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:To observe the changes in the nutritional status of pediatric patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT)for one year,and to analyze the risk factors.Methods:We collected data from 88 pediatric patients who underwent allo-HSCT at the Department of Hematology and Oncology in Children's Hospital of Nanjing Medical University between May 2018 and November 2022.All pediatric patients underwent nutritional status analysis before transplantation,at enrollment,3 months,6 months and 1 year after allo-HSCT.Linear regression model was used to analyze the risk factors for growth rate.Results:The body mass index Z score(BMI-Z)before allo-HSCT was(0.096±1.349),and decreased to(-0.258±1.438)、(-0.715±1.432)、(-0.584±1.444)at enrollment,3 months,6 months after allo-HSCT,and(-0.130±1.317)at 1 year after allo-HSCT(P<0.001).There was no significant change in BMI-Z between pre-transplantation and 1 year after transplantation(P=1.000).Height for age Z score(HAZ)before transplantation was(0.137±1.305)and decreased to(-0.083±1.267)、(-0.221±1.299)、(-0.269±1.282)in 3 months,6 months and 1 year after allo-HSCT(P<0.001).Multivariate linear regression showed that age≥10 years old(P=0.015)and chronic graft-versus-host disease(cGVHD)(P=0.005)were independent risk factors for change in HAZ.Conclusion:The BMI-Z of pediatric patients treated with allo-HSCT returned to the pre-transplantation level after one year,while HAZ continued to decrease.Allo-HSCT may cause impaired growth rate in pediatric patients.Attention should be paid to HAZ changes in pediatric patients before and after allo-HSCT,especially in pediatric patients≥10 years old of age and those with cGVHD.Effective nutritional intervention should be provided in time.

Objective:To evaluate the efficiency of the four domestic language models,ERNIE Bot,ChatGLM2,Spark Desk and Qwen-14B-Chat,all with a massive user base and significant social attention,in response to consultations about PCa-related perio-perative nursing and health education.Methods:We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases,and inputted the questions into each of the four language models for simulation consultation.Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy,comprehensiveness,understandability,humanistic care,and case analysis.We evaluated and compared the performance of the four models using visualization tools and statistical analyses.Results:All the models generated high-quality texts with no mis-leading information and exhibited satisfactory performance.Qwen-14B-Chat scored the highest in all aspects and showed relatively sta-ble outputs in multiple tests compared with ChatGLM2.Spark Desk performed well in terms of understandability but lacked comprehen-siveness and humanistic care.Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis.The overall performance of ERNIE Bot was slightly inferior.All things considered,Qwen-14B-Chat was superior to the other three models in con-sultations about PCa-related perioperative nursing and health education.Conclusion:In PCa-related perioperative nursing,large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support,so as to improve the patient compliance and the quality of clinical treatment and nursing.

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.

[摘 要] 目的：探讨四个半LIM结构域2（FHL2）蛋白对胶质瘤细胞增殖的影响及其分子机制。方法：利用TCGA和CGGA数据库分析胶质瘤组织中FHL2 mRNA表达水平与患者预后的关系。通过WB法检测人胶质瘤组织标本及人胶质瘤细胞U87、T98G、U251、SNB19、GSC23、A172、LN229、G267和星形胶质细胞NHA中的FHL2蛋白表达水平。利用慢病毒载体构建稳定敲低FHL2的U87细胞和过表达FHL2的SNB19细胞，即U87-shGFP、U87-shFHL2-1#、U87-shFHL2-4#和SNB19-3flag、SNB19-3flag-FHL2组。通过CCK-8法、克隆形成实验检测敲低和过表达FHL2对细胞增殖的影响，免疫共沉淀（Co-IP）和液相色谱-串联质谱（LC/MS）法筛选FHL2在胶质瘤细胞中的相互作用蛋白，并用Co-IP和免疫荧光法验证它们的结合作用和共定位情况。使用酶标仪检测敲低和过表达FHL2细胞内乳酸产量和乳酸脱氢酶（LDH）活性的变化，WB法分析FHL2、LDHA及p-LDHA在正常脑组织和胶质瘤组织中的蛋白表达差异及其相互关系。在过表达 FHL2的SNB19细胞中使用LDHA的小分子抑制剂AT-101，通过CCK-8实验和酶标仪比色法验证FHL2在胶质瘤乳酸代谢中的作用，验证AT-101在胶质瘤中潜在的治疗效果。结果：Co-IP和LC/MS检测发现，FHL2与LDHA在胶质瘤细胞中存在相互作用。FHL2过表达可提高LDHA活性和乳酸生成（均P < 0.001），进而促进胶质瘤细胞增殖（P < 0.001）。相反，敲低FHL2会降低LDHA活性和乳酸产量（P < 0.001或P < 0.05）并抑制细胞增殖（P < 0.001）。AT101能抑制LDHA活性，并显著抑制FHL2促进胶质瘤细胞的增殖，同时恢复磷酸化LDHA（Y10）水平（P<0.01或P < 0.001）。结论：FHL2与LDHA蛋白相互作用，FHL2通过激活p-LDHA（Y10）的表达促进LDHA活性和乳酸产生，进而促进胶质瘤细胞的增殖，靶向这种相互作用可能成为治疗胶质瘤的潜在策略。

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Child ; Humans ; Arthritis, Juvenile/drug therapy* ; Macrophage Activation Syndrome/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

Ziziphi Spinosae Semen(ZSS) is an edible TCM derived from the dried ripe seeds of Ziziphus jujube Mill. var. spinosa(Bunge)Hu ex H. F. Chou(Rhamnaceae), which has the effects of nourishing the heart, tonifying the liver, calming the heart, tranquilizing the mind, arresting sweating, and promoting fluid production, and is widely used in the treatment and health care of diseases related to cardiovascular, nervous, and immune systems. Jujuboside B(JuB), one of the main active ingredients of ZSS, possesses various pharmacological effects with application values. This paper reviewed the chemical structure and pharmacological effects of JuB. JuB has sedative, hypnotic, antitumor, anti-platelet, anti-inflammatory, and other biological activities, which shows the potential thera-peutic effects on insomnia, tumors, coronary artery disease, airway inflammation, and liver injury. However, there are some limitations to the results of current studies. More comprehensive studies, including basic research and clinical trials, need to be carried out to provide more reliable evidence.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Saponins/pharmacology* ; Hypnotics and Sedatives ; Sleep Initiation and Maintenance Disorders ; Ziziphus/chemistry*