The Inner Canon of Yellow Emperor （《黄帝内经》） constructs its theoretical system under the influence of the holistic， symbolic， and holographic mental models of traditional Chinese medicine （TCM）. It lays the theoretical foundation of TCM and provides a paradigm for TCM theory construction， serving as an original academic gene and theoretical source for the inheritance and innovation of modern TCM. Based on the theoretical paradigms derived from The Inner Canon of Yellow Emperor， the holistic mental model， the symbolic mental model， and the holographic mental model in shaping nature-human medicine theory， imagery-based theory， and fractal theory， this study revealed that TCM theory relies on the cognitive framework of traditional cultural mental models. On this basis， we proposed that the modern TCM mental model should return to its roots while fostering innovation， integrating tradition with modernity by combining macroscopic with microscopic perspectives， scientific with humanistic cognition， as well as evidence-based research with digital and artificial intelligence technologies. Furthermore， with a future-oriented approach， this paper discussed on the strategies for reshaping the modern TCM mental model from three dimensions of TCM diagnosis and treatment， TCM education， and TCM research， which could not only preserve the traditional clinical thinking characteristics of TCM， but also innovate modern TCM practice.

Dentatorubral-pallidoluysian atrophy（DRPLA） is a rare autosomal dominant neurodegenerative disease caused by CAG triplet expansion in the atrophin 1 （ATN1） gene. Up to now， the pathogenesis of DRPLA remains unclear. The main clinical features of DRPLA include myoclonus， epilepsy， ataxia， choreoathetosis， and cognitive impairment. DRPLA has great clinical heterogeneity， and the number of CAG repeats is negatively correlated with age of onset and disease severity. Some patients with late-onset DRPLA may have atypical manifestations without typical imaging changes， which brings challenges to the diagnosis of the disease. This article reviews the pathogenesis， pathological features， clinical and imaging manifestations， diagnosis， and potential treatment of DRPLA， in order to deepen the understanding of this disease.
Ataxia ; Myoclonus

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

This study intends to establish a colorectal cancer(CRC)organoid model,expand and isolate CRC-reactive tumor-infiltrating lymphocytes(TILs),screen tumor-specific T cell receptors(TCRs)and perform functional verification,in order to provide a technological platform and research foundation for the clinical transformation of individualized adoptive T-cell immunotherapy for colorectal cancer.An organoid model derived from colon cancer patient tissues was constructed using in vitro 3D culture techniques,which then subjected to HE staining and immunohistochemistry for detecting morphological characteristics and representative molecular expression.Subsequently,CRC organoids were co-cultured with TILs for sorting reactive TILs using flow cytometry,and the characteristics of reactive TCR clones was analyzed through single T cell receptor gene cloning technology.Furthermore,the function of TCRs was verified through cytotoxicity experiments.Morphological analysis and representative molecules(CK20 and CDX2)expression indicated that there is high similarity between colorectal cancer organoids and patient tumors.In the in vitro expanded and cultured TILs,colorectal cancer-reactive T cells with upregulated CD137 expression and increased IFN-γ secretion were screened out successfully,among which TCR2-T cells demonstrated superior tumor reactivity and in vitro tumor killing function.In conclusion,a platform for screening and function validation of reactive TCRs based on CRC-Org has been established,providing a technological platform for the translational application of individualized T-cell therapy for colorectal cancer.

Lysobacter harbors a plethora of cryptic biosynthetic gene clusters (BGCs), albeit only a limited number have been analyzed to date. In this study, we described the activation of a cryptic polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) gene cluster (lsh) in Lysobacter sp. DSM 3655 through promoter engineering and heterologous expression in Streptomyces sp. S001. As a result of this methodology, we were able to isolate two novel linear lipopeptides, lysohexaenetides A (1) and B (2), from the recombinant strain S001-lsh. Furthermore, we proposed the biosynthetic pathway for lysohexaenetides and identified LshA as another example of entirely iterative bacterial PKSs. This study highlights the potential of heterologous expression systems in uncovering cryptic biosynthetic pathways in Lysobacter genomes, particularly in the absence of genetic manipulation tools.
Lysobacter/metabolism* ; Streptomyces/metabolism* ; Lipopeptides/metabolism* ; Polyketide Synthases/genetics* ; Multigene Family

Objective To investigate the clinical and neuroimaging features of adults with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease at the first attack. Methods We retrospectively analyzed the clinical manifestations,radiological features,laboratory findings,and outcome of 14 adult patients with MOG antibody-associated disease at the first attack who were hospitalized in the departments of neurology of Jiangxi Provincial People's Hospital and Xinyu People's Hospital from January 2018 to January 2022. Results The 14 patients included six males and eight females,with a median age of 29.5 years. The most common initial symptoms were fever and headache (n=5),seizure (n=3),and dizziness (n=3). The supratentorial lesions were located in the thalamus (n=7),subcortical white matter (n=6),cortex (n=5),corpus callosum (n=2), and basal ganglia (n=2). The infratentorial lesions were frequently located in the brainstem:the pons (n=5),middle cerebellar peduncle (n=3),midbrain (n=2), and medulla (n=2). Three patients had spinal cord involvement,with one case of longitudinally extensive transverse myelitis. Thirteen patients had elevated cerebrospinal fluid cell counts,and seven had elevated cerebrospinal fluid protein levels. The serum MOG antibody titer ranged from 1∶3.2 to 1∶512. All the 14 patients received intravenous pulse glucocorticoid therapy. Only one patient had a relapse with optic neuritis. Conclusion In our study,MOG antibody-associated disease showed a slight female predominance and frequently presented as acute disseminated encephalomyelitis. The supratentorial lesions were often located in the thalamus and subcortical white matter,while the infratentorial lesions were frequently in the pons. Intravenous pulse steroid therapy was effecitve in the acute phase. The majority of the patients had a favorable outcome.

Objective:To explore the mediating effect of self-compassion between family cohesion and loneliness among adolescents.Method:From November to December 2020, a total of 626 adolescents were investigated with the family adaptability and cohesion scale, children loneliness scale and the self-compassion scale short form.Data were analyzed by SPSS 23.0 and PROCESS v 2.16 softwares.The statistical methods included t-test, one-way ANOVA, Pearson correlation analysis and intermediary effect analysis. Results:Compared with girls, boys’ score of family cohesion((63.52±8.47), (65.48±9.07)) was significantly lower but the scores of self-compassion((37.68±5.26), (36.49±5.75)) and loneliness((37.74±10.44), (36.01±10.48)) were significantly higher( t=-2.79, 2.06, 2.70; all P<0.05). There was no significant difference in the scores of family cohesion((63.67±8.71), (64.74±8.85)), self-compassion((37.45±5.71), (36.98±5.49)) and loneliness((36.60±10.52), (36.96±10.49)) between left-behind and non-left-behind children( t=1.29, -0.87, 0.38, all P>0.05). The score of family cohesion of the adolescents from Grade 7 was significantly lower than those of Grade 8, Grade 10 and Grade 11( P<0.01), while the score of self-compassion of the adolescents from Grade 10 was significantly lower than those of Grade 7 and Grade 11(both P<0.01), but the score loneliness of the adolescents from Grade 11 was significantly lower than those of Grade 8 and Grade 10(both P<0.05). Family cohesion(64.50±8.82)was significantly positively associated with self-compassion(37.09±5.54)( r=0.22; P<0.01). Loneliness(36.88±10.49)were significantly negatively associated with self-compassion( r=-0.27, P<0.01) and family cohesion( r=-0.28, P<0.01). The relation between family cohesion and loneliness was partly mediated by self-compassion and the effect of mediation was 20.9%. Conclusion:Family cohesion will not only directly affect the loneliness of adolescents, but also affect loneliness through the mediating effect of self-care.

Post-stroke insomnia is very common in clinic. Most clinicians regard post-stroke insomnia as common insomnia without considering the particularity of stroke patients. There are many kinds of hypnotics in clinic, and the mechanism and side effects of various hypnotics are different; however, the choice of drugs for post-stroke insomnia is entirely based on experience, and the curative effect is different. This review describes the drug selection of post-stroke insomnia.

An intravascular ultrasound-enhanced thrombolysis excitation system with adjustable frequency, amplitude and duty cycle was designed based on FPGA (ZYNQ-7Z020). Firstly, the FPGA generated waveform amplitude binary data based on direct digital frequency synthesis (DDS) technology, and then the data was converted into burst signal through an external daughter card, which included D/A conversion circuit, active low-pass filter, power amplifier circuit and impedance matching circuit. The test results demonstrated that the output waveform reached the target with advantages of simple implementation and flexible control, the peak negative pressure generated from ultrasound transducer was doubled by means of an electrical impedance matching network. In vitro thrombus models were applied to verify the excitation system, it turned out that ultrasound cavitation effect generated could accelerate the penetration of urokinase and increase the thrombolysis rate by about 20%.
Amplifiers, Electronic ; Electric Impedance ; Thrombolytic Therapy ; Ultrasonography ; Ultrasonography, Interventional

Objective To discover the medicinal active molecules from the fermentation extract of sponge-symbiotic Streptomyces sp. LHW2432. Methods Compounds were isolated and purified from the fermentation extract of LHW2432 by silica gel, ODS chromatographic columns, and HPLC. The structures of the compounds were elucidated based on the analyses of modern spectrum technologies and the related literatures research. Through plate coating method and broth microdilution method, the antimicrobial activities were tested by the indicator strains of Bacillus mycoides, methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium smegmatis, Candida Albicans, and Escherichia coli. Results Five compounds were discovered and their structures were identified as descycloavandulyl-lavanduquinocin (1), N-acetyltyramine (2), phomapyrone C (3), germicidin A (4), and germicidin I (5). Compound 1 showed inhibitory activities against MRSA (MIC, 100 μg/ml) and M. smegmatis (MIC, 64 μg/ml), respectively. Conclusion Five compounds were discovered from LHW2432, among which compound 1 was a new natural product and could be used as a precursor of the tricyclic carbazole alkaloids with neuroprotective activity. Moreover, compound 1 showed weak inhibitory activities against gram-positive pathogenic bacteria.