Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To determine whether spinal cord injury (SCI) triggers secondary neuroinflammation and neuronal injury in remote brain regions by impairing the drainage function of the meningeal lymphatic vessels (MLVs).Methods:Fifty-two female C57BL/6 mice were assigned with the random number table into four groups ( n=13 per group): sham group, SCI group, adeno-associated virus negative control group (negative control group), and adeno-associated virus overexpressing VEGF-C group (VEGF-C group). The sham group underwent laminectomy without spinal cord injury. In the SCI group, negative control group and VEGF-C group, T 9 contusion was made to establish the SCI models using a modified Allen′s impactor. At 4 weeks before SCI modeling, the negative control group and VEGF-C group were injected via the cisterna magna with 3 μl adeno-associated virus for negative control or adeno-associated virus for VEGF-C overexpression. At 56 days after injury, Alexa Fluor? 647 ovalbumin conjugate (OVA-647) was injected via the cisterna magna as a tracer. Two hours later, the proportion of OVA-647 in the deep cervical lymph nodes (dCLN) was detected. Immunofluorescence was performed to assess the proportion of MLVs marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and expression levels of microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the cerebral cortex, hippocampus, midbrain, and thalamus across the experimental groups. ELISA was employed to quantify the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and Nissl staining was used to assess neuronal counts in these regions. Results:At 56 days after injury, the OVA-647 proportion in the dCLN was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas the SCI group and negative control group showed a lower OVA-647 proportion in the dCLN than the VEGF-C group ( P<0.05). At 56 days after injury, the dural LYVE-1 proportion was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas it was lower in the SCI group and negative control group than that in the VEGF-C group ( P<0.05). At 56 days after injury, the count of Iba1-positive microglia across all the above-mentioned regions was increased in the SCI group and negative control group ( P<0.01), compared with that in the sham group, whereas it was reduced in these regions in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.01). At 56 days after injury, TNF-α and IL-1β levels in these regions were both elevated in the SCI group and negative control group when compared with those in the sham group ( P<0.05), whereas they were reduced in the VEGF-C group, compared with those in the SCI group and negative control group ( P<0.05). At 56 days after injury, neuronal survival in the regions was decreased in the SCI group and negative control group, compared with that in the sham group ( P<0.05), whereas it was increased in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.05). Conclusion:SCI can induce secondary neuroinflammation and neuronal damage in remote brain regions by impairing the drainage function of MLVs.

Objective:To determine whether spinal cord injury (SCI) triggers secondary neuroinflammation and neuronal injury in remote brain regions by impairing the drainage function of the meningeal lymphatic vessels (MLVs).Methods:Fifty-two female C57BL/6 mice were assigned with the random number table into four groups ( n=13 per group): sham group, SCI group, adeno-associated virus negative control group (negative control group), and adeno-associated virus overexpressing VEGF-C group (VEGF-C group). The sham group underwent laminectomy without spinal cord injury. In the SCI group, negative control group and VEGF-C group, T 9 contusion was made to establish the SCI models using a modified Allen′s impactor. At 4 weeks before SCI modeling, the negative control group and VEGF-C group were injected via the cisterna magna with 3 μl adeno-associated virus for negative control or adeno-associated virus for VEGF-C overexpression. At 56 days after injury, Alexa Fluor? 647 ovalbumin conjugate (OVA-647) was injected via the cisterna magna as a tracer. Two hours later, the proportion of OVA-647 in the deep cervical lymph nodes (dCLN) was detected. Immunofluorescence was performed to assess the proportion of MLVs marker lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and expression levels of microglial marker ionized calcium-binding adaptor molecule 1 (Iba1) in the cerebral cortex, hippocampus, midbrain, and thalamus across the experimental groups. ELISA was employed to quantify the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and Nissl staining was used to assess neuronal counts in these regions. Results:At 56 days after injury, the OVA-647 proportion in the dCLN was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas the SCI group and negative control group showed a lower OVA-647 proportion in the dCLN than the VEGF-C group ( P<0.05). At 56 days after injury, the dural LYVE-1 proportion was higher in the sham group than that in the SCI group and negative control group ( P<0.01), whereas it was lower in the SCI group and negative control group than that in the VEGF-C group ( P<0.05). At 56 days after injury, the count of Iba1-positive microglia across all the above-mentioned regions was increased in the SCI group and negative control group ( P<0.01), compared with that in the sham group, whereas it was reduced in these regions in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.01). At 56 days after injury, TNF-α and IL-1β levels in these regions were both elevated in the SCI group and negative control group when compared with those in the sham group ( P<0.05), whereas they were reduced in the VEGF-C group, compared with those in the SCI group and negative control group ( P<0.05). At 56 days after injury, neuronal survival in the regions was decreased in the SCI group and negative control group, compared with that in the sham group ( P<0.05), whereas it was increased in the VEGF-C group, compared with that in the SCI group and negative control group ( P<0.05). Conclusion:SCI can induce secondary neuroinflammation and neuronal damage in remote brain regions by impairing the drainage function of MLVs.

Chronic pain impairs functions across multiple dimensions,including physical,psychological,and social well-being.The neuro-immune mechanisms involve complex interactions between the immune system and nerve fibers at one or multiple levels of the peripheral or central nervous system.In recent years,research on the neuro-immune circuit mechanisms underlying the generation,transmission,modulation,and integration of chronic pain has advanced rapidly.However,the overall interactive dynamics of neuro-immune mechanisms remain unclear.This article systematically reviews recent advances in the neuro-immune mechanisms of chronic pain,elucidating the cascading transformation from peripheral to central sensitization.These findings provide a theoretical basis for a deeper understanding of the overall pathophysiological basis of pain chronicity and the exploration of effective clinical strategies.

Objective:To observe the functional remodeling of the default mode network (DMN) of patients with post-stroke cognitive impairment (PSCI) in response to transcranial direct current stimulation (tDCS) and to explore the mechanisms involved.Methods:Eighteen PSCI patients and twenty healthy controls were enrolled. The PSCI patients were given 20 minutes of tDCS at 2.0mA on the dorsolateral prefrontal cortex every weekday for four weeks. The subjects were scanned using resting state functional magnetic resonance imaging before and after the intervention to explore any functional changes in the DMN. Montreal cognitive assessment (MoCA) scoring was performed before and after the treatment.Results:Compared to the healthy controls, the cognitively impaired patients showed significant abnormalities in the DMN on admission, including decreased functinal connection (FC) in the posterior cingulate cortex and/or precuneus (PCC/PCu), as well as increased FC in the medial prefrontal cortex (MPFC) and left hippocampus. After the treatment, a significant improvement in the PSCI patients′ average MoCA score was observed. The average FC of the PCC/PCu had also increased significantly, while that of the left hippocampus had decreased significantly, on average. The FC in the PCC/PCu after tDCS was found to be positively related to the MoCA score measured at 4 weeks after admission.Conclusions:PSCI patients show functional abnormalities in the DMN. tDCS applied to their dorsolateral prefrontal cortex can significantly improve their average MoCA scores, which may be related to the increasing FC of the PCC/PCu.

Objective To study the effect of Shenlingbaizhu Pills on hyperlipidemia and gut microbiota in guinea pigs, providing data support for the treatment of hyperlipidemia from the " spleen" . Methods Guinea pigs were randomly divided into control group, model group, ezetimibe group, Shenlingbaizhu Pills high and low dose groups, with 12 guinea pigs for each group. Guinea pig models of hyperlipidemia were established with high fat diet for 8 weeks. Oral administration of the drug began at the fifth week and continued for 4 weeks. The serum lipid levels of guinea pigs were determined after final administration. The pathological changes of liver tissue were observed by HE staining. The mRNA expression levels of ATP binding cassette ( ABC ) A1 in liver, Niemann Pick C1 like 1 ( NPC1L1) and ABCG5/8 in small intestine were detected by realtime PCR. 16S rDNA sequencing was used to detect changes of gut microbiotas in guinea pigs. Results Shenlingbaizhu Pills significantly reduced the serum triglyceride, total cholesterol, and low density lipoprotein-cholesterol levels in guinea pigs with hyperlipidemia ( P＜0. 01 or P＜0.05). The pathological degree of fatty liver was improved obviously by Shenlingbaizhu Pills. Shenlingbaizhu Pills could reduce the mRNA expression level of NPC1L1 of small intestine and increase the level of liver ABCA1 and small intestine ABCG5/8 (P＜0.01 or P＜0.05). At the phylum level, Shenlingbaizhu Pills could reduce the proportion of verrucomicrobia of guinea pigs in model group (P＜0.01); At the genus level, Shenlingbaizhu Pills could increase the proportions of erysipelotrichaceae＿unclassified, ruminococcus＿1, and ileibacterium of guinea pigs in model group (P＜0. 01 or P＜0. 05 ), reduce the proportion of akkermansia and eubacterium＿coprostanoligenes＿group ( P＜0.01). Conclusion Shenlingbaizhu Pills had significantly therapeutic effect on hyperlipidemia, and its specific mechanism was related to the regulation of cholesterol transport and intestinal flora.

Objective To investigate the clinical value of 2 dimension late Gadolinium enhancement MRI (LGE-MRI) technique for the evaluation of atrial myocardial fibrosis in patients with atrial fibrillation. Methods Forty-nine cases of atrial fibrillation in our hospital from March 2015 to December 2016 were retrospectively collected. The LGE-MR was acquired by the Siemens 3.0 T MR machine before the catheter ablation.The findings of LGE-MR were evaluated by two experienced doctors. The left atrium(LA)were manually segmented into 8 regions in axial view.All patients were classified into 4 stages based on the extent of enhancement, stage 0: absence of enhancement, stage Ⅰ: enhancement appeared in minimal two consecutive slices in single region,stageⅡ:enhancement in two regions,stageⅢ:enhancement in three or more regions. All electroanatomic maps were obtained after electrical conversion during catheter ablation. The Kappa test was used to assess the consistency of LGE-MRI left atrial myocardial fibrosis and CARTO system of the left atrial endocardial voltage reconstruction. Results Forty-nine cases of atrial fibrillation with LGE-MRI and CARTO were included. There were 17 cases of atrial fibrosis stage 0,10 cases of stageⅠ,11 cases of stageⅡ,11 cases of stageⅢaccording to LGE-MRI findings;There were 17 cases of atrial fibrosis stage 0,19 cases of stageⅠ,12 cases of stageⅡ,11 cases of stage Ⅲ with reference to CARTO findings. The diagnostic accuracy of the LGE-MRI atrial fibrosis was 81.6%(40/49),of which the correlation was good(Kappa= 0.751,P<0.001). Conclusions LGE-MRI can accurately assess the degree of left atrial myocardial fibrosis in patients with atrial fibrillation,help to select the proper candidate and strategy in catheter ablation.

Objective To investigate the structural changes during the early stage of spinal cord injury,and the relationships between these structural changes and patients' motor recovery.Methods The clinical data of 25 patients with spinal cord injury collected from 2012 October to 2014 March were analyzed retrospectively.The spinal cord injury patients were split into two groups (Good recoverers group and Poor recoverers group) according to the clinical outcome of motor recovery at 6 months follow-up,and there were 10 Good recoverers (ASIA grade:1 A,4 B,3 C,and 2 D) and 15 Poor recoverers (ASIA grade:7 A,3 B,3 C,and 2 D).The study also recruited 25 matched healthy controls.The mean age of Good recoverers,Poor recoverers and healthy controls were 37.9± 13.9,35.8± 11.5 and 36.5±9.3,respectively.Structural MRI was used to investigate the regions with brain structural changes among the three groups.Pearson correlation analysis was used to explore the relationships between these structural changes and patients' motor recovery.Results Compared to healthy controls group,both poor recoverers and good recoverers had significantly decreased cortical thickness in the bilateral primary motor cortex.Poor recoverers exhibited more serious and widespread structural damages,in addition to reduced cortical thickness in the primary motor cortex,poor recoverers also showed decreased cortical thickness in the right SMA and premotor cortex when compared to healthy controls.Compared to the healthy controls group,poor recoverers showed reduced white matter volume in the right primary motor cortex and posterior limb of the internal capsule;good recoverers showed no significant difference in white matter microstructure.Furthermore,these structural changes at the internal capsule and primary motor cortex were associated with the motor recovery rate at 6 months follow-up (r=0.75,P＜ 0.001;r=0.76,P＜ 0.001,respectively).Conclusion These findings suggest that spinal cord injury causes significant anatomical changes in the human sensorimotor system in the early phase,and these structural changes directly affect the motor recovery of spinal cord injury.Future treatment aimed at promoting neural function recovery of spinal cord injury patients should pay close attention to the injured brain.

Objective To compare the short‐term clinical effects of single segment and two segments of Dynesys dynamic in‐ternal fixation system for treating lumbar degenerative disease .Methods 40 cases of degenerative lumbar disease treated by the Dynesys dynamic fixation system combined with posterior approach decompression from 2009 July to March 2012 were selected and performed the evaluation on the clinical effects by the waist and leg pain visual analogue scale (VAS) ,the Oswestry disability index (ODI) and the orthopaedic spinal association of North America (NASS) index .The imaging method was used to observe the mobili‐ty of operative segment and proximal adjacent segment and the degenerative change of intervertebral height .Results All of the 40 cases were followed up .The VAS score and ODI score at postoperative 3 months and last follow‐up were significantly decreased when compared with the pre‐operative scores (P<0 .05);there was no statistically significant differences in the VAS score and ODI score at 3 months and last follow‐up between the single segment group and the 2‐segment group (P> 0 .05) .The NASS index showed no statistically significant difference in the postoperative effect satisfaction between the two groups (P>0 .05);there was no statistically significant difference in the variation of the intervertebral height between before operation and at the last follow‐up (P>0 .05) .There was statistically significant difference in the motility of proximal adjacent segment at the last follow‐up between the two groups (P<0 .05);but comparing the motility of proximal adjacent segment between the last follow‐up and pre‐operation , only the single segment group showed statistically significant difference (P< 0 .05) .Conclusion The Dynesys dynamic fixation system combined with posterior approach decompression operation has good clinical effect in the treatment of lumbar degenerative disease .Meanwhile ,the single segment method has more significant effect on the motility of proximal adjacent segment than the double segments method .