1.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
2.Radiological shoulder parameter associated with postoperative satisfaction in Lenke type 1 adolescent idiopathic scoliosis
Fang XIE ; Dan GENG ; Fei WANG ; Jinggang DANG ; Liyu XIA ; Zhuojing LUO ; Xueyu HU
Chinese Journal of Orthopaedics 2024;44(8):525-531
Objective:To analyze the radiographic parameters of shoulder balance that affect the postoperative satisfaction of Lenke type 1 adolescent idiopathic scoliosis (AIS).Methods:A total of 98 patients with AIS who underwent posterior pedicle screw fusion in Xijing Hospital of Air Force Medical University from August 2017 to July 2020 were retrospectively analyzed. There were 26 males and 72 females, aged 15.2±5.3 years (range, 10-24 years). Distribution of upper instrumented vertebrae: T 2 58 cases (59%), T 3 25 cases (26%), T 4 15 cases (15%); Distribution of lower instrumented vertebrae: T 12 63 cases (64%), L 1 28 cases (29%), L 2 4 cases (4%), L 3 3 cases (3%). Clavicle angle (CA), radiographic shoulder height (RSH), and coracoid height difference (CHD), clavicle-rib cage intersection difference (CRID), T 1 tilt angle, first rib tilt angle, clavicle chest angle difference(CCAD) and Scoliosis Research Society-22 (SRS-22) scale were compared before and after operation. Binary logistic regression was used to analyze the radiographic indicators of shoulder balance that affected the postoperative satisfaction of Lenke type 1 AIS. The receiver operating characteristic (ROC) curve was drawn to determine the threshold value of the imaging index. Results:All operations were successfully completed. The operation time was 260±80 min (range, 220-320 min), and the intraoperative blood loss was 360±110 ml (range, 300-700 ml). There was no nerve, dural or vascular injury during operation. RSH, CHD, CRID, T 1 tilt angle, first rib tilt angle, and CCAD at the final follow-up were 4.0 (0, 13.9) mm, 7.0 (0, 12.9) mm, 4.0 (0, 10.0) mm, 4.8° (3.3°, 8.2°), 5.3°±3.9°, and 5.5° (3.0°, 8.9°), respectively, which were less than the preoperative 10.6 (2.0, 20.3) mm, 10.3 (2.5, 15.9) mm, 8.0 (1.0, 15.2) mm, 7.6° (3.5°, 12.2°), 7.5°±6.9°, 8.5° (3.6°, 18.3°), and the difference was statistically significant ( P<0.05). The SRS-22 function, pain, appearance, and psychological scores at the final follow-up were 4.6 (4.0, 4.9), 4.1±0.5, 4.1±0.7, and 4.2 (3.9, 4.8) points, respectively, which were greater than the preoperative scores of 4.2 (3.8, 4.6), 4.0±0.7, 3.5±0.7, and 4.0 (3.5, 4.4) points, the difference was statistically significant ( P<0.05). Binary logistic regression showed that CCAD was an independent radiographic indicator of shoulder balance that affected the satisfaction of AIS patients after orthopaedic surgery ( OR=0.826, P=0.040). ROC curve showed that the area under the curve and 95% CI was 0.726 (0.572, 0.865), and the threshold was 6.6°. Conclusion:CCAD is an independent radiographic parameter of shoulder balance that affects the postoperative satisfaction of AIS. Patients are more likely to achieve a satisfactory outcome when their postoperative CCAD is ≤6.6°, which can be used clinically as a radiographic parameter to assess the efficacy of orthopaedic spine surgery.
3.Correlation between diameter of sciatic nerve and symptoms or prognosis in patients with lumbar disc herniation
Xiaowei SHI ; Liangliang HUANG ; Dingzhang CHEN ; Hua FENG ; Lu LUO ; Teng MA ; Zhongyang LIU ; Bing XIA ; Jianbo GAO ; Yujie YANG ; Zhuojing LUO ; Jinghui HUANG
Chinese Journal of Orthopaedics 2019;39(2):74-82
Objective To explore the effect of single level lumbar disc herniation on the morphology and diameter of sciatic nerve,and to identify the correlation between the diameter change in sciatic nerve and severity of clinical symptoms,as well as the prognosis of surgical treatment in patients with lumbar disc herniation.Methods From January 1,2017 to December 31,2017,Seventy lumbar disc herniation (LDH) patients who underwent single-level posterior lumbar spine surgery were recruited in this retrospective analysis study.Specific data including age,gender,the level of a disc herniation,the type of disc herniation,symptomatic side,surgical procedure were recorded respectively.In addition the morphological changes and the diameter of bilateral sciatic nerve were recorded preoperatively and postoperatively by B-mode ultrasound.Furthermore,the pain in patients and neurological function were evaluated by visual analogue scale (VAS,back pain and leg pain),Japanese orthopaedic association scores-lumbar (JOA) and Oswestry disability index (ODI).The correlation between the diameter of sciatic nerve and clinical features,as well as clinical prognosis of patients were identified in the present study.Results For patients with acute lumbar disc herniation,the diameter of sciatic nerve in affected side was 5.19±1.03 ram,which is significantly higher than that in the unaffected side (4.57±0.64 mm,t=6.735,P=0.000).In addition,preoperative ratio of the affected side to the healthy side of the sciatic nerve showed strong correlation with the VAS of leg pain (r=0.838,P=0.001),JOA (r=-0.857,P=0.001),and ODI score(r=0.881,P=0.000),but not with the VAS of back pain (r=-0.061,P=0.614).Three months after surgery,the diameter of sciatic nerve in the affected side decreased to 4.58±0.63 mm (t=6.865,P=0.000),while the unaffected side showed no significant change(t=0.300,P=0.765).Clinical improvement was observed in all the patients postoperatively.The changes in the diameter of sciatic nerve postoperatively in affected side showed strong correlation to the rate of improvement in VAS of leg (r=0.624,P=0.003),JOA(r=0.615,P=0.003) and ODI scores (r=0.722,P=0.002),but not to the rate of improvement in VAS of back (r=-0.025,P=0.836).Conclusion Single root compression in patients with single level disc herniation might cause morphological changes such as thickening and edema in sciatic nerve,which were closely related to the severity of clinical symptoms and the prognosis of surgical treatment.
4.Prediction and identification of linear B-cell epitopes in the hemagglutinin of H7N9 avian influenza virus in human
Wei TAO ; Meng GAO ; Limin JIANG ; Hui XIE ; Hongxia NI ; Limei GAO ; Yongneng LUO ; Yan HONG ; Zhuojing HE ; Ting FU
Chinese Journal of Clinical Infectious Diseases 2016;9(4):336-341,348
Objective To predict and identify liner B-cell epitopes in the hemagglutinin ( HA) of human-infected avian-origin H7N9 influenza virus and analyze the specificity of H7 subtype.Methods Three serum samples collected at different times from the same patient who was confirmed to be infected with H7N9 influenza virus were provided by Shaoxing People’s Hospital, and one serum sample from healthy person was collected as the control.The extracellular region of HA protein was predicted by TMHMM Sever v.2.0.The potential B-cell epitopes were predicted by DNAStar Lasergene’ s Protean, BcePred and ABCpred tools, and the immunogenicity of the predicted B cell antigen epitopes was assessed by indirect enzyme-linked immunosordent assay ( ELISA ) .H7 subtype specificity was analyzed by comparing HA protein amino acid sequence with H7N9 and H1-H16 subtype influenza virus from Genbank using Clustal X 2.1 software, and Cn3D 4.3.1 software was used to detect the distribution and 3D structure of predicted epitopes on the HA protein of H7N9.Results The potential B-cell epitopes may be located in 172-183, 363-380, 452-472 and 491-506 of extracellular N-terminus of HA protein.ELISA showed that four predicted eptiopes specifically reacted with positive serums from patient.Multi-sequence alignment demonstrated that peptide 172-183 and 363-380 had higher H7 subtype specificity compared with amino acid sequences of other subtypes.Moreover, the predicted linear B-cell epitopes all located on the surface of HA protein according to the 3D structure analysis.Conclusion Four potential B-cell epitopes were identified, in which peptide 172-183 and 363-380 have higher H7 subtype specificity, and may be used in the design of epitope-based vaccines and diagnostics tests.
5.Imaging features of split cord malformation associated with scoliosis and its correlation with neurologic symptoms
Ming LIU ; Huiren TAO ; Tao ZHANG ; Weizhou YANG ; Tao LI ; Xiangbo CHEN ; Wenrui MA ; Zhuojing LUO
Chinese Journal of Orthopaedics 2016;(2):81-87
Objective To analyze the imaging features of congenital spinal deformity (CSD) associated with split cord malformation (SCM) and other intraspinal abnormalities, and to investigate the relationship to neurological symptoms. Methods 105 cases CSD with SCM were retrospectively studied. Analysis the imaging features of SCM (including type of SCM, location of SCM, location and apical vertebrae, symmetry of divided cord) and other intraspinal abnormalities. To investigate the relationship of the factors and neurological symptoms using Chi?square test of one factor and multiple factors logistic regression analysis. Re?sults 28 cases (26.7%) were formation failure, 33 cases (31.4%) were segmentation failure, and 44 cases (41.9%) were combina?tion of 2 disorders. 41 cases had neurological symptoms, 64 cases were asymptomatic. The distribution of SCM combined with spi?nal deformities:thoracic (11 cases), thoracolumbar (18 cases) and lumbar (20 cases) in type I SCM, thoracic (31 cases), thoracolum?bar (20 cases) and lumbar (5 cases) in type II, none was in cervical. The location of SCM upper than apical vertebrae 29 cases, on apical vertebrae 25 cases, lower than apical vertebrae 51 cases. Spinal cord was splitted symmetric 27 cases and asymmetric 78 cases. 66 cases combined with other intraspinal abnormalities, lower conus 42 cases, syringomyelia 38 cases, meningocele 10 cas?es and sakrale zyste 5 cases. Associated with intraspinal abnormalities, the rate of neural symptoms was different. According to Chi?square test of one factor and multiple factors logistic regression analysis, lumbar SCM, spinal cord asymmetric and lower conus were related with neurological symptoms. Conclusion The predilection spinal deformity of type I is combination, type II SCM is segmentation failure. When SCM patients associated with other intraspinal abnormalities, the incidence of neurologic symptoms is increased. The lumbar SCM, hemicords asymmetry and lower lying conus have significant relationship with neurologic symptoms.
6.Neurological complications of posterior vertebral column resection for severe rigid congenital spinal deformities.
Tao ZHANG ; Huiren TAO ; Email: TAOHR816@FMMU.EDU.CN. ; Jinghui HUANG ; Tao LI ; Chao SHEN ; Bo CHEN ; Xiangbo CHEN ; Weizhou YANG ; Ming LIU ; Zhuojing LUO
Chinese Journal of Surgery 2015;53(6):424-429
OBJECTIVETo analyze the risk factors of neurological complications of posterior vertebral column resection in the treatment of severe rigid congenital spinal deformities.
METHODSThe clinical data of 88 patients with severe rigid congenital spinal deformities who underwent PVCR in Department Of Orthopaedics, Xijing Hospital, Fourth Military Medical University from June 2007 to November 2012 were collected. There were 39 males and 49 females at the average age of 16.9 years (range 6-46 years). To measure the Cobb angle and balance at preoperative, postoperative and follow up, and to record the operation report, neurological complications and at follow up. The relevant factors of neurological complications were analyzed by one-way analysis, including: age, Cobb angle, operation time, body mass index, pulmonary function, blood volume loss, resection level, number of vertebrae fixed, number of vertebrae resected, usage of cage or titanium mesh, preoperative neurologic function, the type of deformity and combination of spinal canal deformity, and further analyzed by multiariable Logistic regression analysis.
RESULTSThe average follow up was 42 months (range 19 to 83 months). The number of resected vertebrae average 1.3 (range 1 to 3), operative time average 502.4 min (range 165.0 to 880.0 min), estimate blood loss average 2,238 ml (range 100 to 11,500 ml) for an average 69.3% blood volume loss (range 9% to 299%). The average preoperative major coronal curve of 93.6° corrected to 22.2°, at the final follow-up, the coronal curve was 22.2° with a correction of 76.8%. The average preoperative coronal imbalance (absolute value) was 2.5 cm decreasing to 1.3 cm at the final follow-up. The average preoperative major sagittal curve of 88.2° corrected to 28.7°, at the final follow-up, the sagittal curve was 29.2°, average decrease in kyphosis of 59.0°. The average preoperative sagittal imbalance (absolute value) was 3.1 cm decreasing to 1.2 cm at the final follow-up. There were 12 patients (13.6%) developed a neurological complications. High rate of neurological complications was occurred in patients with operative time greater than 480 min, pulmonary dysfunction, blood volume loss greater than 50%, T7-T99 osteotomy and preoperative neurologic compromise (P=0.046, 0.000, 0.000, 0.033, 0.043).
CONCLUSIONSPosterior vertebral column resection can achieve satisfactory efficacy in treatment of severe spinal deformities. Pulmonary dysfunction and blood volume loss greater than 50% were significant risk factors of neurological complications.
Adolescent ; Adult ; Child ; Female ; Humans ; Kyphosis ; Male ; Middle Aged ; Neurosurgical Procedures ; Orthopedic Procedures ; Osteotomy ; Retrospective Studies ; Risk Factors ; Scoliosis ; Spinal Canal ; Spinal Diseases ; surgery ; Spine ; abnormalities ; surgery ; Treatment Outcome ; Young Adult
7.Transforming growth factor-β1 induces bone marrow-derived mesenchymal stem cells to differentiate into cancer-associated fibroblasts.
Lei SHANGGUAN ; Email: SHANGGUANLEI@126.COM. ; Xiaojie LI ; Zhe WANG ; Zhuojing LUO
Chinese Journal of Oncology 2015;37(11):804-809
OBJECTIVETo investigate the effect of transforming growth factor-β1 (TGF-β1) on the differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into cancer-associated fibroblasts(CAFs).
METHODSMSCs were cultured in α-MEM with recombinant human TGF-β1 or in tumor-conditioned medium.The expression of CAFs markers were detected by immunofluorescence and quantitative RT-PCR.
RESULTSThe qRT-PCR assay showed that the expression of CAFs markers FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin were 9.92±2.16, 7.76±1.28, 3.04±0.95, 3.28±2.16, 2.13±0.71, 1.41±0.66, 2.25±0.86 and 1.38±0.56, respectively, significantly upregulated in the MSCs co-cultured with TGF-β1 or TCM. The relative levels of FAP, ACTA, CAV, CCL5, CXCR4, FSP1, SDF-1 and vimentin mRNA in the TCM group were 7.52±1.76, 5.02±1.18, 1.98±1.19, 1.82±1.19, 2.95±0.86, 1.44±0.67, 2.08±0.74 and 1.47±0.55, respectively, indicating that MSCs can express CAFs phenotype.TGF beta signaling pathway inhibitor SB-431542 could inhibit the differentiation. Both immunofluorescence and Western blot confirmed the above results.
CONCLUSIONSTGF-β1 induces differentiation of local MSCs to CAFs by upregulating the expression of pSmad3, so as to further promote the growth of cancer cells.
Benzamides ; pharmacology ; Bone Marrow Cells ; cytology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Chemokine CXCL12 ; metabolism ; Coculture Techniques ; Culture Media, Conditioned ; Dioxoles ; pharmacology ; Fibroblasts ; cytology ; Humans ; Mesenchymal Stromal Cells ; cytology ; drug effects ; Organic Chemicals ; Receptors, CXCR4 ; metabolism ; Recombinant Proteins ; pharmacology ; Smad3 Protein ; metabolism ; Transforming Growth Factor beta1 ; antagonists & inhibitors ; pharmacology ; Vimentin ; metabolism
8.One stage surgical treatment of congenital scoliosis associated with split cord malformation.
Chao SHEN ; Huiren TAO ; Hua HUI ; Xiaofan JIANG ; Bo CHEN ; Jinghui HUANG ; Weizhou YANG ; Tao LI ; Zhuojing LUO
Chinese Journal of Surgery 2014;52(6):431-435
OBJECTIVETo investigate the clinical results of one stage surgical treatment in congenital scoliosis (CS) patients associated with split cord malformation (SCM).
METHODSBetween January 2007 and December 2010, 50 patients underwent one stage surgical treatment for CS associated with SCM. Among of them, 38 patients (13 male and 25 female) with an average age of (15 ± 6) years, who were followed up in the clinic at least 2 years longer, were include in the study. There were 12 patients with Type I SCM and 26 patients with Type II SCM Pre-operative, post-operative and the follow-up imaging data were collected and compared by paired t-test, while imaging data between Type I SCM group and Type II SCM group were compared by group t-test. Bony spur was first resected to the Type I SCM while nothing was done to the Type II SCM. Then, all patients were followed by posterior corrective procedure in one stage. Meanwhile, duraplasty were only applied in 5 patients whose dural cleft were more than 1 cm longer.
RESULTSThe average follow-up was 41 ± 13 months (range, 26-68 months). The average operation time was 491 ± 152 minutes (range, 105-780 minutes) and the average blood loss was (1 933 ± 1 516) ml (range, 1 000-8 000 ml). The mean major coronal curve was corrected from 70° ± 26° preoperatively to 312° ± 16° postoperatively with a correction rate of 57% ± 18%, and 33° ± 17° at the final follow-up with a correction rate of 54% ± 20%. The mean major sagittal curve was corrected from 43° ± 31° to 26° ± 16°, and 27° ± 15° at the final follow-up. The postoperative complication occurred in 2 patients (5.3%) with Type I SCM, including neurological deterioration in 1 patient (2.6%) and cerebrospinal fluid leakage in 1 patient (2.6%). There were no paralysis and other serious complications. The patients who suffered from neurological deterioration recovered to the preoperative neurological status at 30 months postoperatively and no further improvement at the final follow-up.
CONCLUSIONIt is safe and efficient to treat the CS associated with SCM by one stage surgery without increasing the risk of neurological complications postoperatively.
Adolescent ; Child ; Female ; Follow-Up Studies ; Humans ; Male ; Neural Tube Defects ; complications ; surgery ; Retrospective Studies ; Scoliosis ; complications ; congenital ; surgery ; Treatment Outcome ; Young Adult
9.Application of Spine Decide software in clinical teaching of spine surgery
Jinghui HUANG ; Teng MA ; Zhuojing LUO
Chinese Journal of Tissue Engineering Research 2014;(36):5896-5898
BACKGROUND:Spine, due to its complicated structure and special functions, is always the difficulty and emphasis in clinical practice and medical education. It is an interesting top how to apply modern software in clinical teaching. OBJECTIVE:To investigate the application of Spine Decide software in clinical teaching of spine surgery. METHODS:Teachers can actively guide students to learn the diagnosis of spine diseases and to design surgery program using Spine Decide software. Then the students wil participate in the surgical operation of the patients, which helps them better understand the diagnosis and treatment of spine surgery disease and the occurrence and development of spine diseases. RESULTS AND CONCLUSION:The students actively participated in the process of learning through Spine Decide software, which helps them learn systematical y, structural y the pathogenesis, diagnosis, treatment and prognosis of spine diseases in a short period. Application of Spine Decide into teaching activities has greatly improved the students’ abilities in self-learning and clinical analysis. Their enthusiasm to the learning and creativity has been greatly improved compared to traditional teaching methods;innovation and exploration have breakthrough improvement, final y achieving a good teaching effect.
10.Gender differences of Scoliosis Research Society-22 scores in adolescent idiopathic scoliosis
Jun QIAO ; Zezhang ZHU ; Zhen LIU ; Yueming SONG ; Yong HAI ; Zhuojing LUO ; Zude LIU ; Hongqi ZHANG ; Guohua LV ; Yipeng WANG ; Jianguo ZHANG ; Jianxiong SHEN ; Xu SUN ; Yong QIU ; Guixing QIU
Chinese Journal of Orthopaedics 2012;32(2):157-160
Objective To compare differences of SRS-22 scores between male and female AIS patients.Methods From October 2007 to April 2009,298 AIS patients from 7 spine centers completed simplified Chinese edition of SRS-22 questionnaire,including 62 males and 236 females with an average age of 15.7 years old,and the average Cobb angle was 52.8°.Of 62 male patients,34 were from urban areas and 28 rural areas.Among 236 female patients,132 were from urban areas and 104 rural areas.A comparison was conducted in terms of age,Cobb angle,the ratio of urban population to rural population,and the scores of all domains and the subtotal scores of SRS-22 questionnaire between male and female patients.Results There was no difference of age,Cobb angle and the ratio of urban population to rural population between male and female patients(P>0.05).The scores of four domains and subtotal scores of SRS-22 questionnaire were significantly higher in male patients when compared with female patients(P<0.05).Conclusion Gender difference should be taken into the consideration when estimating the quality of life in AIS patients by SRS-22 questionnaire.The quality of life in male patients with AIS was better than that of female patients.

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