Xiang thinking is a cognitive approach that reflects the relationships between phenomena and their underlying principles by analyzing their external manifestations through methods such as analogy， reasoning， deduction， and symbolism. This article applied xiang thinking to analyze the etiology and pathogenesis of "wind， fire， phlegm， and blood stasis" in stroke， thereby exploring its impact on the principles of syndrome differentiation and treatment of this condition. Meanwhile， the article traced the construction process of xiang thinking， and interpreted the concept of "toxin pathogen" in traditional Chinese medicine from four perspectives， state， attribute， origin， and law. Furthermore， the relationship between the process of constructing xiang thinking and the origin of etiology， identification methods， pathogenesis evolution， and treatment strategies for stroke with syndrome of combined blood stasis and toxin was explored， so as to provide insights into research on the etiology and pathogenesis of stroke， as well as clinical diagnosis and treatment approaches.

Background Silicosis is a diffuse fibrosis of the lungs caused by long-term inhalation of free silicon dioxide (SiO₂). It has a complex pathogenesis and lacks effective treatment. Brusatol (Bru) has a variety of biological activities, and its role in silicosis fibrosis is unclear yet. Objective To investigate the effects of different concentrations of Bru on SiO₂-induced silicosis fibrosis in mice. Methods Thirty male C57BL/6J mice were randomly divided into five groups: a control group, a silica group, and three Bru intervention groups with low, medium, and high doses (1, 2, and 4 mg·kg⁻¹), with 6 mice in each group. Except the control group, the remaining groups were established as SiO₂-induced silicosis mouse models by using a single tracheal infusion of 50 μL 60 mg·mL⁻¹ SiO₂ suspension. The control group was dosed with equal amount of saline. The Bru intervention groups were injected intraperitoneally with Bru for 5 consecutive days and then injected every other day. After 28 d of exposure, the mice were executed and lung tissues were collected. The lung coefficient of the mice was measured, and the pathological changes of the lung tissues were observed after hematoxylin-eosin (HE) and Masson staining. The levels of apoptotic protein Cleaved-caspase 3, fibrosis-related protein α-smooth muscle actin (α-SMA), type I collagen (Col-I), autophagy-associated protein Beclin1, microtubule-associated protein 1 light chain 3 (LC3), Sequestosome 1 (p62/SQSTM1), Kelch like ECH-associated protein-1 (Keap1), and nuclear factor erythroid 2 related factor 2 (Nrf2) were detected by Western blot. The mRNA levels of Caspase 3, α-SMA, and Col-I were measured by realtime fluorescence-based quantitative PCR. Results Compared with the control group, the lung coefficient of mice in the silica group was significantly increased (P < 0.01); the lung tissues of the silicosis mice showed damaged alveolar walls, along with infiltration of inflammatory cells, fibrous nodules, and collagen deposition; furthermore, the protein and mRNA levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly increased (P < 0.01); the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were increased, while that of Keap1 was decreased (P < 0.05). The interventions with low and medium doses of Bru reduced lung coefficient (P < 0.05) and protected against pathological damage and collagen deposition in the lung tissues of the silicosis mice; the protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I were significantly decreased in the low and medium dose groups (P < 0.05, P < 0.01), the expression levels of Beclin1, LC3-II/I, p62, and Nrf2 were also decreased (P < 0.05, P < 0.01), and the expression level of Keap1 was increased in the medium dose group (P < 0.05). However, compared with the silica group, the differences in lung coefficient, pathological damage, and protein and mRNA expression levels of Cleaved-caspase 3, α-SMA, and Col-I in the Bru high dose group were not statistically significant (P > 0.05). In addition, the high dose of Bru decreased Beclin1, LC3-II/I, and Nrf2 expression levels (P < 0.01), did not change p62 protein expression level (P > 0.05), while increased Keap1 protein level (P < 0.01). Conclusion Low and medium doses of Bru might regulate autophagy through the Keap1-Nrf2 pathway, ameliorate autophagic degradation impairment, reduce pulmonary coefficient, attenuate apoptosis, and delay the progression of fibrosis in SiO₂-induced silicosis mice.

Xiang thinking is the key way of thinking to construct the life model of human body in traditional Chinese medicine （TCM）， and the theory of ascending and descending of qi movement is an important manifestation of xiang thinking in the theory of TCM. Based on the theory of qi movement， this paper interpreted the mechanism of ischemic stroke through the perspective of xiang thinking "earth weakness - wood constraint - fire hyperactivity"， as "earth weakness in the central and dampness accumulated to phlegm" "wood constraint and stirring wind led to blood stasis" and "fire hyperactivity and fire toxin showed flaming upward" due to disorder of qi movement. Combined with the "xiang of medicinal properties and therapy methods" to discuss the treatment and prescriptions of ischaemic stroke， applying wind medicinals to elevate ji-earth （己土） and yi-wood （乙木）， so that phlegm and stasis can be eliminated， and cold medicinals to descend jia-wood （甲木） and wu-earth （戊土） so that fire toxin can be cleared， with a view to restore ascending and descending of qi movement for ischaemic stroke.

Narrative medicine,as an emerging discipline,has rapidly developed in the context of the current era of emphasis on medical humanities.The parallel chart is an essential tool for implementing humanistic practice in narrative medicine,while medical records and medical conversations are the carriers of traditional Chinese medicine(TCM)academic viewpoints and humanistic thoughts.Although there are differences in the textual content between them,the concept of"people-oriented"in TCM aligns with the spirit of narrative medicine.Medical records teaching is an important link for cultivating TCM clinical thinking and medical humanistic thought.Therefore,examining TCM medical records and humanistic education from the perspective of narrative medicine,sorting out the connections and differences between TCM medical records and parallel charts,and emphasizing the educational and guiding value of narrative medicine in the modern TCM diagnosis and treatment process,are of great significance for establishing and promoting TCM-featured parallel charts,thereby guiding the education and teaching of TCM,and cultivating new-era TCM talents with empathy and reflective capabilities.

Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

BCR-ABL1 fusion gene negative chronic myeloproliferative neoplasms (MPN) are a group of malignant disorders that originate from a single hematopoietic stem cells. There are a variety of gene mutations in the blood cells of MPN patients, including "disease driver gene mutation", "clone driver gene mutation" and "passenger gene mutation", which play an important role in the development and progression of MPN, and affect the treatment response and outcome of MPN patients. These gene mutations have been included in the MPN international prognostic scoring system. It is of great significance for the diagnosis and treatment of MPN.

Objective To investigate associations between three-dimensional(3D)morphology of cervical vertebrae and skeletal mat-uration by cone-beam computed tomography(CBCT)and establish corresponding regression models for quantitatively evaluating cervical vertebral maturation(CVM).Methods The analyzed sample consisted of 358 CBCT images(175 male,183 female),of which 277 images were randomly selected as the model development group and 81 as the performance test group.Twenty-one 3D morphological pa-rameters were defined and measured,incorporating all parts of the cervical vertebrae,including the cervical vertebral bodies,transverse processes,spinous processes,pedicles,lamina,and articular processes.The cervical vertebral maturation index(CVMI)was determined by experienced orthodontists as reference standard.Spearman's rank correlation coefficient and multivariable stepwise regression analysis were used to identify the associations and build regression models.The performance test group was employed to ex-amine each model's reliability.Paired-samples Wilcoxon signed-rank test compared the CVMI of the model prediction with the reference standard.Results Three-dimensional morphological changes in various parts of the cervical vertebrae correlated with CVMI(P＜0.05).Six 3D morphometric parameters were each recognized for male and female models,three of which were identical.The adjusted R2 was 0.899 for males and 0.902 for females,with corresponding accuracies of 85.0%and 85.4%,respectively.These models showed no difference as compared with the reference standard(P＞0.05).Con-clusion New associations were found between 3D morphology of cer-vical vertebrae and skeletal maturation.The 3D-driven morphometric CVM assessment method and corresponding regression models exhibited good credibility and high consistency with experts.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Arrhythmia is a significant cardiovascular disease that poses a threat to human health, and its primary diagnosis relies on electrocardiogram (ECG). Implementing computer technology to achieve automatic classification of arrhythmia can effectively avoid human error, improve diagnostic efficiency, and reduce costs. However, most automatic arrhythmia classification algorithms focus on one-dimensional temporal signals, which lack robustness. Therefore, this study proposed an arrhythmia image classification method based on Gramian angular summation field (GASF) and an improved Inception-ResNet-v2 network. Firstly, the data was preprocessed using variational mode decomposition, and data augmentation was performed using a deep convolutional generative adversarial network. Then, GASF was used to transform one-dimensional ECG signals into two-dimensional images, and an improved Inception-ResNet-v2 network was utilized to implement the five arrhythmia classifications recommended by the AAMI (N, V, S, F, and Q). The experimental results on the MIT-BIH Arrhythmia Database showed that the proposed method achieved an overall classification accuracy of 99.52% and 95.48% under the intra-patient and inter-patient paradigms, respectively. The arrhythmia classification performance of the improved Inception-ResNet-v2 network in this study outperforms other methods, providing a new approach for deep learning-based automatic arrhythmia classification.
Humans ; Arrhythmias, Cardiac/diagnostic imaging* ; Cardiovascular Diseases ; Algorithms ; Databases, Factual ; Electrocardiography