Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Objective:To explore the clinical efficacy of the sixth generation CyberKnife (M6) in treating patients with brain metastases, and analyze clinical characteristics and dosimetric factors.Methods:Clinical data of patients with brain metastases who received CyberKnife treatment at Sichuan Cancer Hospital from April 2023 to March 2024 were retrospectively analyzed. All patients were treated with CyberKnife with 6 MV X-ray. According to the maximum diameter of brain metastases, the radiation prescription dose of brain metastases was adjusted. The tumor remission, recurrence, 6-month and 1-year overall survival (OS), local control (LC) of intracranial target lesions, progression-free survival (PFS), distant metastasis-free survival (DMFS) of intracranial brain metastases and adverse reactions were evaluated. According to the median biological dose, the survival difference between the groups was compared. Survival analysis was conducted by Kaplan-Meier method. Survival differences among different groups were analyzed by log-rank test.Results:A total of 63 eligible patients with brain metastases were enrolled, with a median age of 59 years (rang: 36-80 years). Among them, 47 patients were diagnosed with primary tumors originating from the lungs, 16 patients with primary tumors originating from other organs; 44 patients with single brain metastases, and 19 patients with 2-3 lesions, respectively. The median biological dose was 67.2 Gy (rang: 47.4-86.4 Gy), and the median single dose was 8 Gy/F (rang: 4-24 Gy/F). The follow-up was conducted until July 15, 2024. The median follow-up time for the entire group was 9 months (rang: 2-15 months). Among the 87 target lesions treated with CyberKnife, 11 patients corresponding to 14 target lesions experienced local recurrence. And the 6-month and 1-year LC rates were 92.5% and 70.9%, respectively. Ten patients corresponding to 16 target lesions died. And the 6-month and 1-year OS rates were 92.7% and 74.8%, respectively. Thirty-five patients corresponding to 50 target lesions experienced disease progression. And the 6-month and 1-year PFS rates were 64.3% and 25.5%, respectively. Thirty-three patients corresponding to 48 target lesions showed distant metastasis outside the target lesions, with a 6-month DMFS of 67.0% and a 1-year DMFS of 33.9%. Group comparison showed that 43 target lesions in the group receiving ≤67.2 Gy irradiation and 44 in the group receiving >67.2 Gy irradiation. The 6-month LC, OS, PFS, and DMFS rates between two groups were 89.8% vs. 97.7% ( P=0.127), 89.8% vs. 95.4% ( P=0.305), 65.4% vs. 68.5% ( P=0.514), 65.4% vs. 68.5% ( P=0.516), respectively. The 1-year LC, OS, PFS, and DMFS rates between two groups were 54.1% vs. 89.5% ( P=0.003), 67.3% vs. 82.9% ( P=0.219), 19.2% vs. 32.7% ( P=0.370) and 23.3% vs. 33.0% ( P=0.533). During the follow-up, only 2 patients (3.2%) were found to have grade 1-2 radiation-induced brain injury (asymptomatic brain injury) by MRI examination, and there were no other radiotherapy related adverse reactions. Conclusions:CyberKnife therapy is clinically effective for brain metastases, with mild adverse reactions. Increasing the tumor irradiation dose can improve local tumor control and is expected to further improve the OS of patients.

Peritoneal fibrosis(PF)is an important reason that restricts long-term treatment of peritoneal dialysis(PD).Based on the theory of collateral disease,PF is considered to be an abdominal collateral disease,with dampness as the main pathogenic factor,and collateral qi deficiency and stagnation,toxicity and blood stasis as the core pathogenesis.The peritoneum is chronically exposed to an inflammatory microenvironment induced by non-biocompatible peritoneal dialysis fluid,reflecting the pathogenic mechanism of dampness-induced pathology.The resultant pathological processes,including damage of peritoneal mesothelial cells,accumulation of inflammatory mediators and metabolic products,and angiogenesis—elucidate the scientific connotation of dampness impairing collaterals and inducing deficiency,toxicity,and stasis.On this basis,the treatment principles of invigorating qi,detoxifying,resolving stasis and unblocking collaterals were proposed,and the Qixue Huazheng prescription was formed with Astragalus as the main ingredient and Centella asiatica and Ligusticum wallichii as the compatibility,which provides a reference for the prevention and treatment of PD-relat-ed PF by traditional Chinese medicine.

Purpose To investigate the changes of free water(FW)values in the key basal ganglia of dopamine system in the brain of early Parkinson's disease(PD)by free water imaging,and to reveal the potential relationship between the changes and early PD.Materials and Methods From February to December 2023,62 patients with early PD and 27 healthy controls were enrolled in the Parkinson's Disease Progression Markers Project database,and 25 age-and sex-matched healthy controls were self-recruited from Henan Provincial People's Hospital.All subjects underwent clinical scale assessment and MRI data collection.Free water imaging was used to calculate the FW values of key nuclei in dopamine system,and the difference of FW values between PD group and healthy controls group,the correlation between FW values of PD group and clinical scale scores were analyzed.Results The FW values of compact part of substantia nigra(SNc)and ventral tegmental area(VTA)in PD group were significantly higher than those in healthy controls group(Z=2.458-3.914,all P<0.05).Regression analysis showed that FW values of SNc were correlated with the movement disorder society-sponsored revision unified Parkinson′s disease rating scale(MDS-UPDRS)Ⅲ scores and state-trait anxiety inventory(STAI)scores on both sides(r2=0.223,P<0.001;r2=0.125,P=0.018;r2=0.151,P=0.003;r2=0.128,P=0.017),the FW value of VTA on the left was significantly correlated with MDSUPDRS Ⅲ score(r2=0.143,P=0.004)and the FW value of the right VTA was significantly correlated with the STAI score(r2=0.125,P=0.019).Conclusion The FW values of SNc and VTA in PD patients are significantly increased in the early stage,and are correlated with motor and non-motor symptoms in PD patients.FW values may reflect brain degeneration,and this change may be related to the decline of motor and non-motor function in patients.

Objective:To compare the differential regulatory effects of corticotropin releasing hormone(CRH)neu-rons in periaqueductal gray(PAG)and medial preoptic area(MPA)downstream of paraventricular nucleus(PVN)in mediating stress-related abnormal behaviors.Methods:The anterograde labeled virus AAV2/9-hSyn-DIO-hChR2-EYFP and AAV2/9-mCrh-SV40 NLS-Cre was injected into the PVN brain region of mouse,and the projection distribution of PVN axons in the PAG and MPA brain regions was observed after statistical analysis of its projection distribution through Image J.The optogenetic inhibitory virus mixture of AAV2/9-DIO-stGtACR2-EGFP and AAV2/9-mCrh-SV40 NLS-Cre targeting CRH neurons was injected into the PAG and MPA brain regions receiving the corresponding PVN projection,respectively,and the CRH neurons in the PAG and MPA brain regions were inhibited by optogenetic blue light 460 nm to observe the anxiety-related behaviors of mice under acute restraint stress.Results:Densely distributed CRHergic PVN axon terminals were observed in PAG and MPA brain regions.Optogenetic inhibition of CRH neurons in the PAG region of acute stress mice showed no significant change in social preference behavior.The eating latency decreased in the novelty-suppressed feeding test,and the escape latency increased under visual fear stimulation.Optogenetic inhibi-tion of CRH neurons in the MPA brain region showed no significant change in social preference,significantly decreased eating latency in the novelty-suppressed feeding test,and no significant change in escape latency under visual fear stim-ulation.Conclusion:CRH neurons in PAG and MPA brain regions downstream of PVN have differential regulation in a-cute stress-related anxiety behavior,but no difference in social behavior regulation,which provides theoretical support and basis for in-depth exploration of stress-related brain regions and cellular mechanisms.

Inflammatory peripheral neuropathy,also known as immune-mediated peripheral neuropathy,is a rare group of heterogeneous peripheral neuropathy characterized by dysfunction and damage to different structures of the peripheral nerves,including Guillain-Barre syndrome,chronic demyelinating inflammatory polyradiculopathy,autoimmune neuropathy,multifocal motor neuropathy or neuropathy related to monoclonal gamma globulinopathy,etc.The causes of these diseases remain unclear,but B cells and autoantibodies play a key role in their pathogenesis.This group of diseases can be classified as having acute or chronic onset based on the mode of onset.Clinically,it can present as a unipolar course,recurrent or progressive course.Severe inflammatory peripheral neuropathy can lead to flaccid paralysis of the limbs,with a high risk of severe disability and death.With the rapid progress of various studies in the field of neuroimmunological diseases in recent years,the therapeutic tar-gets/methods for immune-mediated peripheral neuropathy have also presented a flourishing situation.The latest progress at home and abroad is summarized as follows.

Inflammatory peripheral neuropathy,also known as immune-mediated peripheral neuropathy,is a rare group of heterogeneous peripheral neuropathy characterized by dysfunction and damage to different structures of the peripheral nerves,including Guillain-Barre syndrome,chronic demyelinating inflammatory polyradiculopathy,autoimmune neuropathy,multifocal motor neuropathy or neuropathy related to monoclonal gamma globulinopathy,etc.The causes of these diseases remain unclear,but B cells and autoantibodies play a key role in their pathogenesis.This group of diseases can be classified as having acute or chronic onset based on the mode of onset.Clinically,it can present as a unipolar course,recurrent or progressive course.Severe inflammatory peripheral neuropathy can lead to flaccid paralysis of the limbs,with a high risk of severe disability and death.With the rapid progress of various studies in the field of neuroimmunological diseases in recent years,the therapeutic tar-gets/methods for immune-mediated peripheral neuropathy have also presented a flourishing situation.The latest progress at home and abroad is summarized as follows.

Peritoneal fibrosis(PF)is an important reason that restricts long-term treatment of peritoneal dialysis(PD).Based on the theory of collateral disease,PF is considered to be an abdominal collateral disease,with dampness as the main pathogenic factor,and collateral qi deficiency and stagnation,toxicity and blood stasis as the core pathogenesis.The peritoneum is chronically exposed to an inflammatory microenvironment induced by non-biocompatible peritoneal dialysis fluid,reflecting the pathogenic mechanism of dampness-induced pathology.The resultant pathological processes,including damage of peritoneal mesothelial cells,accumulation of inflammatory mediators and metabolic products,and angiogenesis—elucidate the scientific connotation of dampness impairing collaterals and inducing deficiency,toxicity,and stasis.On this basis,the treatment principles of invigorating qi,detoxifying,resolving stasis and unblocking collaterals were proposed,and the Qixue Huazheng prescription was formed with Astragalus as the main ingredient and Centella asiatica and Ligusticum wallichii as the compatibility,which provides a reference for the prevention and treatment of PD-relat-ed PF by traditional Chinese medicine.

Purpose To investigate the changes of free water(FW)values in the key basal ganglia of dopamine system in the brain of early Parkinson's disease(PD)by free water imaging,and to reveal the potential relationship between the changes and early PD.Materials and Methods From February to December 2023,62 patients with early PD and 27 healthy controls were enrolled in the Parkinson's Disease Progression Markers Project database,and 25 age-and sex-matched healthy controls were self-recruited from Henan Provincial People's Hospital.All subjects underwent clinical scale assessment and MRI data collection.Free water imaging was used to calculate the FW values of key nuclei in dopamine system,and the difference of FW values between PD group and healthy controls group,the correlation between FW values of PD group and clinical scale scores were analyzed.Results The FW values of compact part of substantia nigra(SNc)and ventral tegmental area(VTA)in PD group were significantly higher than those in healthy controls group(Z=2.458-3.914,all P<0.05).Regression analysis showed that FW values of SNc were correlated with the movement disorder society-sponsored revision unified Parkinson′s disease rating scale(MDS-UPDRS)Ⅲ scores and state-trait anxiety inventory(STAI)scores on both sides(r2=0.223,P<0.001;r2=0.125,P=0.018;r2=0.151,P=0.003;r2=0.128,P=0.017),the FW value of VTA on the left was significantly correlated with MDSUPDRS Ⅲ score(r2=0.143,P=0.004)and the FW value of the right VTA was significantly correlated with the STAI score(r2=0.125,P=0.019).Conclusion The FW values of SNc and VTA in PD patients are significantly increased in the early stage,and are correlated with motor and non-motor symptoms in PD patients.FW values may reflect brain degeneration,and this change may be related to the decline of motor and non-motor function in patients.

Objective:To explore the clinical efficacy of the sixth generation CyberKnife (M6) in treating patients with brain metastases, and analyze clinical characteristics and dosimetric factors.Methods:Clinical data of patients with brain metastases who received CyberKnife treatment at Sichuan Cancer Hospital from April 2023 to March 2024 were retrospectively analyzed. All patients were treated with CyberKnife with 6 MV X-ray. According to the maximum diameter of brain metastases, the radiation prescription dose of brain metastases was adjusted. The tumor remission, recurrence, 6-month and 1-year overall survival (OS), local control (LC) of intracranial target lesions, progression-free survival (PFS), distant metastasis-free survival (DMFS) of intracranial brain metastases and adverse reactions were evaluated. According to the median biological dose, the survival difference between the groups was compared. Survival analysis was conducted by Kaplan-Meier method. Survival differences among different groups were analyzed by log-rank test.Results:A total of 63 eligible patients with brain metastases were enrolled, with a median age of 59 years (rang: 36-80 years). Among them, 47 patients were diagnosed with primary tumors originating from the lungs, 16 patients with primary tumors originating from other organs; 44 patients with single brain metastases, and 19 patients with 2-3 lesions, respectively. The median biological dose was 67.2 Gy (rang: 47.4-86.4 Gy), and the median single dose was 8 Gy/F (rang: 4-24 Gy/F). The follow-up was conducted until July 15, 2024. The median follow-up time for the entire group was 9 months (rang: 2-15 months). Among the 87 target lesions treated with CyberKnife, 11 patients corresponding to 14 target lesions experienced local recurrence. And the 6-month and 1-year LC rates were 92.5% and 70.9%, respectively. Ten patients corresponding to 16 target lesions died. And the 6-month and 1-year OS rates were 92.7% and 74.8%, respectively. Thirty-five patients corresponding to 50 target lesions experienced disease progression. And the 6-month and 1-year PFS rates were 64.3% and 25.5%, respectively. Thirty-three patients corresponding to 48 target lesions showed distant metastasis outside the target lesions, with a 6-month DMFS of 67.0% and a 1-year DMFS of 33.9%. Group comparison showed that 43 target lesions in the group receiving ≤67.2 Gy irradiation and 44 in the group receiving >67.2 Gy irradiation. The 6-month LC, OS, PFS, and DMFS rates between two groups were 89.8% vs. 97.7% ( P=0.127), 89.8% vs. 95.4% ( P=0.305), 65.4% vs. 68.5% ( P=0.514), 65.4% vs. 68.5% ( P=0.516), respectively. The 1-year LC, OS, PFS, and DMFS rates between two groups were 54.1% vs. 89.5% ( P=0.003), 67.3% vs. 82.9% ( P=0.219), 19.2% vs. 32.7% ( P=0.370) and 23.3% vs. 33.0% ( P=0.533). During the follow-up, only 2 patients (3.2%) were found to have grade 1-2 radiation-induced brain injury (asymptomatic brain injury) by MRI examination, and there were no other radiotherapy related adverse reactions. Conclusions:CyberKnife therapy is clinically effective for brain metastases, with mild adverse reactions. Increasing the tumor irradiation dose can improve local tumor control and is expected to further improve the OS of patients.