Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

OBJECTIVE: Treating peripheral nerve injury (PNI) presents a clinical challenge due to limited axon regeneration. Strychni Semen, a traditional Chinese medicine, is clinically used for numbness and hemiplegia. However, its role in promoting functional recovery after PNI and the related mechanisms have not yet been systematically studied. METHODS: A mouse model of sciatic nerve crush (SNC) injury was established and the mice received drug treatment via intragastric gavage, followed by behavioral assessments (adhesive removal test, hot-plate test and Von Frey test). Transcriptomic analyses were performed to examine gene expression in the dorsal root ganglia (DRGs) from the third to the sixth lumbar vertebrae, so as to identify the significantly differentially expressed genes. Immunofluorescence staining was used to assess the expression levels of superior cervical ganglia neural-specific 10 protein (SCG10). The ultra-trace protein detection technique was used to evaluate changes in gene expression levels. RESULTS: Strychni Semen and its active compounds (brucine and strychnine) improved functional recovery in mice following SNC injury. Transcriptomic data indicated that Strychni Semen and its active compounds initiated transcriptional reprogramming that impacted cellular morphology and extracellular matrix remodeling in DRGs after SNC, suggesting potential roles in promoting axon regeneration. Imaging data further confirmed that Strychni Semen and its active compounds facilitated axon regrowth in SNC-injured mice. By integrating protein-protein interaction predictions, ultra-trace protein detection, and molecular docking analysis, we identified myeloperoxidase as a potentially critical factor in the axon regenerative effects conferred by Strychni Semen and its active compounds. CONCLUSION Strychni Semen and its active compounds enhance sensory function by promoting axonal regeneration after PNI. These findings establish a foundation for the future applications of Strychni Semen and highlight novel therapeutic strategies and drug targets for axon regeneration. Please cite this article as: Zhang Y, Zhao XY, Liu MT, Zhou ZC, Cheng HB, Jiang XH, Zheng YR, Chen Z. Strychni Semen and its active compounds promote axon regeneration following peripheral nerve injury by suppressing myeloperoxidase in the dorsal root ganglia. J Integr Med. 2025; 23(2): 169-181.
Animals ; Nerve Regeneration/drug effects* ; Mice ; Peripheral Nerve Injuries/physiopathology* ; Male ; Ganglia, Spinal/enzymology* ; Axons/physiology* ; Peroxidase/antagonists & inhibitors* ; Mice, Inbred C57BL ; Drugs, Chinese Herbal/pharmacology* ; Disease Models, Animal ; Strychnine/pharmacology*

Objective To explore the clinical characteristics of pediatric patients with cerebral palsy(CP)who also have comorbid epilepsy.Methods A retrospective analysis was conducted on the clinical data of 155 pediatric patients with CP and comorbid epilepsy admitted to the Third Affiliated Hospital of Zhengzhou University from January 2019 to December 2022.Patients were divided into 4 groups based on CP subtype:spastic diplegia group(n=29),spastic hemiplegia group(n=33),spastic quadriplegia group(n=73),and non-spastic group(n=20).Differences in sex,season of birth,birth weight,gestational age,and the relationship between gestational age and weight were compared among the groups.Additionally,the relationships between perinatal risk factors,MRI classification system(MRICS),gross motor function classification system(GMFCS),and the age of the first onset of epilepsy with respect to CP subtype were analyzed.Results Among the 155 patients,101 were male and 54 were female.A lower proportion of patients with spastic hemiplegia was observed with a gestational age of 28-31+6 weeks compared with those with spastic diplegia and spastic quadriplegia(P=0.009).The proportion of patients with a history of asphyxia in spastic hemiplegia group was significantly lower than that in the other 3 groups,and the proportion of patients with hypoxic-ischemic encephalopathy(HIE)in spastic hemiplegia group was significantly lower than in that both spastic quadriplegia group and non-spastic group(P<0.05).The proportion of patients in spastic quadriplegia group who had their first seizure at an age of<1 year was significantly higher than that in spastic diplegic group(P=0.041).The spastic diplegia group exhibited a higher percentage of white matter damage compared with the other 3 groups,and had a lower percentage of gray matter damage compared with both spastic hemiplegic group and non-spastic group(P=0.001).The proportion of patients with GMFCS levels Ⅳ-Ⅴ in spastic quadriplegia group was higher than those in the other 3 groups(P<0.001),and the proportion of patients with levels Ⅰ-Ⅲ in spastic hemiplegia group was significantly higher than those in spastic quadriplegia group and non-spastic group(P<0.001).Conclusion Significant differences were observed among pediatric patients with different subtypes of CP and comorbid epilepsy in factors such as gestational age,history of asphyxia,HIE history,age of first seizure,MRICS classification and GMFCS levels.

Purpose To investigate the protective effect and mechanism of A-485 on renal tubular injury in diabetic mice.Methods Eighteen male C57BL/6J mice were randomly divided into three groups:Control group,diabetic kidney dis-ease(DKD)group and A-485 treatment group.The DKD mice model was established by feeding high-fat diet for 8 weeks and intraperitoneal injection of streptozotocin for 5 days.Subsequent-ly,the A-485 treatment group was given A-485(10 mg/kg/day)by intraperitoneal injection every other day for 4 weeks.After treatment,the renal function,P300 enzyme activity and lipid deposition in renal tissue were measured.Western blot a-nalysis was performed to detect SREBP-1,FASN,ACC,ChREBP,P300,CBP,H3K18ac and H3K27ac protein levels.Results Compared with control mice,the levels of FBG,BUN,Scr and UAE were significantly increased in diabetic mice(FBG:2.52 times,BUN:2.89 times,Scr:2.13 times,UAE:4.21 times),while diabetic mice treatment with A-485 exhibi-ted a remarkable decrease on BUN,Scr and UAE(BUN:0.511 times,Scr:0.636 times,UAE:0.574 times,P＜0.01).The results of the transmission electron microscopy and oil red O stai-ning showed that A-485 treatment prevents lipid droplets forma-tion and up-regulation of SREBP-1,FASN,ACC and ChREBP in renal tubular cells of diabetic mice(SREBP-1:0.544 times,FASN:0.449 times,ACC:0.306 times,ChREBP:0.317 times,P＜0.01).Furthermore,A-485 intervention downregu-lated the enzyme activity of P300(0.546 times)and suppressed the expression of H3K18ac(0.337 times)and H3K27ac(0.308 times,P＜0.01).Conclusion A-485 can significant-ly improve renal lipid metabolic disorder in diabetic mice,which may be achieved by inhibiting p300-induced H3K18ac and H3K27ac.

Objective To investigate the risk factors of periprosthetic femoral fracture(PFF)after total knee arthroplasty(TKA)in the elderly and to construct a predictive model for the prevention of PFF after clinical operation.Methods The clinical data of 537 elderly patients who underwent TKA in the orthopedic department of the First Affiliated Hospital of Air Medical University from October 2016 to October 2021 were retrospectively analyzed.The occurrence of PFF during the follow-up period was statistically analyzed and the clinical data were collected.Binary Logistic regression was used to analyze the risk factors of PFF after TKA in the elderly,and a predictive model of PFF after TKA in the elderly was constructed based on the risk factors.Receiver operating characteristic(ROC)curve and Hosmer-Lemeshow(H-L)were used to test the discrimination and calibration of prediction model.Results The patients were followed up for 12 to 72 months after discharge,with a median time of 47 months.During the follow-up period,31 patients(5.77%)developed PFF.Age,osteoporosis,Parkinson's disease and anterior femoral notch(AFN)were the risk factors for PFF after TKA in the elderly(P<0.05),and cross fixation of prosthesis and bone cement fixation were the protective factors(P<0.05).The results of H-L test showed that the risk prediction model of PFF after TKA in the elderly had good calibration(P>0.05).ROC curve analysis showed that the risk prediction model of PFF after TKA in the elderly has high discrimination(area under the curve was 0.858,95%CI:0.826 to 0.887),the sensitivity was 83.87%,the specificity was 88.34%.Conclusion The risk of PFF after TKA in the elderly is high,and prevention should be carried out according to the high risk factors.The prediction model constructed based on the high risk factors has good prediction efficiency.

In recent years, polysaccharides have received much attention because of their high safety and good immunological activity. The study of polysaccharide in vivo process is a key scientific problem that needs to be solved for polysaccharide drug development. Some progress has been made in the field of polysaccharide pharmacokinetics and immunomodulation. However, due to the lack of both chromogenic and light-absorbing groups and the complex molecular structure of polysaccharides, the in vivo processes and immunomodulatory mechanisms of polysaccharides have been slow to be investigated. The effective combination of multiple techniques can break the bottleneck of difficult tracing and unknown immunomodulatory mechanism of polysaccharides in vivo, and promote the development and utilization of polysaccharides. In this paper, we systematically summarize the key techniques in the study of polysaccharide in vivo processes and immunomodulatory mechanisms in order to provide technical references and research ideas for the study of polysaccharide in vivo processes and immunomodulatory mechanisms.

ObjectiveTo observe the clinical efficacy and mechanism of Tongnao Yizhi Formula （通脑益智方， TYF） in treating vascular cognitive impairment no dementia （VCIND） with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome. MethodsNinety-two VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome were randomly divided into control group （42 cases） and treatment group （52 cases）. Both groups received routine basic treatment. The control group was given donapezil hydrochloride capsules orally， 5 mg each time， once at night， while the treatment group was given TYF orally， 1 dose per day. Both groups were treated continuously for 3 months. The scores of Mini-Mental State Examination （MMSE）， Vascular Dementia Assessment Scale-Cognitive Subscale （VaDAS-Cog）， Activity of Daily Living Scale （ADL）， and TCM syndrome scores （the primary symptoms such as sluggish thinking， forgetfulness， temperament changes， and language confusion， and secondary symptoms such as weakness of waist and knees， dizziness and headache， occasional tinnitus， fatigue， heaviness of limbs， insomnia and irritability， poor appetite and abdominal distension， numbness of face） were observed before and after treatment in both groups. The changes in gut microflora diversity and flora abundance structure as well as fecal short-chain fatty acids （SCFAs） levels including acetic acid， propionic acid， butyric acid， isobutyric acid， isovaleric acid， valeric acid， and caproic acid were compared between groups. The feces of 20 healthy subjects in the same period were included as reference. Safety was evaluated during the study. ResultsAfter treatment， both groups exhibited significant increases in MMSE scores and decreases in VaDAS-cog scores （P＜0.05 or P＜0.01）， and ADL scores in the treatment group significantly increased （P＜0.05）. Scores of symptoms including sluggish thinking， forgetfulness， temperament change， language confusion， heaviness of limbs， insomnia， irritability， poor appetite， abdominal distension， and facial numbness as well as the total score significantly decreased in both groups after treatment （P＜0.05 or P＜0.01）. When compared between groups， the treatment group showed substantial reductions in scores of weakness of waist and knees， tinnitus， fatigue， heaviness of limbs， insomnia， irritability， loss of appetite and abdominal distension （P＜0.05 or P＜0.01）. The gut microflora diversity analysis showed that the Shannon index of the treatment group significantly increased after treatment （P＜0.05）.PCoA analysis and ANOSIM test indicated significant differences between groups， suggesting changes in microflora species （P＜0.01）. After treatment， the relative abundance of Bacteroidetes and Fusobacteria in the treatment group increased， while the relative abundance of Actinobacteria， Verrucomicrobia and Cyanobacteria decreased （P＜0.05）； the relative abundance of Faecalibacterium prausnitzii， Bifidobacterium， Lactobacillus， and Ruminococcus increased significantly （P＜0.05）. Compared to the the gut microflora species diversity of the healthy people， it is indicated that the gut microflora structure in the treatment group was close to that of the healthy people， while there was no such trend in the control group. In the treatment group， acetic acid， propionic acid， and butyric acid in the treatment group were all higher after treatment （P＜0.05 or P＜0.01）. ConclusionsTYF can improve the cognitive ability and quality of life of VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome， and this improvement may be related to regulating intestinal microecology.

Objective To evaluate the short-term efficacy and safety of percutaneous liver puncture for local management of portal vein thrombosis(PVT).Methods Variations in thrombus,blood flow,and laboratory examination results were observed before and after percutaneous liver puncture in 197 patients with PVT,and the occurrence of comorbidities was recorded and followed up for one year after treatment.Results After treatment,the thrombus in the main portal vein vessels almostly disappeared in 119 patients(60.41％)with PVT,the thrombus had a significant reduction in 57 patients(28.93％),and the thrombus had a smaller change or an increase in 21 patients(10.66％);146 patients(74.11％)had smooth blood flow in the main portal vein vessels,29 patients(14.72％)showed significant improvement in blood flow,and 22 patients(11.17％)showed no significant improvement or worsening of blockage.The mean portal venous pressure was significantly lower than that before treatment(P＜0.001);thrombin time,activated partial thromboplastin time,and prothrombin time were prolonged compared to those before thrombolysis(P＜0.001),and fibrinogen were reduced compared to those before thrombolysis(P＜0.001).A total of 35 patients(17.77％)occured comorbidities during treatment.One year after treatment,196 patients(99.49％)with PVT survived,of which thrombus essentially disappeared in 141(71.94％),thrombus stabilized(or decreased)in 42(21.43％),and thrombus increased in 13(6.63％).Conclusion percutaneous liver puncture for local management of PVT is effective and reliable in the short-term and requires standardized management of the entire process.

This paper reviews the current situation of dementia care in the emergency setting at home and abroad, and compares the contents of person-centred care practices, such as identifying and assessing dementia patients, changing caregivers ′ attitudes, creating a good emergency environment, and mastering and providing effective nurse-patient communication, with the aim of providing a reference basis for developing a standardised care plan for dementia patients in the emergency setting, with a view to providing more scientific and efficient emergency care for dementia patients.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.