Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

BACKGROUND:Transplantation of stem cell-derived islet β cells has been considered effective for the treatment of type 1 diabetes.Human umbilical cord mesenchymal stem cell is an ideal cellular source,but with a low differentiation efficiency to islet β cells. OBJECTIVE:To explore the possibility of human umbilical cord mesenchymal stem cells modified by MAFA and PDX1 to differentiate into insulin-producing cells. METHODS:MAFA-PDX1 lentivirus expression vectors were constructed.The efficiency and potentiality of human umbilical cord mesenchymal stem cells differentiated into insulin-producing cells with three methods were compared by cell morphology,RT-qPCR,and dithizone staining[protocol A:Simple lentivirus group;protocol B:Drug(nicotinamide β-mercaptoethanol)induction followed by lentivirus group;protocol C:lentivirus and drug induction group]. RESULTS AND CONCLUSION:(1)Morphological change of cells:Cell morphology was all altered after the induction of three protocols.At day 11,human umbilical cord mesenchymal stem cells induced by protocol B showed the most cell clusters among the three protocols,appearing aggregated islet-like cell clusters.(2)Islet-related gene expression detected by RT-qPCR:Horizontal comparison of the three protocols at the same induction time point showed that the expression levels of MAFA and PDX1 genes were the highest in protocol C on day 5 of induction,and those in protocol B were the highest on day 11 of induction.Human umbilical cord mesenchymal stem cells induced by protocol B had the greatest expression of GCG gene at day 5,INS and GLUT2 genes at day 11.(3)Dithizone staining to identify zinc ions:parts of the post-induced cells were stained brownish red by dithizone on day 11.The partial small island cells were stained brownish red with a darker color(positive expression)in protocol B.(4)It is concluded that the overexpression of MAFA and PDX1 can promote the differentiation of human umbilical cord mesenchymal stem cells into insulin-producing cells.The combination of MAFA-PDX1 gene modification and drug induction is superior to the single gene modification.

OBJECTIVE: To investigate the clinical and immunological characteristics of anti-synthetase syndrome (ASS) patients overlap with rheumatoid arthritis (RA). METHODS: A retrospective analysis was conducted on ASS patients with arthritis who were treated at Peking University People' s Hospital. Data collected included demographic information, clinical manifestations, laboratory features, lymphocyte subsets in peripheral blood, and treatments. The patients with ASS were divided into two groups based on the presence or absence of RA for comparative analysis. RESULTS: A total of 104 ASS patients with arthritis were included, among whom 23.1% (24/104) were diagnosed with RA. The ASS with RA group had a significantly higher incidence of rapidly progressive interstitial lung disease (RP-ILD) (41.7% vs. 17.6%, P=0.032), number of tender joints [10 (7, 14) vs. 4 (0, 8), P < 0.001], number of swollen joints [4 (2, 8) vs. 2 (0, 4), P=0.012], and rate of bone erosion (47.8% vs. 2.5%, P < 0.001) compared with the non-RA group. Levels of platelets [(289.57±68.74)×10³/μL vs. (247.94±77.04)×10³/μL, P=0.022], erythrocyte sedimentation rate (ESR) [43 (19, 59) mm/h vs. 18 (10, 44) mm/h, P=0.019], and C-reactive protein (CRP) [19.20 (4.80, 55.36) mg/L vs. 5.68 (1.10, 14.96) mg/L, P=0.006] were found significantly higher in the ASS with RA group than those in non-RA group. Analysis of immune cells in peripheral blood mononuclear cell (PBMC) showed that significantly decreased proportions of CLA⁺ Treg cells [(11.12±4.10)% vs. (17.22±8.49)%, P=0.003], B cells [8.56% (4.80%, 11.90%) vs. 14.55% (8.75%, 20.29%), P=0.025], and natural killer (NK) cells [7.56% (4.65%, 13.20%) vs. 13.25% (7.46%, 19.25%), P=0.045] in the overlap group compared with non-RA group. Proportion of Naïve Th cells [(52.66±17.66)% vs. (40.76±14.96)%, P=0.033)] was significantly increased in overlap group compared with non-RA group. Overlap group had lower rate of complete clinical response than non-RA group (16.7% vs. 43.8%, P=0.031). CONCLUSION Among ASS patients with arthritis, those with RA have more severe lung and joint involvement and a lower treatment response rate, highlighting the need for early recognition and aggressive intervention.
Humans ; Arthritis, Rheumatoid/immunology* ; Retrospective Studies ; Lung Diseases, Interstitial/immunology* ; Male ; Myositis/blood* ; Female ; Middle Aged ; Autoantibodies/blood*

Ulcerative colitis （UC） is a chronic recurrent inflammatory bowel disease which primarily affects the colonic mucosa. The UC patients mainly present diarrhea， abdominal pain， tenesmus， and mucous bloody stools， and even malnutrition and systemic symptoms in severe cases， with rising incidence， which has a significant impact on the health and quality of life of patients. The pathogenesis of UC is not clear， and the Western medical therapies include sulfasalazine， glucocorticoids， and immunosuppressants， which， however， have side effects and unsatisfactory effects. Chinese medicine with high safety， mild adverse reactions， and a multi-component， multi-target， and multi-pathway treatment manner has garnering increasing attention. Therefore， finding the Chinese medicine to treat UC has become a hot spot. Glycyrrhizae Radix et Rhizoma is one of the commonly used Chinese herbal medicines， with the effects of tonifying spleen and reinforcing qi， clearing heat and detoxifying， dispelling phlegm and relieving cough， relieving pain， and harmonizing medicines. Glycyrrhizae Radix et Rhizoma mainly contains glycyrrhizic acid， glycyrrhetinic acid， diammonium glycyrrhizinate and other active ingredients. Modern pharmacological studies have shown that Glycyrrhizae Radix et Rhizoma has anti-inflammatory， antioxidant， antimicrobial， and immunomodulatory activities. According to statistics， Glycyrrhizae Radix et Rhizoma is among the top three Chinese herbal medicines for the treatment of UC. The recent years have witnessed progress in the treatment of UC with Glycyrrhizae Radix et Rhizoma and the related prescriptions. The present study summarized the mechanisms underlying the anti-inflammatory， immunomodulatory， intestinal flora-regulating， cell apoptosis-inducing， and oxidative stress-reducing effects of the key chemical constituents （glycyrrhetinic acid， diammonium glycyrrhizinate， polysaccharide， glycyrrhetinic acid， and isoglycyrrhizin） and compound prescriptions of Glycyrrhizae Radix et Rhizoma. The findings provide a solid foundation for further development and clinical application of Glycyrrhizae Radix et Rhizoma.

Objective:To seek any correlation between cortical activity and the swallowing of dysphagia patients with infratentorial stroke, and to observe any effect of three-needle acupuncture of the tongue on such activity.Methods:Thirty infratentorial stroke survivors with dysphagia were randomly divided into a tongue three-needle group and a sham acupuncture group, each of 15. Functional near-infrared spectroscopy was used to monitor changes in the concentration of oxygenated hemoglobin (ΔHbO 2) at rest, during acupuncture (or sham acupuncture), during real or sham electro-acupuncture, and at rest after the acupuncture or sham acupuncture treatment. The Modified Rankin Scale, a Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale were employed to assess overall functional disability and the swallowing of both groups. Results:At rest the average ΔHbO 2 concentrations recorded in the left primary motor cortex, the left dorsolateral prefrontal cortex and the left premotor cortex in both groups were positively correlated with the PAS scores. During the acupuncture ΔHbO 2 concentration in the right inferior frontal gyrus and the left middle temporal gyrus increased significantly in the tongue three-needle group. It decreased significantly in the left somatosensory cortex and the left primary motor cortex. Conclusion:Three-needle acupuncture of the tongue induces changes in cortical activity in infratentorial stroke survivors with dysphagia, suggesting a potential technique for improving disordered swallowing.

Objective:To prepare a peptide fluorescent probe based on aggregation-induced emission and to investigate its application in the detection of early caries.Methods:Eight aspartate-serine-serine (DSS) were combined with aggregation-induced emission material to prepare peptide fluorescent probes, and an artificial demineralization model was established in vitro. The samples were immersed in the peptide fluorescent probe solution for 1 min, and a fluorescence imaging system was applied to examine the tooth samples and collect images and fluorescence data. Scanning electron microscopy was also applied to observe the phenotype of the teeth, and electron microscopy was applied to detect the calcium-phosphorus ratio on the enamel surface of the teeth. Polarized light microscopy was also applied to observe the enamel area of the teeth. Results:The fluorescence intensity of demineralized teeth was clearly observed to be lower than that of normal teeth in the peptide fluorescent probe-treated area, and the difference was statistically significant ( P < 0.05). The results of scanning electron microscopy showed that the enamel surface of the demineralized group had more irregular pores, while the enamel surface of the undemineralized group was flatter with only some irregular accumulation of flakes. The results of polarized light microscopy showed that a clear birefringence could be observed in the enamel region of normal teeth, while a black area or the disappearance of the birefringence effect accompanied by a partial black dark shadow could be observed in the enamel region of demineralized teeth. Conclusions:An aggregation-induced luminescence-based peptide fluorescent probe was successfully prepared, which can precisely localize the enamel and show some application value in early caries detection.

Objective: Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Methods: Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. Results: It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. Conclusion: This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.

Recent advancement in natural language processing (NLP) and medical imaging empowers the wide applicability of deep learning models. These developments have increased not only data understanding, but also knowledge of state-of-the-art architectures and their real-world potentials. Medical imaging researchers have recognized the limitations of only targeting images, as well as the importance of integrating multimodal inputs into medical image analysis. The lack of comprehensive surveys of the current literature, however, impedes the progress of this domain. Existing research perspectives, as well as the architectures, tasks, datasets, and performance measures examined in the present literature, are reviewed in this work, and we also provide a brief description of possible future directions in the field, aiming to provide researchers and healthcare professionals with a detailed summary of existing academic research and to provide rational insights to facilitate future research.
Humans ; Natural Language Processing ; Surveys and Questionnaires

Objective:To analyze the dosimetric differences of volumetric modulated arc therapy (VMAT) plans for lung cancer caused by different dose calculation algorithms and radiation field settings and thus to provide a reference for designing clinical VMAT plans for lung cancer.Methods:This study randomly selected 20 patients with lung cancer and divided them into four groups of VMAT plans, namely, a group adopting two fields and two arcs based on the AAA algorithm (2F2A_AAA), a group employing two fields and two arcs based on the AXB algorithm (2F2A_AXB), a group using two fields and two arcs based on the MC algorithm (2F2A_MC), and a group adopting one field and two arcs based on the MC algorithm (1F2A_MC). Then, this study evaluated the target coverage, high-dose control, dose homogeneity index (HI), conformity index (CI), and organs at risk (OARs) of the plans using different algorithms and radiation field settings.Results:The planning target volume (PTV) results of two fields combined with two arcs (2F2A) of three groups using different algorithms are as follows. 2F2A_MC achieved better results in both D1% and V 95% (the relative volume of the target volume surrounded by 95% of the prescribed dose) of planning gross target volume (PGTV) than 2F2A_AAA (D1%: t=-2.44, P=0.03; V95%:z=-2.04, P=0.04) and 2F2A_AXB (D1%: t=2.34, P=0.03; z=-3.21, P < 0.01). 2F2A_AXB outperformed 2F2A_AAA ( z=-3.66, P < 0.01) and was comparable to 2F2A_MC in terms of the CI of PGTV. Regarding OARs, 2F2A_AXB and 2F2A_MC decreased the V5 Gy of the whole lung by 0.68% ( z=-2.69, P=0.01) and 3.05% ( z=-3.52, P < 0.01), respectively compared to 2F2A_AAA. 2F2A_AXB achieved a whole-lung Dmean of 1776.44 cGy, which was superior to that of 2F2A_MC ( t=2.67, P=0.02) and 2F2A_AAA ( t=8.62, P < 0.01). Compared to 2F2A_AAA and 2F2A_MC, 2F2A_AXB decreased the V20 Gy of Body_5 mm by 1.45% ( z=-3.88, P < 0.01) and 2.01% ( z=-3.66, P < 0.01), respectively. The results of the two groups with different field settings showed that 1F2A_MC was superior to 2F2A_MC in both the CI of PTV1 and the HI of PTV2 (CI: t=2.61, P=0.02; HI: z=-2.20, P=0.03). Moreover, 1F2A_MC increased the Dmean of the whole lung by 26.29 cGy compared to 2F2A_MC ( t=2.28, P=0.04). Conclusions:Regarding the design of VMAT plans for lung cancer, the MC algorithm is suitable for the target priority and the AXB algorithm is suitable for the OAR priority. When only the MC algorithm is available, it is recommended to choose 1F2A in the case of target priority and select 2F2A in the case of OAR priority.

Immune checkpoint inhibitors are able to reactivate the immune system therefore enhance the anti-tumor effects. However, over-activated T cells may induce immune related adverse events (irAEs). Hematological irAEs are rarely reported, which mainly represent as mono-lineage cytopenia or pancytopenia, including autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), neutropenia and aplastic anemia, sometimes even lethal, such as hemophagocytic lymphohistiocytosis. The clinical manifestations of hematological irAEs will be summarized and recommendations of diagnosis and treatment are proposed.