ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

Objective: To explore the effects of Buyang Huanwu decoction (BYHWD) on vascular neogenesis and hemorheological parameters following cervical spinal cord injury (SCI). Methods: An acute cervical SCI model was established using 84 female Sprague–Dawley rats. Functional recovery of the rats was evaluated using the forelimb locomotor scale score, forelimb grip strength test, and Basso-Beattie-Bresnahan score. The animals were subsequently euthanized at days 7 and 28 postoperatively. The gross morphology, neuronal survival, and myelin sheath in the injured area were evaluated using hematoxylin and eosin (HE), Nissl, and luxol fast blue (LFB) staining, respectively. Immunofluorescence staining was used to observe CD31 expression 7 days post-injury. Furthermore, the expression of CD31, neuronal nuclear protein (NeuN), and myelin basic protein (MBP) were evaluated 28 days post-injury. Additionally, vascular endothelial growth factor A (VEGFA) and VEGF receptor-2 (VEGFR-2) expression was evaluated using western blotting. Whole-blood viscosity, plasma viscosity, and red blood cell aggregation were measured using a hemorheometer. Results: From postoperative days 3–28, motor function in the BYHWD group began to recover considerably compared to the SCI group. BYHWD effectively restored spinal cord histopathology. In addition, the number of NeuN-positive cells, and fluorescence intensity of CD31at 7 and 28 days and MBP significantly increased in the BYHWD group compared with the SCI group (all P < .05). Moreover, this decoction significantly upregulated the expression of VEGFA and VEGFR-2 (all P < .05). BYHWD improved the hemorheology results (i.e., except erythrocyte aggregation index in the low-dose group), revealing statistically significant differences compared with the SCI group (all P < .05). Conclusion BYHWD effectively promoted angiogenesis, improved hemorheological parameters, and protected neurons and myelin sheaths, ultimately promoting the recovery of neurological function after cervical SCI in rats. These findings suggest that BYHWD promotes vascular neogenesis through the VEGFA/VEGFR-2 pathway.

Peroral endoscopic myotomy (POEM) has emerged as a rescue treatment for recurrent or persistent achalasia after failed initial management. Therefore, we aimed to investigate the efficacy and safety of POEM in achalasia patients with failed previous intervention. We searched the MEDLINE, Embase, Cochrane, and PubMed databases using the queries “achalasia,” “peroral endoscopic myotomy,” and related terms in March 2019. Data on technical and clinical success, adverse events, Eckardt score and lower esophageal sphincter (LES) pressure were collected.The pooled event rates, mean differences (MDs) and risk ratios (RR) were calculated. A total of 15 studies with 2,276 achalasia patients were included. Overall, the pooled technical success, clinical success and adverse events rate of rescue POEM were 98.0% (95% confidence interval [CI], 96.6% to 98.8%), 90.8% (95% CI, 88.8% to 92.4%) and 10.3% (95% CI, 6.6% to 15.8%), respectively. Seven studies compared the clinical outcomes of POEM between previous failed treatment and the treatment naïve patients. The RR for technical success, clinical success, and adverse events were 1.00 (95% CI, 0.98 to 1.01), 0.98 (95% CI, 0.92 to 1.04), and 1.17 (95% CI, 0.78 to 1.76), respectively. Overall, there was significant reduction in the pre- and post-Eckardt score (MD, 5.77; p<0.001) and LES pressure (MD, 18.3 mm Hg; p<0.001) for achalasia patients with failed previous intervention after POEM. POEM appears to be a safe, effective and feasible treatment for individuals who have undergone previous failed intervention. It has similar outcomes in previously treated and treatment-naïve achalasia patients.

Objective To investigate the expression and clinical significance of lactate dehydrogenase A (LDHA) in breast cancer.Methods Tissue samples of 76 breast cancers and corresponding paired adjacent normal tissues were collected and made into tissue micrcarrays (TMAs).Immunohistochemistry (IHC) analysis was performed to detect the expression of LDHA and further analyzed the correlation of LDHA expression and clinicopathological variables and prognosis of breast cancers.Results LDHA was frequently upregulated in breast cancer tissues compared to the normal breast tissues (P ＜ 0.05).High LDHA expression was associated with distant metastasis (P ＜ 0.05) and worse patient prognosis (P ＜ 0.05).Conclusions LDHA is closely related to the occurrence and clinical progress of breast cancers.LDHA might be a potential novel molecular marker for diagnosis,prognosis and therapy in breast cancers.

BACKGROUND: It is still controversial that interspinous dynamic stabilization system Wallis and Coflex which one can provide better clinical effects for lumbar degenerative disease.OBJECTIVE: To systematically assess the clinical effectiveness and safety of Wallis and Coflex for lumbar degenerative disease.METHODS: According to the computer-based online search of PubMed, Embase, Medline, Cochrane Library, CBM,CNKI, Wanfang Database, and VIP, articles published before August 1st, 2016 were searched. Articles about Wallis comparing with Coflex for lumbar degenerative disease were included; the quality score of methodology was assessed by MINORS. Research data abstracted and synthesized by Review Manager 5.3 were used for meta-analysis.RESULTS AND CONCLUSION: (1) Six studies were included, and all studies were designed for non-randomized controlled trial. (2) There were no significant statistical differences in Japanese Orthopedic Association, Oswestry disability index, visual analogue scale score, Prolo functional score, segmental lordosis angle, and segment movement degree. Incidence of adverse events was significantlue scale less in the Wallis group than in the Conflex group (P < 0.05).(3) There was no significant difference in clinical efficacy between Wallis and Coflex in the early and mid-term follow-up.We can conclude that Wallis may provide better clinical safety than Coflex.

Objective To investigate the guidance value of TOI classification in treating traumatic T-type atlantoaxial dislocation (ADD).Methods A retrospective case series study was made on 32 cases of traumatic TOI T-type ADD treated between January 2012 and December 2015.There were 19 males and 13 females,aged (38.4 ± 14.7) years.Fifteen cases of T1-type underwent external fixation or internal fixation without fusion,while 17 cases of T2-type underwent internal fixation with fusion.Symon-Lavender clinical standard,Japanese orthopedic association score (JOA),visual analogue scale (VAS),atlas-dens interval (ADI) and space available for the cord (SAC) were used to evaluate the therapeutic effect.Results Patients were followed up for 6-54 months (mean,32.4 months).At final follow-up,ADI was decreased to (2.3 ± 1.4) mm from preoperative (5.6 ± 1.6) mm,but SAC was increased to (15.4 ± 1.9) mm from preoperative (12.0 ± 2.9) mm(P ＜ 0.01).At final follow-up,cervical axial rotation range of motion was 102°-154° in T1-type cases and 57°-93° in T2-type cases.Range of motion for atlantoaxial joint was preserved in T1-type cases,but lost in T2-type cases.According to the Symon-Lavender clinical standard,there were 14 cases of mild disability,nine moderate disability,eight severe disability and one extremely severe disability before operation;there were 21 cases of mild disability,nine moderate disability and two severe disability at last follow-up.Significant difference was observed in the grades according to the Symon-Lavender clinical standard before operation and at last follow-up (P ＜0.05).At last follow-up,JOA score was increased to (14.6 ± 2.9) points from preoperative (9.9± 3.2) points,and VAS was decreased to (2.7 ± 1.3)points from preoperative (6.0 ± 1.6)points (P ＜ 0.01).Conclusions By using TOI classification,reconstruction of stability and improved neurological function can be achieved in treatment of traumatic T-type atlantoaxial dislocation.Non-fusion treatment of T1-type atlantoaxial dislocation can preserve range of motion for atlantoaxial joint.

BACKGROUND: Previous studies have confirmed that rabbit bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts under osteogenic induction in vitro, stably express the specific phenotype of osteoblasts and have osteogenic ability. Calf cortical bone scaffold with partial cancellous bone has good biocompatibility and degradability, which can be used as a carrier material of bone marrow mesenchymal stem cells. OBJECTIVE: To combine rabbit BMSCs with calf bone composite according to the basic principles of bone tissue engineering and to observe the osteogenesis in the New Zealand white rabbits after implantation of BMSCs/calf bone composite into the ilium, thereby providing a direct evidence for preliminary clinical application of tissue-engineered bone products.METHODS: BMSCs/calf cortical bone scaffold with partial cancellous bone (tissue-engineered bone group), simple calf heterogeneous bone (heterogeneous bone group) or autologous iliac bone (autologous iliac bone group) was randomly implanted into the rabbit ilium. The changes of implant surface and tissue reactions around the implant were observed.X-ray examination was performed to observe osteogenic changes at 4, 8, 12, 24 weeks after implantation. Immunohistochemistry staining was used to observe the expression of bone morphogenetic protein 2.RESULTS AND CONCLUSION: After heterogeneous bone implantation, the wound healed well, and there were no systemic or local inflammation and toxicity reactions in all groups. The X-ray results showed that at postoperative 24 weeks, the implant was basically fused with the host bone in the tissue-engineered bone group, but the fusion was unsatisfactory in the heterogeneous bone group. The process of ossifications from cartilages was observed in all groups by hematoxylin-eosin staining, and bone morphogenetic protein 2 was positive for immunohistochemical staining. Findings from in vivo experiments indicate that rabbit BMSCs seeded onto the calf cortical bone scaffold with partial cancellous bone could construct tissue-engineered bone by osteoinductation in vitro in the rabbits.

OBJECTIVE: To explore the efficacy of the resection of periacetabular malignant tumors and the reconstruction with modular endoprosthesis.
 METHODS: From August 2006 to December 2012, 22 patients with periacetabular malignant tumors, who received the resection and reconstruction with modular prosthesis, were retrospectively reviewed. There were 11 males and 11 females, and the average age was 44 (16-65) years old. Pathological results showed there were 13 cases of chondrosarcoma, 5 cases of osteosarcoma, 2 cases of Ewing's sarcoma, 1 case of maligant fibrous histiocytoma, and 1 case of giant cell tumor. According to the classification system by Enneking, there were 11 cases of Type II+III resection, 5 cases of Type I+II+III resection, 3 cases of Type I+II resection, and 3 cases of Type II resection.
 RESULTS: All patients were followed up. The average time for follow-up was 49 (11-103) months. At the last time of follow-up, 13 patients (59%) were still alive, 9 patients (41%) died due to their primary disease. Metastasis occurred in 8 patients (36%), and local recurrence occurred in 5 patients (23%). The mean Musculoskeletal Tumor Society (MSTS) score for 13 cases of alive patients at the latest time of follow-up was (18.5±5.7) months. The mean score for 11 patients, whose limb salvage were successful, was 20.7±2.0.
 CONCLUSION Reconstruction with modular prosthesis after wide resection for periacetabular malignant tumor can achieve satisfied outcome.
Acetabulum ; pathology ; surgery ; Adolescent ; Adult ; Aged ; Bone Neoplasms ; mortality ; surgery ; Chondrosarcoma ; mortality ; surgery ; Female ; Giant Cell Tumors ; mortality ; surgery ; Hip Prosthesis ; Histiocytoma, Malignant Fibrous ; mortality ; surgery ; Humans ; Limb Salvage ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Osteosarcoma ; mortality ; surgery ; Prosthesis Implantation ; statistics & numerical data ; Retrospective Studies ; Sarcoma, Ewing ; mortality ; surgery ; Treatment Outcome

Objective To investigate the expression and tissue distribution of CD31 in the process of the calf cortical with partial cancellous bone xenograft, to explore the healing mechanism and relationship between bone remodeling and revascularization, and to provide a basis for the further study of tissue engi-neered bone.Methods Thirty-six New Zealand rabbits were selected as our experimental animals.All ani-mals were implanted with the calf cortical with partial cancellous bone.Specimens were procured at 4, 8, 12 and 24 weeks after surgery, respectively.The expression and tissue distribution of CD31 were observed in the process healing with general condition, X-ray, histology and immunohistochemistry.The image analy-sis computer system was used for quantitative analysis.The extent of revascularization and remodeling was separately represented by revascularization indexes and new bone areas.The relationship was studied be-tween bone remodeling and revascularization.Results ⑴ The X-ray showed significant healing.⑵ The positive expression of CD31 was seen in the whole process of bone xenograft and was different at various stage and sites.By the 4 weeks and 8 weeks postoperative,the strong positive expression was seen in the pe-ripheral soft tissue of graft bone, the callus of joint and the periphery of cartilage nests.Much positive ex-pression was seen in the cancellous bone.There was seen some single, cord, and cluster vascular endotheli-al cells.The positive expression was seen in the enlarged haversian canals and periphery.By the 24 weeks postoperative,the positive expression was seen in the enlarged haversian canals and periphery with increasing newborn capillaries.⑶ The correlation analysis between new bone areas and revascularization showed a closely positive correlation ( r =0.984).Conclusions The positive expression of CD31 was seen in the whole process of bone xenograft and was different at various stage and sites.The positive expression of CD31 reflected the extent of revascularization and bone remodeling of bone grafts.The extent of revascularization of bone grafts and bone remodeling showed a closely positive correlation.

OBJECTIVE: To explore the difference of bone formation potential between hypertrophic nonunion tissue and atrophic nonunion tissue, which may be beneficial to nonunion therapy. METHODS: From October 2010 to March 2014, 40 nonunion tissue samples were collected in Department of Orthopedics, Second Xiangya Hospital. The samples were divided into a hypertrophic nonunion group (n=20) and an atrophic nonunion group (n=20) according to nonunion character; or a 20 to 35 years old group (n=18), a 36 to 50 years old group (n=18), a more than 50 years old group (n=4) according to different ages; or a 9-12 months group (n=21), 13-24 months group (n=14) and a more than 24 months group (n=5) according to different nonunion time. Semi-quantification was performed by SP immunohistochemical method and IPP6.0 was used to analyze the expression of bone morphogenetic protein-2 (BMP-2) through measuring the mean optical density. RESULTS: The mean optical density of BMP-2 was 0.1540±0.0408 in hypertrophic nonunion tissue, 0.1372±0.0372 in atrophic nonunion tissue, there was no significant difference between the 2 groups (P>0.05). The mean optical density of BMP-2 was 0.1477±0.0379 in the 20 to 35 years old group, 0.1419±0.0399 in the 35 to 50 years old group, 0.1456±0.0595 in the more than 50 years old group, there was no significant difference among the three groups (P>0.05). The mean optical density of BMP-2 was 0.1449±0.0366 in the 9-12 months group, 0.1472±0.0400 in the 13-24 months group, 0.1445±0.0541 in the more than 24 months group, there was no significant difference among the 3 groups (P>0.05). CONCLUSION The present results suggest that the hypertrophic nonunion tissue share similar osteogenic potential with the atrophic nonunion tissue.
Adult ; Bone Morphogenetic Protein 2 ; genetics ; metabolism ; Fracture Healing ; Fractures, Ununited ; genetics ; metabolism ; Humans ; Middle Aged ; Osteogenesis ; Young Adult