Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an immune-mediated inflammatory disease of the central nervous system. However, GFAP-A characterized by progressive encephalomyelitis with rigidity and myoclonus as its predominant clinical phenotype is rare. This article described a case, supplemented with clinical video, of a young male patient who developed fever and neck pain at disease onset. Over the course of the illness, the patient experienced progressively worsening painful muscle spasms, muscle rigidity, and stimulus-sensitive myoclonus, accompanied by autonomic dysfunction. Cerebrospinal fluid analysis revealed positive GFAP-IgG antibodies. The patient showed significant improvement with treatment of high-dose corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an immune-mediated inflammatory disease of the central nervous system. However, GFAP-A characterized by progressive encephalomyelitis with rigidity and myoclonus as its predominant clinical phenotype is rare. This article described a case, supplemented with clinical video, of a young male patient who developed fever and neck pain at disease onset. Over the course of the illness, the patient experienced progressively worsening painful muscle spasms, muscle rigidity, and stimulus-sensitive myoclonus, accompanied by autonomic dysfunction. Cerebrospinal fluid analysis revealed positive GFAP-IgG antibodies. The patient showed significant improvement with treatment of high-dose corticosteroids, intravenous immunoglobulin, and mycophenolate mofetil.

Objective:To investigate the efficacy of posterior reduction and fixation combined with pedicle subtraction osteotomy (PSO) in the treatment of ankylosing spondylitis (AS) kyphotic deformity complicated by upper cervical spine injury.Methods:A retrospective case series study was conducted to analyze the clinical data of 8 patients with AS kyphotic deformity complicated by upper cervical spine injury, who were admitted to First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2022. All were males, aged 32-58 years [(46.9±8.7)years]. Acute injury was found in 1 patient and chronic injuries in 7 patients, including 3 with cervicothoracic kyphotic deformity and 5 with thoracolumbar kyphotic deformity. Five patients were complicated by odontoid fractures, 1 by C 2-C 3 fracture and 2 by atlantoaxial dislocation. According to American Spinal Injury Association (ASIA) scale, 2 patients were with grade C, 3 with grade D, and 3 with grade E. The patients were treated with posterior upper cervical reduction and fixation combined with cervicothoracic PSO or thoracolumbar PSO respectively according to the location of the deformity. The operation time and intraoperative blood loss were recorded. Neck disability index (NDI), visual analogue scale (VAS), C 0-C 2 angle, C 1-C 2 angle, cervical lordosis angle (CL), head tilt angle (HT), chin-brow vertical angle (CBVA), cervical sagittal vertical axis (CSVA), and sagittal vertical axis (SVA) were compared before surgery, at 1 week and 3, 6, 12 months after surgery, and at the last follow-up. The healing of fractures and fusion of osteotomy site were recorded at 12 months after surgery. Recovery of neurological function was observed at the last follow-up. Incidence of complications was observed. Results:Patients were all followed up for 12-24 months [(17.0±5.4)months]. The operation time was 5.5-7.2 hours [(6.2±0.6)hours] and the intraoperative blood loss was 480-800 ml [(629.4±124.0)ml]. The NDI scores at 1 week and 3, 6, 12 months after surgery, and at the last follow-up were (14.6±2.6)points, (13.6±2.8)points, (12.8±2.4)points, (12.8±2.7)points, and (12.8±2.6)points respectively, significantly lower than (29.6±8.5)points preoperatively ( P<0.01). There were no significant differences in NDI scores at various time points after surgery ( P>0.05). The VAS scores were 2.0(1.0, 3.0)points, 1.5(1.0, 2.0)points, 0.5(0.0, 1.8)points, 0.5(0.0, 1.7)points, and 0.5(0.0, 1.8)points respectively, significantly lower than 3.5(3.0, 4.8)points preoperatively ( P<0.01). The VAS score at 3 months postoperatively was lower than that at 1 week postoperatively ( P<0.05), and the VAS score at 6 months postoperatively was lower than that at 3 months postoperatively ( P<0.05). There were no statistically significant differences in VAS scores at 6, 12 months postoperatively, and at the last follow-up ( P>0.05). There were no statistically significant differences between C 0-C 2 angle and C 1-C 2 angle preoperatively and at different time points postoperatively ( P>0.05). At 1 week and 3, 6, 12 months postoperatively and at the last follow-up, the CL values were -8.5(-5.3, -11.9)°, -8.6(-5.5, -11.9)°, -8.4(5.2, -12.1)°, -8.8(-5.6, -12.4)°, and -8.7(-5.3, -12.5)° respectively, significantly higher than 1.2(9.5, -4.8)° preoperatively ( P<0.01); the HT values were 6.1(4.5, 9.6)°, 6.1(4.3, 9.4)°, 6.0(4.2, 8.9)°, 6.0(4.2, 9.2)°, and 6.1(4.3, 9.2)° respectively, significantly lower than 17.0(10.3, 22.0)° preoperatively ( P<0.01); the CBVA values were (23.2±5.0)°, (23.1±4.8)°, (23.0±4.7)°, (23.1±4.7)°, and (23.1±4.9)° respectively, significantly lower than (44.1±9.8)° preoperatively ( P<0.01); the CSVA values were 5.2(4.2, 7.5)cm, 5.4(4.1, 7.1)cm, 4.7(4.0, 7.4)cm, 5.4(4.1, 7.0)cm, and 5.1(4.3, 6.5)cm respectively, significantly shorter than 9.0(7.8, 9.3)cm preoperatively ( P<0.01); the SVA values were 7.7(6.2, 13.7)cm, 7.5(6.0, 13.4)cm, 7.6(6.2, 13.2)cm, 7.4(6.3, 13.1)cm, and 7.5(6.2, 13.2)cm respectively, significantly shorter than 16.8(8.2, 27.2)cm preoperatively ( P<0.05). There were no statistically significant differences among CL, HT, CBVA, CSVA, and SVA values at different time points after surgery ( P>0.05). All the fractures healed at 12 months after surgery and Bridwell grade I healing was achieved at all the osteotomy sites. At the last follow-up, all the patients were classified as ASIA grade E, significantly improved compared with preoperatively ( P<0.01). One patient had transient C 8 nerve paralysis after surgery and recovered after 4 weeks′ treatment. The remaining patients did not develop any infection or internal fixation-related complications, such as broken rods, broken screws, or loose screws. Conclusion:For AS kyphosis deformity complicated with upper cervical injury, posterior reduction and fixation combined with cervicothoracic or thoracolumbar PSO can effectively promote functional recovery, relieve pain, maintain overall trunk balance, improve neurological symptoms, and reduce the incidence of complications.

Objective:To evaluate the safety and effectiveness of single posterior osteotomy in the correction of rigid cervical spine deformities (CSD) and to explore the indications and key surgical techniques involved.Methods:A retrospective analysis was conducted on the clinical data of 9 patients with rigid CSD who underwent single posterior osteotomy correction between June 2012 and June 2023 in the Department of Spine Surgery at the First Affiliated Hospital of Xinjiang Medical University. The cohort comprised 4 males and 5 females, with a mean age of 19.8±27.2 years (range, 7-48 years). Among these, 5 cases were congenital CSD, 3 were post-tuberculosis deformities, and 1 was iatrogenic. Various coronal and sagittal alignment parameters were measured, including C 1, 2 angle, cervical lordosis (CL), structural scoliosis angle (SSA), structural kyphosis angle (SKA), head tilt (HT), C 2-C 7 sagittal vertical axis (CSVA), sagittal vertical axis (SVA), coronal balance distance (CBD), T 1 slope (T 1S), and the difference between T 1 tilt and cervical lordosis (T 1S-CL). Clinical outcomes were assessed using the neck disability index (NDI), visual analogue scale (VAS), and Scoliosis Research Society-22 questionnaire (SRS-22). Results:The average operation time was 273.9±76.1 min, with an average blood loss of 472.2±128.8 ml. All 9 patients were followed up for an average of 45.2±41.8 months (range, 12-116 months). A total of 7 patients underwent single-segment osteotomies (C 3, C 6 and C 7: 1 case each; C 5: 4 cases), and 2 patients underwent double-segment osteotomies (C 2 and C 7, C 3 and C 4). Four cases involved pedicle subtraction osteotomy (PSO), while 7 cases required vertebral column resection. The upper instrumented vertebra (UIV) was located at the occiput in 1 case and in the cervical spine in 8 cases. The lower instrumented vertebra (LIV) was located in the upper thoracic spine in 6 cases and in the cervical spine in 3 cases, with 2 of the latter cases having both UIV and LIV in the cervical spine. The average number of fused segments was 7.6±4.4 segments (range, 2-12 segments). All patients achieved successful bone fusion within an average of 8.8±3.2 months (range, 6-12 months). Preoperatively, the mean values for CL, SSA, SKA, HT, and CBD were 19.8° (17.2°, 30.5°), 27.4°(23.3°, 30.4°), 28.4°(25.6°, 30.1°), 9.0°(6.2°, 12.3°), and 18.5(12.3, 23.6) mm, respectively. Postoperative improvements were noted with values of -11.1°(-8.8°, -14.4°), 1.3°(0.8°, 1.6°), -11.1°(-8.6°, -14.5°), 1.6°(0.5°, 2.2°), and 9.4 (4.8-13.5) mm, respectively. At the final follow-up, these parameters were maintained, with values of -11.0°(-8.8°, -14.3°), 1.2°(0.8°, 1.5°), -11.0° (-8.6°, -14.3°), 1.5°(0.5°, 2.2°), and 9.4(4.8, 13.4) mm, respectively. Statistically significant improvements were observed between preoperative and postoperative measurements ( P<0.05), except for C 1, 2 angle, CSVA, SVA, T 1S, and T 1S-CL ( P>0.05). NDI and SRS-22 scores showed significant improvements postoperatively ( P<0.05), while VAS scores did not show a significant change ( P>0.05). Postoperative complications included transient nerve injury in two patients, one case of right central retinal artery occlusion, and one case of vertebral artery injury. Conclusion:This study confirms the safety and efficacy of single posterior osteotomy for treating rigid CSD of various etiologies. Standard PSO or modified techniques are effective for correcting cervical kyphosis, while hemivertebra resection and concave-side distraction are recommended for congenital scoliosis or kyphoscoliosis.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4,2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Objective:To study the effects and potential mechanisms of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells.Methods:From January 2021 to June 2021, 10 infantile hemangioma specimens (6 males and 4 females, aged 2 months to 6 months, average age 3.5 months) were collected from the Department of Burns and Plastic Surgery of the Children’s Hospital of Nanjing Medical University. Hem-MSCs were isolated from hemangioma in the proliferating phase by adherent screening and identified by flow cytometry. Adipogenic induction was performed after successful identification. Real-time quantitative fluorescence PCR was used to detect the expression of Notch1, Jagged1 and Hes1 genes after 14 days of adipogenesis induction of Hem-MSCs. The Notch signaling pathway inhibitor DAPT, PI3K/Akt signaling pathway agonist 740Y-P and solvent DMSO were added to Hem-MSCs, and adipogenesis induction was performed. The cells were divided into six groups: control group, adipogenic induction group, adipogenic induction+ DMSO group, adipogenic induction+ DAPT group, adipogenic induction+ 740Y-P group, and adipogenic induction+ 740Y-P+ DAPT group. After 14 days of adipogenic induction, real-time quantitative fluorescence PCR was used to detect the expression of PPARγ and C/EBPα genes in the key transcription factors of adipogenic differentiation in the above six groups. Oil red O staining was applied to identify the adipogenic differentiation capabilities; after adipogenic induction for 7 days, the expression levels of p-PI3K, PI3K, p-AKT, and AKT proteins in the adipogenic induction+ DMSO group, adipogenic induction+ DAPT+ 740Y-P group were detected by western blotting. In comparing the two groups, an unpaired Student’s t-test was used to assess the differences, and analysis of variance was applied for the analysis of the mean values among multiple groups. and P<0.05 was considered statistically significant. Results:The expression levels of Notch1, Jagged1 and Hes1 decreased gradually during the adipogenic induction of Hem-MSCs, and the differences were statistically significant ( tNotch1=8.99, PNotch1=0.008; tJagged1=9.49, PJagged1=0.007; tHes1=7.74, PHes1=0.015). After the addition of Notch signaling pathway inhibitor DAPT during the adipogenic induction of Hem-MSCs, the expression of proteins associated with PI3K/AKT signaling pathway decreased, and the difference was statistically significant ( qp-PI3K=4.78, Pp-PI3K=0.014; qp-AKT=5.04, Pp-AKT=0.010) and the expression of adipogenesis indexes increased( qOil red O=6.07, POil red O=0.003; qPPARγ=17.34, PPPARγ<0.001; qC/EBPα=14.8, PC/EBPα<0.001). There was no significant change in adipogenesis indexes after addition of PI3K/Akt signaling pathway agonist 740Y-P ( qOil red O=1.82, POil red O=0.786; qPPARγ=0.97, PPPARγ=0.981; qC/EBPα=1.98, PC/EBPα=0.654). The expression of adipogenesis indexes decreased after adding DAPT and 740Y-P( qOil red O=5.22, POil red O=0.013; qPPARγ=9.78, PPPARγ<0.001; qC/EBPα=16.74, PC/EBPα<0.001). Conclusion:The inhibition of Notch signaling pathway can promote the adipogenic differentiation of Hem-MSCs by reducing the activity of PI3K/Akt signaling pathway.

Objective:To study the effects and potential mechanisms of Notch signaling pathway on the adipogenic differentiation of infantile hemangioma-derived mesenchymal stem cells.Methods:From January 2021 to June 2021, 10 infantile hemangioma specimens (6 males and 4 females, aged 2 months to 6 months, average age 3.5 months) were collected from the Department of Burns and Plastic Surgery of the Children’s Hospital of Nanjing Medical University. Hem-MSCs were isolated from hemangioma in the proliferating phase by adherent screening and identified by flow cytometry. Adipogenic induction was performed after successful identification. Real-time quantitative fluorescence PCR was used to detect the expression of Notch1, Jagged1 and Hes1 genes after 14 days of adipogenesis induction of Hem-MSCs. The Notch signaling pathway inhibitor DAPT, PI3K/Akt signaling pathway agonist 740Y-P and solvent DMSO were added to Hem-MSCs, and adipogenesis induction was performed. The cells were divided into six groups: control group, adipogenic induction group, adipogenic induction+ DMSO group, adipogenic induction+ DAPT group, adipogenic induction+ 740Y-P group, and adipogenic induction+ 740Y-P+ DAPT group. After 14 days of adipogenic induction, real-time quantitative fluorescence PCR was used to detect the expression of PPARγ and C/EBPα genes in the key transcription factors of adipogenic differentiation in the above six groups. Oil red O staining was applied to identify the adipogenic differentiation capabilities; after adipogenic induction for 7 days, the expression levels of p-PI3K, PI3K, p-AKT, and AKT proteins in the adipogenic induction+ DMSO group, adipogenic induction+ DAPT+ 740Y-P group were detected by western blotting. In comparing the two groups, an unpaired Student’s t-test was used to assess the differences, and analysis of variance was applied for the analysis of the mean values among multiple groups. and P<0.05 was considered statistically significant. Results:The expression levels of Notch1, Jagged1 and Hes1 decreased gradually during the adipogenic induction of Hem-MSCs, and the differences were statistically significant ( tNotch1=8.99, PNotch1=0.008; tJagged1=9.49, PJagged1=0.007; tHes1=7.74, PHes1=0.015). After the addition of Notch signaling pathway inhibitor DAPT during the adipogenic induction of Hem-MSCs, the expression of proteins associated with PI3K/AKT signaling pathway decreased, and the difference was statistically significant ( qp-PI3K=4.78, Pp-PI3K=0.014; qp-AKT=5.04, Pp-AKT=0.010) and the expression of adipogenesis indexes increased( qOil red O=6.07, POil red O=0.003; qPPARγ=17.34, PPPARγ<0.001; qC/EBPα=14.8, PC/EBPα<0.001). There was no significant change in adipogenesis indexes after addition of PI3K/Akt signaling pathway agonist 740Y-P ( qOil red O=1.82, POil red O=0.786; qPPARγ=0.97, PPPARγ=0.981; qC/EBPα=1.98, PC/EBPα=0.654). The expression of adipogenesis indexes decreased after adding DAPT and 740Y-P( qOil red O=5.22, POil red O=0.013; qPPARγ=9.78, PPPARγ<0.001; qC/EBPα=16.74, PC/EBPα<0.001). Conclusion:The inhibition of Notch signaling pathway can promote the adipogenic differentiation of Hem-MSCs by reducing the activity of PI3K/Akt signaling pathway.

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca²⁺-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
Mice ; Animals ; Amyotrophic Lateral Sclerosis/pathology* ; Calcineurin/metabolism* ; Motor Neurons/pathology* ; Microfilament Proteins/metabolism* ; Cytoskeletal Proteins/metabolism*

Objective:To evaluate the long-term outcomes of posterior release, reduction, fixation, and fusion for irreducible atlantoaxial dislocation (AAD).Methods:Between January 2005 and June 2016, a total of 31 patients with irreducible AAD who had received posterior approach surgery were included. Among them, there were 13 males and 18 females, the average age was 39.1±13.5 years (range 9-72 years). The clinical data of the eligible individuals were collected and analyzed. Neck disability index (NDI) and Japanese Orthopaedic Association (JOA) scores were recorded to evaluate the recovery of neck and neurological functions. The atlantodental interval (ADI), clivus-canal angle (CCA), and cervico-medullary angle (CMA) were measured to evaluate the reduction of AAD. C 0-C 2 angle and C 2-C 7 angle were measured to evaluate the recovery of cervical alignment. For individuals with basilar invagination, the distances from the tip of odontoid process to Chamberlain line and Wackenheim line were measured to assess the reduction in the vertical direction. The duration of bony fusion and complications were also analyzed. Results:The mean follow-up period was 82.7±26.4 months (range 61-170 months). In terms of functional scores, the NDI dropped from 43.41%±11.60% before surgery to 12.19%±6.97% at the six months follow-up, and 9.45%±7.51% at the last follow-up ( F=89.56, P<0.001). The JOA increased from 9.48±2.41 points before surgery to 14.71±1.42 points at the six months follow-up, and 14.97±1.47 points at the last follow-up ( F=52.89, P<0.001). Regarding the horizontal and vertical dislocations, the ADI decreased from 9.16±2.32 mm before surgery to 1.39±1.04 mm at the six months follow-up, and 1.29±1.08 mm at the last follow-up ( F=189.61, P<0.001). The distance from the tip of odontoid process to Chamberlain line decreased from 11.15±4.35 mm before surgery to 2.03±2.83 mm at the six months follow-up, and 2.15±3.02 mm at the last follow-up ( F=37.58, P<0.001). The distance from the tip of odontoid process to Wackenheim line reduced from 6.81±2.57 mm before surgery to -2.23±1.58 mm at the six months follow-up, and -2.27±1.58 mm at the last follow-up ( F=122.16, P<0.001). For the amelioration of the compression on medulla and spinal cord, the CCA increased from 113.68°±12.67° before surgery to 143.39°±7.38° at the six months follow-up, and 142.39°±7.13° at the last follow-up ( F=67.13, P<0.001). The CMA increased from 115.71°±13.69° before operation to 145.58°±10.78° at the last follow-up ( F=41.44, P<0.001). Regarding the curvature of the cervical spine, the C 0-C 2 angle recovered from 1.94°±15.82° before surgery to 14.84°±6.45° at the last follow-up ( F=11.97, P<0.001), and the C 2-C 7 angle ameliorated from 27.26°±8.49° before operation to 19.26°±5.44° at the last follow-up ( F=11.13, P<0.001). Bony fusion was achieved in all cases, the fusion time was 9.71±2.55 months (range 5-15 months). A total of five complications occurred in the cases (two cerebrospinal fluid leakages, one deep infection, one transient neurologic deficit, and one dysphagia). They were all cured with corresponding treatments. In the last follow-up, none of the cases developed failure of internal fixation or re-dislocation. Conclusion:Posterior approach release, reduction, fixation and fusion technique is a safe and efficient surgical strategy with favorable long-term follow-up outcomes for irreducible AAD.