Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

[摘 要] 目的：探讨分化抑制因子2（Id2）在诱导生成中央记忆性T（Tcm）细胞及增强T细胞抗肿瘤持久性中的作用。方法：磁珠分选CD8+初始T细胞，与负载癌胚抗原（CEA）的树突状细胞（DC）共培养，经白介素-2（IL-2）或IL-7/15/21/23分别诱导培养效应T（Teff）或Tcm细胞；qPCR和WB法分别检测T细胞中Id2和Id3 mRNA、蛋白表达；慢病毒敲减T细胞中Id2基因，用流式细胞术检测其T细胞记忆表型；WB法检测PI3K/AKT通路相关蛋白的表达；Seahorse能量代谢仪分析细胞外酸化速率（ECAR）和耗氧速率（OCR）；斑马鱼结肠癌HCT116细胞移植瘤模型分析Teff和Tcm细胞的抗肿瘤差异，进一步观察敲减Id2基因的Tcm细胞（Tcm-shId2）对第二次移植瘤的生长抑制。结果：Tcm细胞高表达Id3 mRNA（P < 0.05），而Teff细胞高表达Id2 mRNA（P < 0.001）。成功构建敲减Id2基因的Tcm细胞（Tcm-shId2）且其Id3表达明显上调，敲减Id2可促进Tcm细胞的形成（P < 0.05）。Tcm-shId2细胞通过PI3K/AKT通路进行代谢重编程，有效抑制斑马鱼体内结肠癌移植瘤的生长，对第二次移植瘤也能产生显著抑制作用（P < 0.01）。结论：Id2可能通过调控PI3K/AKT通路改变T细胞代谢模式，从而促进CD8+ T细胞向Tcm细胞分化，有效抑制结肠癌移植瘤的生长。

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

[摘 要] 目的：探讨钙蛋白酶小亚基1（CAPN4）调控肺腺癌顺铂耐药性及肿瘤干细胞干性的作用机制，为通过靶向干性逆转耐药提供实验依据。方法：收集2023年1月至2024年1月期间在福建省肿瘤医院手术切除的10例肺腺癌患者的组织标本，通过免疫组织化学（IHC）法检测5例对顺铂耐药与5例敏感肺腺癌组织中CAPN4的表达差异，并进行组织化学评分（H评分）。利用癌症基因组图谱（TCGA）数据库和基因表达谱交互分析（GEPIA）平台进行肺癌CAPN4基因表达相关的生存分析。另收集2例对顺铂耐药、2例敏感的肺腺癌组织标本，建立肺腺癌类器官（PDO）模型，采用H-E、IHC染色评估PDO与原发肿瘤形态学的一致性。采用慢病毒介导的shRNA技术敲减CAPN4基因表达，运用qPCR和WB法检测PDO中干细胞标志物ALDH1A1、CD133、Nanog和SOX9的基因和蛋白表达水平。通过腺苷三磷酸（ATP）法检测CAPN4下调后肺腺癌PDO对顺铂的敏感性变化，使用半胱氨酸蛋白酶-3（caspase-3）活性检测法评估CAPN4下调的肺腺癌PDO经顺铂处理后的凋亡情况。结果：IHC检测结果表明，耐药肺腺癌患者组织中CAPN4蛋白的表达水平显著上调（P < 0.05）。在TCGA数据库肺腺癌患者队列中，CAPN4的高表达与肺腺癌患者的不良预后（OS缩短）显著相关（HR = 1.4，P < 0.05）。耐药患者来源的PDO中CAPN4蛋白表达、干细胞标志物的基因和蛋白表达水平均显著上调（均P < 0.05）。在顺铂敏感性测试中，耐药患者来源PDO的IC50值显著高于敏感患者来源的PDO（P < 0.05）。敲低CAPN4后，耐药患者来源的PDO的干细胞标志物表达显著降低，顺铂敏感性增强（P < 0.05）。结论：敲低CAPN4可降低肺腺癌PDO的干细胞标志物表达，显著增强其对顺铂的敏感性，为逆转肺癌顺铂耐药提供了潜在治疗靶点。

OBJECTIVE To investigate the reference range of steady-state trough concentrations in depression patients taking paroxetine. METHODS Therapeutic drug monitoring data of 890 depression inpatients treated with paroxetine in our hospital from January 1， 2023 to December 31， 2024 were retrospectively collected. Univariate analysis and multiple linear regression analysis were employed to explore the influencing factors of the steady-state trough concentration of paroxetine， as well as the correlation between concentration and efficacy and adverse reactions. The reference range of steady-state trough concentration was obtained by receiver operating characteristic（ROC） curve method. RESULTS Patients with a greater degree of improvement in therapeutic efficacy exhibited higher steady-state trough concentrations of paroxetine （P＜0.000 1）. The steady-state trough concentrations of paroxetine and the ratio of paroxetine steady-state trough concentration to dose （C/D ratio） were significantly lower in male patients and those weighing 60-80 kg compared to female patients and those weighing＜60 kg， respectively （P＜0.05 or P＜0.000 1）. The steady-state trough concentration， C/D ratio， dosage， and concomitant medication all showed a positive correlation with therapeutic efficacy （P＜0.05 or P＜0.000 1）. Both the steady-state trough concentration and C/D ratio were correlated with liver function impairment， and the C/D ratio was also correlated with urinary retention （P＜0.05 or P＜0.000 1）. The critical threshold for the effective concentration of paroxetine was 56.31 ng/mL in the overall population， 56.42 ng/mL in males， 44.91 ng/mL in females， and 198.90 ng/mL in patients experiencing adverse reactions. CONCLUSIONS The reference range for the steady-state trough concentration of paroxetine in the overall population is 56.31-198.90 ng/mL； for male patients， it is 56.42-198.90 ng/mL， and for female patients， it is 44.91-198.90 ng/mL. Dosage of paroxetine should be reduced as appropriate for female patients and patients with low body weight or abnormal liver function.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

Surgical treatment is one of the key approaches for non-small cell lung cancer (NSCLC). Regular postoperative follow-up is crucial for early detection and timely management of tumor recurrence, metastasis, or second primary tumors. A scientifically sound and reasonable follow-up strategy not only extends patient survival but also significantly improves quality of life, thereby enhancing overall prognosis. This consensus aims to build upon the previous version by incorporating the latest clinical research advancements and refining postoperative follow-up protocols for early-stage NSCLC patients based on different treatment modalities. It provides a scientific and practical reference for clinicians involved in the postoperative follow-up management of NSCLC. By optimizing follow-up strategies, this consensus seeks to promote the standardization and normalization of lung cancer diagnosis and treatment in China, helping more patients receive high-quality care and long-term management. Additionally, the release of this consensus is expected to provide insights for related research and clinical practice both domestically and internationally, driving continuous development and innovation in the field of postoperative management for NSCLC.

Objective To construct a predictive model for the survival of transplant kidneys after kidney transplantation. Methods The clinical data of 366 kidney transplant recipients and donors were retrospectively analyzed, and the recipients were divided into low-risk group (n=101), medium-risk group (n=189), and high-risk group (n=76) based on the kidney donor profile index (KDPI). Each group was further divided into Remuzzi score ≤3 group and Remuzzi score >3 group based on time-zero biopsy Remuzzi scores. Kaplan-Meier method was used to analyze the survival of transplant kidneys. Univariate and multivariate Cox regression analyses were performed to identify risk factors affecting long-term survival after kidney transplantation. A predictive model for transplant kidney survival was established and a nomogram was drawn. The predictive performance of the model was evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results The median KDPI was 65%, and the median Remuzzi score was 3. The 5-year survival rate of transplant kidneys was 83.5%. Kaplan-Meier survival curves showed that in the KDPI medium-risk and KDPI high-risk groups, the subgroup with lower Remuzzi score had a higher survival rates of transplant kidneys than the subgroup with higher Remuzzi score. Univariate and multivariate Cox regression analyses showed that KDPI, Remuzzi score, and donor’s age were independent risk factors for transplant kidney loss (all P<0.05). The ROC curve showed that the AUC of the nomogram prediction model established based on independent risk factors for the 1, 3 and 5-year survival rates of transplant kidneys were 0.91, 0.93 and 0.94 for the training set, and 0.89, 0.85 and 0.88 for the validation set. Calibration curves shows good consistency between the training and validation sets of the model. Conclusions The nomogram predictive model based on KDPI, time-zero biopsy Remuzzi score and donor’s age has good predictive value for transplant kidney survival.

Endoscopic thoracic sympathicotomy/sympathotomy (ETS) is the first-line treatment for palmar hyperhidrosis with best minimally invasive effect. In recent years, with the widespread development of ETS in the treatment of palmar hyperhidrosis, many medical centers list ETS surgery as the day surgery. Nevertheless, there is no expert consensus on medical quality control of day surgery for ETS yet. Therefore, the Chinese Medical Doctor Association Thoracic Surgeons Branch Hyperhidrosis Subcommittee, Sympathetic Neurosurgery Expert Committee of WU Jieping Medical Foundation, and Fujian Provincial Strait Medical and Health Exchange Association Hyperhidrosis Special Committee organized domestic experts to conduct repeated consultations and sufficient discussions based on domestic and foreign literatures, to formulate the "Chinese expert consensus on ETS optimization and surgical quality control of day surgery for palmar hyperhidrosis". It aims to provide a reference for the clinical diagnosis and treatment of palmar hyperhidrosis for thoracic surgery colleagues in our country, to enhance their management level and work efficiency, and ultimately to achieve standardized quality control.