Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

CD8⁺ T cell-based immune-therapeutics, including immune checkpoint inhibitors and adoptive cell therapies (tumor-infiltrating lymphocytes (TILs), T cell receptor-engineered T cells (TCR-T), chimeric antigen receptor T cells (CAR-T)), have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases. However, immunotherapy resistance and tumor insusceptibility frequently occur, leading to treatment failure. Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites, immune-inhibitory cytokines, and alteration of gene expression, which suppress the activity of immune cells, particularly CD8⁺ T cells to evade immune surveillance. Therefore, targeting tumor cell metabolic adaptations to reshape the immune microenvironment holds promise as an immunomodulatory strategy to facilitate immunotherapy. Here, we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming, focusing on the regulatory mechanisms underlying tumor cell glucose metabolism, amino acid metabolism, and lipid metabolism in influencing CD8⁺ T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

CD8+T cell-based immune-therapeutics,including immune checkpoint inhibitors and adoptive cell therapies(tumor-infiltrating lymphocytes(TILs),T cell receptor-engineered T cells(TCR-T),chimeric antigen receptor T cells(CAR-T)),have achieved significant successes and prolonged patient survival to varying extents and even achieved cure in some cases.However,immunotherapy resistance and tumor insusceptibility frequently occur,leading to treatment failure.Recent evidences have highlighted the ponderance of tumor cells metabolic reprogramming in establishing an immunosuppressive milieu through the secretion of harmful metabolites,immune-inhibitory cytokines,and alteration of gene expression,which suppress the activity of immune cells,particularly CD8+T cells to evade immune surveillance.Therefore,targeting tumor cell metabolic adaptations to reshape the immune microenvi-ronment holds promise as an immunomodulatory strategy to facilitate immunotherapy.Here,we summarize recent advances in the crosstalk between immunotherapy and tumor reprogramming,focusing on the regulatory mechanisms underlying tumor cell glucose metabolism,amino acid meta-bolism,and lipid metabolism in influencing CD8+T cells to provide promising metabolic targets or combinational strategies for immunotherapy.

Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Chronic subdural hematoma is one of the common central nervous system diseases in middle-aged and elderly people,and the incidence is increasing year by year.Drill and drain surgery is recognized as one of the effective ways to treat chronic subdural hematoma.However,there still exists a non-negligible recurrence after surgery.In addition,with the aging of the population,senior patients may have many underlying diseases.Therefore,the risk of surgery is high and some patients even have contraindications to surgery due to the long-term use of anticoagulant or antiplatelet drugs.In recent years,some progress has been made in the treatment of chronic subdural hematoma,such as oral atorvastatin can promote the absorption of chronic subdural hematoma,small-dose dexamethasone is used in the treatment of chronic subdural hematoma,neuroendoscopy-assisted treatment of segregated chronic subdural hematoma,and middle meningeal artery embolization surgery to reduce the recurrence of chronic subdural hematoma patients.Meanwhile,with the development of imaging,Computed Tomography(CT)and Magnetic Resonance Imaging(MRI)have made some progress in the diagnosis of chronic subdural hematoma.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Objective To explore the effects of remote ischemic preconditioning combined with permissive hypercapnia on brain oxygen saturation and postoperative cognition in patients which undergoing thoracoscopic lung cancer surgery.Methods A collection of 64 patients elective requiring thoracoscopic lung cancer surgery who were divided into control group and combined group according to the randomized grouping method,with 32 cases in each group.The PaCO2 in the control group of patient was maintained at normal,and patients in the combination group were given permissive hypercapnia ventilation strategies and performed remote ischemic preconditioning,PaCO2 is maintained at 45-50mmHg(1mmHg=0.133kPa).Record the cerebral oxygen saturation(rSO2)at the five time points before operation(T0),10min after one lung ventilation(T1),30min after one lung ventilation(T2),10 min after lung recruitment(T3)and the end of surgery(T4),measured the internal jugular venous blood oxygen saturation(SjvO2)and calculated cerebral arteriovenous blood oxygen content difference(CaO2-CjvO2),brain oxygen uptake rate(CERO2).Monitored the average arterial pressure(MAP)and heart rate(HR)of the hemodynamic indicators at the above five time points.The scores of cognitive function were recorded 1 day before operation and 1 day and 3 days after operation;detected the levels of serum neuron-specific enolase(NSE),amyloid β(Aβ)and S100β protein(S100β)in 1 day before surgery,24hours after surgery and 48hours after surgery;Comparison of postoperative related indicators and adverse reactions between the patients of two groups.Results The rSO2 and SjvO2 of combined group were higher than control group in the T1-T4,but CaO2-CjvO2 and CERO2 were lower than those of control group.There was no significant difference in HR and MAP between two groups from T0-T4.The mini-mental state examination(MMSE)score of the combined group was significantly higher than that of the control group on the 1 day after operation.The level of serum NSE,Aβ and S100β in the combined group was lower than those of control group at 24hours and 48hours after operation.There was no significant difference in incidence of postoperative adverse reactions and postoperative related indexes between the two groups.Conclusion Permissive hypercapnia combined with remote ischemic preconditioning can increase cerebral oxygen saturation in patients undergoing thoracoscopic lung cancer surgery,improve cerebral oxygen metabolism and reduce the levels of serum neuron-specific enolase,β-amyloid protein and S100β protein,decrease the postoperative cognitive dysfunction.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Objective To quantify the setup errors for the different anatomical sites of patients who received intensity-modulated radiotherapy (IMRT) with linear accelerator on-board kilovolt fan beam CT(kV-FBCT) as non-isocenter IGRT and megavolt cone beam CT (MV-CBCT) as isocenter IGRT. Methods A retrospective analysis was performedon 70 patients who underwent radiotherapy, kV-FBCT, and/or MV-CBCT scans after each routine setup prior to IMRT. The average displacement (M), systematic error (Σ), and random error (б) at different treatment sites in the left-right, anterior-posterior, and cranial-caudal directions were calculated according to the individual displacements. The formula 2.5Σ+0.7б was used to estimate the PTV margin in respective direction. For each single patient, the root mean square in three directions was used as 3D displacement. Results A total of 1130 displacements were recorded in the 70 patients. The PTV margin was estimated to be 1.9-3.1 mm in head and neck cancer, 2.8-5.1 mm in thoracic cancer, 4.6-5.1 mm in breast cancer, 3.0-5.5 mm in upper abdominal cancer, and 3.5-6.8 mm in pelvic tumor. For the 3D mean displacements, the head and neck, thoracic, breast, upper abdominal, and pelvic cancer were 2.4±1.0, 4.0±1.6, 4.1±2.0, 4.6±2.1, and 4.6±2.1 mm, respectively. The average 3D displacement obtained by kV-FBCT and MV-CBCT were 4.1 and 3.4 mm, respectively (P=0.212). Conclusion The quantitative setup-error data can be obtained using linear accelerator on-board FBCT, and the non-isocenter IGRT induced set-up error cannot be negligible.

Objective To observe the effect of dexmedetomidine combined with goal-directed fluid therapy(GDFT)on hemodynamics and cerebral oxygen supply of patients undergoing cerebral aneurysm clipping.Methods A total of 78 patients undergoing cerebral aneurysm clipping surgery in Jinhua Municipal Central Hospital from January 2021 to December 2022 were selected and divided into control group and observation group according to random number table method,with 39 cases in each group.The patients in control group received conventional fluid therapy,and the patients in observation group received dexmedetomidine pump +GDFT.Mean arterial pressure(MAP),heart rate(HR),cardiac index(CI),brain metabolic markers,neuron specific enolase(NSE),S100β levels and mini mental status examination(MMSE)scores at different time points[before anesthesia induction(T0),immediately after tracheal intubation(T1),beginning of surgery(T2),opening meninges(T3),immediately after aneurysm clipping(T4),end of surgery(T5),24h after surgery(T6),72h after surgery(T7)],and fluid intake and outflow of two groups were compared.Results MAP at T1-T4 and CI at T1-T3 in observation group were significantly higher than those in control group(P<0.05).The colloid volume,total infusion volume and urine volume in observation group were significantly higher than those in control group(P<0.05).The serum levels of NSE and S100β at T5-T7 were significantly higher than those at T0 in both groups(P<0.05).The levels of serum NSE and S100β at T5 and T6 in observation group were significantly lower than those in control group(P<0.05).The oxygen content in jugular venous blood(CjvO2)at T1-T4 was significantly lower than that at T0 in control group(P<0.05).Cerebral oxygen extraction ratio at T1 was significantly higher than that at T0 in both groups(P<0.05).CjvO2 at T3-T4 in observation group were significantly higher than those in control group(P<0.05).At T6 and T7,MMSE scores in two groups were significantly lower than at T0 in this group(P<0.05).MMSE score at T6 of observation group was significantly higher than that of control group(P<0.05).Conclusion Dexmedetomidine combined with GDFT can effectively improve preload and brain function,stabilize intraoperative circulatory function,and improve early postoperative cognitive function in patients undergoing cerebral aneurysm clipping.