1.Analysis of Rheumatoid Arthritis and Periodontitis Multimorbidity from Perspective of Abnormal Collateral Theory
Xiaojing GUO ; Jiuli DING ; Hongyuan SUN ; Lei ZHANG ; Min LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):280-287
The multimorbidity of rheumatoid arthritis (RA) and periodontitis (PD) has drawn increasing attention, as both conditions are characterized by chronic inflammation, immune dysregulation, and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development, and their coexistence mutually exacerbates disease progression. However, traditional Chinese medicine (TCM) currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study, based on the TCM theory of abnormal collateral, thoroughly examines the intrinsic connection between RA and PD multimorbidity, proposing "abnormal collateral as the pivot, with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral", where its pathogens act as toxic factors that invade the joints through collaterals, triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows: the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation, leading to collateral malnutrition; heat-toxins traversing collaterals induce collateral hyperactivity, resulting in pathological angiogenesis; ultimately, toxin accumulation at the pivotal abnormal collateral site erodes bone, activating the receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology, immune-inflammation, and bone metabolism, offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity, the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs", along with TCM therapeutic principles such as "unblocking, clearing, and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration, thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.
2.Analysis of Rheumatoid Arthritis and Periodontitis Multimorbidity from Perspective of Abnormal Collateral Theory
Xiaojing GUO ; Jiuli DING ; Hongyuan SUN ; Lei ZHANG ; Min LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):280-287
The multimorbidity of rheumatoid arthritis (RA) and periodontitis (PD) has drawn increasing attention, as both conditions are characterized by chronic inflammation, immune dysregulation, and progressive bone destruction. Modern research confirms that PD is a significant risk factor for RA development, and their coexistence mutually exacerbates disease progression. However, traditional Chinese medicine (TCM) currently lacks a systematic theoretical explanation for this complex multimorbid relationship. This study, based on the TCM theory of abnormal collateral, thoroughly examines the intrinsic connection between RA and PD multimorbidity, proposing "abnormal collateral as the pivot, with accumulated toxins eroding bone" as the core TCM pathogenesis. The research elucidates PD as the "origin of abnormal collateral", where its pathogens act as toxic factors that invade the joints through collaterals, triggering RA via mechanisms such as molecular mimicry. The dynamic pathological progression of RA-PD multimorbidity can be described as follows: the displacement of Ying and Wei at the microscopic level manifests as immune hyperactivation, leading to collateral malnutrition; heat-toxins traversing collaterals induce collateral hyperactivity, resulting in pathological angiogenesis; ultimately, toxin accumulation at the pivotal abnormal collateral site erodes bone, activating the receptor activator of nuclear factor kappa-B ligand (RANKL)-receptor activator of nuclear factor kappa-B (RANK) signaling pathway-driven osteoclast differentiation. This theoretical framework innovatively integrates modern findings in oral microbiology, immune-inflammation, and bone metabolism, offering a holistic and dynamic perspective to understand the complexity of multimorbidity. Given the limited efficacy of current periodontal treatments for RA and the scarcity of reported TCM compound interventions for multimorbidity, the abnormal collateral theory proposes a systematic intervention strategy centered on "governing diseases through collaterals and regulating collaterals with herbs", along with TCM therapeutic principles such as "unblocking, clearing, and nourishing collaterals". Potential herbal treatments for multimorbidity are also highlighted. Future research should focus on refining TCM syndrome patterns in multimorbid patients and leveraging omics technologies for deeper exploration, thereby providing a theoretical foundation and research direction for TCM in addressing complex multimorbid conditions.
3.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
4.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
5.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
6.A qualitative research on psychological experience of operating room nurses participating in organ transplant surgery
Zhe WANG ; Chunling WANG ; Xiaoyun NI ; Min LIU ; Chengyao GUO ; Minwei SHEN ; Li ZHANG ; Chenwei ZHANG
Chinese Journal of Clinical Medicine 2026;33(4):675-682
Objective To explore the psychological experiences of operating room nurses participating in organ transplant surgeries, providing a basis for medical institutions to develop targeted psychological support programs. Methods Using a phenomenological research method, semi-structured, in-depth, face-to-face interviews were conducted from January to March 2026 with 17 operating room nurses who had participated in organ transplant surgeries at a tertiary hospital in Shanghai. Interviews were recorded, and observations were made. The interview data were analyzed, summarized, and themes were refined using Colaizzi’s seven-step analysis method. Results The psychological experiences of operating room nurses participating in organ transplant surgeries were identified as 5 main themes and 14 sub-themes: emotional impact and empathy load (shock and grief confronting life and death, deep empathy for patients and families, awe and gratitude towards organ donors); pressure experience and physical-mental exhaustion (urgency under time pressure, load of operational precision requirements, excessive consumption of physical and mental resources); cognitive appraisal and meaning construction (reappraisal of professional value, deep reflection on the meaning of life, positioning and identification of one’s role); coping strategies and adjustment process (active learning and experiential reflection, self-emotional regulation and social support); growth experience and psychological transformation (enhancement of psychological resilience, establishment of professional confidence, deepening of professional mission). Conclusions Operating room nurses undergo complex and profound psychological experiences while participating in organ transplant surgeries, enduring strong emotional impact and physical-mental stress while also achieving psychological growth and deepening professional identity through practice. Nursing managers should pay attention to the mental health of this group and construct a multi-level support system to promote their physical and psychological well-being.
7.Effect of family cohesion and adaptability on suicide risk in adolescent inpatients with depression: the mediating role of depressive symptoms and the moderating role of resilience
Can KE ; Guo CHEN ; Jie ZHANG ; Min YU
Sichuan Mental Health 2026;39(4):337-344
BackgroundSuicide is the second leading cause of death in adolescents. Patients with depression have a high risk of suicide, and family dysfunction is an important contributing factor of suicide. However, the mechanisms among these variables remain unclear. ObjectiveTo explore the influence of family cohesion and adaptability on the risk of suicide in adolescent inpatients with depression, and the mediating effect of depressive symptoms and the moderating effect of resilience, so as to provide references for suicide prevention and intervention. MethodsA total of 335 adolescent inpatients with depression were consecutively enrolled from October 2024 to August 2025 in a tertiary Grade A psychiatric hospital in Guangzhou. All participants met the diagnostic criteria for depression in the International Classification of Diseases, tenth edition (ICD-10). They were assessed using the Family Adaptability and Cohesion Scale Ⅱ-Chinese Version (FACES Ⅱ-CV), the Self-rating Depression Scale (SDS), the Connor-Davidson Resilience Scale (CD-RISC), the Suicidal Behaviors Questionnaire-Revised (SBQ-R) and the suicide module of the Mini-International Neuropsychiatric Interview (MINI). A comprehensive suicide risk index was constructed. Model 4 and model 7 in the SPSS macro program Process 4.1 were used to test the mediating effect and the moderating effect, respectively. ResultsCorrelation analysis revealed that the SDS score was positively correlated with the composite suicide risk index (rs=0.663, P<0.01) but negatively correlated with the family cohesion and adaptability dimensions scores of the FACES II-CV and the CD-RISC score (rs=-0.448, -0.386, -0.576, P<0.01). Depressive symptoms fully mediated the association between family cohesion and suicide risk, with an indirect effect of -0.491 (95% CI: -0.646–-0.352), accounting for 89.76% of the total effect. Depressive symptoms also fully mediated the association between family adaptability and suicide risk, with an indirect effect of -0.442 (95% CI: -0.603–-0.293), accounting for 89.11% of the total effect. Resilience significantly moderated the effect of family cohesion on depressive symptoms (β=-0.006, P<0.01) and the effect of family adaptability on depressive symptoms (β=-0.007, P<0.05). ConclusionIn adolescent inpatients with depression, depressive symptoms may play a fully mediating role in the relationships between family cohesion/family adaptability and suicide risk, respectively, and resilience moderated the first stage of this mediating pathway. [Funded by Guangzhou Science and Technology Plan Project (number, 2024A03J0299)]
8.Proteomic Profiling of Qi-blood Deficiency vs Damp-heat Syndrome in Colorectal Cancer: Therapeutic Targeting by Astragaloside IV-berberine
Zhao-Huan LI ; Jing-Wen ZHAO ; Xin ZHANG ; Jian-Jin GUO ; Jie XU ; Zeng-Qiang YANG ; Hao TU ; Min ZOU ; Ming-Bin GUI ; Feng GAO
Progress in Biochemistry and Biophysics 2026;53(9):2462-2479
ObjectiveColorectal cancer (CRC) is a highly heterogeneous malignancy, and traditional Chinese medicine (TCM) syndrome differentiation is widely used in its clinical management. However, the biological basis underlying different TCM syndromes remains insufficiently understood. This study aimed to investigate the proteomic differences between qi-blood deficiency syndrome (QBDS) and damp-heat syndrome (DHS) in CRC patients and to establish a “syndrome-differential protein-herbal component” network for exploring potential molecular mechanisms and therapeutic targets associated with syndrome-specific treatment strategies. MethodsTumor tissue samples were collected from 10 patients with pathologically confirmed CRC, including 5 patients diagnosed with QBDS and 5 with DHS according to standardized TCM syndrome differentiation criteria. Tandem mass tag (TMT)-based quantitative proteomics was employed to identify differentially expressed proteins (DEPs) between the two syndrome groups. Functional enrichment analyses, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, were performed to characterize the biological functions and signaling pathways associated with the identified DEPs. Least absolute shrinkage and selection operator (LASSO) regression analysis was further applied to screen key syndrome-related proteins and construct a core protein prediction model. Subsequently, molecular docking was conducted to evaluate the binding affinities between representative herbal compounds, astragaloside IV and berberine, and the identified core proteins. Finally, cell counting kit-8 (CCK-8) assays were performed in HCT 116 and HT-29 colorectal cancer cell lines to validate the anti-proliferative activities of these compounds in vitro. ResultsA total of 44 DEPs were identified between QBDS and DHS tissues, including 21 upregulated and 23 downregulated proteins in the QBDS group relative to the DHS group. Functional enrichment analyses revealed that these proteins were primarily associated with antiviral immune responses, regulation of inflammatory signaling, NF‑κB signaling pathways, cholesterol metabolism, and other biological processes relevant to tumor progression and host immune regulation. LASSO regression analysis identified eight core proteins with potential syndrome-specific significance. Among them, ST7, GPCPD1, and PODXL were closely associated with QBDS, whereas FAT1, GRB7, KRT7, MAFF, and MMP8 were associated with DHS. Molecular docking demonstrated favorable interactions between astragaloside IV and QBDS-related proteins, with binding energies lower than -5 kcal/mol, indicating stable binding activity. Berberine exhibited even lower binding energies and stronger binding specificity toward DHS-related core proteins. In vitro experiments further confirmed that both compounds inhibited CRC cell proliferation, while berberine displayed significantly greater anti-proliferative efficacy. The lowest 48 h IC50 value of berberine reached 15.21 mg/L in CRC cells, indicating a stronger growth-inhibitory effect than astragaloside IV. ConclusionCRC patients with QBDS and DHS exhibit distinct proteomic characteristics, suggesting that different TCM syndromes possess unique molecular signatures. The identified core proteins may serve as potential biomarkers for syndrome differentiation, while astragaloside IV and berberine may exert therapeutic effects through targeting syndrome-specific molecular networks. These findings provide preliminary proteomic evidence supporting syndrome-guided precision integrative medicine in CRC and offer new insights into the biological basis of TCM syndrome differentiation and individualized therapeutic strategies.
9.Visualization of Wallerian Degeneration of The Corticospinal Tract and Glial Pathological Changes After Ischemic Stroke in Mice
Meng MENG ; Jiao MU ; Mei-Yu LI ; Jun-Yan GAO ; Xiao-Min ZHU ; Liang-Liang LIU ; Ying GUO ; Guo-Hui ZHANG
Progress in Biochemistry and Biophysics 2026;53(10):2808-2819
ObjectiveStroke remains the leading cause of acquired disability in adults worldwide, imposing a substantial socioeconomic burden on patients, families, and healthcare systems. Among the various neurological deficits caused by stroke, motor dysfunction——particularly contralateral hemiplegia——is the most common and debilitating consequence, and it predominantly results from damage to the cortical motor conduction pathways. When motor cortex neurons or their projecting fibers are damaged, the distal axons and their associated myelin sheaths undergo a series of progressive, programmed degeneration, fragmentation, and eventual phagocytic clearance. This pathological process is termed Wallerian degeneration (WD). However, the temporal progression of WD following ischemic stroke and the associated alterations in the local glial microenvironment remain incompletely understood. The present study was designed to systematically elucidate the time course of corticospinal tract (CST) axonal WD after ischemic stroke in mice, and to simultaneously characterize the dynamic pathological changes of astrocytes, microglia, oligodendrocyte lineage cells, and myelinating oligodendrocytes during the WD process. MethodsEight-week-old male C57BL/6J mice were randomly assigned to control and ischemic stroke groups. A focal cortical ischemic stroke model was established in the right sensorimotor cortex using the photothrombotic method. This method induces localized intravascular thrombosis in the target cortical region through precisely controlled interaction between the photosensitizer and laser light of specific wavelength. At day 1 post‑surgery, 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate infarct volume, hematoxylin and eosin (HE) staining for histopathological examination, and Nissl staining for assessment of neuronal injury. For axonal degeneration time-course analysis, rAAV-CAG-mCherry anterograde viral tracing was employed to specifically label CST neurons. Cervical spinal cord sections at the CST region were collected at day 3, 5, 7, 14, and 60 post-injury. Morphological changes of mCherry-positive CST fibers were observed under fluorescence microscopy, and the fluorescence signal area fraction within the defined region was quantitatively analyzed to evaluate the dynamic process of axonal degeneration. For glial response assessment, immunofluorescence staining against Iba1 (microglia), GFAP (astrocytes), Olig2 (oligodendrocyte lineage cells), and APC (myelinating oligodendrocytes) was performed at day 7, 14, and 60 post‑surgery. The numbers of positive cells were counted to quantitatively analyze the dynamic changes in each glial population at different time points after ischemia, thereby revealing the evolution of the glial microenvironment during WD. ResultsThe photothrombotic method stably and reliably established an ischemic brain injury model confined to the sensorimotor cortex. Viral tracing revealed that the proportion of mCherry‑positive CST fibers was significantly reduced at day 7 after ischemic injury to the neuronal soma. Immunofluorescence staining demonstrated that during WD, the numbers of microglia and astrocytes in the CST region were significantly increased, whereas the numbers of oligodendrocyte lineage cells and myelinating oligodendrocytes showed no significant changes. ConclusionWD of CST axons is observed at day 7 post-ischemic stroke in a delayed manner. This degenerative process selectively activates microglia and astrocytes, while leaving the number of oligodendrocyte lineage cells largely unaffected.
10.Shikonin attenuates blood–brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/ Nrf2/HO-1 signaling
Guanghu LI ; Yang'e YI ; Sheng QIAN ; Xianping XU ; Hao MIN ; Jianpeng WANG ; Pan GUO ; Tingting YU ; Zhiqiang ZHANG
The Korean Journal of Physiology and Pharmacology 2025;29(3):283-291
Subarachnoid hemorrhage (SAH) is a serious intracranial hemorrhage characterized by acute bleeding into the subarachnoid space. The effects of shikonin, a natural compound from the roots of Lithospermum erythrorhizon, on oxidative stress and blood–brain barrier (BBB) injury in SAH was evaluated in this study. A rat model of SAH was established by endovascular perforation to mimic the rupture of intracranial aneurysms. Rats were then administered 25 mg/kg of shikonin or dimethylsulfoxide after surgery. Brain edema, SAH grade, and neurobehavioral scores were measured after 24 h of SAH to evaluate neurological impairment. Concentrations of the oxidative stress markers superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in the brain cortex were determined using the corresponding commercially available assay kits. Evans blue staining was used to determine BBB permeability. Western blotting was used to quantify protein levels of tight junction proteins zonula occludens-1, Occludin, and Claudin-5. After modeling, the brain water content increased significantly whereas the neurobehavioral scores of rats with SAH decreased prominently. MDA levels increased and the levels of the antioxidant enzymes GSH and SOD decreased after SAH. These changes were reversed after shikonin administration. Shikonin treatment also inhibited Evans blue extravasation after SAH. Furthermore, reduction in the levels of tight junction proteins after SAH modeling was rescued after shikonin treatment. In conclusion, shikonin exerts a neuroprotective effect after SAH by mitigating BBB injury and inhibiting oxidative stress in the cerebral cortex.


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