Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Objective To investigate the serum levels of semaphorin 3E(Sema3E)in patients with intracranial aneurysms,revealing the correlation between Sema3E and 1-month poor prognosis after interventional embolization.Methods This study was a prospective single-center cohort study,recruiting 102 consecutive patients with intracranial aneurysms who underwent interventional surgery from June 2020 to January 2022 in our hospital.Among them,11 patients were excluded.Clinical and radiological profiles were collected.Peripheral blood was collected after admission,and serum Sema3E levels were determined by enzyme-linked immunosorbent assay.All the aneurysms were treated with endovascular coil embolization or stent-assisted coil embolization.The primary outcome was evaluated with the Glasgow Outcome Scale(GOS)1 month after interventional therapy.The favorable outcome was defined as a GOS score of 4-5,and a poor outcome was defined as a GOS score of 1-3(severe disability,vegetative state,or death).Univariate and multivariate logistic regression analyses were used to identify potential prognostic factors after interventional therapy.Results The average age of 91 patients with intracranial aneurysm was 59.9±11.0 years old,including 70 cases(76.9%)with favorable prognosis and 21 cases(23.1%)with poor prognosis.The mean preoperative Glasgow Coma Scale(GCS)score of the poor prognosis group(9.4±4.5)was significantly lower than that of the favorable prognosis group(13.3±2.5;P<0.001).In the poor prognosis group,the Hunt-Hess grade(3.6±0.6 vs.2.0±1.3,P<0.001)and the serum Sema3E levels[(6.21±1.58)μg/L vs.(4.38±1.77)μg/L,P<0.001]were significantly higher than those in the favorable prognosis group.Logistic regression analysis showed the Hunt-Hess grade(OR =7.150,P =0.003),stent-assisted coil embolization(OR =15.777,P =0.010),and the serum Sema3E level(OR =1.756,P =0.027)were independent prognostic factors for intracranial aneurysms after interventional therapy.Conclusions The serum Sema3E level is closely correlated with the severity of intracranial aneurysms.The serum Sema3E level is a prognostic factor for interventional treatment,which can be used as a biomarker for predicting poor outcomes.

Objective:To investigate the alterations of cholinergic and monoamine neurotransmitters in cerebrospinal fluid in patients with postoperative delirium.Methods:Sixty-eight patients with normal preoperative cognitive functions were enrolled.They were diagnosed with spinal extramedullary intradural space-occupying lesion and underwent surgical resection.Among these patients, 18 developed postoperative delirium (delirium group), 46 had no postoperative delirium (control group), and the diagnosis of delirium was unclear in four cases (excluded). Cerebrospinal fluid (CSF) was collected before the surgical resection of lesions and on the third day postoperatively.The concentrations of acetylcholine (Ach), norepinephrine (NE), adrenaline (E), dopamine (DA) and serotonin (5-HT) were measured using the high-performance liquid chromatography/electrochemical method.Results:Prior to the surgical resection, there were no significant differences in the Ach, NE, E, DA or 5-HT baseline levels in the CSF between the delirium group and the control group (all P>0.05). After surgery, the Ach level in the delirium group ((0.63±0.26) μmol/L) was significantly lower than that in the control group ((0.77±0.19) μmol/L) ( P=0.032), and there were no significant differences in other neurotransmitter levels (all P>0.05). In the delirium group, the level of Ach in the CSF after surgery ((0.63±0.26) μmol/L) was significantly lower than the baseline level ((0.75±0.19) μmol/L) ( P=0.021). The postoperative NE level ((1.58±0.28) μmol/L) was significantly higher than the baseline level ((1.49±0.21) μmol/L) ( P=0.036). There was no significant difference in the adrenaline level ( P=0.497). The postoperative DA level ((0.86±0.18) μmol/L) was significantly higher than the baseline level ((0.82±0.15) μmol/L) ( P=0.045), and the postoperative 5-HT level ((2.94±0.28) μmol/L) was also significantly higher than the baseline level ((2.75±0.35) μmol/L) ( P=0.022). In the control group, only the postoperative 5-HT level ((2.90±0.31) μmol/L) was significantly higher than the baseline level ((2.76±0.26) μmol/L) ( P=0.016), while the postoperative levels of other neurotransmitters were not significantly changed when compared to the baseline levels (all P>0.05). Conclusion:The cholinergic neurotransmitter levels were reduced while the monoamine neurotransmitter levels were increased in the cerebrospinal fluid in patients with postoperative delirium, which suggests that cholinergic hypoactivity and monoaminergic hyperexcitability may be important pathophysiological processes in the occurrence and development of postoperative delirium.

Objective:To develop rapid screening tools for assessing the risk of mild cognitive impairment(MCI)based on neuropsychological scales and cognitive paradigms.Methods:Two baseline datasets from the Beijing Ageing Brain Rejuvenation Initiative(BABRI)cohort were studied: dataset 1 contained 5 593 subjects, with 1 500 cases with MCI and 4 093 cases with normal cognitive function(the control group); dataset 2 consisted of 588 subjects, with 92 cases with MCI and 496 cases with normal cognitive function(the control group). Dataset 1 was used to simplify the Mini-Mental State Examination(MMSE), and the sub-item combination with the strongest MCI discriminative ability was selected to integrate into the cognitive rapid assessment(BABRI-mini MMSE). Dataset 2 with scores of encoding-recognition episodic memory task was used for further MCI discriminant analysis and was adapted into an episodic memory test(BABRI-EMT). We applied the receiver operating characteristic curve(ROC)for those analyses.Results:The control group and the MCI group showed significant differences in multi-domain cognitive ability and episodic memory task performance( P<0.01). Among sub-items of MMSE measured using dataset 1, MMSE12 and MMSE19 had the highest discriminative accuracy for MCI, and the area under the ROC(AUC)was 0.699 and 0.631, respectively.Dataset 2 was used to investigate the discriminative ability of the episodic memory score in combination with the above two MMSE sub-items for MCI, and the AUC value was 0.732, the sensitivity was 0.731, and the specificity was 0.656. Conclusions:The BABRI-mini MMSE and BABRI-EMT are suitable for the large-scale universal screening of MCI risk.

ObjectiveTo study theory of mind(TOM) of youngsters in alexithymia,and to assess the impairment in TOM by analysing affective and cognitive TOM and the first and second order judgment.MethodsTOM of 31 alexithymics and 30 healthy control subjects get be examined by the Chinese version of “Yoni task” and series of tests.ResultsThere were significant differences in affective TOM accuracy scores between alexithymics and healthy controls ( ( 35.81 ± 6.30) vs ( 39.83 ± 6.02),t =-2.55,P ＜ 0.05 ).Particularly,alexithymics got significantly lower accuracy scores in the second order judgement of affective TOM ( (24.55 ±6.01 ) vs (28.80 ± 6.04),t =-2.76,P ＜ 0.01 ).However,there were no in cognitive TOM accuracy scores between alexithymics and health controls ( ( 19.00 ± 2.11 ) vs ( 19.43 ± 2.13 ),t =-0.80,P ＞ 0.05 ).ConclusionAlexithymics are impaired in affective TOM,specially the second order judgement.