1.Research progress of measurement tools for health-related quality of life in patients with spinal metastases
Mengchen YIN ; Wenlong YU ; Lin LI ; Xin GAO ; Luosheng ZHANG ; Dingbang CHEN ; Quan HUANG ; Xinghai YANG ; Junming MA ; Jianru XIAO ; Wen MO
Chinese Journal of Orthopaedics 2023;43(16):1115-1122
The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.
2.The application and insight of single-stage posterior total en bloc spondylectomy treatment on L 5 vertebrae spine tumors
Yujie LIU ; Wei WAN ; Jiongxi WAN ; Jie ZHANG ; Da WANG ; Fanrong LIU ; Xinghai YANG ; Jianru XIAO
Chinese Journal of Orthopaedics 2022;42(24):1615-1622
Objective:To investigate the feasibility and technical points of single posterior total spine resection for L 5 vertebrae tumors, evaluate the effectiveness and safety of the technique, and propose a comprehensive treatment model for L 5 tumors on this basis. Methods:A retrospective analysis was performed on the data of 13 patients with L 5 vertebrae tumor who were treated by total en bloc spondylectomy (TES) through single-stage posterior approach from January 2014 to September 2021, including 4 males and 9 females. The age range was 21-65 years, with an average age of 33.85±14.24 years. Imaging examination showed isolated tumors of L 5 vertebrae without other metastases. All patients were treated with a single posterior L 5 vertebrae tumor TES by adjusting the curvature of lumbar lordosis, and the lumbar nerve root was fully dissociated. The vertebra with tumor was removed entirely and lumbar stability reconstruction via a pedicle screw system. Various parameters, including operative time, blood loss, complications, preoperative and postoperative spine sagittal parameters, Japanese Orthopaedic Association scores (JOAs), tumor control and outcome, were listed and analyzed. Results:Preoperative pathological diagnosis of 13 patients was mainly primary bone tumor including giant cell tumor in 7 cases, and invasive hemangioma, epithelioid hemangioma, aneurysmal bone cyst, chordoma, plasma cell myeloma and bone metastasis of breast cancer in 1 case. The mean operative time was 333.23±99.48 min (range 175-480 min), and the mean intraoperative blood loss was 1 407.69±676.49 ml (range 300-2 800 ml). There were no serious perioperative complications during the perioperative period. The mean follow-up was 54.92±19.29 months (range 28-84 months). JOAs improved from 13.85±3.86 points before operation to 24.31±2.16 points at 6 months after operation, and the difference was statistically significant ( t=8.19, P<0.001). Postoperative delayed wound healing occurred in 2 case. 2 patients showed numbness of the left lower limb, and 1 patient had slightly reduced plantar flexion movement. Conclusion:Single posterior TES is a good surgical method for the treatment of isolated L 5 vertebrae tumors. Although this technique is difficult, it can reduce surgical wounds and postoperative complications and good functional and oncology prognosis can be achieved.
3.Construction of Hsf1 gene-knockout mouse model using CRISPR/Cas9
Zheyu WU ; Zhenhua ZHOU ; Zhipeng WU ; Yufeng ZHANG ; Zhiqiang YANG ; Yufan ZHU ; Yuanlong XIE ; Jianru XIAO ; Lin CAI
Chinese Journal of Orthopaedics 2021;41(8):515-524
Objective:To explore the efficient construction of HSF1 gene knockout mouse model using CRISPR/Cas9 gene editing technology, and to establish the early basis for the mouse model of primary osteosarcoma.Methods:According to exon 9 of HSF1 gene structure, the corresponding GRNA (guideRNA) was selected and screened. Then the transcription template of sgRNA (small guide RNA) was amplified by PCR, and four up stream primers were obtained. Subsequently, sgRNA was transcribed in vitro and screened by Tube Screen platform to screen the sgRNA with effective cutting, and the sgRNA with the highest cutting efficiency was selected from the screening results for subsequent experiments. The transcription template of SPCas9mRNA was amplified by PCR, and then Cas9mRNA was transcribed in vitro. The sgRNA transcribed in vitro and Cas9mRNA were injected into the fertilized eggs of healthy C57BL/6 mice, and the tissue was extracted from the tail of the born mice and identified by PCR sequencing. Heterozygous female mice of F0 generation were selected to mate with wild-type male mice too btain F1 generation off spring. The mutation of gene bases of F1 generation mice was detected by AGAR gel electrophoresis and gene sequencing. The heterozygous male mice of the F1 generation and female mice of the F0 generation were back crossed to obtain the F2 generation daughter mice. The tail tissues were cut and sequenced to obtain the F2 generation homozygous knockout mice. PCR was used to observe the cutting efficiency of sgRNA and the sequencing of rat tail tissue, and SNAPGene software was used for gene sequence alignment to determine the deletion of base fragments.Results:The up stream primers sgRNA-1 Primer-f, sgRNA-2 Primer-f, sgRNA-3 Primer-f, sgRNA-4 Primer-f and down stream primers sgRNA-4 Primer -r were obtained by PCR amplification. After in vitro tran scription and screening of sgrRNA, sgrRNA-1, sgrRNA-2 and sgrRNA-4 had high cleavage efficiency and were selected for subsequent experiments. T7 promoter was added to the 5 'end of Cas9 mRNA, and Cas9 mRNA was obtained by PCR and in vitro transcription kit. Mixed Cas9-sgRNA solution was injected into the fertilized eggs of mice and cultured. The cultured two-cell fertilized eggs were injected into the ampulla of the pseudo pregnant female mice, and the F0 generation mice were obtained successfully. A total of 8 heterozygous mice of F0 generation were obtained by Agar gel electrophoresis. Three heterozygous knockout mice of F1 generation were obtained by breeding the female heterozygous mice of F0 generation with healthy wild-type male mice and PCR and sequencing. Three heterozygous male mice of F1 generation were back crossed with female mice of F0 generation 3 to obtain F2 generation mice. Through the observation of electrophoresis and sequencing results of F2 generation mice, it was confirmed that 7 mice were missing HSF1 base sequence, and the electrophoresis results showed mutant bands and no wild-type bands, which were identified as homozygous. The F2 generation homozygous mice were able to breed stably. As eries of results proved that the HSF1 gene knockout mouse model was successfully established in this experiment.Conclusion:CRISPR/Cas9 technology was successfully used to construct HSF1 gene knockout mouse model, with strong stability and high reproducibility, which laida foundation for further study of HSF1 gene expression products and establishment of mouse model of primary osteosarcoma.
4.Expert Concensus on Triune Personalized Treatment of Pelvic Tumor Based on Three-Dimensional Printing
Songtao AI ; Zhengdong CAI ; Feiyan CHEN ; Kerong DAI ; Yang DONG ; Lingjie FU ; Yongqiang HAO ; Yingqi HUA ; Wenbo JIANG ; Jiong MEI ; Yuhui SHEN ; Wei SUN ; Rong WAN ; Yichao WANG ; Zhiwei WANG ; Haifeng WEI ; Wen WU ; Jianru XIAO ; Wangjun YAN ; Xinghai YANG ; Chunlin ZHANG ; Weibin ZHANG
Journal of Medical Biomechanics 2021;36(1):E001-E005
The adjacent anatomy of the pelvis is complicated, with digestive, urinary, reproductive and other organs as well as important blood vessels and nerves. Therefore, accurate resection of pelvic tumors and precise reconstruction of defects after resection are extremely difficult. The development of medical 3D printing technology provides new ideas for precise resection and personalized reconstruction of pelvic tumors. The “triune” application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis in pelvic tumor limb salvage reconstruction treatment has achieved good clinical results. However, the current lack of normative guidance standards such as preparation and application of 3D printing personalized lesion model, osteotomy guide plate and reconstruction prosthesis restricts its promotion and application. The formulation of this consensus provides normative guidance for 3D printing personalized pelvic tumor limb salvage reconstruction treatment.
5.A surgical classification system for the management of axial primary malignant and aggressive benign tumors and its application in multiple tertiary centers
Nanzhe ZHONG ; Feng LI ; Jinglong YAN ; Tongwei CHU ; Jian YANG ; Chen YE ; Shaohui HE ; Minglei YANG ; Jian JIAO ; Wei XU ; Haifeng WEI ; Tielong LIU ; Jian ZHAO ; Zhipeng WU ; Cheng YANG ; Xinghai YANG ; Jianru XIAO
Chinese Journal of Orthopaedics 2020;40(11):689-699
Objective:To propose and verify a surgical classification system for the axial primary malignant and aggressive benign tumor.Methods:The CZH surgical classification system was originally developed for the axial primary malignant and aggressive benign tumor. The CZH surgical classification system includes seven types, according to the anatomic features and the extension of tumor violation. A total of 136 patients (79 males and 57 females) with axial primary malignant and aggressive benign tumor from multiple tertiary centers who received surgery from July 2006 to July 2019 were included. The average age was 44.40±17.55 years (8-83 years) old. There were 99 malignant tumors and 37 aggressive benign tumors included. The number of patients with each classification was presented as followed, Type I 13, Type II 15, Type IIIa 3, Type IIIb 20, Type IVa 43, Type IVb 12, Type Va 21, Type Vb 3, Type VI 2, Type VIIa 3 and Type VIIb 1. Surgical procedures were selected according to different types in classification. The inter- and intra-observer consistencies were evaluated by the Kendall's W test. The VAS, Frankel score, overall survival and recurrence free survival were recorded during the follow-up. Results:The inter- and intra-observer consistent coefficient was 0.973 and 0.996, respectively ( P<0.05). The single posterior approach was adopted for the Type II tumors. Other patients underwent surgery by the combined antero-posterior approach. The majority in anterior approach (113 cases) was the modified submandibular approach. The reconstruction modes included anterior "T" shape titanium mesh (112 cases) or the 3D printed prothesis (7 cases) combined with the posterior occipto-cervical fusion (92 cases) or the pedicle screw system (44 cases). The average surgical duration and the volume of intraoperative bleeding was 348.40±136.14 min (60-760 min) and 1 225.69±859.40 ml (80-4 000 ml), respectively. The operation duration and volume of intraoperative bleeding among each type were with statistical difference. The patients with Type IV, V tumors had longer operation duration than those with Type II tumors. Those with Type V and VII tumors had longer operation duration than those with Type I tumors. The patients with Type V tumors had more intraoperative bleeding than those with Type I-IV tumors. The average preoperative VAS score was 4.15±2.25 and then was reduced significantly to 0.62±0.71 and 0.38±0.59 at one and three months after operation, respectively. The Frankel score was also significantly ameliorated at one and three months postoperatively. There were 22 postoperative complications (16.2%). The complications included cerebral spinal fluid leak (12.5%), dysphagia and/or dysphonia (7.4%), dyspnea (5.1%), wound infection (3.7%), wound hemorrhage (2.2%) and pharyngeal dehiscence (1.5%). The incidence of postoperative complication was 25.9% in Type IV-VII tumors, while 11.8% in Type I-III tumors. Conclusion:CZH surgical classification system was verified with high observer consistency. This classification system could assist surgeons to select proper surgical approaches, resection modes and reconstruction modes, and thus ensure the safety of surgery and reduce the recurrence. The tumors in Type IV, V and VII may be with more challenging for surgeons. The incidence of postoperative complication in Type IV-VII tumors may be higher than that in Type I-III tumors.
6.Advanced progress in classic genomic and non-genomic regulating mechanism mediated by retinoic acids in anti-cancer treatments.
Shaohui HE ; Wang ZHOU ; Zhitao HAN ; Jianru XIAO
Journal of Central South University(Medical Sciences) 2019;44(1):81-86
Retinoic acid, an active metabolite of vitamin A, exerts multiple effects on regulating embryonic development and inducing differentiation, proliferation, apoptosis as well as resistance in various cancer cells. Apart from the classic genomic action (binding to the nuclear receptors to regulate the expression of its downstream target genes), retinoic acids also play important roles in anti-cancer effect through non-genomic pathways (via extranuclear and non-transcriptional effects).
Apoptosis
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Cell Differentiation
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Genomics
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Humans
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Neoplasms
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drug therapy
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Receptors, Retinoic Acid
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Tretinoin
7.Total en bloc spondylectomy for spinal tumors of the fourth lumbar spine via a posterior approach: our clinical experience
Wending HUANG ; Haifeng WEI ; Wangjun YAN ; Weiluo CAI ; Wei XU ; Xinghai YANG ; Zhipeng WU ; Tielong LIU ; Quan HUANG ; Jianru XIAO
Chinese Journal of Orthopaedics 2018;38(10):580-587
Objective To study the feasibility and safety of total en bloc spondylectomy (TES) for bone tumors of the fourth lumbar spine and evaluate the clinical outcomes.Methods From March 2011 to December 2013,21 patients undergone total en bloc spondylectomy in posterior-only approach were retrospectively reviewed.The patients included 9 males and 12 females,with a mean age of 47.1± 15.6 years old (range,15-71 years old).This series included 12 cases of primary bone tumors and 9 cases of solitary metastases.Preoperative evaluation according to clinical,imaging and pathologic features was performed meticulously to select patients.The length of surgery,estimated blood loss,surgical margins,instrumentation failure,perioperative complications,Frankel scale,visual analogue scale (VAS) for pain,local control rate and overall survival were reviewed and analyzed.Results Total en bloc spondylectomy was performed successfully in all patients.Average operative time and estimated blood loss were 297.6±44.6 min (range,225-420 min) and 2 247.1±904.5 ml (range,900-4100 ml),respectively.The mean follow-up time was 50.4± 17.1 mons (range,24-79 mons).All patients encountered nerve roots stretch and 5 patients (23.8%) showed lower extremeties neurological dysfunction.All of them improved in 2-4 weeks postoperatively and recovered completely at 6-month follow -up.Cerebrospinal fluid leak was found in 4 patients (19.0%).The VAS score was 1.5±1.4 at post-operation,which was significantly lower than the 6.2± 1.6 in average at operation (P=0.008).Three patients with metastatic tumors died during the follow-up.Titanium mesh cage subsidence was observed in 7 patients (33.3%).No implant failure was occurred during the follow-up.Conclusion Total en bloc spondylectomy for tumors of the fourth lumbar spine in a posterior-only approach is feasible.However,there are many intraoperative neurological complications and the indications for TES are extremely limited.
8.Research on cancer stem cells in osteosarcoma: current status, controversy and comment
Chinese Journal of Orthopaedics 2018;38(18):1135-1142
Osteosarcoma is the most common primary malignant tumor of bone in children and adolescents and advanced osteosarcoma patients with evidence of metastasis share a poor prognosis.Osteosarcoma frequently gains resistance to standard therapies highlighting the need for improved treatment regimens and identification of novel therapeutic targets.The composition of cancer stem cells is one of the attractive theoretical studies in osteosarcoma biology.It has been proposed that osteosarcomas are composed of a group of functionally heterogeneous cells.Only a small number of osteosarcoma cells have stem cell characteristics,with self-renewal and differentiation capacities,which facilitates in the generation of different types of osteosarcoma cells.These osteosarcoma stem cells play a decisive role in maintaining the proliferation,invasion,recurrence,and metastasis of tumors.Previous research suggests that osteosarcoma formation may result from the development of cancer stem cells by the deregulation of normal self-renewal pathways of tissue stem cells.The discovery of cancer stem cells in osteosarcoma offers a new approach to understanding the biology of these conditions.Further study is needed to understand both normal and osteosarcoma stem cell development and various signaling pathways which appear to regulate self-renewal of stem cells and CSCs,with dysregulation of these signaling pathways leading to tumorigenesis.Ultimately,new prognostic and predictive markers,as well as targeted therapeutic strategies,may be developed to force osteosarcoma into better outcome or permanent remission.In this review we will discuss the research advance of cancer stem cells in osteosarcoma such as commonly used isolation techniques for osteosarcoma stem cells as well as the identified biochemical and molecular markers and we share our viewpoints on controversy in research of osteosarcoma stem cells.
9. Regulation of Wnt/β-catenin signaling in bone development and bone tumor
Chinese Journal of Surgery 2018;56(10):797-800
The Wnt/β-catenin signaling pathway is crucial in bone development and homeostasis.Normally, it has been suggested to play a significant role in regulation of osteogenic differentiation of bone marrow mesenchymal stem cells, osteoclastogenesis and?偅ibone mineral density. Dysregulated Wnt/β-catenin signaling pathway is responsible for bone tumor, metabolic bone disease, degenerative bone disease and it related to development and invasion of osteosarcoma and Ewing′s sarcoma.Studies of the molecular mechanisms of Wnt/β-catenin signaling pathway provide theoretical basis of a potential target for bone diseases.
10.The application of en-bloc resection of primary sacral chordoma based on 3-Dimensional printing technology
Jinhai KONG ; Ming QIAN ; Nanzhe ZHONG ; Hui XIAO ; Jian ZHAO ; Xinghai YANG ; Haifeng WEI ; Zhengwang SUN ; Wangjun YAN ; Tielong LIU ; Jianru XIAO
Chinese Journal of Orthopaedics 2017;37(10):620-628
Objective To investigate the safety and feasibility of en-bloc resection of a primary sacral chordona based on a 3-dimensional printing model.Methods 31 patients with primary sacral chordoma underwent en-bloc resection via a onestage posterior approach or combined anterior and posterior approaches in our oncology department from January 2013 to December 2014.They comprised 21 males and 10 females of mean age (49.2±12.5) years (range,26-67 years).Preoperative 3-D printing models were created by 3D printing technology,it included tumor tissue,the around vascular and nerves involved in sacral chordoma.The sacral chordomas were en-bloc resection with decompression and internal fixation.Results With the mean (29.0±6.8)months follow-up (range from 19 to 41),all patients underwent en bloc excision via 26 cases with posterior approach,5 cases combined posterior and anterior approaches in one stage.The mean operative time and estimated blood loss were (275.0±58.1) min and (3 250.0±1 304.4) ml,respectively.The visual analogue scale (VAS) score was (5.6±1.9) in average (range from 3 to 9) at preoperation,and (2.0±1.5) at post-operation,which was significantly lower than that of preoperation,and the pain was relief obviously.There were 13 cases in grade C,11 cases in grade D,7 cases in grade E of American Spinal Injury Association (ASIA) grade neurological function before surgery,compared with the pre-operation,there were 5 cases in grade C,6 cases in grade D,20 cases in grade E of post-operation,which was significantly improved.MSTS (Musculoskeletal Tumor Society) 93 score was 6-29 points (20.0%-96.7%) at the follow-up 3 months after surgery,with the average of (19.8 ± 5.8) points,which excellent in 8 cases,good in 14 cases,general in 5 cases,poor in 4 cases.Two cases of dysporia for the reasons of resecting on one side of the S1,2 nerve roots involved by the sacral chordoma,after sacrificing the nerve root of complete tumor resection,the urine left dysfunctional,while the pain of other 29 patients were thoroughly relief after surgery.The ones were relieved with the disturbance of sensation of the perineum before the operation.2 cases were recovery of leakage of cerebrospinal by the drainage of lumbar cistern with normal temperature.One hypostatic pneumonia patient was cured by anti-inflammatory.One with the urinary infection got better by the effective bladder irrigation,which had diabetics mellitus with the bladder stoma before.1 case of skin necrosis due to vascular thrombosis before operation,recevied flap translocation half month after surgery,got recovery 3 months later.Only one underwent tumor resection for the recurrence at 15 months follow-up.Conclusion It is feasible and safe to perform en bloc resection of primary sacral chordoma.This is the most effective means of managing method of the marginal resection of the tumor.Preoperative 3-D printing modeling enables better anatomical understanding of the relationship between the tumor,and can avoid vascular and nerves tissue injury,which can also assist in planning the surgical procedure,and be worth recommendation.

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