[摘 要] 目的：探究着丝粒蛋白M（CENPM）在脑胶质瘤中的表达特征、临床预后价值及其对肿瘤恶性生物学行为的调控机制，为脑胶质瘤的精准治疗提供潜在靶点。方法：基于中国胶质瘤基因组图谱（CGGA）和癌症基因组图谱（TCGA）数据库分析CENPM在胶质瘤中的表达及其与患者临床病理特征和预后的相关性。通过基因本体论（GO）分析、京都基因与基因组百科全书（KEGG）富集分析和单细胞转录组分析探索CENPM的生物学功能和作用机制。WB法检测CENPM在胶质瘤细胞（LN-18、LN-229、U-138MG、U-251MG）和正常胶质细胞（HEB）中的表达；构建CENPM敲低细胞后，通过CCK-8、集落形成、Transwell和划痕实验评估恶性表型改变。结果：CENPM在WHO高级别胶质瘤中呈高表达（P < 0.05），与肿瘤恶性程度正相关。高表达组患者总体生存期显著短于低表达组（P < 0.01），Cox回归证实CENPM是影响胶质瘤患者预后的独立危险因素（P < 0.05）。功能富集分析结果显示CENPM相关基因主要富集于细胞周期调控、PI3K-Akt通路和免疫相关过程。单细胞分析结果显示CENPM主要在CD8⁺ T细胞高表达，并通过PTN-PTPRZ1/NCL配受体调控细胞通信。体外实验证实CENPM在胶质瘤细胞表达高于正常胶质细胞（LN-18：P < 0.01，LN-299：P < 0.05）；敲低CENPM显著抑制迁移（P < 0.05），但增强集落形成，提示其在肿瘤进展中的双重调控作用。结论：CENPM作为胶质瘤独立预后危险因子，通过调控细胞周期、PTN通路和免疫微环境驱动肿瘤进展，其差异化调控机制（抑制迁移、促进增殖）具有潜在的临床转化价值，可作为分子分型和靶向治疗候选标志物。

Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority. Our previous research demonstrated the efficacy of artesunate (ART) in alleviating liver fibrosis by eliminating activated hepatic stellate cells (HSCs). However, the underlying mechanism remains unclear despite these findings. Notably, endocytic adaptor protein (NUMB) has significant implications for treating hepatic diseases, but current research primarily focuses on liver regeneration and hepatocellular carcinoma. The precise function of NUMB in liver fibrosis, particularly its ability to regulate HSCs, requires further investigation. This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs. We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs, exhibiting a negative correlation with the progression of liver fibrosis. Additionally, ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor (P53) axis. We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate. This research examines the specific target of ART in eliminating activated HSCs, providing both theoretical and experimental evidence for the treatment of liver fibrosis.
Hepatic Stellate Cells/cytology* ; Liver Cirrhosis/genetics* ; Artesunate/pharmacology* ; Cellular Senescence/drug effects* ; Membrane Proteins/genetics* ; Animals ; Humans ; Nerve Tissue Proteins/genetics* ; Tumor Suppressor Protein p53/genetics* ; Male ; Mice

Objective:To explore the effect of staged pressure therapy, in addition to rehabilitation training, on scar hyperplasia and motor function after a deep hand burn.Methods:Sixty patients with deep hand burns were randomly divided into a control group ( n=30) and an observation group ( n=30). In addition to specialized burn treatment and early rehabilitation training, the control group was given routine pressure treatment, while the observation group was provided with staged pressure therapy for 6 months. Before the treatment and after 3 and 6 months of treatment, scar hyperplasia and hand function in both groups was evaluated using the Vancouver scar scale (VSS), grip strength and pinch strength tests, and the Jebsen hand function test (JHFT). Total active motion (TAM) and total passive motion (TPM) of the finger joints was quantified, and any complications during the treatment were recorded. Results:After 3 and 6 months of the treatment, all of the observations in both groups had improved significantly, but the improvements were significantly better among the treatment group, on average.Conclusions:Staged pressure therapy can more effectively inhibit scar hyperplasia after a deep hand burn. In conjunction with rehabilitation training, it better improves the mobility of the finger joints, hand muscle strength and the recovery of hand function. It is worthy of clinical promotion and application.

OBJECTIVE To explore the active components of Curcumae Rhizome as well as its potential value for the treatment of chronic pancreatitis(CP)using a combination of network pharmacology and bioinformatic approaches.METHODS Network pharma-cology methods were used to screen the active ingredients of Curcumae Rhizome and potential therapeutic targets for CP,and their ex-pression abundance and distribution in different cell types of CP were further analyzed in combination with CP tissue RNA sequencing data from publicly available databases.Molecular docking was performed to analyze the binding of the active components of Curcumae Rhizome to CP-related targets.Finally,the role of these core targets in pancreatic stellate cell(PSC)activation and related pathways was analyzed by single-cell RNA-sequencing to assess the anti-inflammatory and anti-fibrotic potential of the active ingredients of Curcumae Rhizome in CP treatment.RESULTS The most effective component of Curcumae Rhizome,Hederagenin,was identified by network pharmacological analysis,and its two therapeutic targets associated with CP were identified:LYZ and Rxra.Molecular doc-king results demonstrated that Hederagenin had an extremely strong binding capacity to the Rxra protein(affinity score=-7.392 kcal·mol-1),a core target of CP.Single-cell RNA-sequencing analysis further demonstrated that the hub target Rxra gene was closely associated with PSC activation and played an important role in PTN and TGF-β signaling pathways,the activation of which played a crucial role in the progression of chronic inflammation and fibrosis.CONCLUSION Curcumae Rhizome may provide new clues for the treatment of CP by inhibiting PSC activation.

OBJECTIVE To explore the active components of Curcumae Rhizome as well as its potential value for the treatment of chronic pancreatitis(CP)using a combination of network pharmacology and bioinformatic approaches.METHODS Network pharma-cology methods were used to screen the active ingredients of Curcumae Rhizome and potential therapeutic targets for CP,and their ex-pression abundance and distribution in different cell types of CP were further analyzed in combination with CP tissue RNA sequencing data from publicly available databases.Molecular docking was performed to analyze the binding of the active components of Curcumae Rhizome to CP-related targets.Finally,the role of these core targets in pancreatic stellate cell(PSC)activation and related pathways was analyzed by single-cell RNA-sequencing to assess the anti-inflammatory and anti-fibrotic potential of the active ingredients of Curcumae Rhizome in CP treatment.RESULTS The most effective component of Curcumae Rhizome,Hederagenin,was identified by network pharmacological analysis,and its two therapeutic targets associated with CP were identified:LYZ and Rxra.Molecular doc-king results demonstrated that Hederagenin had an extremely strong binding capacity to the Rxra protein(affinity score=-7.392 kcal·mol-1),a core target of CP.Single-cell RNA-sequencing analysis further demonstrated that the hub target Rxra gene was closely associated with PSC activation and played an important role in PTN and TGF-β signaling pathways,the activation of which played a crucial role in the progression of chronic inflammation and fibrosis.CONCLUSION Curcumae Rhizome may provide new clues for the treatment of CP by inhibiting PSC activation.

Objective:To explore the effect of staged pressure therapy, in addition to rehabilitation training, on scar hyperplasia and motor function after a deep hand burn.Methods:Sixty patients with deep hand burns were randomly divided into a control group ( n=30) and an observation group ( n=30). In addition to specialized burn treatment and early rehabilitation training, the control group was given routine pressure treatment, while the observation group was provided with staged pressure therapy for 6 months. Before the treatment and after 3 and 6 months of treatment, scar hyperplasia and hand function in both groups was evaluated using the Vancouver scar scale (VSS), grip strength and pinch strength tests, and the Jebsen hand function test (JHFT). Total active motion (TAM) and total passive motion (TPM) of the finger joints was quantified, and any complications during the treatment were recorded. Results:After 3 and 6 months of the treatment, all of the observations in both groups had improved significantly, but the improvements were significantly better among the treatment group, on average.Conclusions:Staged pressure therapy can more effectively inhibit scar hyperplasia after a deep hand burn. In conjunction with rehabilitation training, it better improves the mobility of the finger joints, hand muscle strength and the recovery of hand function. It is worthy of clinical promotion and application.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.

BACKGROUND:Rotator cuff muscle degeneration(muscle atrophy,fibrosis and fatty infiltration)is a common condition after rotator cuff tears,which seriously affects shoulder function and surgical outcomes.Ginsenoside Rg1 has biological effects such as anti-oxidation,anti-apoptosis and lipid-lowering.However,the effect of ginsenoside Rg1 on muscle degeneration after rotator cuff tear has not been reported. OBJECTIVE:To investigate the effect of ginsenoside Rg1 on muscle degeneration after massive rotator cuff tear in mice. METHODS:Sixty C57BL/6J mice were randomly divided into sham group,model group,ginsenoside Rg1 low dose group and ginsenoside Rg1 high dose group,with 15 mice in each group.The skin of the right shoulder of mice in the sham group was cut and sutured.Massive rotator cuff tear mouse models of the right shoulder were established in the other three groups.Supraspinatus tendon and suprascapular nerve compression were administrated.Mice in the sham and model groups were intraperitoneally injected with 0.5 mL of saline after operation,while those in the ginsenoside Rg1 low and high dose groups were intraperitoneally injected with ginsenoside Rg1 30 and 60 mg/kg respectively,once a day,for 6 weeks.Mice were assessed for limb function by gait analysis the day after the last injection.After euthanasia,the supraspinatus muscle on the operated side was taken to measure the muscle atrophy rate and muscle contractility.Muscle tissue was stained with oil red O and Masson.RT-PCR was used to detect the expression of atrophy,fibrosis,and fatty infiltration related genes. RESULTS AND CONCLUSION:Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased paw print area and step length(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly increased myofiber cross-sectional area and supraspinatus contractility(P<0.05),and significantly decreased wet muscle mass reduction ratio,fatty infiltration area ratio,and collagen fiber area ratio(P<0.05).Compared with the model group,low-and high-dose ginsenoside Rg1 significantly decreased the expression of atrophy,fibrosis,and fatty infiltration related genes(P<0.05).There was no significant difference in paw print area,supraspinatus muscle contractility,and myofiber cross-sectional area between ginsenoside Rg1 low and high dose groups(P>0.05),and all other indexes were better in the ginsenoside Rg1 high dose group than in the ginsenoside Rg1 low dose group(P<0.05).To conclude,ginsenoside Rg1 could significantly reduce muscle atrophy,fibrosis and fatty infiltration following massive rotator cuff tear in mice,which is beneficial to improve muscle strength and limb function.