Neddylation is a crucial posttranslational modification that involves the attachment of neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to a lysine residue in the substrate via the sequential actions of the E1 NEDD8-activating enzyme (NAE) (E1), E2 NEDD8-conjugating enzyme (E2), and E3 NEDD8-ligase (E3). The most extensively studied substrates of neddylation are members of the cullin family, which act as scaffold components for cullin ring E3 ubiquitin ligases (CRLs). Since cullin neddylation activates CRLs, which are frequently overactive in tumors, inhibiting neddylation has emerged as a promising strategy for developing novel antitumor therapies. This review explores the antitumor effects of inhibiting neddylation that leads to the inactivation of CRLs and provides a summary of known inhibitors that target protein-protein interactions (PPIs) within the neddylation enzymatic cascade.

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Medical imaging technology plays a crucial role in clinical diagnosis and treatment. Image compression technology provides robust technical support for the storage and transmission of massive medical imaging data, serving as an effective safeguard for hospital data backup and telemedicine. The technology holds broad application prospects in the medical field, enabling the processing of various imaging modalities, multidimensional imaging, and medical video imaging. This study elaborates on general image and video compression algorithms, the application of compression algorithms in the medical field, and the performance metrics of medical image compression, thereby providing critical technical support for enhancing clinical diagnostic efficiency and data management security.

The data of 44 scalp acupuncture schools are collected to analyze their commonalities in theoretical foundations, needling sites, techniques, and indications. The integration of these characteristics into an optimized, unified scalp acupuncture protocol has become an inevitable trend. The paper discusses the potential for a unified scalp acupuncture protocol from aspects such as theoretical unification, the relationships between point areas, lines, and sites, and needle numbers. It also explores the primary issues and solutions involved in unifying scalp acupuncture protocols, providing a reference for standardization and unification in scalp acupuncture protocol.
Scalp ; Humans ; Acupuncture Therapy/methods* ; Acupuncture Points

This article analyzes the current status of the researches on acupuncture-moxibustion for idiopathic facial palsy (Bell's palsy). Acupuncture-moxibustion is widely applied in treatment of Bell's palsy and the relevant researches are enriched. But the hierarchical discussion on the effectiveness is reported inadequately. Consequently, the necessity and advantages of acupuncture-moxibustion are hardly prominent. Besides, the safety of acupuncture-moxibustion in treatment is not fully explored. The common shortcomings are presented in professional study and statistical designs, and the quality of the evidences is not high. The recommendation strength of acupuncture-moxibustion is weak in international guidelines. The crucial questions are not deeply discussed, and there are lack of the recognized optimal protocol in clinical practical guidelines. It is suggested that the researches should improve the evaluation of the disease itself that may affect the prognosis of Bell's palsy, such as location, conditions and duration of illness, basic diseases and syndrome/pattern differentiation. The effect of acupuncture-moxibustion should be verified hierarchically, the questions on safety should be emphasized, the quality of study should be improved, the staging of treatment should be specified and the effect of acupuncture-moxibustion should be evaluated in multi-dimensions, and the elements of acupuncture-moxibustion should be optimized systematically in the aspects of timing, acupoint selection, needle devices, manipulation, intervention measures and regimen composition. So as to promote the research of acupuncture-moxibustion for Bell's palsy to a new process.
Humans ; Acupuncture Therapy ; Moxibustion ; Bell Palsy/therapy*

The paper introduces Professor FAN Gangqi's clinical experience in treatment of migraine. Regarding the syndrome/pattern differentiation of TCM, a four-approach framework is established, identifying the nature of illness, analyzing the syndrome/pattern and pathogenesis, determining the stage of illness, and identifying body constitution. In treatment, the principle of treatment is determined in line with syndrome/pattern differentiation, so as to ensure the therapeutic effect by means of "four dimensions". The acupuncture regimens are formulated in terms of the illness stages, "strong needling stimulation in acute stage for analgesia, and needle retaining in chronic stage for long-term effect". "Focusing on neuovascular pathway" is the effective approach to treatment of migraine with acupuncture and moxiubstion. The clinical holistic model by combining acupuncture with medication is advocated because that "the single acupuncture is weak in therapeutic effect, but with medication combined, the effect is enhanced". The different acupuncture techniques are provided comprehensively in treatment of migraine such as horizontal and row-like needling, collateral needling at Taiyang (EX-HN5), acupuncture at Sankong (Yuyao [EX-HN4], Sibai [ST2] and Jiachengjiang [Extra]), acupoint injection at Tianyou (TE16) and Renying (ST9), and acupoint embedding therapy at Fengchi (GB20).
Humans ; Migraine Disorders/diagnosis* ; Acupuncture Therapy ; Moxibustion ; Acupuncture Points ; Female ; Male ; Adult

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

Chronic hepatitis B(CHB)is the main cause of hepatocellular carcinoma(HCC).Early prediction and diagnosis of HCC in CHB patients can further reduce the onset risk of HCC and improve patient prognosis.Scholars at home and abroad have proposed a number of HCC risk prediction models for CHB patients,and these models have achieved new development and opti-mization in the era of antiviral therapy.Due to differences in research backgrounds,these models vary in the use of antiviral drugs,included variables(such as host factors,viral activity,cirrhosis status,etc.)and application scenarios.At the same time,the application of artificial intelligence and liquid biopsy technology in risk prediction models has become a new research highlight.This paper aims to compare the HCC risk prediction models reported so far for CHB patients,clarify the characteristics of each model,explore appropriate HCC risk prediction methods,and provide reference for the risk prediction of hepatitis B virus related HCC.

Background and Aims:Papillary thyroid carcinoma(PTC)is the most common endocrine malignancy in China,with cervical lymph node metastasis being a frequent and critical clinical feature that directly affects patient prognosis and recurrence risk.In recent years,with the rapid increase in the prevalence of overweight and obesity in China,the role of body mass index(BMI)in various tumors has attracted growing attention.This study aimed to investigate the association between overweight and cervical LNM in PTC,analyze sex-specific differences and influencing factors,and provide evidence for precise clinical management.Methods:A retrospective analysis was conducted on the clinicopathologic data of 1 445 patients with classical PTC treated at Xiangya Hospital of Central South University between August 2021 and June 2022.Patients were divided into groups based on the presence or absence of lymph node metastasis.Restricted cubic spline analysis explored the nonlinear relationship between BMI and lymph node metastasis risk.Univariate and multivariate Logistic regression analyses were applied to identify independent risk factors.Furthermore,sex-stratified analysis was performed among overweight patients(BMI≥24 kg/m2)to determine sex-specific risk factors for lymph node metastasis.Results:Among all patients,716(49.6%)had lymph node metastasis.Univariate analysis showed that BMI,sex,age,tumor diameter,multifocality,and extrathyroidal extension were significantly associated with cervical lymph node metastasis in PTC patients(all P<0.05).A nonlinear positive correlation was observed between BMI and lymph node metastasis risk,which was more pronounced in male patients.Additionally,BMI was positively correlated with triglyceride levels and negatively correlated with high-density lipoprotein cholesterol.Sex-stratified analysis revealed that in overweight male patients,younger age(OR=0.954),larger tumor diameter(OR=1.085),and multifocality(OR=2.776)were independent risk factors for LNM;in overweight female patients,younger age(OR=0.943)and larger tumor diameter(OR=1.074)were the main influencing factors.Conclusion:Overweight is closely associated with cervical lymph node metastasis in PTC,and the high-risk factors for LNM differ between male and female overweight patients.Young age,larger tumor size,and multifocality in overweight males,and young age and larger tumors in overweight females indicate a higher risk of metastasis.It is recommended that high-risk populations receive enhanced preoperative evaluation and individualized lymph node dissection strategies to achieve precise treatment and improved risk control.