Chinese Anti-Cancer Association organized a group of multidisciplinary experts to revise the guidelines for this treatment modality. It aims to standardize iodine-125 seed implantation procedures, inclusion criteria, and outcome assessment to prevent and manage procedure-related complications. [ABSTRACT FROM AUTHOR]

Dipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. The purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. The model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. The results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. This study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed. [Display omitted] • It was the first time that the effect of DR before and after salt-processed on kidney yang deficiency syndrome was compared. • Both crude and salt products of DR could have a good therapeutic effect on kidney yang deficiency syndrome. • The effect of tonifying the kidney and strengthening bone of DR might be achieved through the BMP-Smad signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: To establish a pre-therapy prognostic index model (PIM) of the first-line chemotherapy aiming to achieve accurate prediction of time to progression (TTP) and overall survival among the patients diagnosed with locally advanced (stage III) or distant metastasis (stage IV) lung squamous cell carcinoma (LSCC).Methods: Ninety-six LSCC patients treated with first-line chemotherapy were retrospectively enrolled to build the model. Fourteen epidermal growth factor receptor (EGFR)-mutant LSCC patients treated with first-line EGFR-tyrosine kinase inhibitor (TKI) therapy were enrolled for validation dataset. From CT images, 56,000 phenotype features were initially computed. PIM was constructed by integrating a CT phenotype signature selected by the least absolute shrinkage and selection operator and the significant blood-based biomarkers selected by multivariate Cox regression. PIM was then compared with other four prognostic models constructed by the CT phenotype signature, clinical factors, post-therapy tumor response, and Glasgow Prognostic Score.Results: The signature includes eight optimal features extracted from co-occurrence, run length, and Gabor features. By using PIM, chemotherapy efficacy of patients categorized in the low-risk, intermediate-risk, and high-risk progression subgroups (median TTP = 7.2 months, 3.4 months, and 1.8 months, respectively) was significantly different (p < 0.0001, log-rank test). Chemotherapy efficacy of the low-risk progression subgroup was comparable with EGFR-TKI therapy (p = 0.835, log-rank test). Prognostic prediction of chemotherapy efficacy by PIM was significantly higher than other models (p < 0.05, z test).Conclusion: The study demonstrated that the PIM yielded significantly higher performance to identify individual stage III-IV LSCC patients who can potentially benefit most from first-line chemotherapy, and predict the risk of failure from chemotherapy for individual patients.Key Points: • TTP and OS of first-line chemotherapy in individual stage III-IV LSCC patients could be predicted by pre-therapy blood-based biomarkers and image-based signatures. • Risk status of pre-therapy indicators affected the efficacy of first-line chemotherapy in stage III-IV LSCC patients. • Those stage III-IV LSCC patients who were able to achieve similar efficacy to EGFR-TKI therapy through chemotherapy were identified. [ABSTRACT FROM AUTHOR]

Dipsaci Radix (DR) is the dry root of the Dipsacus asper Wall. ex DC., which has the function of tonifying the liver and kidney, continuing tendons and bones, and regulating blood vessels. However, there are few reports on the main active ingredients. This study aimed to find the main active components of DR in the treatment of osteoarthritis (OA) by spectrum-effect relationship and compare the differences between RDR and WDR. Firstly, the high-performance liquid chromatography (HPLC) method was used to establish the fingerprint of DR, and 10 peaks of them were determined by UPLC-Q-TOF/MS. Then, the OA rat model was established by injecting sodium iodoacetate to study the effect of DR on OA. The spectrum-effect relationship was analyzed by grey relational analysis (GRA) and Pearson correlation analysis. According to the pharmacological results, compared with the model group, the cartilage score, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and Mankin score of rats in low, medium and high dose groups were decreased, and the therapeutic effect of wine-processed DR tended to be better than raw DR at the same dose. Finally, the active components of DR were preliminarily determined as 4 (loganic acid), 6 (chlorogenic acid), 8 (caffeic acid), 14 (dipsanoside B), 16, and 17 (asperosaponin VI) which had a large correlation in GRA and Pearson correlation analysis. This study established the spectrum-effect relationship between the raw and wine-processed DR for the first time, which provided a theoretical basis for the study of the pharmacodynamic substance basis of DR before and after processing. This research provided a reference for the subsequent study of DR. [Display omitted] • Dipsaci Radix had the effect of reating OA, but the main active components were unclear. • This was the first time that the raw and wine-processed Dipsaci Radix spectrum-effect relationship had been established. • Loganic acid, chlorogenic acid, caffeic acid, dipsanoside B, and asperosaponin VI might be the main material basis for DR. [ABSTRACT FROM AUTHOR]

[Display omitted] • The chromaticity and NIR spectroscopy were used for the first time to control the quality of RR before and after wine processing. • Two qualitative discriminant models of PR were established and could be used in process control. • The NIR spectroscopy quantitative model of 11 indexes in the whole process of processing was established to predict the quality of RR. In order to quickly determine the processing degree and quality of Polygonati Rhizome (PR), the rapid qualitative and quantitative model for the whole steaming process was established in this study. Firstly, the contents and the chromaticity value of polysaccharide, saponin, 5-hydroxymethyl furfural (5-HMF), 5-hydroxymaltol, polygonatine A, fructose, glucose, sucrose, and the chromaticity value in 98 batches of PR during the whole processing were determined. The chromaticity value was used to establish the qualitative discrimination model of the whole steaming process by partial least squares-discriminant analysis (PLS-DA). Then, the near-infrared (NIR) spectra of all samples were collected to establish the NIR qualitative discriminant model. The samples of four different processing stages, raw products, less processed products, finished processed products, and over processed products, were well distinguished in two qualitative models, and the model validation results were good. Finally, the chromaticity value, the content, and NIR spectra were imported into TQ Analyst software. After screening the pretreatment methods, the optimal pretreatment method combined with partial least squares (PLS) was selected to establish the NIR quantitative model of 11 indicators. The correlation coefficient of models was above 0.9, indicating that the model had high prediction accuracy. Through the establishment of the qualitative discriminant model, the different processing degrees of PR could be accurately distinguished, and the NIR quantitative prediction model could accurately predict the content and the chromaticity value, which provided a scientific basis for the quality identification of PR in the whole process of processing. [ABSTRACT FROM AUTHOR]

SMARCA4, also known as transcription activator, is an ATP-dependent catalytic subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin-remodeling complexes that participates in the regulation of chromatin structure and gene expression by supplying energy. As a tumor suppressor that has aberrant expression in ∼10% of non-small-cell lung cancers (NSCLCs), SMARCA4 possesses many biological functions, including regulating gene expression, differentiation and transcription. Furthermore, NSCLC patients with SMARCA4 alterations have a weak response to conventional chemotherapy and poor prognosis. Therefore, the mechanisms of SMARCA4 in NSCLC development urgently need to be explored to identify novel biomarkers and precise therapeutic strategies for this subtype. This review systematically describes the biological functions of SMARCA4 and its role in NSCLC development, metastasis, functional epigenetics and potential therapeutic approaches for NSCLCs with SMARCA4 alterations. Additionally, this paper explores the relationship and regulatory mechanisms shared by SMARCA4 and its mutually exclusive catalytic subunit SMARCA2. We aim to provide innovative treatment strategies and improve clinical outcomes for NSCLC patients with SMARCA4 alterations. • NSCLC patients with SMARCA4 alterations have a weak response to conventional chemotherapy and poor prognosis. • CDK4/6 inhibitors, the small-molecule OXPHOS inhibitor and ATR inhibitors offer hope for SMARCA4 abnormalities patients. • Cisplatin-based chemotherapy in combination with ICI therapy may be beneficial for SMARCA4- deficient NSCLC patients. • As a key synthetic lethal target in SMARCA4 -deficient cancers, SMARCA2 may serve as a novel therapeutic target. [ABSTRACT FROM AUTHOR]

SMARCA4, also known as transcription activator, is an ATP-dependent catalytic subunit of SWI/SNF (SWItch/Sucrose NonFermentable) chromatin-remodeling complexes that participates in the regulation of chromatin structure and gene expression by supplying energy. As a tumor suppressor that has aberrant expression in ∼10% of non-small-cell lung cancers (NSCLCs), SMARCA4 possesses many biological functions, including regulating gene expression, differentiation and transcription. Furthermore, NSCLC patients with SMARCA4 alterations have a weak response to conventional chemotherapy and poor prognosis. Therefore, the mechanisms of SMARCA4 in NSCLC development urgently need to be explored to identify novel biomarkers and precise therapeutic strategies for this subtype. This review systematically describes the biological functions of SMARCA4 and its role in NSCLC development, metastasis, functional epigenetics and potential therapeutic approaches for NSCLCs with SMARCA4 alterations. Additionally, this paper explores the relationship and regulatory mechanisms shared by SMARCA4 and its mutually exclusive catalytic subunit SMARCA2. We aim to provide innovative treatment strategies and improve clinical outcomes for NSCLC patients with SMARCA4 alterations. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the general rules and future trajectories of deep learning (DL) networks in medical image analysis through bibliometric and hot spot analysis of original articles published between 2012 and 2020.Methods: Original articles related to DL and medical imaging were retrieved from the PubMed database. For the analysis, data regarding radiological subspecialties; imaging techniques; DL networks; sample size; study purposes, setting, origins and design; statistical analysis; funding sources; authors; and first authors' affiliation was manually extracted from each article. The Bibliographic Item Co-Occurrence Matrix Builder and VOSviewer were used to identify the research topics of the included articles and illustrate the future trajectories of studies.Results: The study included 2685 original articles. The number of publications on DL and medical imaging has increased substantially since 2017, accounting for 97.2% of all included articles. We evaluated the rules of the application of 47 DL networks to eight radiological tasks on 11 human organ sites. Neuroradiology, thorax, and abdomen were frequent research subjects, while thyroid was under-represented. Segmentation and classification tasks were the primary purposes. U-Net, ResNet, and VGG were the most frequently used Convolutional neural network-derived networks. GAN-derived networks were widely developed and applied in 2020, and transfer learning was highlighted in the COVID-19 studies. Brain, prostate, and diabetic retinopathy-related studies were mature research topics in the field. Breast- and lung-related studies were in a stage of rapid development.Conclusions: This study evaluates the general rules and future trajectories of DL network application in medical image analyses and provides guidance for future studies. [ABSTRACT FROM AUTHOR]

Comparing drug-injecting risk between cities that differ in the legality of sterile syringe distribution for injection drug use provides a natural experiment to assess the efficacy of legalizing sterile syringe distribution as a structural intervention to prevent human immunodeficiency virus (HIV) and other parenterally transmitted infections among injection drug users (IDUs). This study compares the parenteral risk for HIV and hepatitis B (HBV) and C (HCV) infection among IDUs in Newark, NJ, USA, where syringe distribution programs were illegal during the period when data were collected, and New York City (NYC) where they were legal. IDUs were nontreatment recruited, 2004-2006, serotested, and interviewed about syringe sources and injecting risk behaviors (prior 30 days). In multivariate logistic regression, adjusted odds ratios (AOR) and 95% confidence intervals (95% CI) for city differences are estimated controlling for potential city confounders. IDUs in Newark (n = 214) vs. NYC (n = 312) were more likely to test seropositive for HIV (26% vs. 5%; AOR = 3.2; 95% CI = 1.6, 6.1), antibody to the HBV core antigen (70% vs. 27%; AOR = 4.4; 95% CI = 2.8, 6.9), and antibody to HCV (82% vs. 53%; AOR = 3.0; 95% CI = 1.8, 4.9), were less likely to obtain syringes from syringe exchange programs or pharmacies (AOR = 0.004; 95% CI = 0.001, 0.01), and were more likely to obtain syringes from street sellers (AOR = 74.0; 95% CI = 29.9, 183.2), to inject with another IDU's used syringe (AOR = 2.3; 95% CI = 1.1, 5.0), to reuse syringes (AOR = 2.99; 95% CI = 1.63, 5.50), and to not always inject once only with a new, sterile syringe that had been sealed in a wrapper (AOR = 5.4; 95% CI = 2.9, 10.3). In localities where sterile syringe distribution is illegal, IDUs are more likely to obtain syringes from unsafe sources and to engage in injecting risk behaviors. Legalizing and rapidly implementing sterile syringe distribution programs are critical for reducing parenterally transmitted HIV, HBV, and HCV among IDUs. [ABSTRACT FROM AUTHOR]

Abstract: We examine injecting and sexual risk correlates of hepatitis B (HBV) and hepatitis C (HCV) seroprevalence among new injecting drug users (IDUs) (age 18–30 years, injecting ≤6 years). Participants were interviewed/serotested (HIVab, HBVcAb, HCVab) in New York City, February 1999–February 2003. Gender-stratified, multivariate logistic regression was conducted. Participants (N =259) were: 68% male; 81% white. Women were more likely to test HCV seropositive (42% versus 27%) and men HBV seropositive (24% versus 12%); HIV seroprevalence was low (3%). Among both men and women, HBV seropositivity was associated with ever selling sex, and HCV seropositivity with ever having had infected (HIV, HBV or HCV) sex partners (among those ever sharing injecting equipment). Among women only, HBV seropositivity was associated with ever having had infected sex partners (regardless of ever sharing injecting equipment), and HCV seropositivity with ≥300 lifetime drug injections. Among men only, HCV seropositivity was associated with ≥40 lifetime number of sex partners (among those never sharing injecting equipment). In this new IDU sample, HBV and HCV seroprevalence differed by gender and were considerably higher than HIV seroprevalence. Early interventions, targeting injecting and sexual risks and including HBV vaccination, are needed among new IDUs to prevent HBV, HCV and, potentially, HIV epidemics. [Copyright &y& Elsevier]

Background: Stable disease (SD) has ambiguous clinical significance for patients according to the dominant Response Evaluation Criteria in Solid Tumours (RECIST). The primary aims of the study were: (1) to clarify the clinical significance of SD by comparing the progression-free survival (PFS) of response and SD patients with advanced non-small cell lung cancer (NSCLC) after the first two courses of the standard first-line platinum-based chemotherapy; (2) to explore the relationship between the percentage change in tumour size and PFS among initial SD patients, in order to provide some guidance for clinicians in deciding continuation/termination of the current treatment at a relative early time.Methods: A total of 179 advanced NSCLC patients whose baseline CT image was available for review were included in the study. Another CT image was taken in the initial assessment after chemotherapy. A comparison of PFS between initial partial response (PR) and SD was used to determine whether significant differences exist. The relationship between the early percentage of change in tumour size of initial SD patients and their PFS was investigated. In addition, overall survival (OS), the secondary endpoint in this study, was investigated as well.Results: Patients with initial PR are not significantly distinguished from those with initial SD when their PFS is concerned (median PFS 249 days [95% confidence interval, 187-310 days] versus 220 days [95% confidence interval, 191-248 days], p > 0.05). Their median OS was 364 days (95% confidence interval, 275-452 days) for the initial PR patients versus 350 days (95% confidence interval, 293-406 days) for the initial SD patients, which suggests no significant difference as well p > 0.05). In addition, all the initial SD patients enjoyed similar PFS and OS.Conclusions: Initial PR and SD enjoy similar PFS and OS for patients with advanced NSCLC. Within the initial SD subgroup, different percentages of tumour shrinkage or increase undergo similar PFS and OS. RECIST remains a reliable norm in assessing the effectiveness of chemotherapy for patients with advanced NSCLC before functional assessment has been integrated into the criteria. [ABSTRACT FROM AUTHOR]