Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

OBJECTIVE: To explore the effects and mechanisms of the C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4) signaling axis on apoptosis and autophagy in SH-SY5Y neuronal cells subjected to oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. METHODS: SH-SY5Y cells were divided into the following groups: OGD/R group and non-OGD/R group, with the OGD/R group subjected to OGD/R modeling and the non-OGD/R group receiving no treatment. Cells were also divided into CXCL12⁺ and CXCL12^- groups; the CXCL12⁺ group received 0.1 mg/L exogenous recombinant CXCL12 (rhCXCL12) at reoxygenation, while the CXCL12^- group did not. Another set of cells was divided into CXCL12+AMD3100 and CXCL12 groups; the CXCL12+AMD3100 group was pretreated with 2.5 mg/L AMD3100, a CXCR4 inhibitor, for 2 hours before OGD/R and received both 2.5 mg/L AMD3100 and 0.1 mg/L rhCXCL12 at reoxygenation, whereas the CXCL12 group received rhCXCL12 only. Additionally, cells were divided into small interfering RNA CXCR4 (siCXCR4) and small interfering RNA negative control (siNC) groups; the siCXCR4 group underwent CXCR4 knockdown before OGD/R modeling and received 0.1 mg/L rhCXCL12 at reoxygenation, while the siNC group, transfected with a negative control, received the same treatment. Protein expression of autophagy-related 16 (ATG16), microtubule-associated protein 1 light chain 3 (LC3), aquaporin-3 (AQP3), and CXCR4 was detected by Western blotting. Apoptosis rate and CXCR4 expression were measured by flow cytometry. RESULTS: Compared with the non-OGD/R group, the OGD/R group showed a significantly increased apoptosis rate and markedly decreased protein expression levels of ATG16, LC3, AQP3, and CXCR4 (all P < 0.05). CXCR4 fluorescent expression was also significantly reduced, suggesting that OGD/R simultaneously affects neuronal apoptosis and autophagy while inhibiting CXCR4 and AQP3 expression in SH-SY5Y cells. Compared with the CXCL12^- group, the CXCL12⁺ group exhibited no significant change in apoptosis rate but demonstrated significantly increased protein expression of ATG16, LC3, and AQP3 (ATG16/GAPDH: 1.21±0.10 vs. 1.00±0.00; LC3/β-actin: 1.22±0.10 vs. 1.00±0.00; AQP3/β-actin: 1.26±0.04 vs. 1.00±0.00; all P < 0.05). CXCR4 expression was also significantly enhanced (fluorescence intensity: 1.19±0.05 vs. 1.00±0.00, P < 0.05), indicating that CXCL12 may promote autophagy in OGD/R-injured SH-SY5Y cells via the CXCR4/AQP3 pathway. Compared with the CXCL12 group, the CXCL12+AMD3100 group showed no significant difference in apoptosis rate but significantly lower protein levels of ATG16 and LC3 (ATG16/GAPDH: 0.75±0.08 vs. 1.00±0.00; LC3/GAPDH: 0.86±0.07 vs. 1.00±0.00; both P < 0.05), suggesting that CXCL12 induces autophagy in OGD/R SH-SY5Y cells through CXCR4. Compared with the siNC group, the siCXCR4 group showed no significant change in apoptosis rate but significantly reduced protein expression of ATG16, LC3, AQP3, and CXCR4 (ATG16/GAPDH: 0.76±0.06 vs. 1.00±0.00; LC3/GAPDH: 0.79±0.11 vs. 1.00±0.00; AQP3/GAPDH: 0.81±0.05 vs. 1.00±0.00; CXCR4/GAPDH: 0.86±0.04 vs. 1.00±0.00; all P < 0.05), indicating that CXCR4 knockdown suppresses OGD/R-induced autophagy in SH-SY5Y cells likely via AQP3. CONCLUSIONS The CXCL12/CXCR4 signaling axis can regulate OGD/R-induced autophagy in SH-SY5Y cells through AQP3 without affecting apoptosis, indicating a role for this pathway in neuronal autophagy during cerebral ischemia/reperfusion injury.
Humans ; Receptors, CXCR4/metabolism* ; Chemokine CXCL12/metabolism* ; Autophagy ; Glucose/metabolism* ; Apoptosis ; Neurons/cytology* ; Oxygen/metabolism* ; Signal Transduction ; Cell Line, Tumor ; Cell Hypoxia ; Benzylamines ; Cyclams

Neutrophils are the most abundant circulating white blood cells and play an indispensable role as first responders of damaged tissue and infected sites in the early inflammatory response of healing. Neutrophils provide immediate host defense by engulfing and destroying pathogens, releasing cytotoxic enzymes and metabolites, and spreading inflammatory networks. However, if left uncontrolled, these defense mechanisms can cause significant collateral damage. Focusing on the triggers of harmful neutrophil inflammation and immunomodulatory deficits, as well as grasping the specific drivers of harmful inflammation, is of great significance for recalibrating inflammation to promote endogenous tissue repair. This article, starting from the causes of neutrophil inflammation imbalance, elaborated the main mechanism of neutrophil-mediated tissue injury and related pathological manifestations, and highlighted the therapeutic targets with promising applications.

Objective To investigate the expression and clinical significance of miR-34c and miR-29b in peripheral blood of patients with sensorineural hearing loss.Methods 140 patients with neurological deafness admitted to our hospital from June 2020 to June 2023 were included in the study group,and 40 healthy subjects were included in the control group during the same period.SNHL patients were categorized into 63 cases in the mildly deaf group,42 cases in the moderately deaf group,and 35 cases in the severely deaf group according to their hear-ing impairment.The expressions of miR-34c and miR-29b were detected by qRT-PCR,and VEGF,oxidative stress(TAC,SOD,MDA),NO and Cx26 were detected.Correlation analysis was performed by Pearson test,independent risk factors for SNHL severity were calculated by logistics regression algorithm,and the predictive value of miR-34c and miR-29b on the severity of SNHL patients was evaluated by ROC curve.Results Comparing the levels of NO,TAC,SOD,and Cx26 among the four groups,severe deafness groupmoderate deafness group>mild deafness group>control group(P<0.05).Comparison of miR-34c mRNA and miR-29b mRNA expression levels among the four groups,severe deafness group>moderate deafness group>mild deafness group>control group(P<0.05).Pearson's test showed that SNHL patients'peripheral blood miR-34c and miR-29b were positively correlated with VEGF and MDA,and were negatively correlated with NO,TAC,SOD and Cx26(P<0.05).negative correlation(P<0.05).Multifactorial logistic regression analysis showed that VEGF,MDA,NO,Cx26,TAC,SOD,miR-34c,miR-29b were independent factors affecting the severity of SNHL.Conclusion miR-34c and miR-29b are overexpressed in SNHL patients and can be used as serum markers for predictive assess-ment of disease severity in SNHL patients.

Objective:To investigate the potential source of infection for a cluster outbreak of human brucellosis in Yantai City, Shandong Province.Methods:The information of a human brucellosis cluster outbreak case in Yantai City, Shandong Province in 2022 was collected, the strains were isolated and cultured, and DNA was extracted. BCSP31-PCR was used for species identification, and AMOS-PCR was used for species type identification. Multiple locus variable-number tandem-repeat analysis (MLVA)-16 was used for clustering analysis, and the results were compared with the public database MLVAbank and the monitoring data of Brucella in Shandong Province in 2022. At the same time, whole genome single nucleotide polymorphism (wgSNP) typing was used to analyze the 53 Brucella strains that had completed whole genome sequencing in Shandong Province in 2022, and the wgSNP phylogenetic tree was constructed. Results:According to BCSP31-PCR and AMOS-PCR identification, the three strains related to the cluster outbreak of brucellosis in Yantai City, Shandong Province in 2022 were all Brucella melitensis biotype. The results of MLVA-16 typing showed that the MLVA-16 typing of the three isolated strains was completely consistent, with 16 tandem repeat loci of 1-5-3-13-2-2-3-2-4-41-8-4-4-3-6-5, belonging to the Eastern Mediterranean clade. Compared with MLVAbank, the MLVA-16 typing of two strains isolated from Kazakhstan was consistent with the results of this study. Compared with the monitoring data of Brucella in Shandong Province in 2022, it was found that the MLVA-16 typing of 11 isolated strains was consistent with the results of this study, which were isolated from Zaozhuang, Linyi, Taian, Yantai, and Weifang cities, respectively. The results of wgSNP typing showed that the distance between the 11 strains and the strains of the current outbreak was less than 7 single nucleotide polymorphisms, and the strains were isolated from Taian, Zibo, Linyi, Binzhou, Jinan, Jining, Yantai and Weihai cities, respectively. Conclusion:After tracing the source of a human brucellosis cluster outbreak in Yantai City, Shandong Province in 2022, it is speculated that the strains of Brucella melitensis isolated from Linyi, Taian and Yantai cities are closely related, indicating that sheep in these areas have homology.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective To observe the value of nomogram obtained with multivariate logistic regression based on ultrasound for predicting residue of benign thyroid nodules after microwave ablation(MWA).Methods Totally 101 patients with 133 benign thyroid nodules who underwent ultrasound-guided MWA were retrospectively enrolled.The nodules were divided into residual group(n=21)and non-residual group(n=112)according to follow-up results of contrast-enhanced ultrasound(CEUS)1 month after MWA.The ultrasonic performances of nodules before MWA were compared between groups,and those being statistically different were included in a multivariate logistic regression model to identify the independent predictors for residue after MWA,and the model was then visualized as a nomogram.The discrimination of the nomogram for predicting residue after MWA was assessed with receiver operating characteristic curve and area under the curve(AUC),and its calibration was assessed with Hosmer-Lemeshow goodness-of-fit test.Results High ablation risk and nodules volume shown with ultrasound were both independent predictors of residue of benign thyroid nodules after MWA(both P＜0.05),indicating that benign thyroid nodules with high ablation risk(OR=17.637[2.528,123.019])and large volume(OR=1.297[1.155,1.457])had relatively higher risk of residue after MWA.AUC of the nomogram was 0.756 for predicting residue of benign thyroid nodules after MWA,while Hosmer-Lemeshow test showed good fit(P=0.401).Conclusion Benign thyroid nodules with high ablation risk and large volume shown with ultrasound had relatively high risk of residue after MWA,which could be predicted conveniently and effectively with the obtained nomogram.