ObjectiveTo understand the whole genome characteristics and the information for genetic evolution in the two coxsackievirus A2 (CVA2) strains isolated from patients with herpangina in Shanghai, and to provide a scientific basis for the prevention and treatment of herpetic angina. MethodsTwo CAV2 strains isolated from patients with herpetic angina in Shanghai were performed whole genome sequencing and analysis for phylogenetics, nucleotide homology, and evolution. ResultsA phylogenetic analysis of the VP1 region revealed that the two Shanghai strains both belonged to CVA2 genotype D, with the highest homology to OL357660, a strain from Yunnan. The average nucleotide identity (ANI) of the whole genome between the two Shanghai strains was 98.88%, and the ANI of the whole genome comparisons to other CVA2 genotype D strains and CVA2 genotypes A-C strains ranged from 84.64% to 97.42% and from 79.21% to 84.20%, respectively. The two Shanghai strains had low homology in the 3D region compared to the existing CVA2 strains. The phylogenetic analysis and sliding window nucleotide similarity analysis indicated that the two Shanghai strains and the Yunnan OL357660 strain might constitute a new genetic lineage. ConclusionThe two CVA2 strains isolated for the first time in Shanghai are assigned to genotype D (GenBank: PQ130039 and PQ130040), which is identical to the existing subtype prevalent in China. As represented by the Shanghai strains, a new CVA2 genetic lineage is been identified. This study has enriched the data on genetic evolution and genetic variation of CVA2 in Shanghai, indicating the requirement to strengthen surveillance for the epidemiological pattern of CVA2.

The current classification methods for traditional Chinese medicine （TCM） visceral syndrome differentiation suffer from excessive generalization， which hinders their clinical application. Based on the analysis of the pattern of "one syndrome corresponding to multiple formulas"， this paper focused on the principle of syndrome-formula correspondence， and proposed that formula-syndromes are the smallest units for refining visceral syndromes. By establishing the correspondence between formula-syndromes and visceral syndromes， this study aims to further clarify the refined categories of syndromes and their treatment patterns， providing a new perspective for the standardization and objectification of TCM syndromes.

OBJECTIVE: To analyze the rules of moxibustion for low back pain by ZHOU Meisheng by using data mining and knowledge graph technology. METHODS: Taking the medical cases of moxibustion for low back pain from ZHOU Meisheng's legacy manuscripts and existing works as the research objects, information on disease types, symptoms, tongue manifestations, pulse conditions, syndrome patterns, moxibustion methods and acupoints were collected. Frequency statistics and community analysis were conducted by the ancient and modern medical record cloud platform V 2.3.7, cluster analysis of high-frequency acupoints was performed by SPSS26.0, association rule analysis of high-frequency acupoints was performed by SPSS Modeler 18.0, and the generated linked data were imported into Cytoscape 3.9.1 for complex network analysis. Knowledge graph of moxibustion for low back pain by ZHOU Meisheng was constructed based on the results of data mining. The data storage and display of knowledge graph were realized through the Neo4j 3.5.25 graph database, and the Cypher query language was used for knowledge graph retrieval and discovery. RESULTS: A total of 219 medical cases were collected, involving 14 disease types, 85 related clinical symptoms, 5 related TCM syndrome types, and 6 moxibustion methods. The acupoints were mostly attributed to the governor vessel, the bladder meridian of foot-taiyang, non-meridian and non-acupoint areas. The core prescription of acupoints derived from complex network analysis included tender points, Shenshu (BL23), Jinsuo (GV8), Yinjiao (CV7), Yaoyangguan (GV3), Yanglingquan (GB34), which were largely coincides with high-frequency acupoints. Cluster analysis obtained 4 cluster combinations. Community analysis yielded 6 communities, each corresponding to different acupoints.The constructed knowledge graph contained 187 nodes and 696 relationships, by retrieving clinical elements related to low back pain, the disease-moxibustion association graph, disease-acupoint association graph, accompanying symptom-acupoint association graph and syndrome type-matching point association graph were obtained. CONCLUSION When treating low back pain with moxibustion, ZHOU Meisheng adopts the principle of promoting circulation, distinguishing diseases to determine the treatment, selecting acupoints according to the diseases, and matching points according to the symptoms.And taking tender points, Shenshu (BL23), Jinsuo (GV8), Yinjiao (CV7), Yaoyangguan (GV3), Yanglingquan (GB34) as core acupoints, combined with tenderness point selection, acupoint selection based on meridian and zangfu syndrome differentiation, "sunshine area" acupoint selection, yin-yang acupoint matching. Additionally, he skillfully employs special points, such as Zhongzhu (KI15) and ear tips, pays attention to the reform of moxibustion tools, and innovates the moxibustion techniques, using distinctive moxibustion tools and methods to treat low back pain.
Moxibustion/methods* ; Humans ; Data Mining ; Low Back Pain/history* ; Acupuncture Points ; History, Ancient ; Female ; China ; Male ; Adult ; Middle Aged

Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Learning-associated functional plasticity at hippocampal synapses remains largely unexplored. Here, in a single session of reward-based trace conditioning, we examine learning-induced synaptic plasticity in the dorsal CA1 hippocampus (dCA1). Local field-potential recording combined with selective optogenetic inhibition first revealed an increase of dCA1 synaptic responses to the conditioned stimulus (CS) induced during conditioning at both Schaffer collaterals to the stratum radiatum (Rad) and temporoammonic input to the lacunosum moleculare (LMol). At these dCA1 inputs, synaptic potentiation of CS-responding excitatory synapses was further demonstrated by locally blocking NMDA receptors during conditioning and whole-cell recording sensory-evoked synaptic responses in dCA1 neurons from naive animals. An overall similar time course of the induction of synaptic potentiation was found in the Rad and LMol by multiple-site recording; this emerged later and saturated earlier than conditioned behavioral responses. Our experiments demonstrate a cued memory-associated dCA1 synaptic plasticity induced at both Schaffer collaterals and temporoammonic pathways.
Animals ; CA1 Region, Hippocampal/physiology* ; Male ; Association Learning/physiology* ; Neuronal Plasticity/physiology* ; Cues ; Memory/physiology* ; Synapses/physiology* ; Conditioning, Classical/physiology* ; Excitatory Postsynaptic Potentials/physiology* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Rats ; Optogenetics

Periodontitis has emerged as one of the most critical oral diseases, and research on this condition holds great importance for the advancement of stomatology. As the most authoritative national scientific research funding institution in China, the National Natural Science Foundation of China (NSFC) has played a pivotal role in driving the progress of periodontal science by supporting research on periodontitis. This article provides a comprehensive review of the research and development progress related to periodontitis in China from 2014 to 2023, highlighting the significant contributions of the NSFC to this field. We have summarized the detailed funding information from the NSFC, including the number of applicant codes, funded programs and the distribution of funded scholars. These data illustrate the efforts of the NSFC in cultivating young scientists and building research groups to address key challenges in national scientific research. This study offers an overview of the current hot topics, recent breakthroughs and future research prospects related to periodontitis in China.
China ; Periodontitis ; Humans ; Foundations ; Research Support as Topic ; Natural Science Disciplines ; Dental Research/economics*

OBJECTIVE: Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Huachansu (Cinobufacini) is active extract isolated from the dry skin of Bufo Bufo gargarizans. It has now been widely used in clinical treatment of cancer, this study is to clarify the material basis of down-regulation of thymidylate synthase (TYMS) induced by Huachansu. METHODS: Our study utilized UPLC-MS/MS to identify major bioactive components from Huachansu. Cell Counting Kit 8 (CCK-8) assay and clone formation assay were used to examine the cell viability of tumor cells. TYMS and γ-H2AX level were detected by using quantitative real-time RT-PCR and/or western blotting. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of TYMS could enhance the suppressive effect of Huachansu on cell growth of HCC cells. RESULTS: In our study, firstly, we identify 21 major bioactive components from Huachansu. CCK-8 assay results showed that Huachansu and its bioactive bufadienolides (Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin) significantly inhibited the proliferation of HepG2 and SK-HEP-1 cells in a dose- and time-dependent manner. Further molecular mechanistic investigation demonstrates that Huachansu significantly suppresses thymidylate synthase (TYMS), the enzyme which provides the sole de novo source of thymidylate for DNA synthesis. The inhibition of TYMS could lead to cell-cycle block and DNA damage of HCC cells. Furthermore, we identified that Huachansu markedly increased γ-H2AX expression, which indicated the presence of DNA damage. Moreover, we confirmed that transfection of cells with small interfering RNA specific to TYMS could increase the suppressive effects of Huachansu on the HCC cells proliferation. Quantitative RT-PCR analysis showed that Huachansu treatment had no effect on the transcription level of TYMS. Furthermore, proteasomal inhibitor MG132 could block TYMS inhibition induced by Huachansu, and concomitant administration of protein synthesis inhibitor cycloheximide (CHX) with Huachansu could further suppress the protein level of TYMS, indicating that Huachansu promotes proteasome-dependent degradation of TYMS in liver cancer cells. More importantly, the bioactive bufadienolides of Huachansu such as Bufalin, Bufotalin, Cinobufotalin, Desacetylcinobufagin, Arenobufagin, Telocinobufagin, and Resibufogenin could also significantly restrain the protein level of TYMS, revealing the material basis of inhibition of TYMS exposed to Huachansu. 5-Fluorouracil (5-FU) is a TYMS inhibitor, we also evaluate the effects of the combined treatment of Huachansu with 5-FU, the results show that interactions between Huachansu and 5-FU are synergistic or antagonistic. Thus, in clinical, attention should be paid to the dosage of Huachansu in combination with 5-FU. CONCLUSION Huachansu inhibits the growth and induces DNA damage of human HCC cells through proteasome-dependent degradation of TYMS, bioactive bufadienolides are the material basis of down-regulation of TYMS induced by Huachansu.