From the perspective of circular RNA forkhead box protein O3(circFOXO3) regulating glycolysis in osteoarthritis(OA) chondrocytes, this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC) alleviated OA degeneration. In in vivo experiments, after randomized grouping and relevant interventions, morphological staining was used to observe structural changes in cartilage tissue. The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR). Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and matrix metalloproteinase 13(MMP13). In in vitro experiments, fluorescence in situ hybridization(FISH) was used to detect circFOXO3 expression in chondrocytes from each group. A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3) chondrocytes. RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing, and Western blot was used to assess the regulatory effects of TGXTC on GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions. Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group. The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups, while the expression of the above-mentioned proteins was significantly reduced. FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes. In the circFOXO3 silencing experiment, compared with the IL-1β group, circFOXO3 levels in the IL-1β + sh-circFOXO3 group were significantly decreased. Compared with the IL-1β + TGXTC group, circFOXO3 levels were significantly reduced in the IL-1β + sh-circFOXO3 + TGXTC group. Western blot results indicated that the elevated levels of GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention. However, this regulatory effect was attenuated after circFOXO3 silencing. In conclusion, TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.
Chondrocytes/metabolism* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; RNA, Circular/metabolism* ; Osteoarthritis/genetics* ; Glycolysis/drug effects* ; Humans ; Forkhead Box Protein O3/metabolism* ; Male ; Capsules ; Matrix Metalloproteinase 13/genetics*

In recent years, the study of single-cell transcriptome sequencing technology in the heterogeneity of astrocytes (astrocytes) after spinal cord injury (SCI) has provided new perspectives on post-traumatic nerve regeneration and repair. To provide a review on the research progress of single-cell sequencing technology in astrocytes after spinal cord injury (SCI), and to more comprehensively and deeply elaborate the application of single-cell sequencing technology in the field of astrocytes after SCI. Single-cell sequencing technology can analyse the transcriptomes of individual cells in a high-throughput manner, thus revealing fine differences in cell types and states. By using single-cell sequencing technology, the heterogeneity of astrocytes after SCI and their association with nerve regeneration and repair were revealed. In conclusion, the application of single-cell sequencing technology provides an important tool to reveal the heterogeneity of astrocytes after SCI, to further explore the mechanisms of astrocytes in SCI, and to develop intervention strategies targeting their regulatory mechanisms in order to improve the therapeutic efficacy of SCI. The discovery of changes in astrocyte transcriptome dynamics has improved researchers' understanding of spinal cord injury lesion progression and provided new insights into the treatment of spinal cord injury at different time points. To date, all of these findings need to be validated by more basic research and sufficient clinical trials. In the future, single-cell sequencing technology, through interdisciplinary collaboration with bioinformatics, computer science, tissue engineering, and clinical medicine, is expected to open a new window for the treatment of spinal cord injury.
Spinal Cord Injuries/metabolism* ; Astrocytes/cytology* ; Single-Cell Analysis/methods* ; Humans ; Animals ; Transcriptome ; Nerve Regeneration

Inhibiting glutamine metabolism has been proposed as a potential treatment strategy for improving non-alcoholic steatohepatitis (NASH). However, effective methods for assessing dynamic metabolic responses during interventions targeting glutaminolysis have not yet emerged. Here, we developed a positron emission tomography (PET) imaging platform using l-[5-¹¹C]glutamine ([¹¹C]Gln) and evaluated its efficacy in NASH mice undergoing metabolic therapy with bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a glutaminase 1 (GLS1) inhibitor that intervenes in the first and rate-limiting step of glutaminolysis. PET imaging with [¹¹C]Gln effectively delineated the pharmacokinetics of l-glutamine, capturing its temporal-spatial pattern of action within the body. Furthermore, [¹¹C]Gln PET imaging revealed a significant increase in hepatic uptake in methionine and choline deficient (MCD)-fed NASH mice, whereas systemic therapeutic interventions with BPTES reduced the hepatic avidity of [¹¹C]Gln in MCD-fed mice. This reduction in [¹¹C]Gln uptake correlated with a decrease in GLS1 burden and improvements in liver damage, indicating the efficacy of BPTES in mitigating NASH-related metabolic abnormalities. These results suggest that [¹¹C]Gln PET imaging can serve as a noninvasive diagnostic platform for whole-body, real-time tracking of responses of glutaminolysis to GLS1 manipulation in NASH, and it may be a valuable tool for the clinical management of patients with NASH undergoing glutaminolysis-based metabolic therapy.

OBJECTIVE: This study reports the first imported case of Lassa fever (LF) in China. Laboratory detection and molecular epidemiological analysis of the Lassa virus (LASV) from this case offer valuable insights for the prevention and control of LF. METHODS: Samples of cerebrospinal fluid (CSF), blood, urine, saliva, and environmental materials were collected from the patient and their close contacts for LASV nucleotide detection. Whole-genome sequencing was performed on positive samples to analyze the genetic characteristics of the virus. RESULTS: LASV was detected in the patient's CSF, blood, and urine, while all samples from close contacts and the environment tested negative. The virus belongs to the lineage IV strain and shares the highest homology with strains from Sierra Leone. The variability in the glycoprotein complex (GPC) among different strains ranged from 3.9% to 15.1%, higher than previously reported for the seven known lineages. Amino acid mutation analysis revealed multiple mutations within the GPC immunogenic epitopes, increasing strain diversity and potentially impacting immune response. CONCLUSION The case was confirmed through nucleotide detection, with no evidence of secondary transmission or viral spread. The LASV strain identified belongs to lineage IV, with broader GPC variability than previously reported. Mutations in the immune-related sites of GPC may affect immune responses, necessitating heightened vigilance regarding the virus.
Humans ; China/epidemiology* ; Genome, Viral ; Lassa Fever/virology* ; Lassa virus/classification* ; Molecular Epidemiology ; Phylogeny

The 2024 National Education Work Conference pointed out that at the current juncture of the critical period for achieving the goals and tasks of the 14th Five-Year Plan,the implementation of the Education Powerhouse Construction Plan Outline should be taken as the main line of work,and building first-class disciplines is an crucial task for a higher education powerhouse.In 2022,forensic medicine was officially listed as a first-level discipline under the medical category,presenting an un-precedented historical opportunity for the development of forensic medicine.The forensic medicine dis-cipline of Southern Medical University comprehensively improves the quality of talent cultivation and facilitates the construction of first-class disciplines as its main direction.It aims to initiate and imple-ment a high-level faculty team building plan featuring"combining recruitment and cultivation,inter-disciplinary integration";make vigorous efforts to establish a first-level doctoral program,refine advan-tageous second-level disciplines and research directions;and establish an innovative research platform from a high starting point with deep integration.The discipline adheres to moral cultivation and the Five Domains of Education simultaneous development,to build a high-quality talent joint training model.Guided by the construction of the national legal system and industry needs,the discipline will enhance social service capabilities.The forensic medicine construction in our university will continue to contribute to the rule of law in China and educational power.

Objective To investigate the effect of senkyunolide I(SEN I)on neuronal apoptosis in sepsis-associated encephalopathy(SAE)rats via modulation of the mixed-lineage kinase 3(MLK3)/c-Jun N-terminal kinase 3(JNK3)signaling pathway.Methods Screening for a SAE model by monitoring neurobehavioral and electroencephalographic alterations in rats with sepsis induced by cecal ligation and puncture(CLP).Divided into normal control group,sham operation group,sepsis without encephalopathy group,SAE model group,SAE+MLK3/JNK3 signaling pathway inhibitor(URMC-099)group,SAE+low-dose SEN I group(36 mg/kg),and SAE+high-dose SEN I group(144 mg/kg),with 10 animals in each group.After 30 minutes of successful modeling,intraperitoneal injection was administered according to the group,and the administration was completed within 24 hours.HE staining was used to observe the pathological conditions of hippocampal tissue under a light microscope,transmission electron microscopy was used to observe changes in the morphology of neuronal nuclei,cytoplasm,and mitochondrial ultrastructure,TUNEL staining was used to detect hippocampal neuronal apoptosis,and Western blotting was used to detect the expression levels of p-JNK3,JNK3,p-MLK3,MLK3,and Fas ligand(Fas-L)proteins.Results Compared with the normal control group and sham surgery group,the sepsis without encephalopathy group showed no significant changes in neuronal structural morphology and neuronal apoptosis,and there were no significant differences in the expression of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＞0.05).However,the SAE model group had aggravated neuronal structural morphology damage,increased neuronal apoptosis rate,and increased expression level of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＜0.01);Compared with the SAE model group,the inhibitor URMC-099 and SEN I treatment groups showed significant improvement in neuronal structural and morphological damage,decreased neuronal apoptosis rates,and reduced p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L protein expression(P＜0.01),with the high-dose SEN I group showing more significant improvement.Conclusion SEN I effectively reduces neuronal apoptosis in SAE and exerts neuroprotective effects on SAE by inhibiting the activation of the MLK3/JNK3 signaling pathway.

With the rapid development of information technology， research on ancient TCM books has shifted from the traditional collation and digitization into intelligent knowledge service， thereby achieving the deep integration of ancient TCM books collation and clinical needs. Based on the clinical problem and knowledge element theory， we implemented in-depth indexing and knowledge mining for 600 kinds of ancient TCM books， built a knowledge sharing service platform for ancient TCM books by integrating database， cloud platform， knowledge graph and other technologies， and carried out the thematic literature research and developed databases for four major diseases including stroke， heart failure， liver cirrhosis， and diabetes. The digital intelligence products have been applied in hundreds of hospitals for evaluation and feedback. Finally， through "digital processing plus intelligent application"， the two-way interaction between ancient TCM books and current clinical practice is realized， and the path and paradigm of ancient TCM books knowledge serving the modern prevention and control of major diseases is formed， providing reference for the innovative utilization of ancient TCM books.

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the country.Several guidelines have been used to diagnose and treat liver cancer.However,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual patients.Therefore,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi method.The classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were developed.These recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment prognosis.The findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

Objective To explore the potential mechanism of Erzhi Wan in the treatment of multiple myeloma(MM)based on network pharmacology,molecular docking and cell experimental verification.Methods Network pharmacology and molecular docking were used to screen the key indicators of drugs-diseases-targets-pathways.MM line RPMI-8226 cells were cultured and given Erzhi Wan intervention.Apoptosis was detected by Annexin V-fluorescein isothiocyanate(FITC)staining.Transwell assay was used to determine cell invasion ability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the mRNA expressions of protein kinase B(Akt),cyclin D1(CCND1),glycogen synthase kinase 3β(GSK-3β)and c-Myc.Western Blot was used to detect the protein expressions of Akt,phosphorylated protein kinase B(p-Akt),CCND1,c-Myc,GSK-3β and phosphorylated glycogen synthase kinase 3β(p-GSK-3β).Results Fourteen effective components of Erzhi Wan were obtained.There were 142 targets involved in the treatment of MM by Erzhi Wan.The results of pathway enrichment analysis showed that the key targets may be mainly concentrated in cancer pathways,lipids and atherosclerosis.Molecular docking results showed that luteolin and quercetin had good binding activity and stability with GSK-3β.Further cell experimental verification showed that compared with the blank group,the apoptosis rate of cells in the low-,medium-and high-dose groups of Erzhi Wan was significantly increased,the number of cell invasion was decreased,the mRNA and protein levels of GSK-3β were significantly increased,and the mRNA and protein levels of CCND1,Akt and c-Myc were significantly decreased in a dose-dependent manner,among them,the differences in the medium-and high-dose groups being statistically significant(P＜0.05 or P＜0.01).Conclusion The therapeutic effect of Erzhi Wan on MM may be achieved by promoting the expression of GSK-3β and inhibiting the Akt/GSK-3β/CCND1/c-Myc signaling pathway through key active components such as luteolin and quercetin.