Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

Objective:To establish a prognostic model based on endoplasmic reticulum stress-related genes for evaluating the prognosis of patients with renal cell carcinoma.Methods:This study utilized Non-negative Matrix Factorization to identify molecular subgroups based on endoplasmic reticulum stress-related genes and employed Weighted Correlation Network Analysis to determine co-expressed genes associ-ated with these subgroups.A risk prognostic model was constructed using univariate Cox regression analysis and Lasso regression analysis.Preliminary experimental validations were conducted to elucidate the biological functions of model genes in renal cell carcinoma.Results:Two molecular subgroups with distinct survival prognoses were identified,and an intersection of related genes was used to construct a nov-el endoplasmic reticulum stress-related prognostic model.Patients in the high-risk group exhibited significantly poorer overall survival in both the training and validation cohorts.In vivo experiments demonstrated that PCK1,a model gene,could inhibit the proliferation,migra-tion,and invasion of renal cell carcinoma cells.Conclusions:The risk scoring model developed in this study effectively predicts the survival probability of renal cell carcinoma patients and can serve as an independent prognostic indicator.This model offers a new direction for per-sonalized treatment strategies in renal cell carcinoma patients.

Objective:To compare Jefferson-fracture reduction plate (JeRP) and micro titanium plate in the transoral single-segment fixation of unstable atlas fractures.Methods:From January 2008 to December 2020, 45 patients with unstable atlas fracture were treated by single-segment fixation through an oral approach with a JeRP or a micro titanium plate at Department of Orthopedic Surgery, General Hospital of Southern Theatre Command. They were 24 males and 21 females, aged from 15 to 67 years. By the Gehweiler classification, 11 atlas fractures were type Ⅰ and 34 type Ⅲ; by the American Spinal Injury Association (ASIA) classification, the spinal cord injury was grade D in 7 cases and grade E in 38 cases; by the Dickman classification, the atlas transverse ligament injury was type Ⅰ in 4 cases and type Ⅱ in 11 cases. Of the patients, 26 were treated by transoral single-segment fixation with a JeRP and 19 by transoral single-segment fixation with a micro titanium plate. The 2 groups were compared in terms of baseline data, operation time, blood loss, hospital stay, visual analog scale (VAS) for neck pain and atlas lateral mass displacement (LMD) before operation and at the last follow-up, and intraoperative and postoperative complications.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative general data ( P>0.05). All patients were followed up for 12 to 55 months (mean, 21.8 months). Wound dehiscence or infection was observed in none of the patients after operation. About 12 months after operation, all fractures achieved bony union, neck pain basically disappeared, and neck movement had no obvious limitation. The hospital stay was (13.9±2.2) d for the JeRP group and (14.2±2.9) d for the micro titanium plate group, showing no significant difference between the 2 groups ( P>0.05). The operation time was (203.5±173.4) min and the blood loss (167.3±138.6) mL in the JeRP group, significantly more than those in the micro titanium plate group [(121.5±50.5) min and (98.4±57.2) mL] ( P<0.05). In the JeRP group, the preoperative LMD was (6.7±1.7) mm and the preoperative VAS score (6.8±1.0) points, significantly higher than the last follow-up values [(0.7±0.6) mm and (0.7±0.6) points] ( P<0.05). In the micro titanium plate group, the preoperative LMD was (6.6±1.5) mm and the preoperative VAS score (6.7±0.9) points, significantly higher than the last follow-up values [(0.9±0.6) mm and (0.8±0.7) points] ( P<0.05). However, there was no significant difference in the preoperative or the last follow-up comparison between the 2 groups ( P>0.05). Implant loosening was observed in one patient in the JeRP group while foreign body sensation in the throat was reported in one patient after operation in the micro titanium plate group. Conclusions:Both JeRP and micro titanium plate in the transoral single-segment fixation can lead to effective treatment of unstable atlas fractures. Compared with JeRP, the micro titanium plate can effectively shorten operation time and reduce blood loss due to its smaller size and lower incision.

Objective:To investigate the clinical efficacy of different grade transoral atlantoaxial release for the treatment of irreducible atlantoaxial dislocation.Methods:From January 2010 to December 2019, 297 patients with irreducible atlantoaxial dislocation treated by different grade releases were retrospectively analyzed, including 132 males and 165 females, aged 42.3±12.14 years (range, 10-63 years). All cases were treated by different grade releases, Grade I (196, 66.0%), Grade II (54, 18.2%), Grade III (28, 9.4%) and Grade IV (19, 6.4%). The American Spinal Injury Association (ASIA) grade and Japanese Orthopedic Association (JOA) score were recorded as the clinical evaluation index. The clivus-canal angle (CCA) and cervico-medullary angle (CMA) were measured to evaluate the reduction. The surgery time, blood loss, duration of bony fusion and complications were also analyzed.Results:The follow-up time was 14.8±10.2 months (range, 9-36 months). The surgery time of Grade I-IV were 2.02±0.35 min, 3.00±0.36 min, 4.07±0.96 min and 5.24±0.83 min, respectively ( F=385.43, P<0.001), blood loss was 84.08±27.21 ml, 153.61±31.36 ml, 268.93±48.94 ml and 444.21±109.51 ml, respectively ( F=582.39, P<0.001). The preoperative ASIA motor score of Grade I-IV were 83.85±6.68, 84.06±5.47, 84.07±5.99 and 85.00±4.11, respectively. The last follow-up were 98.34±2.38, 98.67±1.79, 98.86±1.58 and 98.32±2.11, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative JOA score of Grade I-IV were 11.44±1.73, 11.59±1.72, 11.61±1.47 and 11.32±1.80, respectively. The last follow-up were 16.22±1.00, 16.28±1.02, 16.14±1.04 and 16.16±1.07, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CCA of Grade I-IV were 110.19°±8.76°, 112.48°±7.66°, 106.61°±6.54° and 109.05°±7.79°, respectively. The last follow-up were 140.22°±8.04°, 141.86°±7.04°, 142.35°±8.62° and 140.15°±6.49°, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CMA of Grade I-IV were 113.48°±9.54°, 116.03°±8.38°, 109.55°±7.13°, and 112.46°±8.33°, respectively. The last follow-up were 144.28°±7.75°, 146.40°±6.98°, 145.81°±8.27° and 143.24°±6.36°, respectively, with statistically significant differences from preoperative ( P<0.05). Solid bony fusion was obtained except for 3 cases, the fusion time was 9.71±2.55 months (range 3-14 months). Altogether 33 complications occurred in all cases (11.1%), including 3 fusion failure, 3 cerebrospinal leak, 3 wound infection, 2 death (1 case caused by cerebrospinal leak), 11 pharyngeal discomfort, 4 postoperative pain surrounding iliac crest, and 8 malunion of iliac crest. Conclusion:Transoral stepped atlantoaxial release theory could provide guidelines for atlantoaxial dislocation treatment, and make the transoral release technique more effective and safer.

Objective:To report our experience in diagnosis and treatment of posterior atlantoaxial dislocation with odontoid retrolisthesis.Methods:A retrospective study was conducted of the 5 patients who had been treated from July 2012 to August 2018 at Department of Orthopaedics, General Hospital of Southern Theater Command for posterior atlantoaxial dislocation. They were 4 men and one woman, aged from 34 to 67 years (average, 47 years). All of them had a history of trauma. Of them, 4 were complicated with odontoid fracture and one with congenital free os odontoideum. Their posterior atlantoaxial dislocation ranged from 3 to 9 mm (average, 6 mm). By the American Spinal Injury Association (ASIA) grading system, their preoperative spinal injury was rated as grade B in one, as grade C in 3 cases and as grade D in one. All the 5 patients underwent skull traction at 10° flexion. Surgical trans-oralpharyngeal atlantoaxial reduction and internal fixation was performed for the one patient whose reduction had not been achieved by traction while posterior atlantoaxial screw-rod fixation or anterior odontoid screwing was conducted for the 4 patients whose reduction had been achieved by traction. The distance of posterior atlantoaxial dislocation was measured to evaluate their reduction and ASIA grade system was used to assess their spinal function after operation.Results:The postoperative distance of posterior atlantoaxial dislocation was 0 mm, showing a reduction rate of 100%. The 5 patients were followed up for 6 to 36 months (average, 15 months). By the ASIA grade system, the postoperative functional recovery of the spine was grade D in 4 cases and grade C in one. No implant loosening or breakage occurred.Conclusion:As a kind of high-energy hyperextension injury, posterior atlantoaxial dislocation is rare in clinic, but an appropriate treatment can be adopted to deal with its different clinical types to achieve good outcomes.

Objective This review aimed at assessing the diagnostic efficacy of contrast-enhanced single-photon emission computed tomography (SPECT) in the diagnosis of mandibular invasion by oral cancers. Methods Five databases were searched electronically on August 5, 2016. The reference lists of included studies were hand searched. Quality assessment was performed by two reviewers in duplicate with tools suggested by Cochrane's handbook. Furthermore, the data extraction of included studies was delivered. Meta-analysis was performed using STATA 11.0. Results Ten studies with 460 participants were included. One study had a low risk of bias, and two studies had a high risk of bias. The remaining seven studies had an unclear risk of bias. Meta-analysis results showed that SPECT had a pooled sensitivity of 0.99 [95% confidence interval=0.87-
1.00]. Sensitivity was 0.99 on Q* point. The specificity of 0.61 and the area under summary receiver operating characteristic curve (SROC) were 0.93 [95% confidence interval=0.90-
0.95]. The pooled positive likelihood ratio was 2.555. The negative likelihood ratio was 0.015. The diagnostic odd ratio was 5.115. Conclusion SPECT had high sensitivity, which became suitable for excluding bone invasion by oral cancers. However, its specificity was relatively low, indicating its limited capability in confirming diagnosis. Therefore, surgeons should perform this method under certain conditions.

BACKGROUND: With the rapid development of digital orthopaedics, navigational template has been widely used in the field of orthopaedics, but the research status of the technique in China based on bibliometric analysis is never reported. OBJECTIVE: To investigate the application status of navigational template in the orthopaedic field and to explore its tendency and hot spot based on bibliometric analysis, thereby providing reference for the development of digital orthopaedics in China.METHODS: A computer-based retrieval of CBMdisc, CNKI, CSPD, CMCI databases was conducted for articles published before December 1, 2016 using the keywords of navigational template and subject heading orthopaedics and the core orthopaedic journals published in 2016 were searched by manual. The articles were screened according to inclusion and exclusion criteria, and finally were analyzed by bibilometric study.RESULTS AND CONCLUSION: (1) In China, the first paper reporting navigational template was issued in 2008. A total of 199 articles were published in the past 9 years, with more than 10 papers yearly from 2009 to 2014, while there was a rapid increase tendency during 2015 and 2016. (2) The articles were mainly published in the orthopaedic journals and some professional journals closely related to digital orthopaedics, such as biomedical engineering, basic medicine and digital medicine. About 86.9% papers belong to Chinese core journals, including Chinese Journal of Orthopaedic Trauma,Chinese Journal of Orthopaedics, and Chinese Journal of Tissue Engineering Research. (3) There is a 99.5% cooperation rate and 6.15 degree of cooperation. Zhang Yuan-zhi, Ding Huan-wen, Lu Sheng, Chen Yu-bing, Hu Yong,Huang Xuan and Zheng Peng-fei are most productive authors, and core authors contribute to 53.8%, indicating that the group of core authors is being formed. First authors are all from hospitals and universities, mostly from Kunming General Hospital of Chengdu Military Command of PLA, General Hospital of Guangzhou Military Command of PLA, the Affiliated Hospital of Inner Mongolia Medical University and South China University of Technology. The cooperation rate of more than two institutes occupies 54.8%, indicating that the study holds a promising future with the strong support of research institutes in universities. About 59.3% articles are sponsored by funding, the national and provincial foundations accounting for 64.0% in 239 projects, and 57.6% articles were supported by more than two foundations, revealing the high research levels and academic values of this technique. (4) The articles are cited by 763 times; Lu Sheng,Chen Yu-bing, and Zhang Yuan-zhi are the highly cited authors; Kunming General Hospital of Chengdu Military Command of PLA, General Hospital of Guangzhou Military Command of PLA and Nanfang Hospital of Southern Medical University are the highly cited institutes, and Chinese Journal of Orthopaedic Trauma is the highly cited journal. (5) To conclude, based on product design, manufacture and cadaver studies of the navigational template, it has been extensively applied in the spine surgery (especially cervical surgery), orthopaedic traumatology, bone and joint surgery,bone tumor and pediatric orthopaedics, and has obtained satisfactory clinical outcomes in assisting screw placement,osteotomy and precise resection and functional reconstruction. However, there is still a lack of a large-sample,multicenter, and long-term randomized trial.

Objective To investigate the clinical effect of posterior screw-rod fixation fusion for the treatment of atlantoaxial dislocation due to rheumatoid arthritis.Methods From January 2011 to December 2015,15 patients with atlantoaxial dislocation due to rheumatoid arthritis were treated,including 6 males and 9 females,aged 35 to 75 years (mean 55 years).All cases were evaluated about the difficulty of relocation by extension-flexion X-ray and treated with posterior screw-rod reduction,fixation and autogenous bone grafting under general anesthesia.Atlantodental interval (ADI) was measured and collected before and after surgery.Visual Analogue Scale/Score (VAS),American Spinal Cord Injury Association (ASIA) and Japanese Orthopaedic Association (JOA) scores were comprehensively used to evaluate the clinical effect.1 week,3,6,12 months postoperatively and the annual review of the X-ray and CT were checked,in order to evaluate the reduction,internal fixation and bone graft fusion.Results All patients were reducible dislocation and successfully performed the posterior screw-rod fixation fusion surgery.The patients were followed up for 3 to 24 months (average,15 months).Atlantoaxial solid bony fusion was obtained from 3 to 6 months.ADI reduced from preoperative 6.3±1.7 mm to postoperative 2.2±0.8 mm,VAS score reduced from preoperative 5.4±2.7 to postoperative 1.7±1.0,ASIA motor score improved from preoperative 82.3±15.6 to 95.3±4.5 at 6 months after the surgery,JOA score increased from preoperative 13.8±2.9 to 15.5±1.4 at 6 months after the surgery,and the statistical significance was revealed between preoperation and postoperation.Nine cases were in D grade of ASIA,3 cases improved from D to E grade after surgery,2 cases reached E grade in the other 6 cases after 6 months,2 cases recovered to E grade after 12 months and other 2 cases in D grade got uniformity after surgery.Well internal fixation and no redislocation were found on X-ray and CT during follow-up period.Conclusion Atlantoaxial dislocation because of rheumatoid arthritis was numerously reducible genre.Posterior screw-rod fixation and autogenous bone grafting can gain satisfying clinical efficacy.

OBJECTIVETo investigate the role of glycogen synthase kinase 3β (GSK-3β) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs).

METHODSMature DCs (mDCs) induced by LPS were examined for GSK-3β phosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3β in maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3β, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR; the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3β and RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3β gene.

RESULTSLPS exposure significantly lowered GSK-3β activity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3β inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3β obviously down-regulated the expression of RelB.

CONCLUSIONSGSK-3β is a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3β is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3β, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3β overexpression supports GSK-3β as a new target for inducing tolerogenic DCs.

Animals ; B7-2 Antigen ; metabolism ; CD40 Antigens ; metabolism ; Cell Differentiation ; Cells, Cultured ; Culture Media ; chemistry ; Dendritic Cells ; enzymology ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Indoles ; chemistry ; Interleukin-10 ; metabolism ; Interleukin-12 ; metabolism ; Interleukin-6 ; metabolism ; Lentivirus ; Lymphocyte Culture Test, Mixed ; Maleimides ; chemistry ; Mice ; Myeloid Cells ; enzymology ; Phosphorylation ; RNA, Messenger ; Real-Time Polymerase Chain Reaction ; Signal Transduction

Objective To investigate the role of glycogen synthase kinase 3β(GSK-3β) in the maturation and function of murine bone marrow-derived dendritic cells (BMDCs). Methods Mature DCs (mDCs) induced by LPS were examined for GSK-3βphosphorylation level with Western blotting before and after LPS exposure. To explore the role of GSK-3βin maturation and function of DCs, we added SB216763, a selective inhibitor of GSK-3β, in the cell culture of immature DCs (iDCs), and examined CD40 and CD86 expressions in the cells by flow cytometry and the expression of IL-6, IL-12 and IL-10 mRNA by real-time PCR;the changes of the immunogenicity of the cells was evaluated by mixed lymphocyte reaction. The expression of GSK-3βand RelB was examined by Western blotting in DC2.4 cells transfected with a lentiviral vector over-expressing murine GSK-3βgene. Results LPS exposure significantly lowered GSK-3βactivity in iDCs as demonstrated by increased Ser9 phosphorylation and reduced Tyr216 phosphorylation. GSK-3β inhibition induced DC maturation by increasing the expression of surface costimulatory molecules CD40 and CD86, lowered the expressions of IL-6 and IL-12 while enhanced the expression of IL-10 in iDCs, and impaired mixed lymphocyte reaction of the cells. In DC2.4 cells, lentivirus-mediated over-expression of GSK-3βobviously down-regulated the expression of RelB. Conclusion GSK-3βis a crucial enzyme involved in the differentiation and maintenance of an immature phenotype of DCs. GSK-3β is constitutively active in iDCs to inhibit their spontaneous maturation. DCs become phenotypically mature after inhibition of GSK-3β, which also executes a proinflammatory task in DC activation. The reduction of RelB protein levels as a result of GSK-3β overexpression supports GSK-3β as a new target for inducing tolerogenic DCs.